Dr. Reddy's Laboratories, Ltd., et al.
`v.
`Galderma Laboratories, Inc.
`IPR2015-__
`Exhibit 1056
`
`Exh. 1056
`
`

`
`NOTICE
`
`Medicine is an ever-changing science. As new research and
`clinical experience broaden our knowledge, changes in treat-
`ment and drug therapy are required. The editors and the pub-
`lisher of this work have made every effort to ensure that the
`drug dosage schedules herein are accurate andin accord with
`the standards accepted at the time ofpublication. Readersare
`advised, however, to check the product information sheet
`included in the package of each drug they plan to administer to
`be certain that changes have not been made in the recom-
`mended dose or in the contraindications for administration.
`This recommendation is of particular importance in regard to
`new or infrequently used drugs.
`
`DERMATOLOGY IN GENERAL MEDICINE
`
`Copyright © 1987, 1979, 1971 by McGraw-Hill, Inc. All rights
`reserved. Printed in the United States of America. No part of
`this publication may be reproduced, stored in a retrieval sys-
`tem, or transmitted, in any form or by any means, electronic,
`mechanical, photocopying, recording, or otherwise, without
`the prior written permission of the publisher.
`
`1234567890 DOWDOW 89876
`
`This book was setinTimes Roman by Ruttle, Shaw &
`Wetherill, Inc. The editors were J. Dereck Jeffers, Eileen
`Scott, and Julia White; the coverwas designed by Edward
`R. Schultheis; the production supervisorwas Ave McCracken.
`R. R. Donne11ey & Sons Company was printer and binder.
`
`Library of Congress Cataloging in Publiestion Data
`Main entry under title:
`Dermatology in general medicine.
`
`Includes bibliographies and index.
`1. Dermatology. 2. Cutaneous manifestations of generat
`I. Fitzpatrick, Thomas B.
`[DNLM: 1. Skin diseases. 2. Skin
`diseases.
`Manifestations. WR 100 04383]
`RL71.D46 1987
`616.5
`86-10633
`ISBN 0-07-079689-0 (set)
`ISBN 0-07-021205-8 (v. I)
`ISBN 0-07-021206 (v. 2)
`
`Exh. 1056
`
`

`
`(4) The structure of skin leslons and fund amentals of diagnosis
`27
`. r differentiating redness due to vascular dilata-
`Fl
`a~topped papulc with a violaceous hue are charncteristic
`01erhod to
`'l) from redness due to extravasated eryth-
`d
`(
`) lf th
`d
`?fliehen planus. The presence of f1ne, netlike white mark-
`(erythem,
`erytbr()cyte-pro ucts purpura ·
`e re ness
`tngs,.called Wickham' s striae, on the surface of the lesi'on
`(ion
`roC)rtes or der tbe pressure of the slide, the lesion is pur-
`re01ain un
`provides furth er eyidence fo r the diagnosis of Iichen
`planus. Yellow papules are seen in xanthomato. is. Hem-
`.
`.
`punc· . . r. . . 1 is an area of cutaneous necros1s resulting from
`h
`·
`orr. ~gtc or necrotic papule are noted in ctltaneous vas-
`I' ·
`An UIJa ll
`•
`.
`~lusion of blood ves~et~s, as ~ vascu Ltl~ and :acterial
`cuhtls and meningococcemia. Purpuric papules-palpahle
`PL~rpura-are indicative of vasculitis until proved other-
`I' 11 Cutaneous 10 arcts ave a vanegate ' dusky
`oc
`embo 151 :sh hue They are irregularly shaped macules
`B
`wtse.
`rownish, rough (keratotic) papules are quit e typical
`d graYI
`·
`.
`'
`~~~etimes depressed sblightl~nkbelow thef phlane of .the skin
`of keratosis follicularis (Darier's disease). Pigmented nevi
`t.1 n sunounded y a p1
`1.
`zone o yperem1a. They
`and earl
`t
`f
`1
`· Y ma 1.gnan me anoma o ten occur as rounded
`and o e
`brown or black papules and are to be differentiated fro~
`maY be tender.
