NICHOLAS A. SOTER
`HOWARD P. BADEN
`
`1 of 18
`
`Almirall EXHIBIT 2032
`
`Amneal v. Almirall
`IPR2019-00207
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`One of the editors (N.A.S.) dedicates this book to his mother,
`Mildred Elizabeth Soter, and the other editor (H.P.B.) dedicates
`this book to his family.
`
`PATHOPHYSJOLOGY OF DERMATOLOGIC DISEASES
`
`Copyright © 1991, 1984 by McGraw-Hill, Inc. All rights reserved. Printed in
`the United States of America. Except as permitted under the United States
`Copyright Act of 1976, no part of this publication may be reproduced or
`distributed in any form or by any means, or stored in a data base or retrieval
`system, without the prior written permission of the publisher.
`
`7-0 597 47-2
`
`1234567890 HALHAL 9876543210
`ISBN (cid:143)-(cid:143)
`This book was set in Palatino by Monotype Composition, Inc.; the editors were
`William Day and Lester A. Sheinis; the production supervisor was Clare Stanley;
`the cover was designed and the project was supervised by M 'N O Production
`Services, Inc.
`Halliday Lithograph Corporation was printer and binder.
`
`library of Congress Cataloging-in-Publication Data
`
`Pathophysiology of dermatologic diseases / [edited by] Nicholas A.
`Soter, Howard P. Baden. - 2d ed.
`p. cm.
`Includes bibliographical references.
`Includes index.
`ISBN 0-07-059747-2
`1. Skin- Pathophysiology.
`Howard P.
`[DNLM: 1. Skin Diseases--physiopathology. WR 140 P297]
`RL96.P37 1991
`616.5-dc20
`DNLM/DLC
`for Library of Congress
`
`I. Soter, Nicholas A.
`
`Il. Baden,
`
`90-6646
`ClP
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`13
`
`Biology of the
`Sebaceous Gland and
`the Pathophysiology
`of Acne Vulgaris
`John S. Strauss
`
`BIOLO GY OF SEBACEOUS GLANDS
`
`Sebaceous glands are found everywhere on the human skin except for
`the palms, soles, and dorsa of the fee t. The sebaceous glands are part of
`the pilosebaceous unit, and their secretion (sebum) flows through the
`sebaceous duct into the fo llicular canal. Sebaceous glands also are fou nd
`on some mucous membranes. Those in the mouth empty di rectly onto the
`surface thro ugh the gland duc t itself. There is grea t variation in the size
`and density of the gla nds; more gla nds and larger glands are found on the
`face and scalp compared with other areas of the body. On much of the face
`in adults, the sebaceous glands are the predominant portion of the follicle.
`The e fo llicles are ca lled sebaceous fo llicles (Fig. 13-1) and are the fo llicles
`that are involved in acne.
`Sebaceous cells enlarge and contain more lipid as they move in a
`centripeta l direction to the center of the sebaceous acini. Mitotic activi ty
`is restricted to the periphera l basal cell laye r of the gland. Therefore
`ebaceou gland development involves both mitosis and lipogenesis, and
`there is evid nee that these two processes are independently controlled .
`Sebaceou gland ecretion is a continuous process and is holocrine in
`natur . Howeve r, the capacity of the un protected skin to hold lipid is
`limited, and therefore excess lipid is lost. lf the skin is protected, the lipid
`wi ll continue to accumu late.
`
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`196 Disorders of the Epiderm.il Appendages
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`.....
`... -·
`... "':.
`.... .
`Figure 13-1 Sebaceou s foll icle from th<" hum,rn check. The sebaceous duels, as well as the
`widely dilated follicular cana l, an, filled with kt,rat,nou, material. A small vdlus hair i,
`present. !from T/3 FilZ/1'1/m·k rt t1/ fr1/s), Orrm11tology i11 General Mt'dtcmc, 3d cd, N,w York.
