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·THE HUMAN APOCRINE SWEAT GLAND IN HEALTH AND DISEASE

·Publ cat on Aumber 376
AMERIC IN LECTURE SERIES
A Vonograph
WMERICAN I ECTURES IN DERMATOLOGY
rd led by
ARTHUR C CURTIS VID
Charman Depastment of Dermatology and Syah lology
Unterstly of 11 ch gan
Ann Arbor Whoan

·The
HUMAN APOCRINE SWEAT GLAND
in HEALTH and DISEASE
B;
HARRY J. HURLEY, M.D., D.Sc. (Med)
Professor of Dermatulogy
Hahnemann Vedical College
Philadelphia, Pennsylvania
and
WALTER B. SHELLEY, M.D., Ph.D.
Professor of Dermatology
Unuersity of Pennsylvania School of Medicine
Philadelpha Pennsylvania
CHARLES C THOMAS
+
PUBLISHER
Springfield
Illinois
U.S.A

·Publuation Sumber 376
AMERICAN LECTURE SCRII Sky
A Vonograph in
AMERICAN I ECTURES IN DIRMAIOLOGY
doled by
ARTHUR C CURTIS, VD
Chairman, Department of Dermatology and Syphilology
Umesity of Michigan
Ann Arbor, Pichigan

·DEDICATED
to
Jeanne and Marguerite

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·ACKNOWLEDGMENTS We are indebted to Dr Donald M. Pillsbury, Professor and Chairman of the Department of Dermatology, School of Medicine of the University of Pennsylvania, and to Dr Herman Beerman, Professor of Dermatology of the Graduate School of Medicine, University of Pennsylvania, for the opportunity to pursue this course of study, and for the facılıties utilized in the investigational program In special phases of the work we were aided by Dr George B hoelle, Anna Nichols and Dr Fred D Weidman Mr Edward F Glifort, Jr, photographer for the Department of Dermatology, University of Pennsylvania supplied the photographic illustrations We appreciate the meticulous attention he gave to this important aspect of this work Mirs crna Stein, our histology technician, merits our appreciation for the fustologic staining during these studies In addition assistance in various aspects of the work, was given by Drs Herbert L Ratcliffc, F E hral, and Sandra Golomb Tlic entire study was financially supported by United States Public Health Service and United States Army research grants A number of the photographs and photomicrographs used herein had been published in several of our journal publications We are grateful for the opportunity to reproduce these in the present voluine and acknowledge the permission of the respective journals for these figures as follows All Arch Dermat (Shelley II Band Hurics HI ) 69 449 1954 Figures 11 41 42 43 44 45 46 48 11 Arch Dermal (Shelles B and Hurlei HJ) 06 156 1992 Tigure 17 111 Arch Drmat (Shelles WB Hurles J and Nichols AC) 68 430 1993 Figure 38 39 40 and Graphs I II and III AVA Aich Damar (Shelles UB ind Lev E) 73 38 1996 Figure 57 ) ·Vili The luman Sucal Gland i Ilealth and Disease Incest Dermal (Shelles, WV B and Levy, E) 25 249, 1955 Figurc 13, j Iniest Dermal (Hurley, HJ, Shelley, Il B, and Koelle, GB) 21 139, 1953 Figure 14a and b, ) Inzest Derma! (Shelley, WB and Hurley, HJ) 20 285, 1953 Figures 18, 20, 7 Incest Dermat (Hurles, HJ and Shelley, WB) 22 143 1955 Figures 21, 22, 24, 25, Inzest Dermat (Shelley, WB and Hurley, HJ) 28 155, 1957 Figure 34, ) Inzest Dermat (Hurley, HJ and Shelles, WB) 22 397, 1954 Figures 49, 51, 52, 53, 55, But I Dermal (Hurley, HJ and Shelley, 1 B) 66 43, 1954 Figures 29, 30 In addition, Figure I was taken from the work of W Montagna H B Chasc and W C Lobitz Jr published in the American Journal of Anatomy, 92 451, 1953 It is a pleasure to acknowledge the generosity of Winthrop Laboratories whose aid made possible the color reproduction of the frontispiece A final word of appreciation is reserved for the staff of Charles C Thomas Publisher with whom it was a pleasure to work in the preparation of this lolume HJH WBS ·CONTENTS Y11 Ichn clelgi ents C/ after I Introduction 6 6 7 8 II The Anatomy of the Apocrine Sweat Gland A Vethods And Vaterials B Embriology C Morphologs D Topographical Relationship Location in Shin [ Histology and Histochenustry F Blood Suppls lymphatic Drainage G Innervation H Comparative Anatony 12 13 22 22 23 27 27 28 28 28 32 111 The Physiology and Pharmacology of the Apocrine Sweat Gland 1 Vethod and Materials B Phases of Apocrine Sueat Gland I'unction (Ipocrine Sneating 1 General Description 2 Effect of Emotional Stimul 3 Effect of Sensory Sumuli 4 Effect of Heal 5 Effect of Cold 6 Efect of Sea onal Variations 7 Effect of Drugs 8 Effect of Physical Sumul 9 rffect of External Pressure 10 Fffect of Satural factors – Ige Scs Racc 33 35 35 36 36 40 41 41 16 ·42 441 51 55 61 01 62 64 66 11 The Refractor Period Miscellaneous Ob ersations 12 Aron Refle Apocrine Snealing 13 Mechanisin - Role of the Mis oepithelum 14 Comparative Studies 15 The Problem of Two Sccretions D Apocrine Secretion 1 Definition - General Tentures 2 Fffect of Natural l'actor - Agc, Sul, Rice 3 Effect of Endocrinc Starcs 4 Effect of Systemic Dresc 5 Effect of Deodorants 6 Effect of Horinoncs 7 Effect of \r 8 Relation to Pilo sebaceous Activity C D cussion and Summors of Ipocrine Sweat Glind Physiology The Sature of Apocrine Sweat 1 Physical Characteristics B Chemical Characteristics (Bacteriology D Bods Odor 67 62 73 7 78 78 7) 81 83 97 97 99 110 \ Disorders of the Ipocrine Sweat Gland 1 Osmidros Bloc lud Chromidrosis ( Ipocrine Sweat Ketention 1 ss mpcom it Ipocrine Sweat Retention 2 Tor Tordice Disease 3 Hidradentes Suppuratiss Biltorphs 110 123 1.26 131 135 ·THE HUMAN APOCRINE SWEAT GLAND IN HEALTH AND DISEASE ·Irontispune Ino/ike arbarous umut I sin all pokec o teshk < xerse d axillars skin was stained with incthylene bluc (01) and gentle disse ton employed 10 expose the abos structures The stratum curne um at the map of the photo uph has been paralls rtt ckd back In alsnost straight black 11 tiends din from the skin to the center of the photograph Pric conded in 183 of tubules (right lower) 1 an uparine sneat glind Suits upper ble ont en see the apparent beginning of the sine dust Vote that it until thun procreets up ord parallel with the leur user the destulated blue-statning se burunis klands to open at the upper and the hair collude 11 thus Uppt ind of the hour ou le also a srcard apie dat mith prointent diluted funge I sxd opening can lor sen tomt thus sim fellule on thar ujjxxfr side 1 tu dne 15 sevrreu frein is glandular component during the disvetrin ·I INTRODUCTION Within recent years, there has been a rapidly increasing store of information concerning the physiology and pathology of the cutancous appendages of man However, one of these appendages, viz, the apocrine sweat gland, has received considerably less attention than have the others While the eccrine sweat glands are found over almost the entire shin surface, the apocrine sweat glands are limited to certain well-defined areas, such as the axılla, anogenital region, the mammary areola, the ear canal (cerumninous glands) and the eyelid (glands of Moll) The restriction of the apocrinc glands to such sites parallels the regression of terminal body hair and is believed to represent an evolutionary change in lower forms, such as the horse and dog apocrine glands associated with body hair are found over almost the entire cutaneous surface Because of the special localization of the apocrine glands in man, plus the fact that they have been regarded as atavistic organs little effort was made to examine them in greater detail One of the first descriptions of the "large sweat glands” of the axılla was made by Professor Horner of the Department of Anatomy, of the University of Pennsylvania, in 1846 (1) Later descriptions by Krause (3) and by Rolin (2), who described these glands in the inguinal region and pointed out that they were visible grossly, were noteworthy Heynold (4) described the apocrinc glands of the ear canal in detail, in 1876 The first mention of the nature of apocrine sweat was made in 1852 by von Kolliker (5) He described it as "whitish-yellow, tolerablyviscid" matter a rather accurate description in light of our present knowledge One is unable to find any additional information of ·4 The Human Sural Gland in Health and Disease significance regarding the secretion of the apocrine sweat glands up to the present day Other isolated reports on the apocrine sweat gland appeared prior to and after the turn of the century However, it was not until 1922 that Schiefferdecker wrote the first really extensic account of the human apocrine sweat glands (6) This author detailed the anatomy of the apocrine sweat glands, emphasized the racial variations seen, and formulated an anthropological hierarchy based on the number and location of these glands He proposed that the fewer the number of apocrinc sweat glands Present, the higher the developmental state He found the highest level of development to be represented by the Nordic malc, wlule the lustralasian and Negro, with larger and more numerous glands, and with apocrine glands less restricted in localization Were at the bottom of the scale Other races fell in between in general females, with greater numbers of apocrinc swcat glands Mere thought less evolved than males One of the primary points of interest regarding the apocrine sweat glands during thus period concerned the development ol these glands at puberty, and the influence of endocrinc states and age on their function Much of this work was controversial and will be discussed later in this report Inother interesting facet of the development of the apocrinc sweat glands concerned the claim that apocrinc glands may undergo metamorphosis into eccrine sweat glands during adult hfe (von Lggeling) (7) We are promptly reminded of the claims of Kuno (8) and O'Brien (9) that there may be intermediate sweat glands whub possess properties of each, and defy strict histologic classification For all practical purposes, the plıysiology and pharmacology of the apocrine sweat glands have been completely ignored through The innen ation, means of stimulation, mechanisms inrolad in apxxcrine funcyon, and the pliarmacology were un. known and little mention of these features can be found in the literature The study of Ounct and Nauch in 1930 on apocrine sneat gland function was one of the few that was available (10) These authors, studying the histology of biopsy specimens of axillary skin previously stimulated by various drugs, reached thic the years ·Introduchon 5 rather unlikely conclusion that atropine stimulated and epinepirine inhibited the apocrine sweat glands Except for the time honored notion that these were "scent glands" similar to those in the lower mammalia, no other concept of their importance to man was available The pathologist, however, perhaps stimulated by the derniatologist who noted peculiar eruptions limited to apocrine areas, incriminated the apocrine sweat gland in several dermatoses Fox-Fordyce disease (1902) and hidradenitis suppurativa (1933) became known as "apocrine" disorders However, as is often the case where basic knowledge of the morphology and function of a structure is laching, the pathogenesis of these diseases was not understood Our investigative program on the apocrine sucat gland began an May. 1951 It continued through 1956 comprising therefore some five years of study During thus period there was a renewed interest in the cutaneous appendages by some anatomists and histochemists, notably Montagna and this served as a great impetus In addrion, Yas Kuno, the renowned Japanese physiologist who has contributed so much to our knowledge of eccrine sweat gland function, stimulated us by the excellence of his work The bull of the observations made in these studies concerns the apocrine sweat glands of the asılla The axillary apocrine sweat glands are the largest, best developed and most numerous in human shin no matter what the race of the subject studied Furthermore it is relatively easy to utilize the aulla experimencally While some criticism as to extrapolation of our findings to apocrine sweat glands of other regions can be made we feel that for the most part, such extension of our observations may be made with confidence Correlate studies of the apocrine glands of the human car canal liave verified this a«sumption (11) Ipocrine gland tumors have not been included in this book since we have not had an opportunity to study these lesions expersmentalls ·II THE ANATOMY OF THE APOCRINE SWEAT GLAND A. METHODS AND MATERIALS Tuis work is based on observations made on over evo hundred biopsy specimens The great majority of these were taken from the axillae of normal adult male volunteers between the ages of 19 and 75 vears of age Several specimens were also obtained from male and female bodies at autopsy In addition to the axilla, from which most of our material was secured, samples from the inguinal region, chest, abdomen, face, and scalp serc also included Examination of gross morphology was accomplished in some cases by in no study of the axillari structures after incision of the skin and reflection of the skin edges with Allis forceps in addition, micro-dissection of axillary skin specimens after staining with 0 1% methylene blue was employed, along with special techniques for the preparation of whole mounts These methods are described further in the captions beneath the photographs Staining techniques tised included routine hematoxilin and eosin, phospholungstic acid-hematorylin, periodic acid-Schuit stains with and without diastase (12) Goinori's Prussian blue stain for iron (13) silver stain of Perez (14) and the cholinesterase techniquc (Koelle) (15) Appropriate fixatnes were employed throughout In addition, unstained specimens were studied after frozen sectioning (10-20 microns) and «cctioning of parallın. imbedded tissue (6-10 microns) It should be emphasized that all of the biopsies taken sere of adequate size and depth Relatruely large biopsies are necessary in order to insure visualization of entirc apocrine su cat glands as well as adjacent glands and related structures ·7 The Anglomy of the 4pocrine Storat Gland B EMBRYOLOGY The apocrine sweat gland is a derivative of the primary epithelial germ as are the sebaceous gland and hair ſollicic (16) Actually, at an early stage of des elopment, about the fourth to fifth intrauterine month, all hair follicles over most of the shin surface, have the potential to develop apocrine sweat glands At this time, a small nipple-lhe downgrowth appears at the upper end of the hair follicles This downgrowth consists of a solid cord of epithelial cells It continues to extend and develop into apocrine gland rests in only a small percentage of hairs, however, primarily in those of the axılla, ano-genital region, mammary areola and car canal but also irregularly on parts of the trunk, scalp and face In the rest of the skin, the apocrine bud gradually diminishes in size and is cientually lost as a part of the hair follicle or adjacent epidermus It should be noted that the point at which the downgrowth appears is about at the junction of the hair follicle and epidermis This is an anatomical relationship that is retained cien at full des clopment for the apocrine duct of the adult apoerine gland opens at a hugh level far up near the hair follicle orifice While the hair follicle should be regarded as the site of origin of the apocrine loud the close proximity of the bud to the epidermis readily explains the occasional extra-follicular apocrine duct one sees in the adult It would appear that the apocrine Isud migrates or pulls away from the follicle to develop independenth Lxtenson of the apoenne downgrowth is continued with coiling and cleft formation in the center of the cosled cords Eventually, a lumen is formed and subsequent differentiation into glandular and ductal portions occurs by the ses enth to eighth months It birth however and for seleral years thereafter, the apocrine glands mule distinguerable histologically are non-functional and remere rests in essentialls all apocrine areas except the car canal In this site full development of the apocrine glands occurs before birth Thus these apocrine glands, which are called ceruminous glands in sharp contrast with other apocrine glands of the skin, are full functioning at birth and are apparently under a different endocrine control In the apocrine sweat glands, my oepithelal cells are not present at birth but differentiale some time thereafter ·8 The Humar Satrat Cland in Health and Disease NORMAL APOCRINE SWEAT GLAND DUCT SEBACEOUS GLAND SECRETORY COIL HAUR FOLLICLE 3220€ Fig 1 Drauing of apocrine su cat gland Observe shunts and docrticuli along course of tubules in secretory portion of the gland Duct opening into hur follicle ordinanly enters at a higher point than shown in this drawing The secretory cells of the apocrine sweat gland arc devoid of granules at birth with comparatii ely low cytoplasm indicating the lack of secretory activity (17) The puberal era marks the period during which full activation of the apocrine sweat glands occurs Paralleling the change in the apocrine glands is the growth of the terminal hair in the same regions Significantly the mammary gland, an apocrine gland anatomically also does not reach full deselopment until puberty C MORPHOLOGY The apocrine sucat gland can be classified anatomically as ? simple tubular gland with shunts and decrticuli It is simple since it has a single duct which proceeds from the coiled glandular mass below and empties above into the hair folliclc It is a tubular ·9 The Anatomy af the Apoctise Sezat Gland gland in contrast to an alveolar or tubulo-alveolar gland since its secretory component consists essentially of a coiled tube However, careful examination (Fig 1) of the gland reveals that some parts of the tube are bridged by small shunts, while in other areas, pouch-like projections or diverticuli are present It should be recalled that these variations of the simple tube as seen in the apocrine gland are not a ſeature of the eccrine sweat gland coil The apocrine sweat gland is grossly visible without the aid of magnification or special staining If one incises and then reflects the skin of an apocrine gland-bearing area, visualization of the apocrine sweat glands as small yellow or reddish-yellow globular masses approximately 1 mm diameter in the deep dermis and subcutaneous tissue is readily made (Figs 2 and 3) The reddish tint of the glands which has been attributed to increased amounts of iron, is quite variable in its appearance The relatively great size of the apocrine sweat gland should be easily appreciated for the eccrine sweat gland (approximately ten times smaller) and sebaceous gland are visible only after some degree of magnification On casual examination, apocrine glands may appear to be broken into lobules Close inspection, however, reveals that this is not the case, and the apparent lobules are really all part of the same gland Negroes have apocrine sweat glands of relatively great size They are larger than those of the White race (Fig 2) In general, the apocrine duct is much shorter in proportion to the gland than is the eccrine duct to the eccrine gland, (sce frontispiece) However, this is not always true for occasionally the apocrine duct shows a loop or coil along its course, indicating longer length in these instances The point of demarcation of the apocrine duct from the tubule can be precisely marked only under histologic examination, although some change in calibre of the ductal diameter can be seen grossly (see Frontispiece) As in the eccrine gland, the initial portion of the apocrine duct usually begins within the coiled mass but is generally coiled for a shorter distance in the apocrine than in the eccrine gland At its upper end, the apocrine duct becomes funnel-shaped (infundebulum) as the duct opens (above the sebaceous ducts) into the upper end of the hair follicle (Fig 4), or separately onto the shin ·Tig ? 11hite and legro afotine sural glands Ihc axillary skin was incised and reflected with Illus forceps Idult Ihite mans skin (above) and adult Negro man s skin (bel) Globular bodies beneath skin surface are apocrine sweat glands. Although magnification for each photograjta was slightly different glands of the legro are larger vas < 3% (ut per) 4 (toner) ·+3 Tegro apoctine su eat glan: Same as Negro skin of his 2 but under higher magnification (x 8) \ote some of the vessels supplying these glands tportune durf open ne no har fall de Histological view of apocrine duct 35 it enters hair follicle lote dilatation of the duct shows here This resulted frum experimentally produced ductal occlusi n to Apocrine Sweat Retention) and abnormu Comoureuth normal dicto High 5 tandr Nar 100 ·12 The Human Swral Cland in Health and Disease surface Quite commonly, more than one apocrine duct empties into the same liair follicle (frontispiece) On occasion, cien three ducts have been observed opening into the same follicle 17 D TOPOGRAPHICAL RELATIONSHIP - LOCATION IN SKIN Tundamentally, apocrine sweat glands are oriented anatomically in relation to hair, more specifically, the terminal body hair of the area in which they are found Thus they are part of an "apopilo-sebaceous unit As mentioned previously, it is true that a few apocrine ducts are extra-follicular în location, but all are derived embryologically from the primary cpithelial germ and much of their development and functional activity parallels that of the hair of these arcas The main body of the apocrinc gland lies deep in the true skın in the deeper portions of the corium and upper subcutaneous tissue They appear densely packed together in most areas such as the axılla (I ig 2), although there are probably only a few thousand glands per avulla as compared with four to five times as many eccrine sweat glands in the same arca The axılla contains the greatest number of apocrinc sweat glands and it is our finding that the overall size of the individual gland is larger there than elsew here In contrast to the eccrinc sucat glands which are found over almost the entire skin surface, the apocrine sucat glands are restricted to a few well defined areas such as the axilla, thic inguinal region perianal shin the mammary arcola and less consistently on parts of the trunk such as the umbilicus and larry region of the chest In addition there are apocrine glunds in the car canal (ccruminous glands) and in the eyelid (glands of Moll) Tinalls the mammary gland, a cutancous derivative is an apocrine gland Apocrine sucat glands in areas other than the above are con sıdered fietcrotopic in location (18) Iloncicr we have been impressed with the numbers of apocrine glunds found on the face especially the malar region of the checks These fucial glands are considerably smaller than were those of the axili ljut dire is pical structurally Simularly the scalp shows apocrine elements not uncommonly (18) It is our feeling that deeper (uts and inore thorough cxamination (utilizing serial sections) of routine tropics from these areas would disclose the presence of these glands with ·13 The Analony of the Apotnie Sie ert Gland much grcater frequency than has been perceived heretofore The quantities of sweat secreted from these glands is quite small and consistent with the size of the glands Moreover, it is probable that many of these glands are non-functional E HISTOLOGY AND HISTOCHEMISTRY The histologic appearance of all apocrine glands is distinctive The very designation "apocrine” resulted from an interpretation of the method of secretion of these glands based on the histology 10- a Greek root meaning "from" and apocrine secretory cells appear to be losing the apical tıp of the cell histologically, a decapitation (Fig 7) Thus, part of the cell appears to be lost in the apocrine secretion In contrast, eccrine glands form a flud product without appreciable loss of any of the secretory cell This is referred to as mcrocrine secretion Histologic visualization of eccrine sweat glands reveals none of tlie pinclıcd-off lumnal tips of the tubular cells, as seen in the apocrine glands It is interesting in this respect that Kuno has described eccrine secretory cells which do show such changes in Japanese (8) Also, O'Brien has referred to an "intermediate" gland in some biopsies he has studied which have both apocrine and eccrine characteristics (9) The significance of such variations is not entirely clear but may reflect racial differences Finally, the third glandular type, the holocrine gland, is also represented by a cutaneous appendage the sebaceous gland In this type of secretion all of the cell is lost in the secretory process This is a much steadier and slower phenomenon than ecerme or apocrine SCCiction The ductal portion of the apocrine sweat gland is difficult if not inipossible to distinguish (rom that of the eccrine gland on histologic appearance alone Both have a double layer of basophthic staining cuboidal cells devoid of myocpithelium, but with a well-defined basement meinbrane (Fig5) The apocrine duct is toeliced to be of slightly larger caliber and some authors feel the cells show more eosinophilia than does the cccrinc duct, but it is oui fecling that such sariations are insignificant and not of value in differentiation The transition from tubule to duct is quite abrupt in the apocrine skeat gland The intraepidermal ·ipocrine du lori xxsin dut host alls sit entrsh the Several cuts of the du tare seen Obseithiri rette duti i prefontidos cells In II 1 pourine entor tubule (ress stiti ce soit n gull shi * ing single layer of Jumnis se retis cells Bus mint mintyn und epithelsal cells are esident (mpire with lights - 10 ind 'l in study of my epithelium P15 pt nlakra inut she in) i pres nt in (pism! Vtri di #stise incubatt n this disapp ir PIS sidin si duast 15c) with lfarras hem toxilin xerunt est un Societary cells ·15 The traton y of the Ipoche Sural Gland end of the apocrine duct is marked by the presence of a luminal hyalıne fringe, the cuticle, which is similarly visualized at this level in the eccrine duct Unlike the eccrine duct, the intraepidermal portion of the apocrine duct is straight and not coiled in appearance There is some keratinization near the open end of the apocrine duct, also as in the cccrine duct Histochemically, the apocrine duct shows cytoplasmic basophilia which is removable after exposure to ribonuclease Glycogen is absent or present only in minimal quantity in apocrine ducts Acid phosphatase and lipids are present in moderate quantities and Feulgen-positive staining of the nuclet is evident Apocrine duct cells show no metachromasta and no alkaline phosphatase (19-21) Apocrinc seat gland tubules possess a single type of secretory cell surrounded by a basement membrane with myoepithelium interposed (Fig 6) The secretory cells are eosinophilic, and have a round nucleus with prominent nucleolus (Fig 7) The nucleus occupies a basılar position in the ceil The cytoplasm of the secretory cells varies in size from a flat cuboidal type to the high columnır variety with the appearance of a pinched-off luminal tıp (Figs 7 and 8) This variation in cell height is believed to reflect the cyclic nature of the secretory process However, no uniformity of cell height within an individual, a skın area, a single gland or tubule, can be seen, and variations in cell height are evident cven in nearby cells within the same tubule Under high power after frozen sections especially, the luminal border of the apocrine secretory cell shows a "fringe" or row of what appear to be tiny droplets (Fig 9) These were first described by Montagna as possibly representing apocrine secretion (19) I his author has demonstrated that the decapitation" or pinchedoff appearance of the glandular cell is a visual artifact Examinition of serial sections reveals that such cellular projections emanite from adjacent cells below those in the immediate surface plane of section I he myocpithelial cells of the apocrine sweat gland are a pecialized variety of smooth muscle and will be discussed in inore detul in the Physiolo, section 1 bey are better des cloped 111 the pocrine glind than in the cccrine gland but not so prominent as in the mammary gland The cells arc fibrillar, 40-100