`Disseminated small erythematous macu~es occ~r in ex~
`pigmented basal cell carcinoma, which has a somewhat
`anthems such as roseola and drug eruptlons. Con~uent
`similar appearance but is waxy-smooth with a raised ,
`erythematous macu~es m~yll covher a w~ole extremJtfly or
`rolled, telangiectatic border. A dark blue or black rounded
`J·lf of the face, as 10 capt ary emangwma (nevus am-
`papular lesion may suggest a blue nevus, nodular mela-
`~~~us). Macules may be pigmented, such a~ the cafe ~u
`noma, angiokeratoma, or Kaposi's sarcoma.
`1 ·l-colored macules of neurofibromatosts; hypoptg-
`Rounded, skin-color papules may be seen in adenoma
`h
`.
`.
`ai
`mented. as in postinflammatory ypoptgmentat10n; and de-
`sebaceum and amyloidosis. Molluscum contagiosum may
`igmenled , as in vitiligo. Hypomelanotic macules, often
`be identified as a rounded, translucent papule with a central
`~ith an outline resembling the shape of an ash leaf, have
`umbilication; when the papule is punctured , a rounded,
`been identified as the earliest visible marker of tuberaus
`central "molluscum body" is noted. Pedunculated pap-
`sclerosis. Collections of dermal melanocytes may impart a
`ules, darker than, or the same color as, normal skin, occur
`graycolor to the skin, as in Mongotian spots. A blue color
`in neurofibromatosis. Skin tags (acrochordon) are pedun-
`may arise from the scattering of light as it passes throught
`culated or filiform Jesions that are usually skin colored.
`thc turbid medium of the dermis (Tyndall phenomenon),
`Papules may be follicular and perifollicular, as in acne,
`as in nevus of Ota. Fine scaling may be seen in the ma-
`folliculitis, and Darier's disease.
`A papule or plaque (see below) may consist of multiple,
`culosquamous lesions of tinea versicolor, pityriasis rosea,
`and erythrasma.
`· small, closely packed, projected elevations that are known
`Telangiectases are commonly observed on faces of per-
`as a vegeta.tion (Fig. 4-2). Vegetations may be covered
`sons chronically exposed to the wind and sun. They are a
`with thick dry scales, and described as keratotic (as in
`prominent feature of the erythematous color noted in cu-
`verruca vulgaris), or may be soft and smooth (as in con-
`taneous Iupus erythematosus. In addition, periungual te-
`dyloma acuminatum). Seborrheic keratoses are common
`langiectases are an important marker for collagen vascular
`vegetative lesions, especially in older age groups. They
`disorders such as lupus erythematosus and dermatomyo-
`may be yellowish, tan, brown, or black, and often have a
`sitis. In hereditary hernorrhagic telangiectasia, the lesions
`soft, greasy suface. Dry, scaly vegetations occur in actinic
`are usually nonpulsatile, dull red, sharply outlined macules
`keratoses.
`or papules, most commonly present on the tongue, lips,
`All erythematous papules should be examined by dias-
`face, and fingers. Telangiectases arealso a prominent fea-
`copy (see 11Aids in the Clinical Examination of Skin and
`ture of rosacea.
`Hair,'' later in this chapter), inasmuch as a yellow-brown
`color appears in the papules found in a number of granu-
`lomatous disorders, and an erythematous papule that does
`not blanch on diascopy may be a sign of vasculitis (palpable
`purpura).
`Although certain eruptions may have both macular and
`papular compon.ents, we believe that the abused term mac-
`ulopapular is a non sequitur, or at best an oxymoron, and
`we avoid using it for the sake of clear thinking and com-
`munication.
`
`Papules. A papule is a small, solid, elevated lesion (Fig. 4-
`2). Papules are smaller than 1 cm in diameter, and the
`major portion of a papule projects above the plane of the
`surrounding skin. Oblique lighting with a flashlight in a
`~arkened room is often necessary to detect slight eleva-
`lion. The elevation can be the result of metabolic deposits,
`lo~alized hyperplasia of cellular components of the epider-
`mts or dermis, or localized cellular infiltrates in the dermis.
`~u~erficiaJ papules with sharp borders are seen when the
`esron is the result of an increase in the number of epider-
`mal c~Us or melanocytes, as in verruca vulgaris or mela-
`nocytlc nevi.
`Pa~ules may have a variety of shapes. They may be
`acurnmate (pointed), as in miliaria rubra (prickly heat
`rash).; .surmounted with scale or keratin, as in secondary
`syphiJJs· d
`.
`ft t
`• ome-shaped, as in molluscum contag10sum; or
`a topped
`. I'
`.
`~ as m tchen planus.