`McGmw-lli/1, 1987. p 186.1
`
`Sebaceous gland growth is under endocrinologic control. 1 1 The prime
`s timulus for growth in the male is testicular testos terone and its metabolic
`products s uch as dihydrotestosterone. In the female, ovarian and adrenal
`androgens are probably responsible fur gland growth. While the glands
`nrc large nt birth, they undergo atrophy soon afterward and do not enlarge
`ngain until the beginning of puberty. Since the sebaceous glands arc
`nndrogen sensitive, their g rowth is one of the ea rliest signs of the pubertal
`s pectrum. After pube rty, the glands remain s table in size. In women, they
`u ndergo atrophy during menopause, but in men sebaceous gland activity
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`The Sebaceous Gland and Acne Vulgaris 197
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`is maintained until approximately 70 years of age. While androgens are of
`prime importance, there is an important pituitary influence on sebaceous
`gland activity, and in hypopituilarism, sebaceous gland activity is markedly
`diminished.
`Physiological amounts of estrogens do not influence sebaceous gland
`development and, therefore, are unimportant in the normal control of the
`sebaceous g land. However, pharmacologic amounts of estrogen do de(cid:173)
`crease sebaceous gland activity.4 This effect is mediated through central
`inhibition of androgen production. This findi ng is used in the treatment
`of severe acne in women.5
`Because the sebaceous glands are deep in the dermis and do not open
`directly to the skin surface, it has not been possible to collect sebum, the
`product of the sebaceous glands, directly. Therefore, ski.n surface lipids
`have been used to study sebaceous gland secretion and sebum composition.
`The skin surface lipids represent a two-compartment system in that they
`originate from both the epidermis and the sebaceous glands. Since
`sebaceous and epidermal lipids are distinctly different, the composition of
`the skin surface lipids will vary depending upon whether the major portion
`is derived from the epidermis or the sebaceous glands. 6 The approximate
`composition of sebum and epidermal lipid is given in Table 13-1. Triglyc(cid:173)
`erides and their breakdown products make up approximately two-thirds
`of both epidermal and sebaceous lipids. Therefore, the concentration of
`triglycerides and their breakdown products does not vary significantly as
`the percentage of sebaceous and epidermal lipids changes. On the other
`hand, since triglycerides are hydrolyzed by bacterial lipases, the concen(cid:173)
`trations of triglycerides, d iglycerides, and free fatty acids may vary greatly
`in a given individual under various conditions.
`Besides triglycerides, the epidermal lipids are cholesterol and cholesterol
`esters. In contrast, less than 5 percent of sebaceous lipids are cholesterol
`and cholesterol esters. Wax esters and squalene are uniquely of sebaceous
`origin and re present the major nontriglyceride fraction of sebum. Therefore,
`
`Table 13-1
`
`APPROXIMATE COMPOSITION OF SEl3UM AND
`EPIDERMAL LIPID
`
`Glycerides and free fatty acids
`Wax esters
`Squalene
`Cholesterol esters
`Cholesterol
`
`Sebum,
`w t (%)
`
`57.5
`26.0
`12.0
`3.0
`1.5
`
`Epidermal
`Lipid
`WI (%)
`
`65
`
`15
`20
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`198 Disorders of the Epidermal Appendages
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`if most of the skin surface lipids are of epidermal origi n, as in childhood,
`the choles terol content will be high, whereas the concentra tion of wax
`esters and squalene will be low. 7 If, however, most of the skin surface
`lipid is of sebaceous origin, as in the adul t, in whom over 95 percent of
`facial lipid is from the sebaceo us glands, 6 the wax ester and squalene
`content is high , whereas the cholesterol level is low. Under appropriate
`conditions, the relative amounts of cholesterol and wax esters or squalene
`in skin surface lipids ca n be used as an indication of the relative sebaceous
`and epidermal contributions to the skin surface lipid.
