|0URNAL0ttI1e
`‘
`Amemcam ACBDEIIIY or
`D€l‘1\/IEITOLOGY
`
`VOLUME 16 NUMBER 2 PART 1
`
`february 1987
`
`CME article‘.
`
`Etretinate therapy
`
`CHARLES N ELLIS M.D., and IOHN 1. VOORHEES, M.D., Ann Arbor, MI
`
`Dr. Reddy’s Laboratories, Ltd., et al.
`v.
`Galderma Laboratories, Inc.
`IPR2015-
`Exhibit 1061
`
`

`
` 5;AT|QURNAL ofjhe
`L
`¥
`” AmeRIcaN Acanemv or
`DerMaToLoGY
`
`VOLUME»16 NUMBER 2 PART 1
`
`-
`
`february 1987
`
`Etretinate therapy
`CHARLES N. ELLIS, M.D., and JOHN]. VOORHI-IEES, M.D., Ann Arbor, ‘MI
`
`CME article‘:
`
`I PUBLISHED BY THE (..\/i MOSBY (?().'\1F'A.‘\'Y
`srmuls; M|SS()lJRI 53:46
`ussm 0190-9622‘ .
`
`fl
`
`'" 01
`
`Exh. 1061
`
`

`
`JOURNAL Of the
`AmeRICaN ACaDemy OF
`DerMaTOLOGY
`
`Copyright © 1987 by the American Academy of Dermatology, Inc.
`
`Editor
`
`J. Graham Smith, Jr., M.D.
`
`Associate Editor
`Donald C. Abele, M.D.
`
`Editorial Office
`Department of Dermatology
`Medical College of Georgia
`Augusta, Georgia 30912-7400
`404-828-4684
`
`Assistant Editors
`Philip C. Anderson, M.D.
`Waiter H. C. Burgdorf, M.D.
`Richard L. Dobso~, M.D.
`John H. Epstein, M.D.
`Stephen I. Katz, M.D.
`W. Clark Lambert, M.D.
`Walter G. Larsen, M.D.
`Alan R. Shalita, M.D.
`John S. Strauss, M.D.
`
`Vol. 16, No. 2, Pan I, February 1987, the Journal
`of the American Academy of Dennatology (ISSN
`0190-9622) is published monthly by The C. V. Mosby
`~ompany, 11830 Westline Industrial Dr., St. Louis,
`, .. o 63146.
`Annual subscription rates: $57.00 for individuals,
`$!04.00 for institutions.
`Second class postage paid at St. Louis, MO, and
`additional mailing offices. Printed in the U.S.A.
`Copyright © 1987 by the American Academy of
`Dermatology, Inc.
`Postmaster: Send address changes to The C. V.
`Mosby Company, 11830 Westline Industrial Dr.,
`St. Louis, MO 63146.
`
`February, Part 1, 1987
`
`Contents February, Part 1, 1987
`
`CONTINUING MEDICAL EDUCATION
`
`Etretinate therapy
`Charles N. Ellis, M.D., and
`John J. Voorhees, M.D.,
`Ann Arbor, MI
`
`CME examination
`
`Answers for CME examination
`(Identification No. 887-101, January 1987
`issue of the JOURNAL OF THE AMERICAN
`ACADEMY OF DERMATOLOGY)
`
`CME examination answer sheet
`
`CLINICAL AND LABORATORY STUDIES
`
`lsotretinoin treatment of pityriasis
`rubra pilaris
`Charles H. Dicken, M.D. , Rochester, MN
`
`Zinc deficiency in two full-term breast-fed
`infants
`Lynne J. Roberts, M.D.,
`Constance F. Shadwick, M.D., and
`Paul R. Bergstresser, M.D., Dallas, TX
`
`Bullous pemphigoid controlled
`by tetracycline
`Carl R. Thomfeldt, M.D., and
`Andrew W. Menkes, M.D.,
`San Diego, CA
`
`Syringoma presenting as milia
`Stephen J. Friedman, Major, MC, USA,
`and David F. Butler, Major, MC, USA,
`El Paso, TX
`
`267
`
`292
`
`294
`
`295
`
`297
`
`301
`
`305
`
`310
`
`Continued on page 7A
`SA
`
`Exh. 1061
`
`