·to
The 1 in C Sieat Glan/ in Ilali (1) Pro
rig 7 portine warto all Ispuul ap verine seat I starlle un ietwSu1
(* 1200) showing decapitation ppxurante ! Jurunil up fall itp
ment granules of varying size round nucleus dad prom in duk sustinh
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Showing segments with high column ir scenery <!! is well as met with
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·17 The Anatomy of the Apocrine Surat Gland 200 WM. Ipocrine secretion Drawing by Dr 11 m Montagna depicting luminal Iringe or droplets (0) This may be mechanism of apocrine secretion Best seen after frozen sections Luminal fringe also ecen under electron microscopy (109) microns in length and arranged so that tlıcır long axis 18 roughly parallel with triat of the tubule They stain with hematoxylın and cosin lut are seen especially well suith phosphotungstic acid. liematoxylin and periodic acid-Schiff icchniques (Tig 10) The apocrine secretory cells contain numerous pigment granules which are readily visualized in an unstained section They are of ·18 The Human Surat Cland in Health and Disease www.hr rig 10 11yorputhelium of apocrin su eat gland Tinger like projections surrounding apocrine tubules (here filled with luminal cast) are myoepithelial cells Mose are cut obliquely in this section This is a PIS stain after diastase note also absence of glycogen in secretory cells of apocrine sweat gland Vag 330 varying size and are brownish-vellow in appearance (lug 11) The number of these pigment granules varies grcally from cell to cell Chemically thcsc granules are in the lipoſuscın family, similar to the "abnutzung or 'weir and tear' pigment found in the inner spleen peripheral vessels and other parts of the body They have a spectrum of properties depending on their oxidase state, showing aryin degrees of sudanophilia acid fastness, reducing activity and fluorescence (20) It is this pigincnt wluch is responsible for the occasionil color in aporrinc sucat and in the section on chromidrosis we shall discuss it further Sigorta cantly, the ceruminous glands (apocrine glands of the cir cinal) contain great numbers of these granules in the Caucasian although they are reduced in numbers in the Oriental Histochemically *pocrine Strefort (clls contI culgeripositive nuclear material miljonucleuse-sensitic cytoplasını bacoplulta minimal icd phosphatase (much less than in the ducis),

·19
ile natonty of the perine Sceal Glad
*1
rig 11 Parent granules in apo tine secretary cells Section of unstained axillary
skin shuning variably sized round or irregularly shaped pigmented granules
wwm i wlasm secteun tells (vypres) Compart with loner phoimeto
graj h of sume section showing fluorescence of some of these granules aſter er
posure to ultra violet light (4200 A) Vlag 2000

·20 The plurian Siscal Glan/ # Hlealih ar I Duere and some alkaline phosphatase (19) Ilic latter is present in the myoepithelium, also, and might in part represent diſfusion from nearby blood vessels which contain great quantities of this enzyme Small cosinophilic granules of quite consistent size and supranuclear position are seen also along with a variety of lipids Bunting et al (21) described four distinct types of lipids 1 After Sudan black, a delicate gray cytoplasmic stippling probably associated with mitochondria 2 Sudanophilic droplets which give a plasmal reaction, and are accione-insoluble, but pyridine-soluble at 60° C 3 An acctone-soluble, natural yellow pigment dissolved in the sudanophilic droplets, which emits a yellow-orange fluorescence under ultra-violet light and 4 abundance of bircfringent material soluble in acetonc Montagna was unable to define clearly more than the first type described by the above authors (19) Mitochondria are present in great numbers in active apocrine tubular cells, and are most numcrous ncar the nucleus Iron is present in many of the apocrine cells (Fig 12) especially in relation to the small yellow-brown granules The iron content of the apocrine cells shows some induu dual variation It is not found within the glandular lumen Miloses are a rarity in adult apocrine glands (Ig 13), but are seen with greater frequency in "agcing' glands in clderly individuals (22) Apocrine secretory cells contain very little, if any, glycogen Montagna has found some increased amounts within inguinal apocrine sweat glands, but much less than one sces in the resting eccrine sweat gland (19) Monoaminc oxidase is found in granular form in the secretory cells of the apocrinc glands and similarly localized in the eccrine sweat glands (23) Succinic dehydroant in cccrine glands is reduced in the apocrine tubules Consersely non-specific estcrase is much more highly concentrated in apocrine than in eccring sucat glands (24) It has been suggested that these enzymes may be used to distingursh these glands when necessary as in unusual cutaneous tumors of apparent appendagcal origin The lumen of the apocrine sunt gland may contain cellular casts or debris I his is much more marked a feature after frozen sections or s3th freezc-crying methods, but is still endent after routine formalın fixation genase, ab ·29 11 In the to F1 Smut Cl? Dari sing material th cytoplasm of in sriri *** :rPri SCRIS r rang 200 ron <lose study reveals it to {* so the fagin 138 granules ra thc m4 Voit the absence of tron in dy kant als Prusst in bile Itag in + 1 fra ut runt ell Vikut bgive n vrbe in center of photoish 31 3r rare in apexrin qiandi II and I Mag 1370) ·22 TI: Iluman Sueat Glad in Health and Orcase F. BLOOD SUPPLY-LYMPHATIC DRAINAGE The secretory portion of the apocrinc sucat gland is supplied by small arterial branches from the deep dermal arterial plexus. in the main Tiny arterioles follow and partially ens clop the tubules brcaking up into small capillaries The blood-filled seg. ments of many of these vessels can be discerned on cvamination of the apocrine sweat glands in vivo in incred, and reflected axıllary shin (Fig 3) Venules follow the course of thosc cssels and ulumately drain into the deep dermal ple us of veins Asus truc of the cccrine duct, a small arteriole and senule follow the apocrine duct as it progresses upward In the axılla, thc arterial supply is dcrn cd from branches of the subscapular and anterior circumflex humoral arteries, the axillary artery itself and occasionally from the intercostal arteries (25) This shows some indı dual variation Similar branclies from the avillary vein carry the venous blood to the deep dermal plovun of veins We will make no attempt at description of the blood supply in the other apocrine gland-bearing arcas Ilus informartion is available in any anatomical text The lymphatic drainage for all cutaneous appendages in var plexus of vessels in the dermis just decp to the vascular plexus In the axilla, the axillary nocles recente this return sending elleront essels to larger lymphatic vessels which empat cientually into the thoracic and right lymphatic ducts G INNERVATION The innervation of the frunan ipocrine sweat gland is derned from adrenergic fibres of the autonomic nervous sustein Prool that this supply is of functional importance is supplied on the section on physiology Siker stains outline these fibres poorly und suther from the fault that they do not deline neri e fibres selecicly Ilustre tissue and possibly myofibrils may be stained alo preventing Hear-cut icientification of the norie fibres is a result we could not calar mine the precise site of termination of the nerics supplying the apocrine sucat yland with this technique Vyocpithelial che me men certainly seem to be innerated but se cannot state whether or not the secretors calls are similarly supplied 11'e could not con ·The fialosny of the Abaine Steal Glad 23 firm Woolard's observation that only the myoepithelial cells of the apocrine sneat gland are innersated (26) Furthermore, we could not make out an end plate or any specialization of the nerveendings supplying the myoepithelium, although such are commonly encountered in other muscular structures Shelley and Cahn using a suprauital technique with methylene blue confirmed these findings (27) It is noteworthy that the apocrine ducr, like che eccrine duct, does not receive nerve fibres (107) With the cholinesterase (Che) teclinique (hoclle) at the usual incubauon times (30, 120 minutes), we demonstrated (Figs 14a und 14b) an absence of specific cholinesterase about apocrine sweatgland tubulcs (28) In contrast, the eccrine sweat glands show heavy concentrations of the enzyme Non-specific cholinesterase was not visualized about these structures Absence of specific Che about the apocrine sweat gland tubules at 30, 60 and even 120 minutes incubation persods usdxcates that these glands are not supplied with cholinergic fibres while the eccrine sweat gland tubules which showed the presence of the enzyme, do possess this type of autonomic supply These observations corroborate the physiologic and pharmacologic studies indicating an adrenergic innersation for the apocrine sweat gland and a cholinergic one for the cocrine glund Interestingly, if the incubation comes for the ChE icchnique are prolonged to four hours or beyond, some of the adrenergie libres supplying the apocrine sueat gland will betnnce Houcier the stuning is incomplete (Fig 15) consistent with the very low concentrauons of the enzyinc in adrenergic neric Wrough most of our studies with nerve stairs were done on unin ulir skin ve also examined the shin of the human urcinul in collaboration with Perry and Wood with similar itahmuen 139) I hese studies indicated an adrenergic innerition for the <eruminous glands also H COVPARATIVE ANATOVI (uncus and we are an itomu alls pox tine in iu pe tre terenul mt N! 151 1133m als althouzh their asserstrution varios to the Pranks le murends and plaiyrsnes lare only apocrine hands wie is the (parthine monkeys also poners eccrine

·24
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·1! com.my ) wo fre 1 tatra nf (h imsingit ## REFY fibras to ofruarin elinds Shorter incubauon 3X ra xds (10 s iv 120 min ) with the sholinesterase recha Kue revealed no st naine abi apskrine surat slands indicating the lack of a cholinergic toner Un Fernsion of the inevbanda period for subsijait-enzyme reactivity w { xur hours of besond resets some slight rregular staining of nerve fibres about the anxanne tuules as shown abx sc This is consistent wath an adrenergi upph W Counterstin Inculwiwn period 4 hours Viac 360 Stens gland log tastaturk seçlumn if the skin of the frunl of di sht nunc transcird sira gland subules lote rremblance esf these secreion cells sth of the human 4pxxrine gland fl and F Vag 1 450 ·26 The Hun an Sieral Gland in Health and Disrase glands, though the numbers of cach type varies in different species. Thus, in the macaques, thc apocrine glands greatly out. number the cccrine wule in baboons, the two varieties occurred with almost equal frequency (30) The orangutang possesses both types of sweat glands in the avilla with the apocrine bcing more numerous (31, 32) Of the anthropoids, the chimpanzec has been studied extensively, and apparently possesses both apocrine and cccrine glands in the aulla (33) The "axıllary organ" of gorillas is usually apocrine, it seems, but there may be some individual variations (30) Apocrine steat glands are found over all of the skin surface of the gorilla except the bach, palm and solc This is not surprising in view of the well-developed terminal hair present in these animals over most of the skin surface Other mammals possessing apocrine type sweat glands are the dog (rig 16), horse, sheep and ox (34) These glands are found over most of the skin surface of these animals and, at least in the horse and sheep, are the only variety of sucat glands ſound I hc hippopotamus apparently also possesses cutancous apocrine glands which elaborate the well-known 'bloody" sweat of that animal In addition, apocrine glands somewhat more restricced in localizate tion and productive of specialized colored secretions, are found in the clephant, hangaroo gazellc, and antelope (34 93) We have also examined histologically the scat glands of the horse and we shall discuss thus in some detail in a later section (page 51) It is agrecd that for the most part, animal apocrinc glands are quite similar though not identical with those of man majority show ducts which, as in man empty into hair follicle orifices or quite close thereto Schiefferdecker las pointed out that man, representing the highest level of development, is an eccrine gland animal (6) Ilc cmphasized that apocrine glands are the more primitne, being the typical cat glands of maminals The anthropoids such as the chimpanzee and gorilla, appear to be closest to man in scat gland distribution It Icast they possess both types of sweat glands and in a dirbution more like min than.m other in mu The great ·III THE PHYSIOLOGY AND PHARMACOLOGY OF THE APOCRINE SWEAT GLAND A METHODS AND MATERIALS For the most part these studies were performed on acute wale solunteer Honerer some children and women as well as clinical paucnis male and female were studied in certain instances as described farer During the course of the various imesugations seneral hundred men Negro and Ilhite, were used It was found necessary to screen gseat sumbers of men in order to secure wubjects who produced adeqnare quantities of apocrine sweat and at the ame time did not have much eccrine swearing (which would be confusing and would dilute the apocrine sueat) in the area The axilla vers ed as the test site for the vast majority of these studies No anatomic abnormale were present in the axillae of ans of the subjects The tests were made during all seasons of the 1er la vome subjects, antiperspicints were interdicted for * least one wech prsor to our otisers atson period Honeser in the the nellae nere merch cleansed thoroughly prior 10 exlinnanon to remove such material as dirt debris and old cerrian The \ac were shared using either a safers razor or electric chpper The Indniduzls arm was extended lateralls to heep che Willar vault exposed during the player non period), eru also ton of the spoerine seat droplets as achieved with the athed ose and is ith an otoscope or sereoscopic nignificanon (2 301 Specimen were collected in means of finc capillan pprettether placed <lireet un the 2133 surface or in oried to chhur follicie (1?luuruce Was deltrained in the use ur i kundasWood light 27 ·28 The Tluman Sierat Cland in Ilealth ard Disease Pharmacologic agents were prepired in sterile phonological salınc solution in concentrations as indicated in the specific sections In some instances, a stock cominercial cpinephrine volution was used, while in others, a bultered salıne solution (Sørenson's phosphate buffer, pH 7 4) was employed to minimize local pain during injection Heat stress was produced by having the subjects remain in a specially constructed infrared heat cabinet for periods up to one hour Special apparatus utilized included a Raytheon microwane (radar) deathermy unit to produce deep tisuc heating, a standard clectrical square naie stuulator and an electrical skin resistance recorder It was necessary to use histologic techniques for portions of these studies also These included routine hematoxylin-cosin preparations and the phosphotungstic acid hematoxylın stain Additional descriptive details of special methods used in certain parts of these studies will be supplied in the appropriate sections B PHASES OF APOCRINE SWEAT GLAND FUNCTION During our studies of the plıysiology of the human apocrine sucat gland we soon learned that t was possible to divide apocrine incat gland function into two distinct phases, viz , Ipocrine su eating, the appearance of apocrine sweat on the shin surface, and Ipocrine seothon, the actual formation of the sucat in the secretory tubulos below That there are two such distinct functional plases will become apparent as this section is read for the purposes of luciicr organ- 17ation and convenience of description we have uulucd these licadıngs at the outset C. APOCRINE SWEATING 1. General Description | Apocrine seat is seen to appear usually at the hair follit ir orifices (119 18) Characteristically it is usualıved as a turbida in hite fluid which gradually sells up in the ſole e forining rather flat globular droplee ihis is in contrast with the droplet of cccrine sweat such as spherical and extn Du vento (11n te