`Since the sebaceous glands are holocrine structures, their secretory
`activity provides a rough measurement of gland size, and for many years
`measurements of sebum production have been used to study changes in
`sebaceous gland activity. It is best to collect the lipids of th e forehead by
`trapping them on absorbing materials such as paper! or a dried bentonite
`slurry. 9 Then the trapped lipid is extracted for quantitative or qualitative
`analysis. An essential element that must be considered is the contribution
`of the lipid reservoir of the epidermis. In th e most commo n method, in
`use for over 20 years, surface lipids are depleted for onl y 30 minutes. 8 It
`has now been established that cutaneous reservoir depletion takes as long
`as 12 to 14 h , and a new collection method takes this fact into consideration .9
`The surface samples are obviously contaminated by epidermal lipids, but
`less than 5 percent of fore head lipids are of epidermal origin. Therefore,
`within the limits of the techniqu e, the collected lipid s do represent a
`measure of sebum production and ca n be used to detect physiological as
`well as drug-indu ced cha nges in sebaceous gland s .
`
`ACNE VULGARIS
`
`Acne vulgaris is usually classified as a disease of the sebaceous gland ,
`but it should be classified as a disease of the pilosebaceous unit since the
`lesions de velop in th e upper portion of the fo llicu lar cana l and do not
`in volve the gland s primarily . Acne is the most common di ease seen by
`derma tologis ts, accounting for over 25 percen t of all derma tologic office
`visits. Physicians involved in primary care delivery are also likely to see
`acne as a presenting complaint quite frequently . Nonetheless, si nce 80 to
`90 percent of all individuals develop some acne in the second and third
`decades, it is obvious that only a small percentage of those with acne
`actually consult physicians.
`Acne is occasionally present at birth or in the neo nata l period . However,
`it is not until pube rty that it becomes a common problem. The disease
`may be an ea rly manifestation of the pubertal pectrum, and in young
`females it may precede menarche by more than a year. Acne reaches a
`peak incide nce during the middle to late teenage p riod , and then the
`number of cases g rad ually decreases. In wo men, acne may persist th ro ugh
`the third decade o r even la ter. Acne is slightly more common in male ,
`and severe acne is definitely more common in males.
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`The Sebaceous Gla nd and Acne Vu lgaris 199
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`Etiology and Pathogenesis
`
`While the basic cause of acne is unknown, there is considerable
`information on its pathogenesis. The disease is multifactorial. Knowledge
`of the various factors in volved in the disease is important, since treatment
`ma y be directed at o ne o r m ore of these ca usative factors.
`Acne develops in sebaceous follicles (Fig. 13-1). These fo llicles open to
`the surface by a widely dilated follicular orifice (visible as the so-called
`pore of the skin of the face) a nd are wide throughout their en tire length.
`A vellus hair is always present in the follicle, but as it is very small , it
`may not be appare nt from exa mination of a single microsco pic section .
`Short du cts connect the huge, deeply situated , multiacinar glands to the
`large follicular duct.
`The follicu lar ca nal contains keratinous material from the wall of the
`canal, sebum from the sebaceo us glands, and a variable microbial flora .
`These are all involved in the pathogenesis of the d isease.
`The primary structural change is an alteration in the pattern of kerati(cid:173)
`nization in the low r portion of the follicular infundibulum (the infrain(cid:173)
`fundibulum). 10 Normally the keratinous squamae in the follicular canal are
`loosely organized. In the earliest lesion (the microcomedo), which is not
`visible clinically, the ke ra tinous material becomes more dense. The cells
`of the microcomedo are much more cohe rent and contain amorphou s
`m a terial, which i probably ge nera ted by lipid during the process of
`kera tini zation. Kinetic studies have demonstra ted that there is an increase
`in cellular turnover, so that more cells are gene rated per unit period of
`tim . 11
`As a group, patients with acne produce more sebum th an do normal
`p e rson , a nd patients with severe acne secrete more sebum than those
`with mild acne. 12 Nevertheless, there is conside rable va riation in sebum
`produ ction wi thin the g ro up of patients with acne, indicating that the
`dis ase is not re lated solely to sebaceou s gland activi ty. Many other facts
`indica te that sebum plays a role in the overa ll pathogenesis of the disease.