`0
`ide t~fier f~atures, such as color, are also important in the
`f
`.
`·
`·
`·
`nl! catl
`Pso . . on o papular Ies10ns.. Red papules are seen m
`d
`nasls
`ft
`.
`' 0 en With a superimposed scale that pro u~es
`bleect·
`scali rng When removed (Auspltz's sign). Papules· with
`Per ~glare.referred to as pqpulosquamous lesions. A cop-
`0 or IS noted in the )esions of secondary syphilis.
`
`Plaques. A plaque is a mesalike elevation that occupies a
`relatively large surface area in comparison with its height
`above skin Ievel (Fig. 4-3). Plaques are often formed by a
`conftuence of papules, as in psoriasis. The typical psoriatic
`Lesion is a raised, erythematous plnque with layers of sil-
`very scale, often described as micaceous.
`Repeated rubbing, especially in people with ehrenie
`eczema, leads to areas of lichenification. Proliferation of
`keratinocytes and stratum corneum, in combination with
`changes in the collagen of the underlying dcrmis, causes
`lichenified areas of skin to appear as thickened plaques
`with accentuated skin marking~. ·The lesions ·may resemble
`·tree barkf
`The presence of atrophy, especially in the presence of
`
`Exh. 1056
`
`

`
`(4) The structure
`
`t k" 1 ·
`o s 1n estons and fundamentals of diagnosis
`
`31
`
`Fig. 4-5 Wheal. A wheal, shown in the drawing (a), ls a
`rounded or flattopped elevated lesion that ls characterlsti-
`cally evanescent, disappearing wlthin hours. Wheals may be
`tlny papules 3 to 4 mm ln diameteras in chollnerglc urticaria
`whlch is shown ln the clinical photograph (b). They may be
`large, coalesclng plaques as in allerglc reactions to penlcll·
`lln, other drugs, or alimentary allergens, as shown in (c). An
`eruptlon conslstlng of wheals is termed urtlcar/a and is char-
`acterlzed by ltchlng.
`
`lesions of pustular psoriasis. Pustules may vary in size and
`shape and, depending on the color of the exudate, may
`·appear white , yellow, or greenish yellow. Follicular pus-
`tules are conical, usually contain a hair in the center, and
`generally heal without scarring.
`Pustules are characteristic of rosacea, pustular psoriasis,
`Reiter's disease , and some drug eruptions, especially those
`due to bromide or iodide. Vesicular lesions of sorne viral
`diseases (varicella, variola, vaccinia, herpes simplex, and
`herper zostcr), as well as the le.sions of derrnatophytosis,
`may become pustular. A Gram's stain and culture of the
`exudate from pustules should always be performed.
`Aluruneie is a deep necrotizing form of folliculitis, with
`pus accumulation. Several furuncles may coalesce to form
`a carhuncle. An abscess is a localized accumulation of
`purulent material so deep in the dermis or subcutaneous
`tissue that the pus is usually not visible on the surface of
`the skin. It is red, warm, and tcnder. An abscess frequently
`begins as a folliculitis and is commonly a manifestation of
`cutaneous streptococcal or Staphylococcus aureus infec-
`tion.
`A slnus is a tract leading from a suppurative cavity to
`the skin surface, or between cystic or abscess cavities. A
`sinus near the rectum may be seen in rectal abscess, car-
`cinoma of the bowel, or inflammatory bowel disease. Si-
`nuses of the neck suggest actinomycosis, crofula, bran·
`chial pouch, or dental sinus. Deep sinus tracts may occur
`in hidradenitis suppurativa and acne conglobata.
`
`. Cysts. A cyst is a sac that contains liquid or semisolid
`material (fluid, cells, and cell products). A sphcrical or
`
`c
`
`When the epidermis is lost, usually as a result of vesi-
`cation, the circumscribed denudation is known as an ero-
`sion and appears as a moist, slightly depressed lesion (see
`below).
`
`Erosions. An erosion is a moist, circumscribed, usually
`depressed lesion that resutts from loss of all or a portion
`of the viable epidermis (Fig. 4-9). After the rupture of
`vesicles or bullae, the moist areas remaining at the base
`are called erosions. Extensive areas of denudation due to.