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·30 7h Iluman Sterat Cland in Iltalih and D sease from a tiny porc Cxcept in unusual instances, when the amount of apocrine sweat is great, or where it is diluted by cccrine Sucat, spreading of the apocrine sucat droplet far beyond the follicle does not occur This is primarily because the quantities of apocrine sweat wuch appear at a given follicle after stimulation are small and also because of the siscosity of the secretion In addition, apocrinc sw car dries rather quichly, forming an adlierent, Shstening, glue-like residue over the follicle orifice within a fcu mutes after appcaring Tius residue is opalescent and reminiscent ol clear plastic or dried varnish (Fig 18) This property is a charatteristic feature of apocrine sneat and is not sech aller cccrine sweating It is not uncommon in the careful craination of the axilary skin, to find such dried apocrine sıcat droplets or or the follicular ortices ahhough they are usually remoı ed In ung and profuse sweating In some subjects, a fairly large number of apoe rinc suell drop Iets may be nored at extra-folhcular orificos 11'c found that airs was more common in Ilote subjects and was never more than 1-2 % of the total number of droplets sen While apocrine su cat is usually lucish or gruas an appeals athce il occasionally shows a definite yellowshmi and rarely even blue, green or blach apocrine sweat may be obserıcd ( Section on Localızed (bromidrosis) Ipocrine meat is trans Jucent but not transparent However the mount ut carbuscar shous creat indusdual variation (I 15 19) In some sukces the sweat may be almost Ulear and identification can bx made only after collection in a capillon tube and examination garanti black background in others lonecr, commonly the cro the secretion may be mithi ulete and thick lang the con of local y cream in these instances it may be spowbir to collere in capillary tube The total quantity of aporrie med product is finute KS compared with the volume of ecurine set ushur must be wees A fair estimate of the amount of apocrine shell poreclerce 1x » indtal gland in response to a gnen steus 110 11 Thus, the total qumurs of apocrine shout it buc lt < !!! PR menad from a single gland may be only a snall (rac son of 33b2011 1 ·31 The Phytory and there acoluty of the trackin surut bland 1x 19 urban afkrine szint Pooled samples of apocrine sıcat are shown 18 test tube on the left Cumpare kus simples of pure eccs sueat on the *ht The rurludits of the apxxcrine surat varies greatly from those which are mits to those which are almost clear Howeser some degree of cloudness is 23was evidens 19 apocrint sweat The nesro produces greater amounts of apocrine sweat more commonly than door any other race, although the quantities are il relately smal} It is important to stress that once an apocrine gland has been cmplied no further sweat may be made to appear on the skin surface unuttere is me for its formation in the secretory tubules belon 11c leve repeatedly demonstrated that after any stimulus which cohes good apocrine sucaling subsequens cumulation (.1le to produce further apocrinse scating for a period of twentytour to forts-cight flours This inserial is called the refractar fieriod and apparently represents the time required to form a nou uppks of apocrine scat Such a finding ssendence enough that the pfx ttance of apocrine sweat on the shin x a luncuon distinct trown the formation of the sweat itself (34) ·32 The Blunt : ut eat (lay! In II lih un/ Disrae In many of the subjects, the apocrine scat whether dried or recently secreted, showed fluorescence »hen eyposed 10 IVood! Jight (rig 20) Eccrine and apocrine sıcat can be icadıly distinguished on tlus basis In general, increase in color tended to increase the fluorescence although dark blue and black sucat did not fluoresce at all (cf Section on Localized Chroinidrosis) 2. Effect of Emotional Stimuli Apocrinc sucating was scen in response to such stresses os levoked fear or apprehension In an occasional patient on a routine clinic visit, apocrine sweating was observed 1 his was inorc common in those patients apprehensive concerning the possibility of skin cancer or in those about to have minor surgery Honcier, It was far less common than the usual emotional eccrine su cating scen under similar circumstances It was our impression that an cmotional stimulus which was rather marked in intensity was required to produce an apocrine response Honever, this varied somewhat from individual to individual and in an occasional subject, apocrine sweating in response to emotional stuinuli appeared more readily than an axillary cccrine response Seventeen patients were examined prior to being subjected to a lumbar puncture These people were all admittedly ſcarful of the procedure and most had questioned us regarding its dangers In four of these individuals axıllary apocrine sucating was ols served This compares favorably with a scrics of observations on consecutive clinic patients in yliom two out of fifteen chibited apocrine swcating Inother study of the effect of apprehension or fear as con ducted on thirty-three experimental subjects I live incn were entirely unaware of what experimental procedures might be con. ducted and many of the showed distinct apprehension llos. cier, only five of the thirts-three shoked axlart aprine sue in prior to testing It was not possible to study the apocrine response following other forms of emotional stimulation such as smal stimulation or anger However it is probable that the response to these stimuli would correspond with that described those ftor Irir. producın stimule ·Yu 15 of sy ! Pha uchi wahe gurke < kazal Card 1 Fluper mace of apott ne jucat droples Three small droplets of apocrape $ cat were placed on a glass slede pon exposure lo Wood light (UVL 3660 A) tie Cuorescence shown abone las en 3 Effect of Sensory Stimule It mas found that rather severe pain was required to elicst zpocrine weiling In the series of observations on seventeen patients having a lumbar puncture three of these individuals showed apprune swearing immediately following pain produced by the puncture I lie application of an electrically heated wire to the skin of the back produced apocrune sutaung in two of eles en subjects studied Radiant heat nuch was focussed on a wall area on the forearm 1 inch in diameter was used as a painful simulus in luo subjects In both severe pain was produced and apocrine sweating resulted in menty five subjects a lo 18 needle *31815erted into the palm to produce pain Ipocrine Heating was obsen ed in ten of these subicces The effect ol pun in the production of apocrine gheating was tye tunfully illustrated in womes during labor It was found that mild uterine contrations were nos associated »ith an apocrine response However intense contractions producing severe pain could be correlated with Epocrine cu ciung \thuna few seconds ·34 The Ilu nan Sical Glonlullealth an / Puscast after the onset of each intense labor pain, si to ten apocrine su cat droplets appeared Observations over a period of one hour indicated that cach burst of apocrine sucating involved now glands Secretion did not reappear at former sites of actuity It was found possible to block the apocrine sheat gland response to pain by the introduction of procain into the aullary skin Sixteen subjects recened an injection of 4% aqueous procain intradermally Inve to ten minutes later, after local anesthesia in the axilla had been produced, the sixteen subjects recented a painful stimulus consisting of the introduction of a needle into the palmar shin In four of these, apocrine si cating was itsualized in the unanesthetized control zones In none of these subjects was apocrine si cating eudent in the anesthetized areas Asimilar local inhibition after procain was produced following emotional stimulation The apocrine response to pain was further studied by the use of a localized external pressure which oblucrated the circulatory supply 1 pressure of 225 mm of mercurs was applied to a small area of aullary skin of fourteen subjects using a cup device, with an attached splurgmomanometer Control observations 112d shoun that this pressure did not produce apocrine sweating nor did it dımınish an apocrine response in any The fouriccn indusiduals were given a painful stimulus consisting of the introduction of a needle into the palm In Inc of the fourteen subjects «pocrine sweat was noted in the normal control areas (outside the pressure zone) In four of the fouricen subjects apocrine swert was noted simultaneously in the pressurized are.is The apocrinc sucit (response to pun appeared thin one second and was generalized throughout the aullary region unlike that to be described in response to drugs and other local stimuli (35) It should be emphasized that the apocrine responses to emotional and sensory stimuli appeared within one second and scre yercralized in nature They insolied potentially all of the apocrine sweat glands of the axillae unlike that to be described in response to drugs and other local stimul In this regard we often noured responses from apocrine sweat grands of the mammars arcolz, thc pubic area and from occasionil glands of the trunk as well as the axillic after the above emotional and senior stimul ·35 The Physiology and Pharn acology of the pactint Sitrat Olard 4. Effect of Heat (0) General Nineteen subjects were placed in an infra-red cabinet for periods of approximately turty minutes Apocrine su eating was seen in only one of these subjects as a result of this heat stimulus, although profuse eccrine sweating was observed in all subjects Interestingly, most of these subjects showed "follicular" eccrine sweating That is, the eccrine sweat appeared to originate from the follicle This was quite prominent in the axsllae and the thighs Capıllary tubes were placed in the follicular orifices of fie of these subjects and it was impossible to demonstrate the secretion of any apocrine skeat The one subject in whom apocrine sweat was observed during heat showed definite signs of anxiety and apprehension, and it was assumed that has apocrine sweating on the basis of an emotional stimulus rather than the therital One (6) Local ("Deep") Heal Four healthy adult males were used in this study in a room at 22° C, these men had their axıllae shaved and were placed at rest No apocrme sucating was seen at this time Deep heat was applied to the axilla using a microwave (radar) dathermy machine with a corner reflector for twelve In all four subjects studsed, definste apocrine sweating mas scen berueer five and ten minutes after the application of the heat While minimal in amount, the secretion was readily identified It is to be stressed that the subjects experienced only slight warming of the skin (1 2° C elevalion by thermocouple determination of external shin temperature) Honeser the shin icmperature of the subcutintous tissue was elevated between four and tinc degrees (41 - 42° C) The control zone the focussed area winch recen cd the largest amount of heat contained 90% of the apocrine sweat droplets 5 Effect of Cold minutes (a) General in subjects were examined for apocrine sucating Isefore and upon remos al fram a cald raam Amal C) men had been fully clothed in Irctic wear and were lying at rest on a non conducting bed for fort) fise minules The temperature of the ullir hin fell about 30 ( (10 34°C) during this period 1 of these subjects scensed to be apprehensile upon remos al ·36 Ihr Ilunian Sixcat Gland in flealth and Desrase An from the cold room No fresh or dried a xillary apocrine scat was observed when thiese subjects were examined on removal from this cnvironment Unfortunately, we did not have the opportunity to use drugs or other stimuli in an effort to induce apocrine sweating (6) Local ("Deep") Cold: Decp cold was applied to the axılla in such a manner as to effect structures at a dcep dermal and subcutaneous level The shared a ullae of four localthy adult male subjects were procainized in a block technique leaving a central area free from the pressure effects of the procain 18 gauge ncedle was inserted 3-4 mm beneath the skin surface adjacent to a hair follicle in the central zone Frequently, some mechanically stimulated apocrine sweating could be seen This was minimal in amount, however, and was allowed to subside so that after 2-3 minutes following the insertion of this large needle a chilled 20 gauge needle was inserted into the same hole 'Thuis 20 gauge needle, two inches in length, was placed through the tip of a 30 cc syringe The needle hub remained within the barrci which was then pached with dry ice In a 2-3 mm zonc immediately around the needle, no pocrine sucat could be visualized Honeer at the periphers of this zone, small amounts of apocrine sweat could be visualized It is probable that a temperature gradient was present and that in this central ronc where the temperature was coldest paralysis of the gland occurred A suitable temperature was reached however in the tissue at « 3-4 mm distance 6 Effect of Seasonal Variations .Ipocrine su cating was studied in over forty subjects during all seasons of the year Unlike eccring sweating which was grcater during the summer months we were unable to detect an appreciable change in the quality or quantity or apocrine sweat seen during the various seasons IVe have not had an opportunity to cxamine the effects of acclinatization to heat and cold on the apocrine sweat gland responses 7. Effect of Drugs (a) Adrenergic In twents-ike male subjects, epineplane in a 1 1000 (oncentration in sterile saline solution was injected ·37 7hr llysinlogy and P/armacology of the 1pocrine Sural Gland intradermally The quantities injected varied from 001 cc to 0 10 cc In each of the twenty five subjects, apocrine sweating appeared usually at follicular orifices, although a few extrafollicular droplets were seen in some of the men The larger quantities of the drug produced stunulation of more glands since there was a greater spread of drug latent period, representing the time required for spread of the drug and reactivity of the The gland was seen and was never less than fifteen seconds average latent period was 30 secs although in some instances it was as high as 120 seconds Tlie response continued for a period of from five to ten minutes with an ever-widening zone in which Glands began to show activity The active glands were almost invariably located in the zone showing blanching from the epinephrine This was an indication of direct pharmacologic stimulation of the glands It was possible also to produce apocrine sweating by the systemıc administration of epinephrine In these cases, it was necessary to give rather large doses of the epinephrine Apocrinc sweating was not seen until systemic signs of the drug were also cvident It could usually be produced by the hypodermic injection of 10 cc of 1 1000 solution of epinephrine The local introduction of nor-epinephrine (levo-phed bitartrate, 005 cc of 1 1000 solution) in seven subjects also induced apocrine sweating in all of them The use of epinephrine (1 1000) in a buffered solution (ph=74) in an effort to minimize local pain, in ten subjects also produced in apocrine response corresponding to what was described above after epinephrine in salıne Epineplırıne in dilutions from 1 10,000 to 1 1,000,000 were also employed to stimulate apocrine sweating The response was less consistently produced in the lugher dilutions, above 1 500,000 (b) Cholinergic Freshly prepared acetylcholine 005 cc of I 1000 aqueous solution was introduced intradermally in the axillar shin of ren slupets In verse of these 25 vue apoctite sucating observed However Tollicular" ecerne sucating could le seen leher dilutions 1 100 000) of the drug were also used without production of an apocrine response ·38 77. Huma Siteal Cland in Health and Derase Pilocarpine (0 05 cc of 1 1000 sterile buffered salınc) was injected! intradermally in the axılla of twenty-five subjects In thuec of these, true apocrine sweating was scen In these of them clcar "follicular" eccrine sweating was observed Normal cccrine sucating was seen in all of the subjects Physostigmine (1 10,000 in sterile buffered saline) was injected intradermally in the axilla of four subjects Apocrinc sucating did not occur in any of these, but an eccrine response was readily visualized in all four (c) Antr-adrenergic The administration of Dibenzylınch) (20 mg ) prevented subscqucnt auillary apocrinc sucating in response to 0 15 cc, of 1 1000 local epinephrine in to normal adult male subjects A blood pressure drop and reduction in pulse rate was observed in cach indicating systemic elect Local inunction of Dibozane frydrochloride, ma a potent antiadrenergic ſound to be effective when applied locally in animals was used in three adult male volunteers Thic concentration of the drug was 50 mg Gm of ointment (polyethylıne glycol 4000) and effort was made to rub the ointment into the shin 1fici tuo such applications one hour «part 015 1 1000 cpinephrine in normal salıne was injected into the treated axillary shin Apo crine sweating was observed in all of the subjects with no cuden of inhibition There was no vasodilatation in the dibozanc-treated skin and no inhibition of vasoconstriction to epincplirine Ergolamıne tartrate which blochs soinc adrenergic responses after local administration did not inhubit (pincprint-induced apocrine sweating in three male subjects in whom st Was attempt Dosage used of the crgotamine tartrate 15 011 1 1000 solution (d) Anticholinergic The local injection into llary skin of 0 10 cc of atropine solution (1 1000) failed to produce pocrine scating in nine male sulyjects Subsequent introduction of cpinephrine (01 cc 1 1000) into this atropinized area produced apocrinc sucating in all of the subjects studied Systemic adiniinistration of atropine "at nor cmposed Honcier Prantal administered oralls in 100 mgm tablets (2-6 tablets q1d) to file normal adult male subjects dxd not Re producc inhibition of apocrine seating after epinephrine duction in curing sweating was noted only alter syn of systemie ·39 The Plus !ar! l'h rn selag, of the port e Serat Glid effects of the druy Prantal ointment was also without effect on apocrine or eccrine sweating in the axilla (e) Local Anesthetics In sıxteen subjects, a small area of avillary skin was anesthetized by the local injection of 10 cc of 4% procain solution Epinephrine given into the normal un anesthetized areas produced apocrine sweat in all sixteen In the anesthetized areas apocrine sweating was produced after cpinephrine in 15 of the 16 subjects It is to be recalled that the response to emotional and sensory stimuli can be blocked with local procaine (see page 34) (1) Antispasmodics-Smooth Muscle Relaxants Papalenine nutrale, 2-10 mgm in 02 cc normal salıne, was injected intra dermally in the axillary skin of three subjects Subsequent injection of 005 cc of 1 1000 to 1 100,000 epinephrine produced apocrine sweating in all three In a similar series of experiments utılızıng sodium nitrite, 1 so called relaxant of smooth muscle, we were unable to inhibit apocrine sweating to epinephrine Subcutaneous administration of 01 cc of 1 1000 solution of sodium nitrite brought about prompt i asodilation Subsequent injection of 01 cc of 1 1000 to 1 300 000 epinephrine then produced blanching in this same area and as the blanching developed areas of apocrine sweating appeared It is felt that the action of epinephrine was more pro nounced and because of its high potency, overcame the original rclaxant effect of the nitrite (9) Effect of other Drugs Putocen the oxytocic principal of the posterior pituitary such contracts uterine musculature so charac teristically will also produce copious apocrine sweating The subcutaneous injection of various strengths of pitocin varying from 01 to 1 international unit produced such a response in each of 30 male subjects Injection of 001 international unit produced pocrine sweating in 21 of 30 individuals studied Ilustamine vluch is also a consistent stimulant ſor many varieties of smooth muscle was injected subcutaneously in nine healthy adult male subjects The phosphate salt was used in a concen tration of 1 10 000 True apocrine sweating was observed in onis one of these nine individuals Histamine urticaria developed in all nine ·40 Ti u Sreal Clanlı 11 aliha Isa Ianual cupri 19 in in all 17 id I will ry shri compressed ! ( cen (01 srs 14 S It drits d. dal ve u Ithe hur follicle rices The effect of nicoline on apocrine si cating us discussed below in the cction on axon reflex apocrine senting 8 Effect of Physical Stimuli Ipocrine swcat may be manually expressed from thic txillary skin Compression of the rullars shin in a gentle sliding action resulted in the appearance of ipocrine saat it lollie ui ir oricey in lol sixty subjects studied Ipocrine seit H I not seen it all of the ſolhcular orificos ol the compressed sin bowser 114 21) Apprrently these slands had been impued short time provosh froin some other stimulus Thus in this besence ni mcrctors stimul tion ont may instantly exprespune cut by simple manual compression of the villars shin Ilus would indictie such sucat is preformed ind is pooked in de lubrutor lumen aunting in expulsive clicuitin, force 1. we shall learn litcr thus force is supplied by the myocpithelium Stroking of the villary skin with 1 ton, bate will in the subjects produce a line ir response in the one of strokinn is ·41 The Physalagy and Pharmacol ş) of the Apostin Skral Gland phenomenon is discussed in more detail tater (page 47) and apparently results from a mechanical stimulation of the myoepithelium 9 Effect of External Pressure Using a glass cup apparatus attached to an aneroid sphygmomanometer by means of a side arma, it was possible to subject a localized area of the axilla to higłi external pressure. In five subjects, it was determined that the application of this pressure did not stimulate any apocrine sweat gland activity The following experiment was then conducted Epinephrine (015 cc of 1 1000) was injected intradermally Wichun 1 to 2 seconds, a pressure of 225 mm (plus or minus 10 mm) of mercury was applied to the injection site and maintained for three minutes During this period apocrine sweating was observed in the pressurized area, but not in the surrounding zone Houeser, within a minute after removal of the pressure, apocrine sweating could be seen to appear in the surrounding skin Thus was presumably due to lymphatic spread of the epinephrine, which had been pressously prevenred by the pressure of the rim of the cup 10 Effect of Natural Factors. Age, Sex, Race Eleven cluldren ages five to ten years were studied for apocrine sweating The group comprised three Negro boys, three Negro girls three Wute boys and to Whic garis Lach was given 0015 cc of 1 1000 solution of epinephrine intradermally in the anillary shen In none of them was apocrine sweating voualized pam sumulus also has ghen to cach of the children Thuis consisted of the introduction of a hypodermic needle, No 25 gauge into the skin of the forearm Again no apocrine cating It should be pointed out that none of these cudron had axslları harr other than the lanugo type I hurts the normal healthy adult males (19 \\ hite 17 Negro) ringing in age from 19 10 50 ye scre also examined Each of this group was quen a painful stimulus by means of the intro duction of a lo 18 needle in the palm Tourteen of chiese in duule (of whom 8 Here Yegro) showed apocrine sweating after this sirmułuis These subjects also were studied after 0 15 cc of 1 1001) epinephrine was introduced into the skin of the aulla Was ser11 ·42 The Iluman Sicat Gland ? Itralth and Durise Definite apocrinc seating was seen in each of the thirty-five subjects Howcier, the degree of response slowed marked variation An older age group was also studied This consisted of 11 male subjects (8 White, 3 Negro) ranging in age from 60 to 75 ycars The pain of the palmar injection produced axillary apocrino sweating in three of the 11 men (all Wlute) Lack of them also received an intradermal injection of 0 1 cc of 1 1000 cpinephrine in the axilla Sıx of the eleven subjects des cloped apocrine sneating in response to this drug Limited studies were also made, with similar findings, on the apocrine response in female subjects Five women varying in age from 23 to 38 years were examined for apocrine sweating after local cpinephrine and pain The response was less than that scen in adult males of the same age group Racial variations in apocrine sweating arc remarkable Comparison of turty Negro and thirty White adult male sulyjects after local epinephrine and emotional stimulation revealed that the Negro consistently produces greater quantities of apocrine sweat than does the White In addition the apocrine sucat of the Negro generally showed more turbidity and was elicited more readily after minor stimuli, such as produced by stroking These features also reflect the racial superiority of the Negro Various groups within the Caucasian race showed no signihcant variations 11 harc not had the opportunity to study Oriental or Indian races for apocrine sweating 11 The Refractory Period-Miscellancous Observations It was pointed out carlier that the individual apocrine gland has a definite refractory period After the initial injection of epinephrine it is impossible to produce apocrine sucat from any unit which has responded until a period of hours harc clapsed The exact duration of this period always exceeds twenty-four hours and varies from individual to individual, een from glind to gland In general Vegroes with larger glands, tend to have shorter refractory periods. The maximum duration of thus period 15 about 72 hours No spontaneous apocrine sucating 1.5 aluerved in subjects at rest One individual had cjpillary pipettes placed in the follicular ·43 11 Platalogy and Ilarme aloey of the theme Strol (Glan! orifices, and during a period of three hours, no fuid or follicular sccrction could be seen to enter these pipettes, nor was any dried apocrine sweat seen At the end of this period, 0 15 cc 1 1000 epinephrine was injected intradermally into the observed axılla and a typical apocrme response nated Apocrine sweat never appeared at all hair follicle orifices in response to a gnen stimulus in one such study, 63 har follicles were observed folloning local epinephrine Sixteen glands were actnated, 14 of these being ſollicular, whereas 2 were extra- Sollicular In fise adult male volunteers, we also studied the electrical skin resistance (ESR) of the axillars shin Each of these subjects was carefully selected on the basis of his ability to produce an adequate apocrine response and failure to slios emotional or sensory axillary eccrine sweating The aullae were shared and cleansed carefully The arıllary skin was moistened with a nad of cotton saturated with normal salıne A small hole was cut an dic cotion just large enough for the metal electrode (05 cm in dameter) A base linç electrical shin resistance (resistance to the passage of direct current, thus not a measure of mpedance) reading was taken so the aula Normal saline has constantly dropped onto the cotton to insure its saturation Following this 1) 10 «c of pitoon was injected into the axillary skin to induce apocrine subting In four of the fire subjects, the ESR showed No change hon that of the previous pre-stimulation level 01 subcut a decrease of 2 ma from the base line ESR was recorded I hus subject showed no outward manifestation of pain or apprchornton at the time Ten minutes later after apocrine su cating had craved another "saturation baseline reading was tahen und found to be within 1 ma of that taken before the injection of pitorin f} } ce of 1 1000 pilocarpine was then introdured into the alarn skin to induce eccris sweaung Wahn 1) veronds the FSR was seen to fall an additional 4 to 7 ma and even 10 mi louer in one subject Thus lowered ESR was muned for 10 to 30 minutes apparently as long as thic cccrine 13Cting continucci arrok In ingenous esperinichts, using a set' electrode Mehrique has somn that the drop in LSR seen after cocrine ·44 7 he llaman bu cat Gland 19 Ilealth and Disease siscating is not merely the result of adding fluid to the skin surface, but results froin a change withun the skin apparently related to the active eccrine secretory process per sc (36) It is noteworthy that Lobitz and Campbell in studying the apoerine wax glands of the car canal also found no drop in skin iesistance as a result of apocrine stimulation wlule they did record the usual drop in the CSR of the palmar shin simultaneously (37) These findings are in agreement with ours and lend support to the concept thst no active cellular secretion occurs at the time of apocrine sweating 12 Axon Reflex Apocrine Sweating Efforts were made to induct apocrine axon-reflex sueating, heretofore not demonstrated in man In thirty experiments on fifteen adult malc subjects, utilizing appropriate concentrations (1 50,000 to 1 150,000) of acetylcholine and nicotine sales introduced iontophoretically or by local injection, we were unable to produce the instantaneous, is ide area response characteristic of the axon-reflex While distant glands were activated the response was irregular and inconstant This may have been due in part to the long refractory period (24-48 hours) following a bout of apocrine sweating It is pracucally impossible to prevent some apocrine sucating since many emotional and physical stimul may prompt its occurrence thrus emptying some or many of the apocrine test glands While the anatomic and physiologi cvidence of the innervation of this gland suggests that apocrine avon-reflex sweating should occur, we were unable to demonstrate the phenomenon to our satisfaction in thus regard, ius interesuns to note that lohi using appropriate concentrations of nicotine and acetylcholine, could not induce alon-reflex seating in the dog except in ccrtan restricted arcas (38) It should be recalled that the dog possesses a sucul gland such at least Ivy wtulogu ol criteria, is apocrme in type 13. Mechanism-Role of the Myocpithelium Earlıer we described the well-developed band of smooth muscle which investh the tubular portion of the apocrine sweat gland This layer of cells las been calledł mio piheum sind , aparan also in the curine and m.immary glands in varying degrees of ·13 hnolou en 1 Pescolar ef te Apam Surat Cland 171ecpuhelium of anacrine gland Phosphorungstic acid hea loxylon stain darbas skis showing my oepithelium un transverse oblique and langteudenal planes of section May 750 development Sehare pointed out in recent pages, the need for a contractile force so empty the apocrinc tubules and thus produce ayxocrine sweating It is the moepithelium which prossdes this force V of the physiologic and plarmacologic phenomena concerned with apocrine savealing reflect the reactivity of the band of smooth muscle It s our purpose ilien in ths section to carefully resicu the edence already presented indicating that such a mechanism esis and to present additional corroboratae data which prove 11 (33) a Anatomical Evidence The lustologıc findings suggest that miyorpithelium xx smooth muscle lira sell descloped fibrillar fuyer of myod cuk which is present about the secretory portion of the apex sine eucal gland but absent about the duct Indsidual 133soppstal cells are almost linear or spindle-shaped (Tis 22) and on iloplasmic branching in rare instances They have in itu ke width of 8-10 microns and reach: a length ol 40 to 101) antrron In elongate! Bisoplule nucleus can be visualized ne ar lu end prirtion of the cytoplasm ·46 The Iluman Stral Cland 19 Ilealth and Disease The arrangement of the myocpithelial cells is suggestic functionally for they run longitudinally with tlieir long axis roughly parallel with that of the apocrine tubule. Large sheets of these fibril-like cells may be seen on roulinc sectioning of the tubule is cut longitudinally (Fig 22) Although the myoepithelial cells take som muscle stains poorly, a fact wluch has led some histologists to exclude thein as plain muscle, they are easily visualized under routine hematoxylın and cosin preparations or with the periodic acid-Schiff procedure Hou ever, they stain more completely with the phosphotungstic acıd-hematoxylın stain as blue fibrils in contrast with brown tubular cells Under high magnification a faint longitudinal stration may be seen When examined with proper illumination, the myocpithelial cells exhibit a birefringence which is posit with respect to the long axis of the cells This indicates the presence of longitudinally arranged rodlets or fibrils (21) Suchi a property is common to smooth muscle in general Woolard has stated that the innen ahon to the apocrine sweat gland is to the myoepithelium cxclusively As mentioned carlucr, We would agrec that these cells do recen e fibres although we are unable to state categorically that the secretory cells are not also innervated An attempt was made to secure some indication of myocpithichal function by studying its appearance before and during apocrine sweating Biopsies were secured from the exiſlac of fic normal subjects Procain block anesthesia was used to minimize pressure effects on the histologic appearance Similar biopsies were secured from the subjects in whom apocrine sweating had been induced 3-4 minutes previously by the local injection of epinephrine A11 biopsy material was sectioned serially and stained with heinotoxylin and cosin Comparison of the sections from the two group did not reveal any consistent morphologic differences No cuidence could be obtained from these studies which would support or refute the victs that my oepithelium is contractile I ailure to proude evidence with this study is apparently due to technical difficulty, primarily the inability to present some myocpithelial activity from non-specific stimuli encountered in the study flow. ever, many segments of apocrine tubules of "unstunulated" ·47 The Physiology and Pharmacology of the Apocrine Sweat Gland נJ 3000 hg 23 Peristaltic Uare in apocrine tubules Chance secuioning of rather long stietch of an apocrine tubule showing muluple compression and dilatation along its course These glands were not purposely stimulated Changes seen are reminiscent of peristaluc wave as seen in the GI tract H and E Mag 310 glands after routine staining show changes which could be easily interpreted as contraction (Fig 23) Physiologic & Pharmacologic Evidence The fact that apocrine sweat, in the complete absence of any other stimuli, may 'bc manually expressed, as described earlier, is a strong indication that a contractile force is required to deliver the apocrine sweat to the skin surface Furthermore, the induction of apocrine swcating by stimuli selective for smooth muscle suggests that a contricule force is responsible for sweating These stimuli are as follows (a) Mechanical stimulation of the axıllary skin will result in the appearance of apocrine skeat on the skin surface In fifteen healthy adult male subjects, the shaved axilla was firmly stroked in a linear fashion 10-15 times Within 20 seconds, a linear band of apocrine shent was seen in the zone that had been stroked in nine of the 15 men (Fig 24) The amount of sweat produced with tlus stimulus was small wlien compared with the quantity ·48 The Human Sueal Gland in Health and Dispas om rg 21 4pocrine su calling after stroking arıllary skin After lightly stroking the axıllary in a linear fashion with a tongue blade 10 15 times 2 lancar band of apocrine sweat was seen in the area strolcd as shown above This is the result of physical sumulation of the myopithelium seen on other occasions in these indnduals It should be noted that the stroking was not overly forceful and that no compression or excessive stretching of the axillary skin was scen It was ſuc that apocrine sweating following stroking of the axillary shin occurred as a result of mechanical stimulation of the myocpithe- Tium surrounding the apocrine tubules In three subjects in whom half of the axılla was anestlictized with procain (4%) anesthesia, stroking across the normal control area and the anastlietized zone produced the same effect Ilie apocrine sweating was sharply dejineated to the arca of <troking Both of these observations suggest that the sucating was not induced by neural stimulation (b) Thermal stimuli, such as heal or coll, when propcıly applied at a deep level so as to produce actual thermal tunulation of the myoepithelium can induce apocrinc seating Iliesc cyxrlments were described carlier in the Physiology chapter (pp 35-36) ·The Mysrology and Pharmacalagy of 1 Aparne Bucal Glana $0 It should be stressed that this is an artificial mode of stimulation and one that is very unlikely under physiologic conditions It has been previously shown that the external application of heat and cold, as would be produced in a hot box or a cold room, would not generate an apocrine response apparently because there is no myoepzthelial stimulation (c) Electrical stimuls, when applied directly, also prompt ipocrise sweating apparently through direct electrical stimulation of the myoepithelum The use of a square wave stimulator with needle electrode allowed for unit gland stimulation Tsve healthy adult males were studied The axillae were procainized in a block technique as previously described The active electrode was then inserte into the axillary skin During the two minute interval Collow insert apocrine su eating was occasionally scen as a result of meclianical stimulation This was allowed to sub side and then the square wave current is applied The voltage applied ranged from 0 1 to 28 0 v, frequency was 50 to 200 pulse and the pulse duration 01 to 30 milliseconds Definsic though not pronounced apocrine sweating in the form of 7 unst gland response was seen in all subjects (d) The pharmocolagie susetult which produce apocrisie sucating will also prompt contraction of other varieties of smooth muscle Epinephrine and non epinephrine have been shown to be powerful pharmacologic stimul for the apocrine swert glud Thesc drugs stimulate a wide range of smooth muscle such as the dilator muscle of the pupil of the mind the smooth muscle round blood vessels Palacin the oxytocic principal of the soxterior pituitary which stimulites ulerine musculature will also produce copious ypocrine sweating as described curher Pitocin sunil zriy sumulares mo epithelial contraction in the mari sland and complishes the Ict down or milk (108) Ifastamine how it is pptrently not ! Stuus for the mu palvelem of the YSTYK tym ? núů not yixtur Apocrine «ucating contents Is well known tonic that the drug ssal! 21nulat nins its of sincet mitte le Direct Visual Evidence of Contractile Mechanism letempte to olxerc the oleels of $131 cputhes al contron in unsere ·50 The 11 iman Jeet Glasli Health and Derae uniformly unsuccessful After removal of thin strips of axillary skin and subscqucnt immersion in warm oygenated mamının salıne solution, we were unable to detect any tubular changes which might indicate myocpithelial contraction In vch of our failure with tlus approach, an in no technique was tried for an intact nerve supply is a requisite for the proper function of certain types of smooth muscle The axillac of five selected subjects were procainized and slightly curved incisions, approximately 17 inches long, made Little attempt was made to control blood flow except for mile compression temporarily One edge of the incision was cueried with Alles forceps The other edge was depressed and the apocrine glands then readily observed through a stercoscopic microscope (30 x magnification) No staining of tissue was necessary Thic addition of a fen drops of cpineplırınc (1 1000 solution) prompted peristaltic waves in the apocrine tubules of so of the subjects However, ruo or threc drops of full strength pitocin solution initiated similar wave motions in the tubules of all of these subjects These contractile changes cre more readily clicited and secmed more vigorous after pitocin than ufter op nephrine Electrical stimulation as well as the direct application of heat or cold was not attempted It is to be emphasized that the peristaltic wave lihe (lunges in the apocrine tubules coincided with the appearances of ipocrine sweat at thic skin surface Thracates are schernaucally illustrarcd un rigure 25 They are gentle, delicate constractic changes wide progress smoothly and rather slowly alons the tubulc to result in cvacuation of the gland Yo estreme segmentai contrar un were seen as are common in tlic sinall boucl Iloncici 10 KS possible to detect sermform movements in the bulk of the gland itself These were thought to represent the grada i propression of the peristaltic lanes along the tubules It should be noted that in order to see such changes in tubular lumen necessir 10 concentrate on a small segment of the tubule High 12016 otion and critical Jumınition are essential in addition, not all of the glands acen during these suces were responsiit to umuh Although the blood supply to these grande apped its lx exsel. lent during the entire procedure perhaps the stands the sea ·51 The Physiolacy and Phim xcology of the loctine Steal Gland APOCRINE SWEAT GLAND TUBULE Fig 2) Peristalhe rares i apocrine tubule Schematic drawing of apocrne sweat gland tubule showing progression of peristaltic wave or innervation of some of the glands had been damaged during the actual incision The array of evidence thus presented provides us with more than adequate proof of the contractility of the apocrine myoepithelium This same myoepithelum has been shown to function similarly in the mammary gland, providing the “let down of mill" in response to the same drugs In the eccrine gland, howescr, where a less well-developed myoepithelium prevails, no real evidence of my oepithelial activity is available Eccrine sweating can be explained satisfactorily on the basis of its secretory activity 14 Comparative Studies Our studies in otlier animals have been significant, although limited and supply us with cogent data with which to compare in immahan apocrine function The house is one animal we had the opportunity to observe carefully The sucat gland of thus animal is more "apocrine" than * cccrine anatomically while having some of the features of both giand First the horse sweat gland is found over most of the skin ·52 Ihr II in Seat (land in Ililih Disedir surface as is the human cccrinc sucat glind, and is not restricted in localization as is the human apocrine sucat gland The oi crall sizc of the individual su cat gland in the horse is considerably smaller than the human apocrine gland, but larger than that of the eccrine sueat gland (Fig 26) Howeier, when one compares the overall body size of this animal with that of man, perhaps the horsc's sweat gland is proportionately cquivalent to that of the human ecerine gland It appears that the sweat glands in certain cutancous areas are somewhat larger than on the general skin surface This is true about the anus for example, but it is equally truc that eccrinc glandular size in man will vary somewhat from region to region The palmar sucat glands in man arc comparatively large, for example Histologically, nc arc again faced with a dilemma for the horse s sweat gland again appears to be intcr. mediate The tubular diameter is small, consistent with that or the cccrine sweat gland in man (Iig 27) However, only one type of sccictory cell may be seen as in the human apocrine sucat gland and unlike the cccrine tubule which shows two distinct types of secrctory cells In addition the secretory cells of the horse s sweat gland show what appears to be decapitation secretion the pinched-off luminal buds characteristic of an apocrine type of secretion It should be stressed, however that luminal casts occasionally seen in the human apocrine gland but not in the cocrine were not cudent in the sucat glands of the horse We decided to extend our comparatne studies to physology and pharmacology in an effort to determine the nature of the horse sucat gland Iwo healthy nature animals were used for thus study through the co-operation of Dr F hral of the School of Icterinary Medicinc University of Pennsylvania Philadelphia Pa The following stimuli ucre employed to stimulate sweating (1) I lot room 100] (2) Lxercise (3) Manu il expression of suelt (4) Stroking with tongue blide (5) Lpinephrine (1 1000 and 1 100 000) (6) Acetyk haline (1 1000 and 1 100 000)