`
`Bullous pemphigoid controlled by tetracycline
`Carl R. Thomfeldt, M.D., and Andrew W. Menkes, M.D. San Diego, CA
`
`Two men with nonscarring, persistent, localized bullous pemphigoid, whose
`eruption is completely controlled with daily doses of oral tetracycline, are
`described. A review of the literature on persistent, localized bullous pemphigoid
`is presented. The effects of tetracycline on leukocytes that may play a role
`in the response of these patients are discussed. (J AM ACAD DERMATOL
`1 987; 16:305-10.)
`
`Bullous pemphigoid is an autoimmune disease
`~~aracter~zed by large, tense, subepidermal bullae.
`ese lesiOns arise on urticarial plaques, erythem-
`atous macules, or normal-appearing skin. They
`coll_lmonly involve flexural areas, especially the
`grom and axillae. 1.2 In contrast to pemphigus, Ni-
`kolsky'
`·
`·
`.
`s Sign IS absent. Nearly 80% of the indi-
`VIduals afflicted are at least 60 years old, and gen-
`erally the severity of the disease increases as the
`age of onset increases. Bullous pemphigoid begins
`at a localized site and rarely remains localized
`throughout its course. 3-5 On the basis of the clinical
`P~~se~ta~ion,_ ~ersis_tent, localized bullous p~m­
`f, gold Is divided mto scarring and nonscamng
`orms. Corticosteroids, systemic and/or topical,
`~e usually employed for the treatment of all types
`? bullous pemphigoid, although in severe cases,
`•m~unosuppressive agents or sulfones are re-
`quired. 2
`6 Recently erythromycin has been suc-
`-
`cessfully used to control this disease, as has a
`combination of tetracycline and niacinamide. 7"8
`CASE REPORTS
`Case 1
`~ 66-year-oJd Filipino man with hypertension and
`angma complained of a pruritic eruption of 10 years '
`duration on the lower part of both legs, which was not
`ass
`·
`·
`oc1ated With pustules, painful lymph nodes, or fever.
`
`From the Division of Dermatology, University of California, San
`Diego, School of Medicine.
`Accepted for publication July 17, 1986.
`
`Re · Pnnt requests to: Dr. Carl Thomfeldt, 1021 S. W. 5th Ave., On-
`tario, OR 97914.
`
`He had received nitroglycerin, isosorbide, and nifedi-
`pine for his cardiovascular illness .
`Physical examination revealed a healthy-appearing
`Oriental man with lesions distributed symmetrically
`over both pretibial surfaces. The lesions consisted of
`multiple hyperpigmented macules, several tense, clear
`vesiculobullae on erythematous and nonerythematous
`skin, and a few brown-black crusts on erythematous
`skin (Fig. 1). There was no fever, inguinal adenopathy,
`or signs of lymphangitis. The white blood cell count,
`differential count, erythrocyte sedimentation rate, fast-
`ing blood sugar level , and urinalysis results were nor-
`mal, and there were no antinuclear antibodies. Biopsy
`of a blister on normal-appearing skin showed a non-
`acantholytic, subepidermal bulla containing a few eo-
`sinophils. There was also a mild papillary dermal and
`perivascular infiltrate consisting of mononuclear cells
`and a few eosinophils (Fig. 2). Direct immunofluores-
`cence was positive for IgG and C3 in a linear pattern
`along the basement membrane zone. No circulating an-
`tibodies were detected by immunofluorescence with
`guinea pig esophagus used as a substrate.
`The eruption was refractory to topical therapy with
`betamethasone valerate and dipropionate, the latter with
`plastic occlusion. A therapeutic trial of oral tetracy-
`cline, 250 mg twice daily for 2 to 3 weeks, cleared all
`the bullae and inflammatory lesions. This therapy was
`discontinued on two occasions, and within 3 weeks the
`bullae and erythematous plaques recurred. Reinstitution
`of oral tetracycline on each occasion resulted in clinical
`remission for over a year on a regimen of only 250 mg
`of tetracycline daily.
`Case 2
`A 48-year-old Mexican American man with a seizure
`disorder was referred for a 5-year history of an inter-
`305
`
`Exh. 1061
`
`