`These include the fo llowing: sebum is com edogenic13; sebum causes
`infla mmatio n w he n injected into the skin 14; acne occurs in the neonata l
`period w hen th sebaceous g la nds a re well developed; acne appears as
`pa rt of the pubertal spectrum a t a time when sebaceous gland development
`occurs; a nd acne ca n be co ntrolled by ora lly administered estrogen s,
`antiandrogens s uch as cyproterone acetate, and s pironolactone a nd reti(cid:173)
`noids, a ll of w hich inhibit sebaceo us gland activity .
`Severa l sh1di
`have been done to attempt to demonstrate that sebum
`fro m ac ne pati nts is different from that in normal individuals. In gene ral,
`no con iste nt patterns of change have been observed. 15 However, there is
`a sig nificant de rease in the level of linole ic acid in sebum, 16 and consid(cid:173)
`erable evidence ha be n presented to link the low levels of linoleic acid
`to the pathogenesis of acne. 17 It has been postulated tha t the low levels
`of linoleic acid repre ent the dilution of this esse ntial fatty acid , which is
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`200 Disorders of the Epidermal Appendages
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`not synthesized in the sebaceous gla nds, by the newly synthesized
`sebaceo us lipids in the large sebaceous glands characteristica lly fo und in
`patients w ith acne . In turn, the low concentration of linolea te in sebum
`induces a localized essential fo llicular fa tty acid deficiency, with the
`characteristic responses of h yperkeratosis and decreased barrier function
`within the fo llicle.17
`The pred ominant organism in the follicular flora is an anaerobic pleo(cid:173)
`morphic diphtheroid, Propion ibacterium acnes. In the acne age range from
`11 to 15 yea rs, practicall y no P. acnes are fo und in individuals w ithout
`acne, w hereas in patie nts with acne the geometric mea n is 114,800 P. acnes
`per square centimeter. 18 Similar d ifferences are fo und in 16- to 20-year-old
`groups, but in older individuals the number of organisms is the same in
`those with and without acne. While staphylococci, micrococci, and yeasts
`(Pityrosporum species) are also fo und in the follicle, there is n o evidence
`that they are involved in the acne process.
`In spite of the importance of P. acnes in the pathogenesis of acne, acne
`is no t a bacterial disease per se, and its response to thera py w ith antibiotics
`is not what one wo uld expect from a bacterial disease. Instead , P. acnes
`generates inflammatory agents. Extracellular products of P. acnes include
`enzym es such as lipases, proteases, and hyaluronidases, as well as
`chemotactic fac tors . It is these ex tracellula r products and, in turn, their
`products that cause inflammatory changes.
`Indirect evidence that P. acnes is responsible fo r lipolysis and inflam(cid:173)
`mation is supplied by experiments in w hich suspensions of this organi m
`have been injected into cysts. 19 The injection of viable orga nisms causes
`rupture of the cysts and severe inflamma tion of the surrounding tissues .
`Very little inflammation is produced by the injection of non viable organisms
`into cysts, and injection of living orga nisms into th e dermis induces only
`a slight to moderate infiltra te of neutrophils.
`
`Clinical Manifestations
`
`The primary site of acne is the face, and tc, a lesser degree the back,
`chest, and shoulde rs. On the trun k, lesions tend to be more numerous
`near the midline. Acne is a pleomorphic disease consisting of noninflam(cid:173)
`matory and inflammatory lesions. While one ty pe of lesion may be
`predominant, close observa tion usually revea ls several ty p s of lesions.
`Comed ones, which are the primary lesions of acne, are noninflammato ry
`(Fig. 13-2) . Closed comed o nes (whiteheads) may be difficult to visualize.