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·5 The Iluman Surat Cland in Italth and Durgir Direct visualization of shared (and thoroughly cle inscd) and unshaved arcas of skin was employed Areas studied included the nech, axıllae, trunk (side), and extremities It was found that the sweat glands of the horse respond to licat, cxercise, epinephrine (both concentrations) and acetylcholine (both concentrations) However, stroking of the skin did not elicit a response nor could any sweat be expressed manully It should be stressed also that the swcat gland of the horsc has no refractory period as does the human apocrine gland The horse sweat gland continues to secrete until the stimulus ceases I urthermore, the turbidity ascribed to horse's perspiration is apparently due to contamination with dander Whule unshased arcas showed turbid sweat, the shared skin which had been thoroughly cleansed showed clear watery "eccrinoid' secreuon Lians and Smith have demonstrated also that the horse sucat gland responds to both epineplırınc and acetylcholinc, as well as licat Interestingly they were unable to inlubit the thermal sucating with atropine (41) Through the courtesy of Dr Herbert Ratcliffc Curator wc had the opportunity to observe the secretion of bloody 5*cit by the huge hippopotamus Jimmy at the Philadelphi lou This slimy, mucoid reddish secretion appears in response to cmotional stimulation such as anger or ſear Thc anmai dislike of hus handlers is so intense that we were able to provohe him quite readily by having one of these mon approach in Arcas wbuch seemed to show the greatest response were the face (forchead rcgion) and rostral bach We were unable to stimulate the animal with drugs or other stimuli because of the risk involved The glands responsible for thus secretion are purportedly apocrine in typc (34) The similarities of the sweat of the hippo its turbidity Siscosity and color) as well as the responsiveness of this gland 10 emotional stimuli would fully support this It'e also crammed dite pigmz kroppopotamur a different spears from South Imerica under similar conditions Ilus animul did not secrete a colored sucat, but did produce s frothy, white product when angrs or frightened over the trunk and neck A large gorilla tightly caged because of violence as obrera Although Ius fur prevented identification of any cutancours secre- ·55 The Physiology and Pharmacology of the Apocrine Sleat Glad tion the strong, acrid body odor of the animal was quite apparent Dogs possess apocrine glands over most of the skin surface Thesc glands do not usually respond to heat, but will be activated when the thermal stimulus is excessive, suggesting that an associated emotional stimulation is brought into play (42) Sheep, like horses, possess apocrine glands over most of the skin surface which secrete large quantities of a clear fluid Like the horse, the sweat glands are apocrine histologically, but eccrine physiologically, at least in many respects A number of other animals possess special localized skin glands which produce colored or odoriferous secretions in response to ſear or anger-provoking stimult (34) The skunk and musk ox are prime examples In addition, the elephant elaborates a blue fluid from a gland near the eye when angry Kangaroos secrete red sweat, antelopes and gazelles a blue or blue-black sweat when frightened These originate from tubular glands which have apocrine characteristics It is indeed interesting and informative to compare the function of the sweat glands of these various mammalia Yet one should be hesitant in the extension of interpretations from one species to another Study of the horse and human sweat glands is an excellent example in point A tally of the properties of the horse sweat gland will reveal that it is more like the human eccrine gland functionally than the human apocrine gland, although we still generally regard it as intermediate between the two Yet because of the histological appearance of the secretory cells the horse sweat gland is usually thought of as an apocrine gland This points up not only the folly of basing interpretations of functional activity on anatomical evidence but also the danger of using comparative data to draw conclusions regarding functions in another animal such as man Wlule such evidence is helpful and corroboratise it should be considered only in light of all of the available evidence 15 The Problem of Two Secretions Herrmann has described avllary apocrine sueaning in response to ficat ind acetylcholine (43) Furthermore Rotliman has added that the human apocrine sweat gland is apparently capable of producing the secretions, totally different in appearance and ·56 The Ilun on Seat Gland » Ilealth and lease resulting ſrom totally different stimuli (40) Onc sccrction viscid, turbid-hite liquid appears at hour follicic orifices following emotional (fear, anger), sensor) (pain), mechamcal (stroking) and pharmacologic (epinephrine, pitocin) stimuli Thuis fluid does not appear in response to heat, and cannot be inhibited by atropino Moreover, it can be produced by simple, manual compression of the axillary skin It is probable that all observers, including Herrmann and Rothman, will readily agree that this secretion is apocrine in origin However, a second secretion, a clear, colorless, watery fluid will also appear to cmanatc froin the same hair follicle orifice in response to heal and cholinergic (acetylcholine, pilocarpine) drugs Atropinization of the arens prevents the appearance of this huid It is this product which the above authors feel is derned from thic apocrine si cat gland We have clamined the problem in detail and inzie concluded that the human apocrine sucat gland produces only one sccrction the uscid turbid white sncat The clear, aqueous, "follicular flud is in reality eccrine sweat which arises froin adjacent (ccrine sweat duct pores and collects at the follicui ir orificos going false impression of its origin It the bottom of this problem is the fact that simple inspeccion even with stereoscopic magnification (30 ) does not enable one to identify the points of ongin of these secretions Idditional cudence both direct and deductric is ncceieck to justift our conclusion We should like to review this csidence now a. Anatomical It can be shown that cccrine sucat duct poren are often so situated as to allow the eccrine şucat to flou down into the hair follicles is shown in lig 28 the occasion al cocrin duct lies in extreme provimity to the ſollicle orifice Others opening into the sides of small shin grooves which are directed into a bar follicle orifice can supply sucat which gravits will drav down into the follicle openin L'sing pool tomu dissection techniques we have further demonstrated the must in relationshup between the hus follele onlices and ecorine duct pores (119 24 319) Application of water repellent (stlit one ) to the paremont eccrine sueat droplet formation and reduces true prekin, of Sucat in film form In subjects su treated with slicone it is not ·LG Extine dit opening near hm follide Photomicrograph of section of aullary shin showing hair follicle with an apocrine duct empfung into one side of the follicle (on the left) In addition on the right an eccrine duct can be seen as It colls upward and opens quite close to the hair follicle orifcc H and C Mar 110 bye » Var Julius id allaches que tine du! Wer morsian 1032 ammamuun hodruxdr small puere of axillary skin is stripped of its epidermis The underfair the detached riderints is shu nate Tunir follici arc sero pure rcling downward from die epidermis la apxxrlac duct is scenemusing into one of these follicles On each side of the follicles is an cccrinc duct the chindular portion of which was retained by the corium Vas 2" ·58 The Ilxman Surat Glandon Health and Disease lug 30 Pore pattern in atilla Another specimen of axillary skin was imuncrsed in 3 ammonium hydroxide for 3 hours and the stratum corneum stripped off Transıllumination of this skin reveals the cpidermal surface with large and small pores The larger pores arc hair follicle openings some receiving small apocrine duct pores The small round light areas not associated with the hair ſollicles are eccrine duct orifices Note the proximity of many of these to hair follicle openings Mag 2 possible to see any primary sweat droplets dev cloping in response to heat On other hairy areas of the skin in which no apocrine sweat glands arc found, such as the leg or thugh, the hair follicles may also appear to be the sites of origin for cccrine sucat Here 11 is apparent that physical factors are responsible for this finding b. Histological and Histochemical. A study of the apocrine secretory cells reveals the uniformity of character \ single typ of secretory coll speaks for a single ) pxe of secretory proderi Histochemically it is significant to note that the axillary pocrine sweat gland in man possesses little or no glucogen in contrast with the well-known glycozon deposits of the urine sweat gland It is our belief that if the pos rinc scal gland were to produce an additional cretion which is ccrine-like not only in appearance ·59 Tlr Plys ology a d Pha acology of the Apott Saleat Gla! nu lg 31 Wathlone blue nad on in rccrine sural After injection of 02 cc or 01% methylene blue solution into the axillary skin subsequent injection of 005 cc of pilocarpine (1 10 000) produced bluc cccrine sucat dropleis in this area More prominent blue droplet in center of photograph Other 1 luc droplets were also seen but are not evident in black and white photo Stimulation of apocrine sweating in this area produced only wlite apocrine ki cat but also physiologically it should show glyconen in at le ist some of the secretory cells We have demonstrated that the apocrine swert gland 1115 adrenergic but no cholinergic nerves It is difficult to accept the view therefore the cholinergic stimuli affect this gland ¢ Physiological Tlie physiological observations made also fully support our conclusion regarding the origin of the clear colorless fluid It always appears in response to measures which invariably stimulate the cocrine siert glind 1 be quititative response incl Intent period correspond with those of cccrine sweating Mixing of the two sccretions is not obsersed when one scare 1100 x 15 m de to appear immediately after the other Tlus would cettunk lx expected at both were 111ng from the lind Tess lons been known that the inject100 of methylene blue into the shin will result in the color of corine ikel (los 31) ·60 The Hun Sreal (laid in Iralth and Disease We have found that this docs not occur in the apocrine sıcat gland This differential dyeing techniquc was used to distinguish cccrine from apocrine sucating in the axilla After thic injection of mcthylene blue, the subsequent injection of acetylcholine led to the production of a blue follicular fluid, while stimulation with cpinephrine resulted in cloudy wintc secretion d. Pharmacological: 1) of the drugs wluch result in the appearance of the clear, colorless, "follicular" flud are specific for the production of eccrine sıcat Moreover, atropine will block this response, just as it inhibits cccrine sucating e. Chemical The colorless "Pollicular" flud is chemically identical with eccrinc seat It is free of protein such sharply soparates it from apocrine su cat In addition, its pH matches that of samples of hnown cccrine sucat from the same avillac Theoretical. From a speculatıc viewpoint, there is no necessity for the aullary apocrine sucat gland scricin a thermoregu latory role, and it would be difficult to understand any apocrine gland response to heat The aulla abounds in cccrinc sucat glinds and normally an excessive quantity of eccrine sweat is prouded The proponents of the dual secretion theory hasc raised objections to our concept regarding the origin of the clear follicular fluid It has been stated that the apocrine sucat gland is capable of producing sweat in large volume I his notion is based on the fact that the horse which possesses only apocrine type sueil glands secretes large volumes of clear sucat in response to thermal stimuli However as we noted earlier it is not at all certain that the sucat gland of thus animi is truly apocrine function ulls comparable with the apocrine gland in man I urthermore wc do not feel it is possible to predict the function of a human gland on the basis of comparatne physiologic studies in loner forins It has also been cited that the apocrine gland is capable of producing an eccrinoid type of secretion in rather large volume because patients with congenital cetodernial defect House buen shown in many instances to be completely ankrotic ciept in the auillac In these patients the ulla ny present i relatives norinal amount of it and it lys been considered that l of thus arises from the apocrinc glinds It is now known that this is not necessariis true lle have seritied the presence of well ·61 The Physiology and Plarmacology of te ffocrine Surat Glan! developed eccrine, as well as apocrine sweat glands in the aullae of such patients and it is our belief that the eccrine glands present were responsible for the normal sweating seen in the axilla In conclusion, we feel that the evidence is overwhelmingly in favor of the view that the human apocrine sweat gland produces a single type of secretion, the viscid, turbid white product The clear, aqueous secretion one may see at the follicle orifice is in reality, eccrine sweat It is D APOCRINE SECRETION 1 Definition--General Features Apocrine secretion is the designation we have employed to describe the formation of apocrine sweat in the secretory tubules to be regarded as a process separate and distinct from apocrine sweating the appearance of apocrine sweat on the skin surface Tlus the apocrine sweat gland is much like the mammary gland, another apocrine gland, in which there are two such distinct functional phases The eccrine sweat gland, on the other hand, differs markedly for its secretion is not formed continuously or gradually but rather immediately, in response to some stimulu such as heat, emotion or a drug A casual examination of the histologic appearance of the apo crine secretory cell would quickly lead one to believe that the decapitation phenomenon is in reality the mode of secretion operative in these glands However, some doubt has been raised regarding the veracity of this notion Montagna, examining frozen scctions unaltered by tissue fixatives, has demonstrated the presence of a finc fringe at the luminal border of the secretory cells (Figs 9 19) This is seen only at the higher limits of magmfication under the light microscope and not well with thick sections or fixed material Electron microscopy has recently been utilized to cxamine the human apocrine sweat gland and has confirmed the presence of this luminal 'fringe (109) Montagna believes that it may represent tiny droplets a aportuos sweat as thes Tre being released from the cell It was pointed out that the apocrine sweat gland tubular cells slios mirked varnition ranging from the lugh columnar cell full of cytoplasmic granules to the low cuboidal or flat cells with a ·62 The llumar Sitrat Gland in Health and Disrare ininimum of cytoplasmic clements Somc cells are so flat as to appear atrophic and in some cases they probably arc As we shall point out later, it is not uncommon to find a segment of an apocrine tubule with atrophic sccrctory cells or perlaps an entire gland in this state Usually luminal casts may also be seen in such tubules and we feel that most develop as a rcsult of ductal obstructions above, following maceration or other injury to the stratum corneum The presence of pigment granules, probably lipafuscin, has been mentioned and will be discussed latcr under clirondrosis Iliesc granules are responsible for the occasional color in apocrine swcat Intracellular vacuolation is not uncommon in the sccrctory cell of the apocrinc sweat gland (Tigs 7, 32) The significance of this is not known, but it is apparently related to the secretory process Ilus vacuolar appearance is sccn principally in the cells with higher more columnar epithelium The absence or at best presence of only minimal amounts of glycogen in the apocrine secretory cells is indeed significant Glycogen is an energy substance and is present in cells with a Iugh rate of secretory actility for example, the cccrine secrctory cells contain abundant quantities of glycogen and after ex music cccrine sweating this glycogen is decreased or depleted from the gland The cocrine gland is capable of producing great quantities of secretion also up to one liter or more per hour under heat stress The apocrine sucat glands secretory (ells, however operite at a low rate forming a small quantity of sccrction entirely consistent with their glycogen content 2 Effect of Natural Factors--Age, Sex, Race The amount of apocrine scat one sees on the skin surf ice i naturally reflection of the amount of .pocrine scrrction that has procecucd below in the tubulos The amount of pocrint secre ton in turn is dependent on the state of glandular activity and on the glandul ir sile We have shown that age can alloct .poxrine sweating The primarily the result of the secreton state of the gland In thic chuld with 100 1** une sue at there ireless if ans del curring cells At puberts such scretion begins with the netu i prih of activity reached during adult sexual bic Iftar the climateric ·The Plis ploey ond Pharo acology of the Ipocr ne da cal Clared 1 la la uolut on napon tactory Sejm nt of apocrine tubule showing aXxsin secretory irits Sulev u laied appearance of many of the cells Olxcrne dls (plasm granule pincrd-oll i mina stl secretor cells ind as in kan testul B and I Vlag JK Irglind the dialy Schon l xiliars shit from a health Whar non ( Vett small xerall s17t el gland plus i edulaled tubules fined by strihu Rat ejethelx m f{ and I Vagy 303 ·Mie llun i Sztrat Gliniu lleth ar I Durise secrctory ſunction again wanes with conscquent diminution in the amount of apocrine sweat It should be recalled loncier, that we have seen apocrine sheat in individuals even as old as 75 Years However, as is apparent ſrom a hustological elamination of the axillary shin of the aged (I ig 33), the apocrinc glands are smaller and slow considerably fewer actic sccrctory cells with ugh columnar epithelium The influence of ser on apocrinc sccretion is not marked The apocrine sweat glands of the adult ſeinale appear to be someuliat smaller than those of the male and show comparably smaller quantities of apocrine sucat Profound differences in apocrine secretion may be seen as a result of racial variations The Negro has apocrinc sucut glands which for the most part are significantly larger than those of the Caucasian (Iig 2) This, of course, results in greater quantities of apocrine sweat which appear on the skin surface In addhton chromdrosis of a ullary glands is more common in the Negro Indeed we have rarely observed axıllary apocrine chronidrosis in white subjects although two of our patients with localized chromidrosis of the face were 11 lute It seems that the Negro alpocrine sucat gland secretory cells function at a lugher rate of JCI also 7 bey appear to base more actuy bustologically and the refractory period for apocrinc sucating in the Negro is generally shorter It is realized that the latter could castly reflect the greater size of the gland rather than an increascci secrctory me Schucfferdecker stated that the lustralasians possessed the largest and most acune apocrine sweat glands (6) He have not examined any individuals who would fall into this racial cutegory However it is well-known that Orientals particularly the japin ese have little or no body odor as a general rule and thus of is a definito indication of apocrine sweat gland an (8) We have cvamined several Japanese and Chinese men inci laic confirmed thus to our satisfaction Morda rices were presumed by Schiefferdecker to lase the singutest and least oncloped apocrine sui cal glands 3. Effect of Endocrine States The impact of puberti un apocrine sneal gland function is narled indeed as is also that of the clim icteric In addition course ·The Płystology and Plarmacology of ile Al xrme Strol Gland 65 liay been stated that other endocrine states will influence this gland For example, numerous observers lave described cyclic changes in the apocrine tubules which correspond with various periods of the menstrual cycle The majority feel the secretory activity is greatest premenstrually or during the menstrual flow (45, 46, 47) Others have stated that no correlation can be made relating to menstrual activity (48) Our experience would support this latter view, as does Montagna in his recent careful study (22) As this author points out, and we fully concur, the secretory cells may normally show such marked variation from gland to gland that it is difficult to assess the overall functional state of the gland Montagna found no histochemical alterations of note either While there may be changes occurring they are not detectable by present methods of study Pregnancy has also been described as a period in which dramatic changes in apocrine secretory activity occur Again the literature contains conflicting reports on whether there is an increase or a decrease in glandular activity during pregnancy and there seems little point in detailing them here (49, 50, 51, 52) We have not noted a remarkable increase or decrease in the amount of apocrine sweat in the pregnant women we've studied, but would hasten to add that these women were not seen before their pregnancy nor studied for a long period after puerperium Interestingly, in the few women examined within the first week after delivery, at a ume when the mammary gland is quite active, we were unable to detect a significant increase in apocrine sweat It is significant to note that one subject examined seemed to show a diminished rate of growth of the axillary hair during pregnancy If hair growth is to be used as an index of appendageal (at least those appendages that are derived from the primary epithelial germ embryologically) activity, then perhaps some decreased apocrine functional actity did occur in this patient However, the apocrine response in this patient showed no appreciable change In addition, other women failed to show a comparable decrease in aullary hair growth There is one bit of endence, honeser, that suggests that apocrinc secretory activity is diminished during pregnancy This is the fact that most patients with ror-I'ordsce disease improve ·06 The llunan foil Gluud 11 Il afth and Driente dhamutcsths during pregnancy and that the discase rccurs again «ftcr clelismy Winle it is true other explanations may be offered for this improvement, se feel it may spcal strongly in fasor of decreased secretory activity during this period The chmaclare represents the cra in which the apocrinc sucal glands shou the light of their functional acinity Tic basc cumined clderis males for apocrine su cating as described in an cirlier section In general the response was decreased in the elderly but we have seen some apocrine sucating in a subject 75 years of age Histologically, the retrogressive changes are spurte apparent lhe glands are smaller in overall size, and there are (cwcr tubules showing actre secretors actnaty There is an incrcased number of atrophic tubules also, with cellular caste in many of the tubular lumens (Fig 33) e fave not had the opportune to study bistological specimens from the wilac of women of the post-climacteric crat although Montagna fras descubeul changes similar to those outlined above in oui male subjects Honcier, we have cumined the axillac of such women for the presence of apocrine sıcat Similar results in eight nomen over 55 years of age as in the males referred to above acre recorded The apocrine response hac deminslied in all, although the eldest woman observed 67 years of age, showed some dehuute apocrine sweat in her auline 4 Effect of Systemic Disease To our knowledge, involvement of the apocrine sneat gland by systemic disease processes has never been described Wełaıc not studied thus problem specifically Honcierne haic scen normal axillary apocrine su cating in response to local epineptırınc and to mental stimul an one individual with sarcoidosis, in tuo with moderately advanced pulmonary tuberculosis one with Jeuhema, in one subject with diabetes mellitus, and in one man with hemochromatosis The latter did not slow colored apocrini sweat interestingly It should be recalley at the color in chromidrotic apocrine sille has been attrit increased quantities of iron in the secr te e unable to secure chech this point more carefully a biopsy of the ·The Misraloc> and Pharmacalary of the ipocrine Strei Glad 67 It is quite possible that people with marked debilitating discases resulting in cachexia and inanition or where there is prolonged agony ray well shou degeneraine changes in the apocesne sucht gland We have offen noted that this gland slows wutolysis relatively early post mortem and such changes may cren begin before death in processes such as those referred to above 5 Effect of Deodorants In 1949, Sulzberger, Zah and Herrmans showed listologically in biopsy specimens from the aula that aluminum chloride preparation produced a degeneratne change in the apocrino tubular cell (53) They also recorded diminished eccrine sweating incidentally, presumably because of ducial occlusion resulting from perductal inflammatory changes Ous prelmusary work suggested that aluminum chloride paste preparations mught reduce or abolishi apocrine sweating Because of the importance of deodorants in our modern society, we decided to nestigate thurs problem in some detail Although greatest emphasis was placed on the aluminum preparations, we also studied the effect of the surface actre agents and the newer zirconium salts and their effect on axıllary sucaring He shall not describe our studies on elle eſTecs of deodorants on ecerine glandular actrity in ths secuon (of Bad Odor) Rather we should like to focus on the apocrine sucat gland While our special interest in this chapter is related to apocrine secretion per se we must use our observations on af ocrine sit rating responses 153 these subjects Obviously an alteration in this laster clay could reflect a change in apocrine sccretion MICTUOD AND NUTERIUS mens were selecid from approum teh 16 years fuss 7 study of apocrincezung ut of these men had abundans and * munetnical equal apocnnc aueat response The aulae were the ed ind Hartung 34 fututed to unde das's Nothing *apped viher than the product under studi The follos ang propositions fudied in 1) nich nach ial 2,346 chloride 15) (queurs solstion ih spyras de extor snt iconmcress contuning amnum chlorul ·68 The Iluman Siceal Glan? 17 Health and Disedie (c) spray deodorant (commercial) containing an aluminum salt (d) cream deodorant (commercial) containing an aluminum salt (c) stick deodorant containing an alumunun salt (1) stick deoclorant containing a zirconium salt (s) a creum deodorant containing a zirconiunı salt (h) a cream deodorant containing a surfactant (1) zinc oxide pasto In the case of the aluminum chloride solution, the application technique consisted of placing gauge pledgets (10 10 cins ) saturated with the solution in the avulla for five minutes daily for scien dars All other test substances were applied in one axilla for five minutes once a day for seven days in all instances, the oppoutc axilla served as a control and was untreated except for the usual washing At the end of a week, the axillae were carefulls cleansed with 706 alcohol to remove all debris accumulated cream peste or liquid deodorant, so that there would be no difficults in identification of apocrine sueat The e men were then given a standard test dose of epinephrine (O 15 cc of 1 1000 solution) subcutancously in cach avla Comparison of the response in treated and control sides was then made In addition in at least three men in each group biopsies of the treated and control axillae were taken for histologic study of the glands after such treatinent These were fived in formalin and stained with hematorilon and coun OR$CRVATIONS In all subjects studied, there was no significant decrease in the quantity of apocrine sweat in the treated or untreated axudae In some of the men who had used the aluminum chloride preparatrons miliarial vesicles were produced on the treated areas The zinc oxide was used to determine the possible mechanical blocking effect of such a thick preparation it 100 was ineffecine which is not surprising since the glands will 'sweat' against an external pressure of 225 mm of mercury Histologically we could find no degenerative atrophic or other change within the apocrine secretory cells, in the ducts or in the stratum corneum These as well as other structures obserı cd were entirely norinal and indistinguishable from the control shin Comment regarding the effect of these substances on odor reduc ·The Pyst logy and tarmacel igy of the furent Sie eat Clar? 62 tion in the auillae will be discussed later in the section on Body Odor It is concluded that none of the materials studied has any apocrine antipersprant effect 6 Effect of Hormones The natural fustory of the apocrine sueat glands in man india cares that they arc under endocrine control The precise relationstrip of such hormonal control is not at all clear, however There is fu{}e experimental ch.dence which indicates that any hormonal principles can induce changes in apocrine acinity Shelley and Cann, in an exhaustive study using topical and systemic administra tion of adequate doses of various forms of estrogens, androgens, progesterone, thyroxine, the growth hormone of the pituitary, prolactin and chorionic gonadotrophin, alont, and in vanous combinations, found no appreciable alteration in apocrine sweating or in the lustologic appearance of the apocrine sweat gland (54) These authors noted no changes in any of the other structures found in aulary skin as well Hormonal effects on cutancous structures which have been described in ammals have not been satisfactorily reproduced in man probably because of species variations and dosage differences In man, significant changes have been seen in the skin only after long term Ingh dosage hormonal therapy in clinical disease such as breast carcinoma (55) In such instances however histologic and control observanons were usually lacking and the underlying discase process may have altered the observed tissues Some of the prime difficulties in previous studies on htaman skin may has been lach of absorption relatively low dosage levels and short term trials In an effort to abusate these difficulties we decided to emplos hormone containing pellets implanted sub cutancously in the study area as an experimental approach Because of the importance of androgens und escrogens in sexual cenelopinent and because these substances have long been im plicated for the changes in human shin believed to be induced endocrinologically it was decided to use these sulissances in this study osige varied from one to three pellets in the sites to be olyamai and they were left alue for person's varing from one to inc months The hormone was intimately in contact much Sessels «ppendors and other skin strurfures with th»s iechnique ·72 The Iluman Sutedt Gland in Ilealth and Disease LADI 10 of Subjects B: Ps1 Comments llormone(s) V7 ani Dotace Progynon - 25 mm Progynon - 25 cm Progynon - 25 ingin Progynon - 25 mqm 1'rozynon 25 mm 1 month 2 months 3 inonths 4 months 5 months 1 5 Two of the suspects desclope! bilateral gynecomastia and one subiect descloped unilateral fynecomast on the treated sudde Oreton - 15 mgm Orrton - 75 mg Ort ton - 75 min (reton - 75 mgr Oreton Progynon - 75 mgin 1 month 2 months 3 months 4 months 5 months 3 months 75 mm Bilateral gynrcom att de cloped In toth sut jrets 2 2 150 mg 225 mm 3 months I month 3 mor ths 3 months 1 1 Bilateral gynecomastia Oreton Oreton Oreton 225 mg Orrton 150 mm in on drilla 15 I'rogynon 75 mgin in opposite dulla Oreton one axilla \$ Progynon 7 mgm in opposite zuilla 75 ingmin 3 months Bilateral gynecomastia des cloper un both subjects Lmphasis should be placed on the fact that in this study, the hormone-containing pellet was actually in contact with many of the structures of the skin (Fig 34) Using the implant technique, the local concentration of the hormone in the skin was far higher than that which could be achieved by any systemic or topical administration The failure of these large local' dosages of estrogen and androgen to produce change in the apocrine sucat gland and other shin structures, in the face of obscrvable hormonal effects (gynecomastia) indicates that deakon of androgen and estrogen concentrations in the skin (of the adult male) were with out effect, despite the fact that these very substances may be responsible for the conunued activity and normal function of this skin and its appendages furthermore, these findings support thic viest that neutralization of one liormone cannot be achievca lvy ·The Physiology and Pharma logy of the fou nine Suecol Gland 73 the administration of another Certainly, the estrogen levels in the axillary skin of our subjects with progynon implants far exceeded the plıysiologic levels of androgen normally present An obvious objection to these as well as previous studies of the effects of hormonal substances on human skin might concern the subject material used It may well he that one will be able to determine the controlling endocrine principle or principles only by studying pre-pubertal children We fully recognize this possibility Unfortunately, such subjects were not available to us at the time of these studies In conclusion, we were unable to postulate the specific hormone or hormones which may regulate apocrine secretory activity, despite extensive investigation in this direction The recent work of Lorincz et al indicates that the activity of the sebaceous gland may be regulated by a specific trophic factor of the anterior pituitary (57) It may well be that the human apocrine sweat gland is similarly controlled by this same or another pituitary hormone 7 Effect of X-ray The effect of X radiation on the cutaneous appendages has always attracted great interest because of the use of this modality in a variety of the dermatoses affecting these structures It is stated that a total of 1100 roentgens will depress the holocrine activity of the sebaceous gland A dosage of approximately 350 r will cause temporary cpilation of scalp hair and over 600 r is required to produce permanent alopecia (58) It should be emphasized that other shin arcas require different dosages for similar epilatıng effects The beard, for example, may only yield temporary and perhaps partial hair loss after 850 r It is recognized that this dosage is approaching that at which skin damage (radiation sequellae) may eventually develop In contrast to holocrine function, however, the merocrine organ of the shin, the eccrine sucat gland, requires about 2200-2300 roentgens, it is believed, to cause inhibition of its secretion (58) This has not received experimental confirmation, however, and this figure may be quite inaccurate To data are available regarding the amount of X radiation required to affect apocrine secretion Because it is thought of ·The Iluman Sacal Glard in Ilralih and Dease as intermediate between the cocrine and schaccous glands, it has been speculated that a dosc of 1700-1900 roentgens might produce tlus effect. The problem of size of the gland and its greater depth must also be considered however, and perhaps would necessitate an incrcased quantity of irradiation It is note. worthy that kc detected adequate quantities of apocrine sucat in the axillae of a young man who had recchied 1000 r of heavily filtered (05 mm (u) X-ray 5 ycars earlier for cccrine hyperidrosis of the axillac lhe cocrine sucating was also not depressed, and axillary hair growth was as luxuriant as before it is probable that niuch of the X-radiation geen in this case was actually received at a much accper level than in the skin because of the great filtration employed In another subject, we administered 800 r (1) min Al filter) in air at onc sitting to a 50 cm arca in the vulla The subject was observed at woehly intervals for onc month then monthly for three additional months No apparent change in apocrine sweating was noted (his axillary odor was not decreased) nor was there any hair loss In conclusion, it may be restated that the amount of X-radiation required to produce a significant decrease in apocrine sccretory activity is unknown It is in excess of 800 roentgens and probably above 1000 roentgens 8. Relation to Pilo-sebaceous Activity Because the apocrine sweat gland is a derni atne of the same parent germ it was thought that the function of thus gland might be related in some way to pilo-sebaceous activity However, no specific changes have been noted in any studies to date but such may be extremely subtle in some 'shin cycle animals, such as the mouse and rat, parallel changes in the sebaceous glands, metabolic activity of the skin and other functions have been demonstrated (59 60) Since all of the hairs in these animals arc in the same stage of their cycle simultaneously it is relainely casy to examine this problem In man houever, as in some other animals, hairs do not reach anagen or telogen together 15 no synchronization of hair growth These animals are not "shin cycle animals and no constant relationship between hair growth and other cutancous activities has been demonstrated However, if "unit" appendageal function were considered, perlaps - there ·75 The Physiolo ani tham acology of the Jan Stral Glon! some relationslup between hair and associated glandular function could le appreciated After studying several axıllary biopsies carefully with this in mind, we could come to no conclusion regarding the possible relationship of hair cycles and glandular activity Axillary hairs in anagen may have associated glands (whose ducts empty into that follicle) which are indistinguishable histologically from those whose related hairs are in telogen Sırlarly, after manually epilatıng several hairs in the axillae of 4 subjects and subsequently biopsying these areas at 2 and 4 week inter als, we could not influence apocrine glandular activity despite produring an abrupt change in the growth cycle of associated har follicles It should be emphasized that serial sections, properly cut in the long axis of the hairs, were necessary for this study Wlule there is every reason to belie that there might be a functional relationslup between hair follicles and derivative apocrine sweat glands, we are as yet unable to demonstrate it E DISCUSSION AND SUMMARI OF APOCRINE SWEAT GLANY PHYSIOLOGY Probably the most decisive single piece of evidence provided by our studies of the physiology of the apocrine sucat gland was the observation that apocrine sweat could be made to appear by inere manual compression of the axillary skin This simple fact proics al once the following 1 That the actual secretion of apocrine sweat must be a process independent of that whuch causes its appearance on the skin surface This latter more dynamic phase of apocrine function we have chosen to designate apocrine su cating pocrinc secretion is in fact a slow more or less continuous acuity much like the formation of milk in the mammary gland 2 flat an expressue or contractile force which empties the tubules of preformed apocrine sweat, is responsible for tocrine sueing lle subsequently identified this coniritule forct as the myocpithehum the smooth muscle layer which enclops the apocrine tubules all of the plicnomena concerned with apocrine cheating se dependent upon acti- 1a11on or inhibition of the myocpithelium let us treapulaid the sabent features characterizing the con- ·76 Ile Il an Sieral Glan / in