`erosions may be seen in bullous diseases such as pemphi·
`gus. Unless they become secondarily infected, erosions
`~sually do not scar. If inftammation extends into the pap-
`.1ary dermis, an ulcer is present and scaning results, as
`10 ~accinia and variola, and less often in herpes zoster and
`vancella,
`SP~tn.tes and other pyodermatoses. A pustule is a circum-
`Ctibed
`· d
`ig
`'ratse lesion that contains a purulent exudate (F .
`4.10
`deb ).' Pus, composed of leukocytes with or witbout cellular
`ns, may contain bacteri.a or may be sterile, as in the
`
`Exh. 1056
`
`

`
`. 1 h)'drolase by polymorphonuclear leukocytes is a11 t ...
`d
`d
`.
`·[lf'l'lll
`I
`~. 001rs ant~body _epen ent [44]. There is other evidence
`tn the Immune response as demonstrated by
`. ·hange
`oi c
`. .
`.
`t) P
`. . acnes InJecttons in patients with
`tncreased re s po~ e .l
`[45 461 110 111crease m thc lymphocyte transfor111at'
`ton
`·
`•
`.1cnc
`.
`.
`·
`: fter exposure to P. acnes anttgens m patients with severe
`ol dtdocystic acne [47], and an increase in leukocyte mi-
`t p
`.
`.
`(10
`. acnes m pat1ents with severc
`(TJ"-l tion' upon exposure o
`;c,ne [48).
`.
`.
`.
`Androgemc st11nulat10n at puberty induces sebaceous
`l!lnnd development, as already indicaled, and it has been
`~roposed that acne results from hormonal imbalances be-
`~wecn androgens and. estrogens with an increase in the
`androgen/estrogen ratJo. Most of the data to support such
`a contention are based on studies using lcss accurate ste-
`roid measurements. Plasma and urinary testosterone Ieveis
`have been reportcd to bc normal in bolh men [ 49-51] and
`womcn [52] with acne. However, there are now several
`reports o[ cndocrinologic changes in patients with acne.
`These are as follows: (1) it has been shown that during
`early puberal development, plasma testosterone levels are
`higher in those with acne (53]; (2) it has also been shown
`rhat urinary androgen metabolites are increased in young
`children if acne is present [54]: (3) in female patients with
`acne. it has been shown that there may be increased pe-
`ripheral tissue conversion of testosterone to androstene-
`diol, and this is presumed to have occurred in the skin
`[52]; (4) direct incubation of skin from men and women
`with acne indicates that there is an increase in the meta·
`bolic conversion of testosterone to dihydrotestosterone,
`and the increase is far in excess of that which could occur
`from an increase in the volume of sebaceous tissue [55];
`(5) in a small group of older women with recalcitrant acne,
`a partial t 1- or 21-hydroxylase block has been demon-
`strated [56,57] (the detection ofthisbleck was made easier
`by the use of a 24-h ACTH infusion); and (6) there are
`ne\.v studies that have demonstrated an increase in various
`androgen blood level.s in men and women [50,51,53,58-63].
`These studies have been summarized [64], and include
`eievatians of total plasma testosterone in men [53] and
`women (51 ,58,60,61 ,63], of free tcstosterone in womcn
`[60], of u4-androstenedione in women [58], of dehydro-
`epiandrosteronc in women [59,62], of dehydroepiandros-
`terone sulfate in men [63] and women [62,63], and free
`17ß-hydroxysteroids in women [50]. Still, there are other
`studies that report normal values for all of these androgens.
`As the signifkance of all these endocrinologic abnormali-
`lies becomes clear in the next few years, there may be
`changes in the therapy of acne.
`Acne also may be aggravated by the administration of
`hormones such as testosterone, anabolic agents, gonado-
`tropins, corticosteroids, and ACTH. In addition, these lat-
`ter two agents are the cause of steroid acne, an entity to
`be described tater. Because of the influence of hormones
`on acne and the information given above, the sudden
`appeara~ce of acne. in an adult should alert the physician
`to the possibility of an underlying disorder of the pitui~ary­
`gonadal or pituitary-adrenal axis. Furthermore, emotmnal
`8tress may aggravate acne. While no definite evidence ex-
`ists to show that such stress increases sebaceous gland
`activity, the pituitary-adrenal axis may be involved, since
`~t has becn shown that patients with acne have ~ great~r
`tncrease in urina1-y glucocorticoid Ievels after corttcotropm
`administration than that seen in normal persons [65].