`Th ey appear as pale, slig htly eleva ted, small papule . They often d o not
`have a clinically visible orifice. Stretching of the skin is a n aid in detecting
`these lesions. Since the closed comedones are the precursors of the large
`inflammatory lesions, they are of considerabl cl inica l impo rtance. Op n
`comed ones (blackhead s) develop fro m closed comed ones as the orifice
`dila tes. The open comed o is fla t or slig htly raised , w ith a central fo lljcular
`impaction . While comed ones are the primary lesions of acn , they are not
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`The Sebaceous Gland and Acne Vulga ris 201
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`Figure 13-2 Blackheads and whiteheads on the temple. (From JS Strauss, AM Kligman. '9)
`
`unique to this disease, since they may be seen under other conditions
`(e .g. , so-called senile comedones commonly seen in the periorbital area of
`older persons).
`Inflammatory lesions in acne vary from small papules with an inflam(cid:173)
`matory areola to pustules to large, tender, fluctuant nodules (Fig. 13-3) .
`All these lesions show an inflammatory infiltrate in the dermis and, as
`indicated below, have a common pathogenesis; their appearance depends
`on the size and location of the infiltrate.
`
`Pathology
`
`Comedo development starts in the midportion of the follicle as an
`expanding mass of lipid-impregnated keratinous material, resulting in
`thinning and ballooning of the follicular wall. Gradually, more keratinous
`material accumulates, and, as it does, further thinning and dilatation of
`the fo llicular wall occur. The fully formed comedo has a thin wall and
`minute sebaceous appendages, if these can be found at all . The open
`comed o has a patulous orifice, and the keratinous material is arranged in
`a lamellar concentric fa shion (Fig. 13-4) . With lipid stains, it can be shown
`that the keratin is permeated by lipid. P. acnes is ala present. In cross
`sections, the orderly arrangement of the keratinous material consists of
`smaller w horls of lamellar material centered on appendageal structures
`such as the hairs. In fact, most comedones contain multiple hairs. The
`closed comedo differs from the open comedo in that the keratinous material
`is not as compact, as the follicular orifice is narrow and not distended
`(Fig . 13-5) .
`The fully developed open comedo usually is not the site of inflammatory
`changes unles it is traumatized by the patient. Inflammatory changes
`develo p in closed comedones. Initially there is an area of inflammation
`along the follicular wall, w hich then ruptures. Once complete rupture has
`occurred , the entire contents of the comedo are extruded into the dermis,
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`202 D1-.onkr., of the Lp1dermal Appcml.igl.'.,
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`The Sebaceous Gland and Acne Vulgaris 203
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`Figure 13-4 Open comedo. The mouth of the follicle is widely dilated . The comedo is
`composed of a lamellar ke ratinous mass impregnated with lipid . Bacteria are also present.
`The sebaceous gland s have undergone atrophy. (Fro111 JS Strn11ss, AM Klig111a11 . 19
`
`)
`
`Figure 13-5 Closed comedo. The structure of the lesion is simila r to that of the open comedo.
`However, the ori fice is small and the contents of the comedo are not as compact. (Fro111 JS
`St m11ss, AM Klig111a11 . 19
`
`)
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`204 Disorders of the Epidermal Appendages
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`Figure 13-6 Ruptured closed comedo. In the upper port ion of the lesion there is lamellar
`kerati nous material from the comedo. Below th is, necrotic materia l is being enca psulated by
`new epithelial cells. These new cells are shown in higher magnification in the insert.
`Multinuclcated giant cells are present in the innamma tory infiltrate in the dermis. (From JS
`Strauss, AM Klig111a11. '")
`
`exciting a greater inflammatory response. Depending upon the site and
`extent of the inflammation, these ruptured lesions may appear as a pustule,
`a nodu le, or a nodule surmoun ted by a pustulP.