the alth and Disease trol of cach of the functional phases of apocrine sucat gland physiology Ipocrine stealing is under the control of adrenergic fibres of the autonomic nervous system Neural control is operative because an instantancous widespread response is seen following the proper emotional and sensory stimuli Moreover, local anesthetics will block thus response while local arrest of the circulation will not Thic adrenergic nature of the innervation is apparent since apocrine sucating may be produced by adrenergic and not by cholinergic drugs In addition, the absence of specific CHE about the apocrine sucat gland tubules indicates an absence of cholinergic neries, thus confirming the observation that there is a single, adrenergic supply There are no inhibitory fibres to this gland Ipocrinc sweating may also be produced by other local, somewhat artificial (unphysiologic) stimuli Drugs, such as pitocin, which cacite myoepithelial contraction, can induce a local response Physical stimulı, such as strohing or rubbing of the axillary skin may also activate the myoepithelium resulting in apocrine sweating It is conceivable that a similar stimulation may be effected in our daily lives by the rubbing of the axillary skın as produced by the swinging of the arms in walking or running This may well represent a normal means by which the apocrine glands are empted periodically The regulation of aporine secretion is not perfectly understood as yet although the importance of the endocrine system cannot be au cremphasized The influence of puberty, the climacteric and endocrine states such as pregnancy have been mentioned However despite extensite experimental ini csuganon, the spe cific hormones which produce these alterations have not been identified We know of no systemic disease which effects apocrine glandular activity although the early development of autolysis post mortem suggests that degeneratis changes may occur after prolonged cachectic illnesses one of the deodorant preparations presently available have any effect on apocrine secretory activity Indeed they have relatiely little antiperspirant effect in the axilla. They function mainly as deodorants The dosage of X-radiation required to depress axillary apocrine secretion is unknown is certainly in excess of 1000 r ·77 The Physiology and Pharı acology of the Apocrine Steat Glan! Eccrine Steal Gland Eccrtne sweat gland germ 1 Derived from 2 Secretory cells TABLE II 1 poctine Surat Gland Primary epithelial germ Iike hair and sebaceous glands Single type, variable height depending on stage of se cretion Numerous gran ules no canalicul Well developed Func tonal importance Con tracts to produce apocrine sweating Two types Cell height constant Hare inter and intracellular canaliculi no granules Poorly developed Prob ably non functional Pres sure generated from sec retory activity forces eccrine sweat to surface 3 Myoe pithelium 4 Character of Sweat Clear watery Turbid may be colored and may fluoresce Restricted Generalized Generalized Very restricted or absent 5 Localization in man 6 Localization in other mammals 7 Autonomie innerva tion Adrenergic only 8 Beg ns to funct on 9 Secretion of sweat At puberty Slow gradual process re sulting in storage of minute amounts equal to tubular volume Does not occur at tume of apocrine sweat ing Under endocrine con trol Once gland is emptied for 24 72 hours Cholinergic Adrenergic supply if present of no importance functionally Al birth Very rapid process Great quantities can be formed up to one liter per hour Actual secretion takes place at time of sweating 10 Refractory period None seen after any physi ologic stimulus Sweating continues as long as studiu lus remains Heat emotional stimul 11 Responds to 12 Physiologic impor Emotional stimuli not to heat Little or none Itayistic scent gland Important primarily because of local disease tance Vital in hot environments Major thermoregulatorv organ Is a final note it is of value to contrast the mode of function ind activity of the two varieties of sweat glands in man, the apocrine and the eccrine This is conveniently done in tabular form Inatomical and comparative features are included also since they provide a hetter understanding of the physiology of these glands. It should be enphasized that eccrine secretion and ecerine su eating the place at the same time whereas apocrine suciting is a process independent of apocrine secretion ·IV THE NATURE OF APOCRINE SWEAT A. PHYSICAL CHARACTERISTICS Arockin sweat is a turbid fluidi (lig 35) Ius this property of turbidity which is of great importance in the differentiation from eccrine sıcat, a clear, watery secrction However, the cloudy nature of the apocrine sneat varics greatly from person to person In some, cspccially the Negro, it may be so thick as 10 resemble crcam, while in others, in order to identify it with certainty, it is often neressary to collect some of the material in a small capıllary tube for examination against a black background By so doing, one can readıls distinguishi apocrine sucat which always shows some turbidity, from clear, aqueous eccrine sweat It is worth noting that it may be difficult or Impossible to even collect some of the very truck apocrine sweat in a capillary tube because of its viscosity It is apparent therefore that the specific gravity of apocrine sweat will vary from that close to water to that equnalent to milk or cream Apocrinc sweat may also show some color Most commonly, a yellowish tint can be perceived although green, blue and bluishblack sweat may be observed infrequently Apocrinc sweat while odorless when it initially appears on the skin surface, develops a distinctive ador within a short time because of bacterial decomposition If undiluted by cccrine sweat, apocrine sweat dries quickly to appear as alghieans, glucide cap resembling drud varnish or plastic If collected in a tube, curd like parucles will settle within the swcat as it ages (Fig 36) Finally, whether drsed or recently secreted, apocrine sweat may exhibit a true fluorescence when exposed to Woodlight (1 ug 20) 78 ·79 The Qiure of 1pocrine Surat h 3 Aparrine de ea! I wo capillary Cubes containing sweat are shown The upper tube contains clear per ne skext The lower tube contains turbid apocrine subat ne 36 Cards apocrine sieut Capillary tube containing apocrine sweat was allowed to stand for 21 heure Examinadon at this time revealed the develop ment of curd-like aggregates (above) in the sweat B CHEMICAL CHARACTERISTICS The pH of apocrine sweat was measured using pHvdaron Unsversal indicator paper with which 05 pH unit dianges can be derected Samples of apocrine sweat were collected from iwenty normal, heality adult male subjects Both Negroes and Whites were studied and extremes of apocrine sweat ranging from the very turhd viscid variety to that close to eccrie si cat in appearance included Pure micro samples were collected in capillary tubes just after appearing at the axillary follicular orifices in response to epistephrine or emotional stimulation Pure samples of eccrine su cat were collected in similar tubes after emotional stimulation also It was learned thaj me pH of aullary apocrine sweat ranged ixtueen 5 and 6 5 lucreas the eccrine sneat readings were fx tu een pli 40 and 60 liigsen individual, the apocrine Call appeared 19 hore a pit approximately 05 pH ustit lugher trun the cccrine sweat but the differences were 100 slight to be of pricilsal salue in differentiation of the two secrctions ·BO The Iluman Surat Cland in Health and Disease W Iron in apocrine su eat on shirt 1 spot test (a al dipyridyl) for iron was applied to the axillary section of a shirt stained with apocrine sweat The dark line in the right half of the photograph indicates the presence of iron It should be emphasized that this test 15 positie in onks a small percentage of cases The minute quantities of the apocrine sucat samples that could bc secured necessitated the utilization of ultra-micro analytic techniques Spot tests proved to be the most satisfactory methods of determining the chemical composition (61) It was found that apocrine sweat in contrast to cccrine sweat, contains protein (using the 2 nitroso Bonapthol test for tyrosine), carbohidrate (reducing sugars using silver nitrate), and ammona (manganese nitrate silver nitrate) Although we were unable to demonstrate lipids by means of spot tests we feel certain of the presence of these compounds from the bustochemical studies The spot tests for lipids are relatively insensitive procedures in addition iron in the form of ſome iron (a a dipyridul after reduction) is present in apocrine sweat although in no great quantitics I positive spot test on the axillary section of a white shirt is shown in fig 37 Note the dark line indicating the presence of iron Apparently, migration of the iron was greatest produring this location for the ·81 7 he Nature of Apocrine Sucrar iton deposit in the mosstened slurt These results were quite irregular however, and in most people negatre "shurt" tests were noted Samples of apocrine sweat collected in capillary tubes gave a similar pattern on filter paper provided enough apocrine sweat was used We have not studied the chemical characteristics of apocrine sweat in other races, in women, after dietary restrictions or indiscretions, in areas other than the axilla or in patients with systemic disease C BACTERIOLOGY The axilla is a most intertriginous skin site and as such harbors a maximal number of resident and transient shin micro organisms We attempted to outline the normal range of the bacterial flora found in the human axilla Swabs were taken from the axillae of twenty healthy men and were inoculated on blood (horse) infusion agar In general, the following bacteria were found routinely (1) Micrococcus pyogenes, var aureus (coagulase-positive Staphylococcus, (2) Micrococcus pyogenes, var albus (congulasenegative Staphylococcus), (3) Corynebacteria (4) Aerobacter aerogenes (5) Sarcina lutea Strauss and Kligman, in a later study of the axillae of twentynine healthy male subjects, found essentially the same organisms along with an occasional E coli and Proteus vulgaris as additional transient organisms (57) Little was known, however, regarding the bacteriologic state of apocrine si cat Because of the possible importance of bacteria in the production of axillary odor, we felt it imperative to deterinline what organisms of any might normally reside in apocrinc sucat itself This information would be cqually cogent in a consideration of the etiology of diseases of the apocrine sweat gland McTHOD AND MATERIAIS Twenty healthy adult niale volunteers with no abnormalities of the sulte sere used as subjects The aulae were prepired in the following manner The rening before the collection of the specimens the avillac were clovek shred and clcuned carefullt with lyurt «ap gain 17 the If on arising the aullae were cleansed with liory soap ·82 The Ilu on Jailand in U alth Dae Three hours later immediately prior to collection of the $1671 suples the villae ucrc cleinsed 1 third time with liory soap Víter riasing the axillac were muabled with a pad sorked in 70% tihyl alcohol finall 1 10 10 cm Steri pad curated with 70°, cahil alcohol 175 applied to the avilla and left in place for 5 minutes Collection of sent simples Upon removal of the alcohol saturated Steri pad un film of alcohol nas scen on the surface 1 1000 cpinephrine injected subcutaneously to induce apocrinc Seating Eccring sweating 175 not obseried in these subjects during this collecuon period 1s soon as the ipocrine sweat appeared it was collected in 1 sterile capillars tipped glas pipette ipproumack 20 cm in kingth The diluted dital portion of the collecting tube * ?> plugged with cotton to insure sterility The narros capilar end of the tule 7s then dipped in a tule containing storilc perro latun thu scaling the end of the collecting tube 10 nord cont im ination and evaporation of the pecimen The entire collecting cules is then placed in a large sterile gli seule capped inth cotton and prompils ir in ported to the laborator for 1 c teriologic studs BACTERIOLOGIC TECHNIQUES Thic contents of the villary tubes were placed in 1 cc of brin heart infusion broth Cultures w cre incubated acrobicit ind anicrobically Hanging drop and Gram st un prepirations were made of the broth cultures and subcultures made to nutrient agır and blood (horse) igar When Gram ne, 011e brul were present in the cultures subcultures were iso mude to rosin methylene blue agar and SS ngar The Brouci jar mcthod »ys employed in the in nerobic studies Micro crophilic conditions were established with titis method also but the method modified in that hydrogen 7s added and the jar not completely exh rusted of owsen RISULTS The bacteriologic studies of apocrine sweat showed the follonin, ferol is traerolic 1ficroaerophilie 24 No of specimens 5 5 () 0 No with bacterial growth ·The Aal me of Adottle Surat 83 or the four specimens which showed bacterial growth, two contained organisms of the genus Corynebacterium, one of the genus Aerobacter and one of the genus Sarcina The first are normal resident organisms of the skin surface while the latter two may be found in the transient flora of the skin surface We feel that their presence in the four specimens was the result of accidental contamination of the apocrine sweat during collection of interest that no anaerobes were found apocrine sweat since sebum has been shown to contain such organisms (Propionbacterium) On the basis of the above described studies, we concluded that human apocrine sweat is normally a sterile Aud on its appearance on the skin surface It is D BODY ODOR Because of the purported significance of the apocrine sweat in the production of body odor, we undertook to study this problem in detail In studying the physiology of the apocrine sweat gland, we were impressed by the lack of appreciable odor in pure apocrine sweat as it initially appears on the skin surface Moreover, it was noted that after standing, such sweat later developed a definite ſoul odor which increased in intensity as time progressed In thuis investigation, we were particularly interested in the possible roles of bacteria, apocrine sweat and deodorants in the production of axıllary odor (61) Our preliminary studies indicated that apocrine sweat was sterile and odorless when it initially appeared on the skin surface (1) We then proceeded to study aulları apocrine odor in vitro and to determine the rol of the axillai bacterial flora in the production of this odor MCTHOD AND MATERIALS Ten healthy Vegro men were chosen for this study No abnormalities were present in their aullae Preparation of the yıllac One axilla was prepared exactly as described above under Bacteriology of Apocrine Sweat The opposite axilla was unshaved and was not cleansed for at least 24 hours prior to collection ·84 I ke llum in Sucat Gland in Health and Duroir Collection of the specimens Collection of the specimens was identical with that described under bacteriologic study Ten microtubes (Pues No 1) were filled with pure apocrine eat talon from the cican ed axilla, and 10 tubes (Tulcs No 3). 11 cre filled with pure apocrinc sucat taken from the uncleansed axilla In addition, another series of tubes (Tubes No 2), especially prepared sith a thin film of hexachlorophene in alısolute alcohol lining the interior of the tube, were filled with pure apocrinc sucat collected from the uncleansed axilla All of these tubes were then allowed to incubate at room temperature and studied at varying intervals Several similar specimens were hept refrigerated at 0°C Examination of the specimens The specimens incubated at room temperature were then examined for odor in a careful consistent manner at 1 hour, 6 hours and 24 hours, then once the fifth day Later cxaminations were made on the 8th, 11th and 14th days. They were read in the same order at cach cramın ition, ie, Tubes No 1 (containing pure apocrinc sueat from the prepared axilla) Iulses No 2 (containing pure apocrine sweat from the unprepared aulla with hexachlorophene lining the interior of the tube) Tubes No 3 (containing pure apucrine sıcat from the unprepared axilla) The tube was broken at the capillart und and then tested for odor by two examiner, and the results were recorded independently lys each evanuner without hnowledge of the other s reading daily up RESULTS IND DISCUSSION No odor could be detected in any of the tubes at one hour after collection, as illustrated in Graph I In tubes No 1 no odor developed throughout the entire 14 day period Tubes No 2 had no percepuble odor until the final reading on the 14th day, when a faint odor was recorded Tubes No 3 at 6 hours generated a strong odor which became very strong at 24 hours and remained at this intensity throughout the rest of the readings In the refrigerated speciniens no odor ever developed Of great significance is the fact that tie odor de cloped »» these tubes was, as far as we could tell, identical with thar wirach we denufy with the axilla of man It is not surprising that she refrigerated samples failed to develop any odor since the necessary Ivacterial activity would be absent under such conditions ·85 The detyre af fpon. Surat Very Strong odos tube 3 Strong odor No odor in any tube at one hour after collection Faint odor tube2 No ador tube 1 44 1 11 14 2 3 4 5 8 Days ofter collection GRAPHI In summary axillary odor was reproduced in the "test tube' It developed within sil hours after collection of pure apocrine sweat from an uncleansed, unshaved axilla No odor was noted ! samples of pure apocrine sweat collected from the sterile' axtlla even after 14 days The addition of hexachlorophene prevented any odor from deseloping until the 14th day, when a faint yet typical axıllary odor was recorded 1. It was concluded that bacterial action is necessary for the production of odor from apocrinc sweat This experimentally repro duced odor was indistinguishable from the classical axillary odor sech in man (2) An in uilo sludy of anillory odor was then devised in order to fest the afore mentioned principlc (in vitro) that bacterial action upon apocrine sweat would result in the typical body odor and that such odor could be presented or diminished by inhibition of bacterial activity in the auilla A popular germicidal detergent pHisober as used as the antibacterial agent in the study ·86 11. llunian Sumur Gland in II, alth and these Group NE PUTODS AND MATERIALS 1 wents-lise licalthy Negro men were chosen for this study and ucre divided into two groups of 10 (Group 1) and 15 (Group 11) men cach No abnormalities were present in their juille, and axillary hur growth sdh good in all subjects Preparation of the anıllae No shaving of axillars hair was done in these subjects One axilla was carefully washed for ne ininutes with phuches once daily for seven days the opposite avilla was alo carefully washed for five minutes with pHisoderm once daily for seven dass Thorough rinsing of the axilla with tap water was donc in cach case following cach wash, but no other soap, deodorant, or alcohol was applied to these areas during this trial period Cramination of the axillae These men were tested for the presence of axillars odor at 1, 2, 8, and 18 hour periods Subjects were placed in a supine position with their hands beneath their head and elbous directed laterally Two examiners, unaware of what the previous treatment had been, carefully appraised these axillae for odor cach independentis stating their findings to a recorder A rest period of 10 minutes between readings nas proided Obscrvations were recorded as negative (absence of odor) or portie (presence of odor) and no attempt was made to grade the readings The odor of hexachlorophene which w in itsell pleasant, very faint and casil's distinguished from the classic axillar odor was recorded as negatne (no odor), unless in axillary odor co-crested in which cave a positive reading was made Dil ferences in readings when they occurred were recorded as positive Group II Preparation of the axillae "The axillary hair was un Shaved in these men also for three days a daily five-minute wash with pHroHex (to one axilla) and piłisoderm (to the opposite xilla) was done Thorough rinsing of the aulae with tap water followed the washing and no other soap deodorant or tlcohol was applied to the are? during this trial period Collection of specimens Tho and one-half hours after the last axılları ash 10 of these men were seen and placed in a vupine position with their hands beneath their heads and elbous directed laterally liith sterile scissors and forceps axillars hair, were removed from the respecte axillae and placed on blood ngar plates Only one hair sas placed on each plate They were then incubated at 37 50 C for 48 hours In the other five men, ayıllary hairs were remosed and cultured in the same manner 20 hours after the last axıtları wish ·87 The Valar of sportsne Surat te the trial ffat thisober in tilla Hair frum ptinllcx kathod auilla sht sine absrnce di bracierial growth on tfond agar is illustrated in alkur places graph Compare with hair Irlou from pllisderm washed uwita showmg heavy hutorul grimsth y trat RSSIIS Division (oup 1 Is the graphs I? 24 }}}} .cates the plisollex-treated mutta honed i gue tatis greater extor protection than did the control passarela med rust (noup ll O tre his rolstof (11) and one balf hours after tine. Ne {X}31 frsf li plesalke -usliecl ssde showed ·88 The Iluman Sital Glandia Ilealth and Disease 10 Phisexkrm Number of subjects with oxillory odor Phisohex 1 2 4 6 16 18 8 10 12 14 Hours after lost wash GRAPH II growth whereas all of the hairs from the pHisoderin-washed axilla showed luxuriant growth (Fig 38) In the test 20 hours after the last wash, only one of five axillary hairs from the pHisoHer-washed axıllac showed bacterial growth, while four of five pHisoderm-Hashed axillary hairs showed excellent growth after incubation at 37 5° for 48 hours It has been shown that pHiso Hex greatly reduces shin flora when used exclusively and repeatedly for cleansing The effect of the hexachlorophiene was revealed by using the same detergent base, pHisoderm, as a control This abolition of odor in the axıllae of subjects using pHiso Hex along with the concomitant aullary reduction in bacterial flora provides in vivo evidence that bacterial action is necessary for the production of body odor from the axilla (3) The role of the apocrne cu eat has yet to be elucidated should be stressed that the secretion cxamined in the buteriologic and odor studies thus far will not mind a killary secretion apocrine sweat alone The sweat droplets were collected in their points of origin immediately after their appearance No other secretion or at least only negligible quantities was muluded but ·The Aaluure of potrine Sweat 89 Further proof of the importance of apocrine sweat is the fact that the appearance of the axıllary odor can be correlated with the development of the apocrine sweat gland Thus, in the child before puberty, axıllary odor is absent It is also diminished in the post climacteric cpoch as actinty of the apocrine sweat gland hranes We studied five healthy adult males, ranging in age from 65 to 70 years for apocrine sneating and axillary odor It was found that four of the five had the usual axıllary odor while the fifth, a 69 year old white man, did not show the typical axillary odor, but rather a flat, somewhat vague scent This patient also produced no apocrine sweat after stimulation with cpineplırıne We concluded that apocrine sweat is the necessary substrate for the production of the classic axıllary odor in man (4) Other factors, notably axıllary hair and eccrine su eal may also influence the development of the axillary odor It is felt that the terminal hair of the axillary increases axillary Odor production since it acts as a collecting site for apocrine Sheat and debris and because it makes cleansing of the area more difficult Moreover, bacteria may cling to such hair ceeded to investigate the role of hair in the development of the axillary odor We pro- MICTHOD AND MATERIALS Ten healthy Negro men were chosen for study No abnor mallies of the aullac were present Preparation of the axillae One auilla was shared and care fully washed with Ivory saap for 10 minutes. The opposite axilla was unshaved and was alo washed with liory soap for 10 min. cs Lach axilla was thoroughly rinsed with water Txanınation of the axillae Olfactometric ol, ervations were then made in the same manner as presiously described RESULT IND Discussion The results are clearly illustrated in Graph 111 The unshared axillae or wo men had a definite odor at the one lour reading, and at 6 hours of these subjects showed such odor It 48 hours, all 10 of the group had the usual axillary ·90 Ihr Iluman Niccal Cliniu Ilealth and Disease 10 Unshaved Number of subjects with axillory odor 2 Shaved 40 24 Hours ofter preparation GRAPH NI scent Contrast those with the shaved axillac where no odor could be detected at 6 hours and at 24 hours only one man showed the usual odor At 48 hours, however, most of the shaved axillac de cloped odor These findings substantiate the concept that retention of axillary sccretion and bacteria will prompt an increase in odor The Jeffect of shaving was quite remarkable, and it is understandable iherefore, that in women who share their axillae regularly, there is a markedly reduced aullary odor Eccrine siled is regarded as a sterile odor oss fluid upon tron, but it has been said that it develops an odor after standing for ses cral hours, presumably because of bacterial action (64) However, this conclusion was reached after studies in which collection techniques were such as to allow for contamination of the specimens hith keratin scales, debris, etc The necessity for the study of purc normal cccrine secretion in any investigation of its odor-producing capacity should be obvious In our study therefore, appropriate tecliniques were employed to pornit collection of uncontaminated eccrine sycat ·The Nature of discrete Stucat 91 METHOD AND MATERIALS Prolusc thermal sweating was induced in a normal healthy man in whom the axıllae had been thoroughly cleansed and shaved Uncontaminated eccrine sweat droplets were collected from the asıllae in the small glass pipettes in the manner descrilied earlier It should be stressed that the secretion was absolutely clear and watery in consistency Two sets of five tubes each were collected, vz, Tubes A, containing pure cccrinc sweat, Tubes B, containing pure eccrint sweat and with a thin film of hexachlorophene lining the interior of the fulses In addition small vials of contaminated eccrinc sweat were collected from the trunk, legs, and neck A "scraping technique, that is running the niouth of the vial along the skin of these sites, was used The fluid in these vials was not clear, but was turbid white in appearance These tubes were then incubated and were cxamined for odor at 2, 24, 48, 72, and 96 hours try (No investigators independently RESULTS AND DISCUSSION It was found tliat no odor whatsoever developed in any of the Itubes of pure eccrine sweat that were collected from the axillae "ppraisal of the small vials containing contaminated eccrine sweat from the trunk, legs and neck revealed that a distinct odor was present at 48 hours This odor was not pungent or at all offensive and was markedly different from the ‘axıllary odor' previously de cloped in vitro Thuis odor increased slightly in intensity at the end of 96 hours These specimens were cultured for bacteria, and all showed definite heavy grow th both in brainheart infusion broth and on blood agar plates in 48 hours It seems apparent that cccrine sweat is of no importance as a primir odor source It is practically all water thus providing an cntirely inadequate substrate for bacterial activity Such con Caminants in improperly collected sweat as sebum keratin and debris could be responsible for some odor in eccrine sucat How Cler unless apocrine sweat is also present the odor generated in samples of contimin tid rccrine sue it is als shown above, no1 the typical dwillin clor I cerme cal in the villa m ty provide an added impetus to fricterial growth however and in addition ·92 The Iluman Sucat Gland in Health and Disease Iresh apocrine aid in the volatilization of the odoriferous products of bacterial decomposition Thus the apparent "flush" of odor at an emotional crisis, whicn emotional eccrine sweating occurs su cat, while odorless when it initially appears on the skin surface, could also aid in the volatilization process (5) Any investigation of axıllary odor icads inevitably to a study of the cffects of antiperspirant-deodorant preparations in an carlıer section of this monograph, wc demonstrated that none of, the available products used today produces a significant reduction in apocrine su cating furthcrmore, we were unable to detect any changes in the histology of the apocrine sueat glands, as had been) reported carlier, and thus concluded that there was no impairment in axillary secrctory activity following the use of such preparations In these subjects, c also studied the effects of such preparations (see page 07) on axillary cccrine sucating The Randall starch paper-lodine technique was used as an indicator and representatie prints are shown in Figure 39 It is apparent that no significant decrcase in the amount of eccrine sweating was observed It should be stressed that these post-treatment prints were compared with similar ones tahen before the application of the deodorant and rev calcd no differences in eccrine swcating It is probable that the eccrine sweat of the axilla washes away the aluminum salts and thus prevents the usual effects of these substances elsewhere sız, keratin damage and poral occlusion Wule it has been shown that the aluminum preparauons as commonly used in the xxilla possess no remarkable anuperspirant activity it is possible that they may act as deodorants We confirmed this suspicion during the studies described above on the effect of antiperspirant-deodorint preparations on apocrine si cating Examination of the axillae of these subjects for axillary odor revealed a significant reduction in odor in about 60% (12 of 20) of the men studied as compared with normal odor production on the control de Even at 18 Jours 3 of the men still showed absence of axillary odor while the others had des cloped such odor in the interiin It was concluded that these aluminum preparations and zirconium products also) apparently act as deodorants in abolicion of axillary odor ·Tl, la urt of incrine Sweat 3 *5 39 La h of ant perspiral effect in a illa after aluminum Imprints (Randall techniq e) of ax llary skin showing amount of eccrine sıcating one week after daily applicat ons of aluminum chloride solution to the r glt auilla and distilled water to the left Observe the lack of antiperspirant effect on the aluminum treated side (6) The final phase of this part of our investigative program was concerned with the mechanism of action of the deodorant preparı tions containing aluminum salts now that we were convinced of their efficacy as axillary deodorants It was felt that the action might be intibacterial and or chemical in nature Tiie following studies were done to explore these possibilities VIETHODS AND MATERIALS Ten health men were again cho en for studs The avillac Avere unshaved and were cleaned daily as usual On onc axilla 1 Surated pledge of ?, ? Juoi al minum chloride solution was applied d ik tor five minute for three days sul ir applicti in of it was u cd on the control aulli Two and onc holl hours after the last 1 i licntion the men were cymuned and ·14 The Human Su cal Glard in Itralth and scare avallary hairs were selected from the aullic and placed on blood agar plato These hairs were collected with scissors and forceps which were kept sterile at all times Onc hair was placed on cich culture plnic 1 he cultures were then incubated at 375 for 18 hours Pooled apocrine sweat w3s then collected from 20 normal healthy men and placed in a small val At the end of 48 hours a ieri strung odor des cloped in this nel One-tenth cubic centimuter aliquots of this apocrine su cat were then added to 3 cc of distilled water and 10 a 23.queous aluminum chloride solution respectack The specimens were then cxamined immediately for any octor change RISULTS IND DISCUSSION of the aluminum-chloride-treated a ullary hairs from the 10 subjects, six showed no bacterial growth on the agar plates, four showed good growth The aullary hairs of the control side all showed luxuriant bacterial growth at 48 hours An csample is illustrated in Figure 40 The specimen containing water plus apocrine sucat gave the typical acrid odor one miglit espect However an instantaneous odor change occurred in the solution containing the aluminum chloride and apocrine su cat The resultant odor was decidedly different from the original one and may be described as a some. what sharp yet relatively inoffensile scent Dilution of this Solution of the apocrine wiveat and aluminum chloride resulted in a gradual dimunution of the odor to the point where it became pleasint A similar odor ds Occasionally noted in the saillac of men treated with aluminum chloride in the previous experiment The antibacterial effect of aluminum is well known However, It is apparently not as marked an effect as is that of hexachlorophene It is our impression that the major deodorint effect of tire aluminum preparations is antibacterial nature although in addition there appears to be a clicmical action thus rendering the normal odoriferous products of bacterial duomposition inoffensive Speculation upon the date olleets ol thics arious bu 1871] } interesting He concluded that almost any of the oilanisins of the axillary flora # is capable of producing elus odor lus possible, ·95 The lature of l{vnine Serg! 1 int ba mial offer of a cm num in aula Hau los aluminum treated avilla uppies) shot ing absence of bacterial growth can be compared with hair from a stol axilla treated with distilled uater showing heavy bacterial grow? of rourse that individual variations in axillary odor reflect either chemical differences in apocrine sueat or differences in resident bacteriologic fora or both Strauss and hiigman, confirmed our Conclusion that any of the organisms found in the axilla could prekluce axıllary odor They found that a wide drersity of species uf bacteria could produce the axillary odor from apocrine sweat Burth Gram negative and Gram positie organisms were repre senind (63) Furthermore than was able to eliminate aulary odor using a ponder containing a mixture of amon cation exchange resins He ·102 The llam in Surat Glan/ in Ilealth and Ducase TAB IV TOIT VITAL STUDIES OF PICHENTES GRANULTS OF NouvAL AND CHRISTI ASOCRINE SKEAT GLASPs (1 ORHALEN FIND SPECIMENS) Lapalu Tipusein Stain Crror/ Iron Suhy Biopsi Gran- Stain (Schmorl (Ilund (I'rarse) (Prile) to Site conce Rraction) Jian) Clinical Chiron. Case Idrotic race tttt Icllow +++ + 7 1x) ++++ Yellow ++ 0 8 Txilli +++ Trow + 11 Iulla ++++ Yellow ++ Mormal 1 Ixell? + Yellow + 2 Txi + Yellow he +++ ++++++ T++ Titt + + + TTTtto ナナオ Paper chromatography rei caled that the fluorochrome and the pigment had the same migratory pattern The question of solubility of the pigment was explored Dried colored sweat was insoluble in water but did disiniegrate in 70% cthyl alcohol Although initially it was felt the pigment dissolved, obscrvation under the microscope rei caled that the pigment particles remained discrete and did not go into «olution Purthermore the pigments proved to be insoluble in carbon disulfide, chloroform, carbon tetrachloride and pyridine The initial pH of the colored sucat was approvmately 60 Hierations of the pH of blue sncat had no effect on the color Upon the addition of a crystal of the strong reducing agent sodium hydrosulfite, blue sweat became decolonized Normal wote apocrine sweat became yellow-brown on standing for several wechs I crude nonspecific test for carotenoids was positive - addruon of sulfuric acid to a drop of yellow sweat on filter paper produced delicate strands of reddish material later becoming a diffuse volet The Carr-Price antimony reacuon for vitamin I was negative Bacterial cultures of colored sucat tahen under sterile conditions were negative The histologic data obtained from biopsies of three of these subjects, Case No 1 (to be described on page 106) and normals can be sumin nized in Table II Clinical Studies Because of the preponderance of apocrine sweat glands in the auilla, this site looms as the prime area in such apocrinc cironid ·Disorders of the ipocrine Surat blind 103 rows can occur The fact remains lowever, that the great majority of clinical cases of localized chromidrosis are in areas not thought to contain apocrine glands Localized cliromidrosis has bcen described most frequently on the face, an area generally regarded as devoid of apocrine sweat glands We were fortunate to have reſerred to us for diagnosis, two cases of true, localized chromidrosis of the face Each was from the same city, curiously, and both proved to have colored sweat of apocrine sweat gland origin This was evident from the pharmacologic and physiologic studies and was confirmed by biopsy of the involved area in Case No i Case do 1 This healthy 29 year old unmarried white woman from Wilmington, Del first noted the appearance of "black sweat" on her cheeks when she was 19 years of age The fluid would appearat times of excitement, tension, or overheating and was immediately preceded by an aura of warmth in the involved areas The fluid dried to form a very dark flahe or scale which was adherent to the shin The process was worse in the summer and showed short unexplained remissions from time to time Its appearance or severity had no relationship to diet, menscs, or general health Her menarche had been at age 15 and a 6 month period of amenorrhea preceded the onset of the chromidrosis Sweating elsewhere was normal Other physicians had been consulted Over th, condition and all forms of topical therapy provedl unsuccessful All cosmetics had been avoided for two years without effect A general physical examination revealed no abnormalities Her skin was normal except for a few pitted acne scars on the face After five to ten minutes in a thermal chamber, tiny, blachand brown puncta and droplets appeared on both checks Before dring the droplets could be wiped away readily Ilowever, if undisturbed and in the absence of eccrine sweat, they dried rapidh forining an adherent shiny-black, grayish-blach, blueblack or brown flaki material (I ag 41) Many of these appeared lo le in the chaceous orifices At urdinary room temperature in injection of 0 10 cc of 1 1 000 epinephrine solution (cominercial) in the left chech produced about 25 droplets Many of these were sack but soint were white blue and injection of 1 cc of 1 100 pilocarpine nitrate solution in tlic nght check give a norin il colorless cccrine gland response At a later date the local injection of ( 1 cc of 1 1000 atropine sulfate solution sad no effect ind tuled o present the appearance of colored grech An ·Ile Ilu in Sec Gland in Iralih and Desrare ! 11 Chror idr 1 of in Cul Noie ty dark droplets of chromidrotic po tine sise it on check sweat in response to pinephrine linally it was found that the colored fund could be expressed manuall The li_hter colored 14 at showed uellow Duorescence under blood light (I 1g 42), whereas the biich fluid and cale showed minimal or no fluores conce Souds of purring incating in the auth resealed it to be norinal ind of the common white i riety The cirunen o showed the norm rellou brokin color Fin da pitch tests with fine of the patient s cosmetics were negative and surb cquent eccrinc seating in the area ? colorless Her uirint snorm in color and no nfluorescent I rernained unchanged upon