`
`(67) Sebaceous glands
`
`669
`
`Clinical manifestations
`
`The primary site of acne is the face, and to a \es er degree
`the back, ehest , and shoulders . On the trunk , \esion, tend
`to be numerous nenr the midline. The diseasc is charac-
`terized by a great variety of clinical lesions. \Vhile one
`type of Jesion may be predominant , close observation u 'U·
`ally reveals several type · of lesions (Fig. 67-3). Thc lesion
`may be either noninflammatorv or inftammatory. The non-
`inflamrnatory lesions are co~edones (Fig. 67-4). These
`mny be either open (bJackheads) or c!osed (whitehcads) .
`The open cornedo appears as a flat or slighrly raised lesion
`with a central follicul ar impaction of keratin and Iipid. The
`brown or black color is not the result of accurnulation of
`dirt nor duc to the compaction of the keratinaus material
`at the follicular orilke. There is evidence that (here are
`melanocytes at the follicular orifice and the pigment of the
`blackheacl has been identified as melanin [66-681. The
`closed comcdones , in contrast to the open comedones.
`may he diflicult to vi.sualize. They appear as pale , slightly
`elevated, small papules. They do not have a c!inically
`visible orifice. Stretching of the skin is an aid in detecting
`the lesions. Since the closcd comedones are the precursors
`for the !arge inO(unmatory lesions , they are of considerablc
`clinical importance. Comedones are the primary lcsions of
`acne, but they are not unique in this diseasc since thcy
`may be seenunder other conclltions (e.g. , so-called senile
`comcdones which are common. particularly in thc perior-
`bital arca of older persons; comedones wbich are seen in
`the a.trophic skin resulting from x~ra y therapy) .
`The intlammatory lesions vary from -mall papttles with
`an inflammatory areola to pustulcs to !arge tendcr nuctuant
`nodules and cysts (Figs. 67- 5 and Al-l). Allthese lesions
`show an inflammatory infiltrate in the dermis, <tnd their
`clinical appearancc depends on the size und locution of
`this infiltrate.
`In addition to the above-described lesions, patients may
`have varying-sized cysts and scar". The charactcristic scar
`of acne is a sharply punched-oul pit. These are ordinarily
`single, but where int1ammation has been marked, Lhe pits
`may have multip1e openi.ngs. Less commonly, broader pits
`may occur and in rare instances, especially on the. trunk,
`the scars may be hypertrophic .
`It has been mentioned that seborrheic dermatitis is com-
`monly seen in association with acnc, but there does not
`appear tobe nny reJation between these two disea:es .
`
`Laboratory findings
`
`Many laboratory studies have been done in the pas(, but
`in general the findings have not been significant. More
`details on sebum, microbiologic and hormonal changes
`have been mentioned in the section on '' Etio\ogy and
`Pathogenesis" above. X-ray studies in a few inslances
`have demonstrat.ed locaJized calcit1m deposits in areas of
`severe scarring (69].
`
`Pathology
`
`As already stated, acne deveJops in the sebaceous follicles,
`and the primary lesion is the comedo. Comedo develop-
`ment starts in the midportion of the follicle as an cxpanding
`mass of lipid~impregnated keratinaus matetial, restJ!ting in
`thinning and ballooning-out of the follicular wall . Grad.u-
`
`Exh. 1056
`
`

`
`1
`
`•
`
`•
`
`•. 1110re common in males (Fig. 67-IS) T
`Rh . phymu JS
`• h
`. af the nose is invo]ved first. There is irre
`e
`10°
`Jowcr portwn_ h sk1·0 and the follicular orifices argular
`·
`·
`ot t e
`'
`.
`.
`e e
`thJckentng
`r of the kin. wh1ch 1s not uniform v . n.
`d The co o
`• ane
`1
`!arge · .
`t red to purplish red. The amount of thickenin s
`fro1:1 bngdh . sc>me instances , the adjacent portians o[ thg
`. ,s an
`e
`II
`111 •
`•
`lved Rhinophyma JS usua y seen in se
`vatit;
`'.
`h, ks are mvo
`·
`.
`vere
`c t:e '
`1ay occur as the only manifestation of th
`rasacea but n
`e
`f
`A
`·
`disease.
`vanety o ocular les1·0
`S[c '\L FINDfNGS.
`ns
`OTHER PHY ~
`11y ros 8cea [146, 147]. Blephant1s, canjunct1•
`.
`m'lY accornpa
`··
`. .
`v.