`The sheaths of cells grow out from the epidermis and/or the appendageal
`structures in an attempt to encapsulate the inflammatory reaction (Fig.
`13-6). This encapsulation may be complete, so that the inflammatory
`infiltrate appea rs to be within the follicle, but it often is far from complete,
`and further rupture may occur, leading to multichanneled tracts, as can
`be seen in many acne scars. Fibrous contraction also contributes to scar
`formation.
`
`Therapy
`
`There are four principles of therapy, which are based on the current
`knowledge of the pathogenesis of the disease. These principles are: (1)
`correct the pattern of altered keratinization within the follicle, (2) decrease
`sebaceous gland activity, (3) decrease the P. nC11es population and/or
`decrease the generation of inflammatory substances by the bacterial
`population, and (4) produce anti-inflamma tory effects. However, rigid
`guidelines cannot be established, since there is likely to be considerable
`overlap in the type of lesions in any o ne case, and often combination
`therapy is indicated.
`
`To Correct the Defect i11 Kerati11izntio11
`
`The most effective drug used to change the pattern of keratinization is
`topically applied vitamin A acid . Vitamin A acid is comedolytic, 20 and at
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`The Sebaceous Gland and Acne Vulgaris 205
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`an ultrastructural level the process of follicular wall keratiniza tion returns
`toward normal. 2 1 The drug may produce irritation, and some patients
`cannot tolerate its use, even if it is applied as infrequentl y as every 2 or 3
`days. Patients should be ca utioned about sun exposure while using vitamin
`A, beca use the drug may ca use an exaggerated sunburn . Salicylic acid also
`is comedolytic. Benzoyl peroxide, although predominantly an antibacterial
`agent, also has weak comedolytic activity.
`When acne surgery is d one, the comedo is extruded to the skin surface;
`thus this procedure can be considered an aid in changing the pattern of
`keratinization. If acne surgery is not performed with care, the contents of
`the comedo can be extrud ed into the dermis, resulting in increased
`inflammation. For this reason, this procedure should be done by a trained
`person and not by the patient.
`
`To Decrease Sebaceous Gland Activity
`Suppression of sebaceous gland activity is important in treating acne,
`especially inflammatory acne. It is known that pharmacologic dosages of
`estrogens will inhibit sebaceous glands, 4 and estrogens, usually given as
`oral contraceptives containing high concentrations of estrogen, may be
`used in the management of acne. 5 Estrogens are not indicated for routine
`use; they should be given to women with recalcitrant acne, and the
`physician must assess the risk/benefit ratio carefully before starting any
`patient on therapy. Since estrogens do not have any known effect on
`existing lesions but appear to work by limiting the contribution of sebum
`to the inflammatory process in new lesions, their clinical effect is delayed
`while the preexisting lesions undergo their natural involution.
`There are new developments in the use of antiandrogens in the
`manage ment of acne . Cyproterone acetate, used in conjunction with
`estrogen (an oral contraceptive combination available in Europe), is more
`effective in suppressing sebum production and improving acne than
`e trogen alone in women 22; cyproterone acetate given alone is effective in
`men, although it has many side effects .23 While cyproterone acetate is not
`ava ilable in the United States, spiro nolactone, which also has locally acting
`a ntiandrogenic properties, has been shown to be useful in the management
`of severe acne. 24
`There is evidence that a few patients with acne have partial hydroxylase
`blocks that influence adrenal steroid metabolism, leading to increased
`androgen production .25 In these patients, excess androgen production can
`be blocked by the administration of exogenous adrenocorticosteroids
`through a feedback m chanism .