·Disor lant of the Apocrine Suceat Glan/
105
----
25 $3 Colored strat on chees und higher memlt in I wo diopless of colored
crine sucat from the check out 1 Vult their follicula location in the
ouer photograph observe the fluorescence of these stint drepile is on ex sure
to loud It

·107 IIIin ccal Cla! ilealth an! 1) sa Ipo 13 Ilustology of drom frotu glanls Case 1 Biopsy of face of Case 1 with facial chromidrosis revealed the presence of apocrine seal glands as shown above H and I Mag x 250 Manding at room temperature Specimens of the colored fluid collected unc er sterile precruijons revealed no bacterial growth The dried scales were insoluble in water but di integrated in ether and alcohol Houcier the pigincnt itsell did not appear to be truly soluble in these solvents Local treatment with on cichange ponders and hydrogen peroxide * 25 without effect With local procune (40) anesthesia 1 small biopsy was secured from the left check On grony examinition four small dark areas could be seen on routine cctioning and staining These corresponded to the size and location of apocrine glinds In hemorylin ind eosin sinned sections these apocrine as well as eccrinc gland could be scen (tig 43) The apocrinc glands were mall The tubular secretory cells appeared more Dzsophilic chan normal and showed numerous yellow brown granules of trying size ind cellular location Alorcover un stained histologic sections revealed these in cllow ind brown piginent granules (Fig 44) Iluore cent microscopi demon crated that the egrinule sert utolluore cent (fig 45) Mivepithelium could be seen about the apocrine gland Specit! tuns for lupolu cin (Schmorl Huech) (1) resented posita els statning