`. 1. ··t·s iritis and kerat1t1s have all been seen Th
`'
`e
`itis e pt SC Cl I I ,
`'
`.
`.
`·
`. tJ·ents studied wtll mfluence the observed inc·
`' ·
`f
`group o pa
`'
`.
`1-
`f these eye changes. Thus, m 134 rosacea patient
`dence o
`.
`s
`4
`in a generat hospital, there were
`cases. With ocular le.
`· cantrast 99 of 104 rosacea patJents seen in a
`.
`SIOO S : JJ1
`'
`.
`. •
`0
`eye hospital had ocuJar les.tons [146]. BlephantJs and con.
`junctivitis are most common, and the ~ormer may reftect
`the concurrent appearance. of seborr~eJc d~rmatitis. Ker-
`. t'tis while less common, JS more senous smce ulceration
`f
`d. I
`,
`.
`,
`and ultimate jmpairment of vtston o ten occurs. The ocular
`iesions are chronic and frequently progressive. In one-fifth
`of Borrie's [146] cases, the ocular lesions preceded the
`cutaneous lesions by periods of up to 30 years. While many
`theories have bcen proposed for the relation between the
`ocular and cutaneous lesions, none of these is proved.
`
`d related d1sorders
`Disorders of epidermal appendages an
`
`680
`
`Laboratory findings. Achtorhydria is of no significance,
`since it is seen in just as many normal persans of similar
`age. Nevertheless , various gastrointestinal complaints
`have been reported in rosacea patients. Furthermore, on
`gastroscopy. either atrophic, hypertrophic, or superficial
`gastritis has been found in most rosacea patients. Usher
`[148] found gastritis in 18 of 19 patients, and Conrad et al
`[149] observed abnormal stomach patterns in 10 of 12 ro-
`sacea cases. Changes are not restricted to the stomach,
`
`Flg. 67·15 Marked rhlnophyma of nose ln rosacea. The ad·
`jacent portion of the cheeks ls also tnvolved.
`
`Fig. 67·14 Rosacea wlth acneform lesions.
`
`in women, but more severe involvement is found in the
`male. Blacks are rarely involved.
`
`Etiology and pathogenesis. There is no adequate explana-
`tion for the vascular dilatation. The affected skin shows a
`normal response to chemomediators such as epinephrine,
`norepinephri.ne, acetylcholine, and histamine [ 141] and
`there is no evidence of vascular instability after local cool-
`ing of the skin [142].
`It has been proposed that this disease is related to the
`presence of the mite, Demodex folliculorum. Since this is
`a normal follicular inhabitant, and since the topical appli-
`cation of sulfur ointment will improve rosacea without
`affecting the mite population [143], the etiologic impor-
`tance of this parasite in the disease process is doubtful.
`The same may be said for many other constitutional factors
`such as focal infection, vitamin deficiencies, and endocrine
`abnormalities. Psychogenic stress also has been mentioned
`a.s an etiologic factor, although this has not been proved in
`a controlJed study.
`The acneform component, which i.s not always present,
`is similar to acne vulgaris. While these patients have a
`prominent poral pattern, suggesting the presence of large
`sebaceous glands, sebum secretion is not elevated [144].
`However, this has been measured on the forehead, and not
`at .the site of the disease, so local enlargement still may
`extst.
`
`Clinical manffestations. CUTANEOUS LESIONS. The onset of
`rosacea (Fig. Al-2) is insidious; most patients cannot state
`when it actually started. Initially, there is transient vascular
`dilatation with varyi.ng erythema. Primary involvement oc-
`curs over the blush area of the cheeks and nose. The chin
`and. central P?rtion or. the fo~ehea~ also may be involved.
`"Yhlle the les10ns are mtermtttent mitially, eventually per-
`ststent erythema accompanied by telangiectasia appears.
`The areas of erythema blanch on diascopy In certa' ·
`.
`.
`·
`m m-
`s~ances, only telangtectasta appears. The predominant le-
`stons. are papules and pustu1es (Fig. 67_14), althou h in
`rare mstances, nodules also may appeor ln
`g
`•
`cantrast to
`1
`acne vu gans, comedones are rare. Granulomatous Ia ues
`may be seen. These result from a merging of the . : ~
`lesions [145]. This form of the dfsease is ve
`tn tvt ual
`. ry rare.
`.
`
`ljW. •
`
`Exh. 1056