`Probably the most exciting development in acne therapy in recent years
`has been the use of th e sy nthetic oral retinoid , isotretinoin (13-cis-retinoic
`acid) . This drug has proved to be extremely effective in the control of
`severe nod ulocystic acne. 26 Not only has it produced remarkable improve(cid:173)
`ment, but the remissions after cessa tion of treatment have been very
`long .27 While th re may be long-term inhibition of sebaceous gland
`secretion , this is by no mea ns een in all patients28 and ca nnot be considered
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`206 Disorders of the Epidermal Appendages
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`the sole reason for the lo ng-term remission s. The other possible mecha(cid:173)
`nis ms of action, as well as the clinical effectivenes of isotre tinoin, have
`recently been su mma ri zed. 29 The drug also has been s hown to be effective
`in con trolling di sord ers of keratinization a nd to have anti-infla mma tory
`effects, but these activities do no t explain the protracted remiss ion . P.
`acnes counts are s uppressed for long periods of time,10 but it is not known
`whet her the d ecrease is responsible fo r the lo ng-te rm re missions .
`The excite me nt urrounding th e use of isotretinoin must be temper d
`by the many side effects produced by this drug . In esse nce, every patient
`trea ted with isotre tinoin develops s igns a nd symptom s of chronic hy per(cid:173)
`vitaminosis A. Most of these side effects a re integum nta ry (dry kin, dry
`mucous membranes, cheilitis, d erma titis, pruritu , desquamation o f the
`palms and soles). Ce rtain la boratory ab normalities, such as a reversible
`hypertriglyceride mia accompanied by a decrease in high-den sity lipopro(cid:173)
`tei ns, are also common. Othe r side e ffects, such as keletal hyperkerato i
`and pseudotumor cerebri, both of w hich a re part of the hy pervitaminosis
`A syndrome, hav also been reported. Of grea tes t importance, however,
`is the fact that the dru g, while no t mutage ni c, has marked teratoge nic
`effects on orga nogenesis during early fetal d evelopm ent. Re tinoid embry(cid:173)
`opathy is severe. 3 1 The proble m is a serious on , 12 and because of thi ,
`there are strict guidelines* for its use in women of childbea ring age. 33
`These guidelines mu t be fo llowed , a nd tho e physicians who are not well
`informed and well trained in the use of i o tr tinoin should not use the
`drug under any circums ta nces.
`Superficial x-ray th e rapy ca n produce t mpo ra ry inhibition of th
`sebaceous gland s. Alth ough it was used in th e past for th e trea tment of
`acne, it is not used now.
`
`To Reduce the P. acnes Population
`
`P. acnes is probably res ponsible for the ge ne ratio n of inflamma tory
`substances; therefore, th e su ppression of the intrafolli cular bacterial pop(cid:173)
`ulation is important in controlling infl ammatory acn . B nzoyl peroxide is
`a n extremely effective topica l antimicrob ial age nt, 14 a nd pre parations
`containing benzoyl pe roxid e are the most popu la r age nts for the topica l
`control of the folli cula r P. acnes po pulation . Topica l a ntimicrobials are used
`for the sa me purpose .
`tr atment of acne .
`Orally admi ni stered antibiotic a re widely u ed in th
`In fact, 10 percent of all te tracycl in e sold in th e United States is used fo r
`the treatme nt of acne. Since acne is no t a bact rial di ease pe r se, th
`thera pe utic res pon e i no t fast, as in true bacterial infections uch a
`cellulitis . Imp rovement may Lake a m onth or more, since tha t much time
`is req uired fo r the exis ting le ions to und e rgo in vo lution . While te tracycl ine
`i
`th e mos t common ly used antibiotic for a ne, e ry thromycin is eq uall y
`effective. Minocycline is proba bly th e most effective a ntibio tic for cont rol-
`
`*C11ideli11es nre nlso provided l1y tlt1• l//(llll//11ct11rcr i11 the p11ckngc 111 ,crt.
`
`This m3t eria l w as. copied
`at the NLM and may be
`Subject US Copyright La w s
`
`14 of 18
`
`

`

`The Sebaceous Gland and Acne Vulgaris 207
`
`ling the inflammatory component of acne, but its comparative cost at th is
`time precludes its use unless the patient does not respond to other
`antibiotics. In addition, pigment deposition may occur in the skin d uring
`minocycline therapy.