·Diserans of the line Sztrat Glan /
107
lo
ha
L
ng !! Pigment granule in hy medretic apo rin gland Case I In unstained section
of the facial biops from Case ] shuns increased numix rs of pigment granules
(compare with non mal gland Tig 11) Mas 2009
Tis 17 Fluorescence of pigment granates 17 thromidretic glands Same section as
Itzure 44 after exposure to LIL 14200 1°) Vote Auorescence of some of the
pigment granules Compare with ligure 11 Vas 2000

·108 The Ilumon Siccal Cland in lealth and Disease . lig ormal and chramidrarı (1) apne glands Schmorl stain Segment of sccretory tubuk of chromdroit sproeiine gland (uppes) showing abundance o! dark-staining Schmorl-positive (hipolusein) matrial is to be contrasted with tubule from normal alle same stanu Vlag x 3000 granular material in the apucrine tubular ull cytoplasın itig 461 The Hueck stain for melanin was negative The Pearne rain (19) for demonstrating acid-last lipoſukcins (ceroid) was weals ·109 Disorders af te pakten 3 eral Cland le Chromedsosis of face Case Phonograph of check of Case 2 shoning dned droplets of colored sweat These were made to appear in local injection of pstoch e Perls fersici anide slain for son was negalne (1 able ) On the base of these cimual histologic and physiologic onera tonn It was concluded that the puient had as pical chronydrons and that the colored sent was raing from wherrantis placed apexrin it stand Dictars restriction of carotenoids failed tu toss in improsement of tht condirun in th> vonan This 26 sear old uninarried while sale sa isviseen In us ar tot hnor his whiskel 5 Irmi corporal He was In cuxd general health #74 blond and fair hinged He was Horn in Baltimore, Md frut had pent his reten vers in 11 ·110 The lluman Surat Gland in liralth and Despace mington, Dul, und lived there before induction in the Army He had not noted ans abatenent in the amount of colored sweat scen during the car while in the Army in Kentuchy He stated that for about three years (age 23) he noticed blue-black "smoky" droplets on the malar areas of both checks (Tig 47) "These were not seen before this age, during puberty or adolescence, and his de clopment during these period, was normal inciery respect He first noted these black droplets after taking a hot shower and they have generally been noticed since (1) after a hot shower, (2) after shaving (wet shave), (3) before getting reads for a date, (4) after cmotional disturbances He has ohscrued also that the colored secretion could be easily expreyscd manuallı He used to " queeze" these shin areas about once a wcch to try to empty the glands Although he could not emply every gland, he would be essentially free of such exudation for about 6-7 days following such an expression No aura ol warmth was recalled preceding the appearance of the colored sweat There was no apparent cycling or seasonal variation concerned with this secretion He did not tan cash usually developing a good erythema uſon exposure to sunlight He noted no change in the chromidrosis after such cxposure No colored secretion has been noticed clsewhere in the body and none in other apocrine areas such as the axilla or pubas His urine showed no changes in color initialls or on standing Although he was a consumer of moderately large quantities of carotenoids in his daily diet, restriction of the loods failed to produce significant change in the chromdrose Lyanınation of the skin of the face revealed i definite dust pigmentation over the malar eminenc This was slight but distinctly present and appeared to be deep within the skin Stroking of the skin of the face did not prompi a response Manual expression of the colored sweat was readily accomplished however The injection of 0 15 cc of 1 1000 epinephrine solution produced a beautiful response as did 0 1 cc of pitocin at a later camination Atropine failed to inhibit cyther response and procain did not block the responses to local injection of these drug. Pilocarpine (01 ec 1 10 000 volution did not stimulate the appearance of the colored sweat Examination of the alla for apocrine steaung after epincphrine and pitocin resealed an absence of colored sweat although the usual white apocrine product as evident The colored secretion was cxfremels minute in amount o mail that it was difficult to esen collect a representatie sample in ·Disorders of the Ipocrine Surat Clan/ 111 dscapillary tube Moreover, it dried very quickly forming the typical shiny cap over the orifice, almost alvavs follicular Water and alcohol (with greater use) would remove the dried cap of colored material There was no fluorescence of any of this dark blue black sweit to Wood light we were unable to secure a biopsy from the face of this patient for he refused this procedure However, the observations above are quite typical and leave little doubt that the origin of the colored secretion was from the apocrine sweat glands "ahnormally" placed on the face DISCUSSION An examination of the literature concerning localized chromidrosis reveals striking similarities between our clinical cases and those described earlier (64-90) It is remarkable that so few cases were recorded after 1900 Actually, some 38 cases were described up to 1869, nine by LcRoy deMericourt alone, who gave the condition its name and later wrote a magnificent survey of the subject in 1884 The significant clinical findings and ctiologic vicus for the great majority of the cases may be summarized as follows 1 Chromidrosis usually occurred symmetrically on the faces of young women (Fig 48) Níost frequently, it had been seen on the lower eyelids but had usually been noted on other parts of the face also The abdomen chest, and thigh were involved occa sionally The age range was from 15 to 57 years the as crage being 22 years The patients were in good health 2 In the vast majority of instances the color was black or very Brown, blue and yellow color tones were also described In more recent years (1934 1939) red sweat in the axilla following bismuth injections and in the perianal region lave bo reported also However side from obous cases of red chromidrosis duc to external contamination with trichomycosis organisms in the axilla there were no other bona fide reports of red chromidrosis 3 The color appeared intermittently often 45 tunes a day and even during sleep It was preceded by a priching or warın Emotional stimuli uli at teir an cr, agiiition and lqugluing regularly ined the secretion to ippar Usually the problem was more esere in the sumuiner In one instince the condition improscut during Tictation dark sccrction ·112 7 llumar Saxar Gland in Health and Durase 1) Tag ** Facial chromidrosa in pieni desenbed in 191) Illustration reproducrd from lithograph in original article Patient noud onset of chromidros 11 age 15 Sucat was allowed to accumulate for 2 days on left half of fore he id and for 5 days on right Lower evelids also involved 4 A thuch liquid secretion was seen initially This would dry rapidly to form an adherent glistening cap usually at the hair follicle Several observers described the dried secretion as lung the appearance of dried varnis! 5 Chemical studies revealed that the pigment was annorphous contained carbon and iron, was soluble in acids espet ially sul ·Disorders of the Apocrine Sural Glan! 113 furic and insoluble in water alcohol and ether Melanın, indigo, cyanurine, etc, could not be positively incriminated as the pigment involved 6 The source of the colored secietion was not agrecd upon The sebaceous glands and eccrine glands were mentioned early as the sites of origin as was the pigmentary system of the eye Others believed it was due to bacteria or to external contamination with dirt, or carbon in the air Colored skin secretions were described by Weber in 1888 in a study of the comparative physiology of mammals (93) He concluded that all such secretion arose from tubular glands The red sweat of hippopotamı and kangaroos, the blue sweat of antelopes and the black sweat of gazelles were mentioned Interestingly, Grieg also pointed out that milk and colostrum may at times be colored (98) Yellow, blue and green milk have been recorded by various observers As stated, the origin of the colored secretion in our clinical cases with facial chromidrosis as well as our experimental subjects was the apocrine sweat glands of these arcas All of the evidence, anatomic, physiologic and histologic, supports this conclusion as docs comparative data on other mammals The vast majority of the cases described in the older literature are so remarkably similar to our own that we would postulate an apocrine gland source for the colored material observed in these cases, also While we know the glandular origin of this colored secretion, the precise abnormalities involved in apocrine gland function were still unknown It was not possible to study the colored material chemically because of the very minute quantities that could be secured We directed our efforts to histologic and histochemical proccdures to determine the nature of the pigment in the colored apocrine sucat The one constant change noted histologically in the chromidronic apocrine glands both on the face (where the glands are small) and in the axilla was an increase in the number of pigment granules seen in the secretory cells (Tig 44) These granules are found in the gland producing wbite apocrine sucat in smaller numbers Ilicy are variably sued, round or oval at times irregular granules They may be found anywhere in the ·114 IlIluman beral Glandan Ilealth and Disease cytoplasın but are most abundant supranuclearly In color they range from the large, round, golden-scllow variety to the smaller bronn-black types Many of the cells may contain few or none of these granules Most possess a yellow autofluorescence and show the ability to reduce ferricyanide (Schmorl reaction) (Fig 46) Some of the granulcs show a positive test for iron Aqucous and hydrocarbon sok ents do not remove these granules We found no qualitate difference betucen the granules of the chromidrotic and normal apocrine glands the difference was primarily quantitative The chemical nature of this pigment was the next question of the threc main divisions of pigment, the frosine group (including mclanın chromaffin and argentaffin granules), the hacm group (porphyrın including hemoglobin and its derivatives) and the lipopigments (ccroid carotenoids and lipofuscin), we have eliminated the first two Ilie members of thic tyrosine group are nonfluorescent, and melanin stains were negatnic The porphyrın group was excluded on the basis of differential solubilitics and fluorescence A comparison of the histo-chemical properties of the lipofuscin group with those of the pigment granules of the apocrinc sucat gland convinced us that our pigment was a lipo fuscin The lipofuscins represent a broad spectrum of progressively oxidized compounds The lipid precursors at one extreme possess all of the chemical and physical characteristics of fats Gradually by a process of oxidation the following changes arise - the color increases and gradually darkens basophilia develops and incrcases in intensity and fat solubulity and sudanophilia diminishes fluorescence is prominent in the intermediate stages but faces or is absent at the extremes Thus very light colored or very darkcolored lipofuscins do not fluoresce There is a progressive increase in the number of reducing groups reflecting their level of oxidation This is demonstrable by the Schmorl reaction which has been used as a test for lipofuscins Ceroid is commonly riched as a unique acıd-fast pigment but is probably an intermediate form of lipofuscin Interestingly it was found in our chromidrotic glind, but was absent in the normal ones lending support to the notion that lipoſusuns are increased in amount in the chromidrotic gland ·Deaders of the larte suell Glan? 115 Iron docs not appear to be increased in the chiroinidrouc apocrine glands It is possible however that it enters into the oxidation processes responsible for lipoſuscin We have not found significant effects on axillary chromidrosis following hormone administration or dietary restriction Indican or indigo blue was excluded because of its inability to fluoresce and because it would not explain some of the other colors seen Curiously, the apocrine glands of the ear canal in Caucasians and Negroes contain numerous hipofuscin pigment granules while those of the Mongolian show markedly reduced granule content It is to be recalled that the latter race also shows diminished apocrine sweat gland development in the avulla and elsewhere on the skin Paralleling this difference in granule content between these races is a difference in the color of the ear war in Negroes and Caucasians it is yellow-brown while in the Mongolian it is usually colorless One might say therefore, that the former groups normally show chromidrosis of the ear canal An altempt was made to examine colored apocrine sweat by means of ultra-micro-spectrophotometric techniques Dr Roy Korson of the Department of Pathology, Uns ersity of Vermont School of Medicine, collaborated with us in this effort We sent Dr Korson samples of blue-black sweat from the faces of each of our chpical cases as well as two samples of greenish-blue apocrine su cat from the axillae of two of our experimental subjects for study included also were five additonal samples of white apoerine sueat for comparison Dr Korson s analysis of these specmens was consistent for all of the colored specimens studied and rescated the presence of two distinct pigments in the secretion rach with characteristic absorption curies An alternative possblay was that one is an oxidation product of the other a notion much more likely according to our observations histochemically of the chiromidratic glands In summary, localized chromidrosis is veually a disorder os the apocrine seat glanc regardless of its location on the skin surface The presence of apocrine sıcat glands Outside the usual Apocrine areas is well-documented The pigment responsible for thic colorauon is apparently a lipofuscin which is found in the ·116 7he Hamax col Glan / in ilealth and Disfare pigment granules of all apocrine glands In the chromidroti gland there is primarily an increase in the number of these granule although some increase in the state of oudation may also be seen Thus, all apocrine sweat glands probably produce some pigmen but because it is relatis cly small in amount or is diluted by large amounts of colorless apocrine seat, it is not seen In this regard It is notcworthy that white apocrinc sweat drics 10 Icaic a yellow residue IVe intcrpict tus as a concentration phenomenon Furthermore, although normal white apocrine sucat usually haa faint white fluorescence, many samples show a distinct yellow fluorescence Ilus yellow fluorescence may be attributed to the presence of lipoſuscin which may be detected more readily under Wood light than under visible light Ordinary localized chromidrosis as seen in the aulla is a normal condition and as such, requires no treatment When the condition occurs on the face a cosmetic problem evists and some treatment is necessary Topical mcasures are incllectie cicept to aid in the removal of the colored secretion Systemic measures such as antr-adrenergic drugs have not been satisfactory Destructive measures are 113 practical because of the large number of glands inoked As stated dietary restriction of carotenoids is not helpful iti intcresting to note in this regard that we were unable to induce auillary chromidrosis in twenty selected experimental subjects on a daily intake of 200 000 U of carotene for two months CAPOCRINE SWEAT RETENTION 1 Asymptomatic Apocrine Sweat Retention In recent years great interest has been evinced in the effects of poral doswe on the various appendages of the skin. The path ogenesis of the Sarious forms of miliariz is clearly a result of ductal obstruction (99 100) Estension of this concept to int lude discuses of the sebarrous glands, ibe acneiform dermatoses 117 also been recognized and occlusion of the sebaceous duct with kcratın is considered a fundainental step in the desclopment of these disorders (101 102) Little effort has been made to examine the effect of ductal obstruction on the diseases of the apocrine sweat gland Because ·Disorders of the Incine Steal Gland 117 ve felt that this process may be of prime importance in the aporine disorders, ke proceeded with the following studies (103) METHOD AND MATERIALS Seven healthy adult White males between the ages of 20 and 28 were selected for this study Antiperspirants had been interdicted for at least one month The axillae of these subjects were shaved and the apocrine sweat glands emptied by the local suficutaneous injection of 0 15 cc 1 1000 epinephrine solution When the apocrine sweating had subsided 5-10 anillary hairs in a circular area 12 inches in diameter) were pluched with a fine forceps These ſollicular orfices were then treated in esther of the following was (a) Application of concentrated nitric acid, or (b) Electrodesiccrtion (Roue Upipolar srtting at 5) In addition several extra-follicular apocrine duct orifices were similarit damaged Three days later, the apocrine sweat glands were again stimulated in these subjects in the local injection of 0 15 cc 1 1000 epinephrine Biopsies of the created axillac of two of the seven subjects were then tahen after local procain anesthesia in a "block' technique The other sulyjects were again examined for apocrine andross (epinephrine Stimulation locally) and then loped at 7 (two subjects) 9 14 and 21 days Tissues were fixed in formalın, Sectioned serus and stained with hematoxulin and cosin OBSERVATIONS AND DISCUSSION In all of the subjects examined, apocrine anidrosis resulted Tlus anidrosis was evident as early as 3 days after treatment and persisted throughout the three week observation period Under stercoscopic mucroscopy (30x) one could usually outline a small heralın plug' in these follicular orifices This was especially prominent at the 7-9 day period Millarial changes were absent at these sites and no clinical signs either objective or subjective, were discernible except for slighe eruthema during the first 2-3 days following the application of the acid or electrodesiccaton The pathologic alterations of the apocrine seat gland which Occurred secondary to these damaging procedures were at a ·Fe 19 heral n plug n apocal da B opsy of avllt skın 7 drys after aji! car on of concentrated nitr c d d slosc my act kerat no s plug of apocr a duc Contrast th slerann w h the normal loose S brillar mater al in telarui cle Ha de Mag Y 300 Fg 0 Dlatet apo rine du l ull ng ſom poral o lus on 17 d.) ) Seat n of ar llary sk n shos ing extra foll cular apocr ne duct with occluste kcrat o lug and progress ve dilatat on of the duct do ynward Duct vas traced t aj ocr ne gland belo v H and T Mag x 100 ·Disorders of the Aporpine Surat Gland 112 he 51 Apocrene su eat releniton - 14 days Low power view of histology of apocrine siedt retenuon process Observe compact kerajinous plug in apocrino duct orifice plus dilated segmen of duct belon Some portions appear to be almost cystic H and C Mag 35 Isistologic level They are illustrated in the photomicrographs (Pigs 49-55) and are listed below, 117 (1) Focal hyperheratosis and heraun plugging of the hair folficles and apocrine ducts both ſollicular and extra-ſollicular (2) Dilatation of the apocrine dura progressively down toward the apocrine tubule In some instances there neat (WLIC change of the duct (Fig 54) and dilatation of the tubules futreme

·120
11 lulu at Cland in 11 lth an! Dac
Igy
Dlated af
n dut
71 day
Ano her extra Coll cular ap rin
dct
sho ving the sequence of changes in s eat retent on keratin 11 g in duct le
or fce and d lata on of ds al segm ni of the du! H and I
Vlag x 10)
fattening of the lining cells was scen ulon, with luminal casts
in many sections
Chest chan, were not endent in the biopsies
removed 3 days after follicular dimace It this stage the blinds
appeared normal except for the heratin plu, s above The miximal
dilatation and cellular futeni 13 is seen in the 7 ) diy peo
mens
At 14 and 21 dars these chines did not appear ole
increased nor was definite evidence of glandut ir rupture present