`A rare complication of antibiotic therapy is the development of a gram(cid:173)
`nega tive folli culitis .35 With prolonged antibiotic thera py, gram-nega ti ve
`organisms may proliferate in the anterior nares and spread out onto the
`surrounding skin . The clinical lesions of gram-nega tive folliculitis are either
`multiple pustules with an intense inflammatory areola or deep, indolent
`nodules. This complication may easily be overlooked and is suggested by
`a sudden inflammatory flare w ith pustules or nodules in a patient who is
`otherw ise improving on antibiotic therapy. Culture is necessary, and
`appropriate antibiotic therapy should be governed by the resul ts of
`sensitivity studies.
`
`To Produce an Anti-inflammaton; Effect
`
`The anti-inflammatory effect of adrenocorticosteroids may be utilized in
`the treatment of acne. It is preferable to use them intralesionally in order
`to prevent the side effects that may follow high-dose oral therapy. If proper
`attention is given to the concentration of the drug as well as to the total
`d osage used , intralesional steroids are safe and highly effective in severe
`nodulocystic acne.
`Since inflammatory lesions develop in closed comedones and closed
`comed ones are removed during acne surgery, this form of therapy can be
`considered to have an anti-inflammatory effect.
`
`OTHER ACNE-LIKE DISEASES
`
`Acne Conglobata
`
`Acne conglobata is generally considered a separate entity from acne
`vulgaris because of its occurrence at a later period and its chro nic,
`unremitting course. Patients with acne conglobata have a mixture of
`comed ones, papules, pu stules, nodules, abscesses, cysts, and scars on the
`back, buttocks, chest, and, to a lesser extent, the abd omen, shoulders,
`neck, face, upper arms, and thighs. The comedones often have multiple
`openings. The inflammatory lesions are large, tender, and dusky colored,
`and they discharge a foul-smelling serous, purulent, or mucoid material.
`Subcutaneous dissection with the form ation of multichanneled sinus tracts
`is common . Healing results in depressed or keloidal scars.
`While some lesions may be sterile or show only the presence of residen t
`coagulase- nega tive staphylococci and anaerobic diphtheroids, it is common
`to isolate coagulase-positive staphylococci. Occasionally, ~-hemolytic strep(cid:173)
`tococci are fo und. The presence of a chronic in fec tion may be reflected by
`the presence of a normochromic, normocytic anemia, an eleva ted white
`blood count with an increased percentage of neutrophils, and an increased
`
`This materi a l w a s copie-d
`a tthe•NLM a nd may he
`Subject US Copyright laws
`
`-
`
`15 of 18
`
`

`

`208 Disorders of the Epidermal Appendages
`
`sedimentation ra te. There is no evidence that these patie n ts have decreased
`gam ma globulins, and the gamma globulins may even be eleva ted . The
`fas ting blood sugar and glucose tolera nce tests are usually normal.
`Since lesions may occur in the axillary a nd ingu inal regions, the disease
`may resemble hidrad enitis suppurativa. In fact, the la tter disease has been
`conside red to form part of a triad w ith d issecting pe rifolliculitis of the
`scalp . It would a ppear, however, tha t these are separa te en ti ties, especially
`since both dissecting perifo lliculitis of the sca lp and hidradenitis suppur(cid:173)
`ativa may occur alone.
`The ma nageme nt of these patie nts is a ve ry difficult problem, and even
`if there is improvement, it often is tempora ry. Thera py wi th the a ppropria te
`systemic a ntibiotic as de termined by in vitro sensitivity studies is indica ted,
`as a re injectio ns of corticosteroids directly in the lesions on frequent
`occasions. Systemic corticosteroids are useful; however, recurrence of the
`disease is common w hen they are discontinued . Surgical d ebridement,
`surgical incision, and surgica