·Dods of the iper au Sweat Glas/
121
O
cu
I 53 Dlated apoca ne du 1 u th cas! 7 fars Mearl transverse sect un of
dlated ajmerine duci juse beneal! poral block Trapp d apocrine sve at is
csident as cast in lumen H and C Mag x 250
15 i apartine lulules schon sło się markedly dilated C stic apo
Crine 1 bules visualized ?1 dass altxoral o el sin Cast in cistic tubules
Tapi arent Contrast cell leight of ad acenti rial apocrine tul ules suh that
of the cystic ones
H and C Vag 90

·122 7 he luman Surat Glani in Ilealth ani Disease (3) These sections were otherwise normal in every respect Fur. thermore, the sebaceous glands appeared unaltered Comment should be made regarding the techniques employed to close the follicular orifices While it is relatively easy to produce cccrine duct occlusion with the milder injury produced by maceralion ultraviolet light or adhesive tape, it is apparent that greater injury is necessary to close the more patulous hair follicle orifice Concentrated nitric acid and electrodesiccation were utilized effectively in this respect Both techniques allowed for the treatment of a singlc hair follicle orifice The acid was of additional valuc since it flowed down into the hair follicle and produced damage along its path including the rather superficially placed apocrinc duct orifice The presence of a terminal hair was something of a detriment to our plugging technique and prompted an additional preliminary step in this procedure, vz, removal of the hair with forceps Apparently the hair acted as a stylette in maintaining pitency The subjects were not cxamined before 72 liours since studies on the physiology of the apocrine sweat gland showed that apocrine sweating cannot be induced for 24 48 hours after completc emp rying of the gland This refractory period is necessary for refilling of the tubular reservoir with apocine sweat The progressive dilatation of the apocrine duct and tubules confirms thc purely mechanical nature of these changes The gradual secretion of apocrine sweat in this closed system is accompanied by an increase in intraluminal pressure with consequent ductal and later tubular dilatation Eventually this pressure arrests further secretion Apparently the duct is the more dis tensible part of the apocrinc glandular hy stem perhaps because of an absence of myocpithelium Examination of routine axillary biopsies has indicated that asymptomatic apocrine 511 cat retention occurs rather commonly for it is not unusual to sec changes in the so-called normal axillary skin which closely resemble those cxperimentally produced here The extreme tlaitening of the apocrine cells seen in these resting secuons was thought heretofore to represent (ither a gland or atrophy of the tubular cells of undisclosed origin 5 ·123 Disor lers of the sportine Sural Gland 10 Fig) Fibrosis about dilated apocrine tubule 1 days Dilated apocrine tubule showing peri tubular fibrosis This was a late but not constant finding as a consequence of apocrine sweat retention H and E Vag 300 is clearly demonstrated in this study, the low cuboidal state of the apocrine gland cells in the resting or early secretory phase can be casily distinguished from the markedly flattened atrophic cells of the "blocked gland These atrophic tubules are more common in the axillary skin of the aged patients The absence of an inflam mitory reaction accompanying these changes is not surprising Rupture of the apocrine system did not occur even at 21 days It is to be recalled that such a 'break" is necessary in the production of miliaria, with resultant eccrine sweating into the skin Such factors as infection endocrine variation and individual susceptibility may so modify the apocrine sweat gland so as to Permit such a rupture At any rate at the end of this study it was our feeling that rupture of the apocrine system was requisite for the production of the clinical changes seen in lox Fordyce disease and hidradenitis suppurativa 2 Fox-Fordyce Disease Ilus disorder is characterized by the presence of numeroun prurilic papules primarily follicular in location in apocrine gland ·124 The llum in Sucot Gland in Hralth and Disease Vir Jo Clinical appearance of lor-Pordsce discase in aulla Photograph of axillary shin op 19 year old girl showing follicular papules characteristic of Fox Tordyce disease on bearing areas such as the axıllae, pubes mammary arcola and so It occurs predominantly in females and often appears during early adolescense or just after puberty Pruritus is frequenily related to emotional stimulation although often occurs spontaneously Generally the course of the disease is progressive involving more and more of the apocrine areas, although unexplained remissions have been described Peculiarly the discase frequently abate completely during pregnancy, even with clearing of the skin lesions, only to recur during the puerperium Treala ment has been uniformly unsuccessful over the years Examination of the involved skin of patients with For Fordyce disease will reveal some loss of axillary hair in many cases but except for the fallicular papules, these arcas shon no abnormalities (Fig 56) Our early studies of patients with this disease revealed apocrine anidrosis in the region of the papular lesions in thorec cases studied after local cpine phirine or pitorin, no apocrine sweat could be made to appear in the involved areas The patients usually cxperienced some pruritus in these areas aiter such stimu- ·Diserders of the Ipocrine Storat Gland 125 lig u7 Diagram shouing deurlopment of Fox Fordyce disease Schematic drawing showing point of rupture of apocrine duct in Fox Fordyce disease brg > Pathology of For fordyce disease Pathognomonic vesicle of Fox Furdyce disease found at a level of the intra epidermal poruion of the apocrine duct Compare with Figure 57 H and E Nag x 400 lation These observations led us to believe that apocrine sweat retention was a feature of these lesions In the previous section we described subclinical changes which can becur in the apocrine sweat gland as a result of experimentally produced poral Closure These changes were revealed after careful study of serial sections of the involved skin Shelley and Levy fave described a second change resulting from occlusion of the apocrine su cat duct (104) This consisted of a rupture of the cpidermal duct as a result of the increasing distention and the formation of a sneat retention vesicle within the epiderinis (Fig 57) Ictually, this vesicle is formerl in the intra epidermal portion of die apocrine duct (rig 58) It appears that in addition to the ponzion and cdema produred there is also acanthosis of ille epidermal cells surrounding the portion of the apocrine duci In this regard, it is significant dit Hambrick and Blank have ·126 Wellman Surat Gland in Health and Discase described thickening of the apocrine duct in whole mounts of the axıllary skin of patients with l'ox-Fordyce disease (105) Their studies were at a comparatively gross level however, and did not rcu cal the changes cydent microscopically as described above It should be empliasized that visualization of the sncat retention i csicles of for-Fordyce disease may be impossible unless one does serial sections of the tissue Moreover, individual susceptibility allowing ductal rupture to occur is essential for the production of this discase In the absence of this rupture, which is apparently duc to an inherent weakness of this tissue, there would he only anidrosis and possibly dilatation of the duct with eventual shutdown of the apocrine secretion in miliarja, a similar story with regard to cccrine duct rupture has been told Finally, the pruritus of cccrine miliaria and Fox-fordyce disease is caused by e\tra- Vasation of apocrine sweat into thc epidermis There is no adequate treatment for this disease At present, our only approach is symptomatic, directed toward relieſ of the pruritus Antipruritic lotions corticosteroid lotions and sprays and scdation have been used with some success Temaril, in doses up to 20 mg a day has been helpful in some cases but often lails to relieve the intense paroxysmal pruritus associated with this conditron X-ray is of no value in the management of this discase and systemic corticosteroids are not recommended since their prolonged use in moderatc to high dosage is required for relief of symptoms Antibiotics systemically and local, should be cmployed in those cases in which secondary infection is present In recent years marked improvement in several patients with this disease has been achieved with estrogens in dosages higher than those previously used Premarın up to 5 mg duly seemed to accomplish an involution of the process (110) Further clinical study with this drug is necessary to confirm its efficacy in this discase, however 3. Hidradenitis Suppurativa Hidradenitis suppuratna is a chronic cicatrizing suppur itile process involving the apocrine gland-bearing regions primirily the aulac and ino-genital ireas It usu i}} begins 2 a wall, firm erythematous lesion fairly deep-seated and panfuł Oc casionally these subside clinically More often however the ·127 Disorders of the Apocrine Sural Gland rig 59 Clinical view of hidra lenitis suppuratla Photograph shows dense scarring and sinus tracts tvpical of bidradenitis suppurativa Process involves most of axilla Inguinal involvement was also observed in this patient process extends beneath the skin producing larger confluent masses These eventually erode through the skin producing sinus tracts and healing with thick scars (Fig 59) The ultimate outcome is a more or less chronic suppurative process, with draining sinus tracts and cicatrization Exacerbations, which consist essentially of acute abscesses, occur at irregular intervals At times hidradenitis and Fox-Fordyce disease may coexise (112) In five cascs studied clinically by us, we were impressed by the fact that as in Fox-Fordyce discase the areas of involvement with hidradenitis shox apocrine anidrosis This would obviously be found in a far advanced case with much scarring and fibrosis However, we examined early lesions where scarring was absent and the absence of apocrine sweating (after local pharmacologic stimulation with epinephrine), was quite evident This lead us to lielieic that this disease was also the result of apocrine sweat retention, with rupture of the apocrine system but with the added factor of bacterial infection ·128 The Ilumon batral Gland vollealsk and Immer An extension of our original cxperimental studies on the effects of apocrinc sucat retention by Shelley and Cahn proved this concept to loc correct (106) 'Ihese authors produced heratinous plugging in the axillae of 12 normal adult male subjects by the application of perforated belladonna adheshe tape to a shin arca that liad been manually epilated All of the subjekts developed apocrine anidrosis in these areas at the end of one week in three of the swelse, however, clinical cudence of hidradenitis was observed Three men presented small, deep tender nodulcs sharply localized to the tape sites Histological study of these carly cascs rescaled the following changes (1) keratinous plugging of the apocrine duct, (2) dilatation of the apocrine duct, (3) severe inflammatory changes limited to a single apocrinc sweat gland Thc atc apocrine duct became filled with polymorphonuclear lcucocytes The bacteria, which had been trapped beneath the heratinous plus multiply rapidly, finding apocrine sweat an excellent milieu Subsequently, rupture of the apocrine duct occurred with spread of the pyogenic process through the dermis Because of the proximity of the apocrinc sheat glands to one another as illustrated in an earlier section, it is easy to understand the ready extension of the process to other glands It should be stressed that eientually, many or most of the apocrine sweat glands are destroyed by this same inflammatory reaction, leaving fibrous and isolated atrophic tubular remnants This is what is visualized by the pathologist as he studies a tropsy of advanced or chronic hidradenitis suppurativa It is only by reproducing the discase experimentally and examining carefully the early changes histologically, that an accurate reconstruction of the pathogenesis of this disease can be made Treatment of Pudradenitis is usually quite satisfactory of the process is secn carly Anubioucs, in adequate dosage and focal anti-bacterial measures are cffective at this time Tight fitting apparel is to be strictly avoided in resistant cases, management may be extremely difficult X-radiation has becn Exadvocated but we are not impressed with its effectiveness posure and destruction of residual, chronically infected sinus tracts may be beneficial in those chronic cases in which the process has become localized to such foc! Some have used the electro- ·Disorders of the Apocrine Suecal Gland 129 be necessary coagulating current to destroy such exposed ſoci As more and more glands are destroyed or fibroscd secondary to the inflammatory process, the disease may tend to "burn itself out" In severe protracted forms of the disease extensive surgery with cxcision of the involved area and full-thickness skin grafting may Even with this more radical approach, however, recurrences may be seen Corticosteroids have recently been used with success in the treatment of this disease Hydrocortisone, in doses up to 80 mg per day or other steroids in comparable dosage when maintained at this level for 1-2 weeks and then grdaually reduced and stopped within 4-6 weeks has been quite helpful in a number of cases (111) The mechanism of action is unknown but may be a local anti inflammatory effect and or result from a depression of pituitary activity, with some possible dımınıshed apocrine secretion

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·VI BIBLIOGRAPHY 1 Horner, W E im j U Sc, 11 13, 1846 2 Rolin, C1m ) 11 Sc , 11 439, 1846 3 hrause, W Handbuch der Menschlichen Anatomie Erster Bond Berlin, 1876 4 Heynold, H I chore Arch f path inat , 61 77, 1874 5 Kõlliler, A von Janual of Human licroscopic Anatomy Philadel phia, Lippincott, 1854 6 Schieſſerdecker, P Zoologica, 27 154 1922 7 Eggeling, H von Hautdrusen Handb zergl Anat Il'erbeltirre, 1 633 1931 8 Kuno, Y Human Perspiration Springfield, Thomas, 1956 9 O Brien, JP Personal communication 10 Oliver, I and Nauck, E T Etschr ges exper fed, 71 786, 1930 11 Perry, E T The Human Ear Canal Springheld Thomas, 1957 12 Villanus, I FA Stain Technol, 23 99, 1948 13 Gomori, G Am Ì Path , 12 655, 1936 14 Perez, T Trab Lab Incest Biol C'nı lfadnd, 27 123, 1933 15 Kolle, G B ) Pharm & Exper Therap, 103 153 1951 16 Vavimow, A A and Bloom WV Ilistolog; of the Shin Philadelphia Saunders 1943 17 Rorvetto PL Arch Ital Inal ? Embryol 56 332, 1951 18 Szodoray, L Onost henl Budapest, 4 360, 1948 19 Montagna ll, Chase, H B and Lobitz 1 C4m Anal ,92 451 1953 20 Pearse. A GE Histochemistry Theoretical and Applied J and A Churchull Ltd, London 1953 21 Bunting H, Haslochi, G B, and Dempses, L " Inat Rex 100 61 1948 ?? Vlontagna Ciba Foundation Colloque on Igung Tol 2, pp 188-199 llolstenholme, GE11 and Mullar ECP cds I and 1. Churchill Ltd, London 19561 Also ] Iniest Dermot 33 151 1959 23 Shelley, Is B. 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J B Am ) Anal 85 41 1949 61 Feigl F Qualitative Analysis by Spot Tests New York Flsevier 1947 67 Shelley II B Hurley H J Jr and Nichols AC Arch Dermal 69 430 1953 63 Strauss J S and Lligman A M J Inzest Dermat 27 67 1956 64 kilian J A and Panzarella FP Proc Scient Sec Toilet Goods GA 73 1947 65 Thai kỳ Inzest Dermat 23 411 1954 66 Shelley W B and Cahn M J A V4159 1736 1955 67 Mutta H and Ikar I nagoja M ) 1 217 1953 68 Brock!churst J K Brit + 3 1 541 1953 69 Orinsly O and Montgomery H Diseases of the Skin Philadelphia Lea 1953 70 Shelles W B and Hurley HJ Arch Dermat & Syph 69 449 1954 71 Yonge | Philos Tr Roy Soc London 26 424 1709 72 Teevan Med Chir Tt London 10 611 1845 73 LeRoy de Mericourt H Ann Ocul Brux 1 110 1863 74 Foot 1 W Dublin Quart v Sc418 68 1869 75 LeRoy de Mericourt H Bull icad lted Belgique 7 977 1864 De la Clromidrose Chromornine Partielle et Cutanes de M LeRoy de Mericourt Paris G Steinheil 1891 77 Collmann 11 ur b Med Cischt 7 251 1866 78 von Barensprung GF Die Hautkrankheiten Erlangen 1859 79 lui on E The Student s Book of Cutaneous Medicine and Diseases of ile Skin 4 Ed London 1865 80 Duluc V Essai sur la Cromocrin e Partielle de la Peau Part 1861 D bln Quart Sc 11 64 1866 Bul! Icad med 76 812 1860 83 Elliot on J A Times & Hosp Ga 15 288 1857 Dubl n Quart v Sc 19 293 1855 Ga hebd med Pars 615 1859 hop Paris 34 263 1861 $* Binks J T Dublin Quart 7 in s 75 257 1858 76 Foure 81 Foot AW 87 Robin C 84 \eligan | M 8 Leros de Mericourt H AG Suzia Turenne J A Ga ·134 The llun an Seeot Gland in Ilealth and D stase 88 Bulard C Lancet 1 105 1831 89 Tox TC Tr Clin Soc I ondon 14 211 1881 90 hey AN Rec 1 540 1880 91 Babestu Centralbl med It issensch Bril 70 146 1882 92 LeRos de Mericourt H Bill drad med Paris 13 425 1884 93 lieber M Archie mikrosh Anal Bonn 31 499 1888 94 Herdingsſeld M L jili 39 1519 190? 95 Blanchard R Bull Soc Frant der mat et siph 1939 1908 96 Pozzo A Gior veneto di se med 8 486 1934 97 Samberger T Dermat Il chnschr 100 806, 1939 98 Grieg D M Edinburgh / 737 524 1930 99 O Brien 1 P Brl Dermal Sipke 59 125 1947 100 Shelles B dd 15' 670 1953 101 Sulzberger MB Acne lugaris and Its Mangmement T7, 1919 1 carbook of Dermatologi and Syphilology Chicago Ir BK Pub 1950 102 Shelley " B and Kligman 1 M Arch Dermal 75 689 1957 103 Hurley HJ Jr and Shelles 11 B7 Iniest Demal ?? 397 1954 104 Shelley HB and Lei E Arch Dermat 73 38 1996 105 Hubrich G1 and Blank H Inatomy of Iliman Shin lainn 11 / ole 110 mts Ishibat American Icademy of Dermatology Chicago II 1955 106 Shelley 11 B and Cahin M Irci Dermat 73 562 1955 107 Thies W Acta Neurou get 18 191 1958 108 Linz 11 JL P/ Stol Rer 39 534 1959 109 Charle A inat (I ond) 93 226 1959 110 Montez LT Contes A Baher BI and Curus ( fre Dermat 80 549 1959 111 Danto 7 Iniest Dermat 31 295 1998 112 Spiller R r and hno J M J Incest Dermat 31 197 1958 ·INDEX (Unless other ist specifcd, terms refer to Ipocrine Su cat Gland) A physical characteristics 78 quantity 30 racial variations 30 31 residue 30 Apocrine sweating 28 44 55 75 effect of external pressure 41 effect of age 41 effect of sex 41 effect of race 41 electrical stimulation 49 two secretions 55 Apo pilo sebaceous unit 12 Autonomic nerves 22 Axıllary organ gorilla 26 Iron reflex apocrine sweating 44 Abnutzung pagment 18 Acid Phosphatase duct 15 tubule 18 Idrenergic nerve 22 23 15 41 Ikal ne phosphatase duct 15 tubule 20 Vuminurn 92 chloride 67 94 Inatomy 6 Anesthes a local effect on apocrine sweatin 34, 39 Inunal glands 26 chron drous 113 Inthropoids glands of 26 Anthropology 4 Int perep rants 92 Aoki 41 Ipocrnir Secretion 28 61 75 effect of are 69 effect of ses 64 cffect of race 64 effect of ep lat on 75 effect of ray 73 fetent on of 116 123 "pocrine sweat stroking 49 47 Apprarance 3 28 c! rmustry 6C 79 color 30 78 100 fluorescence 3? relation to color 32 manual express on 40 m lang 40 B Bacteriology of apocrine sweat 81 Basement membrane 13 70 Basoph lia cytoplasmic duct 15 tubule 18 Blank 125 Blood supply 20 anatomv 20 Visualization 20 Bloody sweat of hapropotamus 26 Brocklehurst 96 Bromidrosis 96 Bunting 20 с Cahn 73 123 Campbell 44 Carotene 116 Casts 20 Ceroid 114 135 ·136 The llaman Srleat Gland tu lealth and Distaxe Ceruminous gland, 7, 18 granules, 18, 115 Innervation 23 racial differences 18 Chlorophyll, 96 Cholinergic nerve-bers, 23 Cholinesterase, 23 Chromidrosis, 09 Chromidrosis, 18 99 histochemical findings in, 192 of animals, 113 Chracteric, 66 Cold cficct on apocrine sweating 35 48 Colored sweat, 18 100 Comparative anatomy 23 physiology 54, 55 Congenital ectodermal drſect, (0 Currcir duct, 15 pilocarpine, 38 pitocin, 39, 49, 50 pranta), 38 procain, 39 sodium nitrite, 39 Duct histochemistry, 15 histology, 13 innervation, lack of, 23 typhology, E Iccrine sweat relation to axillary odor, 89, 911 Focrine sweat glands 71, 73 Electrical skin resistance, 43 Electron microscopy, 61 Tlephant, 55, 26 Imbryology, 7 I'motional apocrinc gweating 32 pilation, effect on apocrine secretion 75 pinephrine 36, 43 Esterase non specific, 20 Estrogen 70 Tuans 54 Exchange resins, 95 Fatrafollicular apocrine sweat glands 7, 9 apocrine sweating 30, 43 D Darrow 43 Decapitation 15, 61 de Mericort 111 Deodorants 67 92 93 Distribution apocrine sweat glands 3 Diverticuli ? Dog 26 44 55 Drugs acetylcholine, 37 44 55 adrenergic 36 anesthetics local 19 antı adrenergic 38 anti cholingerie 38 antispasmodics 39 atropine 38 cholinergic 37 dibenzyline 38 dibozanc ® hydrochloride 38 epinephrine 37 50 crgotamine tartrate 38 histamine phosphate 39 miscellaneous 39 nicotine, 40, 44 norepinephrine 37 papryerine nitratt 39 physostigmine 38 F Tluorescence, 20, 32 Fox Cordyce discase, 65, 123 Function 28 G Gazelle 55 26 Glycogen duct 15 importance to cccrine and apocrine secretion 62 in eccrine secretory celts 58 Lubule 20 Gorilla 26 55 Granules cosinophobic, 20 monoaminr ordur, 20 pigment 17 ·I der 13 Greg 113 Gynecomastia 71 Lorincz 73 Lymphatics 22 H Hair ax Ilary 71 73 cycles 75 relat on to axillary odor 89 Hambrick 125 Heat effect on apocrine sweating 35 48 55 60 Herrmann 67 Hexachlorophene 84 Heynold 3 H draden tis suppurat va 127 Il ppopotamus 26 54 Jlistochemistry 13 18 20 Histology 13 Mormones 69 Horner 3 Horse 26 51 60 h stology of sweat glands 52 pharmacology of sweat glands 52 phys ology of sweat glands 52 M Mammals glands of 26 sweat gland phystolooy of 54 55 Mammary gland 8 12 let down of milk 49 Menstrual cycle 65 Methylene blue 59 Mhana apocrine 123 cccrine 68 Mitochondria 20 M tosis 20 Moll glands of 3 12 Mondam nc oy dase 20 Montagna 5 15 20 61 65 66 Vyoepithel um birefringence of 46 electrical stimulation 49 embryology 7 function 44 histology 15 45 inntryatron 27 46 mechan cal st mulat on of 41 47 peristaltic waves 51 pharmacologic st mulat on 49 Tole 75 stains 17 20 46 visualizat on of contraction 49 I Ikai 95 96 Ingu nal apocrine sweat glands 20 Innervat on 22 myoep thelium 46 fron 20 80 Intermed ale gland 4 13 к N Nauck 4 Nitta 96 Number of glands 12 Kangaroo 76 55 Wigman 81 95 horson 135 hral 52 hra e 3 huno 4 5 98 0 O Brien 4 Odor 83 94 97 Olset 4 Osmidros s 97 L Levy 125 I pds, 20 Lapſuscio 106 114 lab tz 44 Locat on 12 beterutope 12 P Pas apocrine su catine from 33 Peristalt c waves in apocrine tubule 50

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