`
`306 Thornfeldt and Menkes
`
`Journal of the
`American Academy of
`Dermatology
`
`Fig. 1. Case 1. Several vesicles, crusts, and hyperpigmented macules on the pretibial
`area.
`
`·~··
`'.......-..
`\
`
`"
`
`mittent pruritic, blistering eruption of the medial aspect
`of the left thigh . The eruption was not associated with
`other cutaneous lesions nor with systemic symptoms.
`It had been refractory to mid- and high-potency topical
`corticosteroids and topical and systemic antimycotic
`agents. The eruption also was refractory to short courses
`of diaminodiphenylsulfone and chloroquine. The pa-
`tient had partial relief of itching and diminished blis-
`tering with 60 mg of prednisone daily for 2 weeks. He
`had initially received phenobarbital and phenytoin for
`his seizure disorder but had switched to carbamazepine
`shortly thereafter because of overt seizure activity.
`Physical examination revealed an obese man with
`multiple tense bullae on erythematous plaques and on
`nonerythematous skin of the proximal medial portion
`of the left thigh and the left crural fold (Fig. 3). Multiple
`striae were present. There were no pustules, fever, or
`lymphadenopathy. Bacterial cultures from the blister
`fluid were negative. A Tzanck smear from the bulla
`base revealed no multinucleated giant cells, and a po-
`tassium hydroxide smear showed no hyphae. The white
`blood cell count, differential count, erythrocyte sedi-
`mentation rate, fasting blood sugar level, and urinalysis
`results were normal. There were no antinuclear anti-
`bodies. Biopsy of a bulla on an erythematous plaque
`showed a nonacantholytic, subepidermal bulla contain-
`ing eosinophils. There was a dense, diffuse papillary
`dermal mixed infiltrate consisting predominantly of
`neutrophils, with many eosinophils and few mononu-
`clear cells (Fig. 4). Direct immunofluorescence was
`positive for linear IgG and C3 along the basement mem-
`
`brane zone. No circulating antibodies were detected by
`immunofluorescence.
`Oral tetracycline, 500 mg twice daily, and predni-
`sone, 60 mg in a single morning dose, produced com-
`plete resolution of the eruption in 3 weeks. Ten weeks
`after tapering off these two agents, the lesions recurred.
`Both this and a later episode completed cleared after 2
`weeks of oral tetracycline, 500 mg three times daily.
`The patient has now been in clinical remission for 9
`months on a regimen of 500 mg of tetracycline in a
`single daily dose.
`
`DISCUSSION
`Only fifty-eight cases of persistent, localized
`bullous pemphigoid have been documented in the
`English-language literature in the past 25 years,
`but the true incidence of this entity may be much
`greater. On initial evaluation of patients with bul-
`lous pemphigoid, 16.5% of patients in one large
`series had lesions localized to a single site. How-
`ever, the lesions on only one fourth of them re-
`mained localized. On the other patients, the lo-
`calized lesions eventually generalized, some even
`14 years after the initial eruption. 4 ·6·9.22 Lesions
`appearing first over areas of traumatized or preex-
`isting skin disease or lesions distributed perium-
`bilically are especially prone to generalization. 3
`Persistent, localized bullous pemphigoid is di-
`vided into Brunsting-Perry pemphigoid, which
`
`Exh. 1061
`
`

`
`Volume 16
`Number 2, Part I
`February 1987
`
`Bullous pemphigoid controlled by tetracycline 307
`
`•
`
`~,
`
`•
`
`" ... ,
`..
`
`Fig. 2. Case 1. Subepidermal bulla containing a few
`eosinophils. ( x 25.)
`
`• • . ' • ~
`.....
`:--
`,
`
`'¥ ..
`
`...
`.#'
`
`Fig. 3. Case 2. Tense vesicle on erythematous plaque
`and tense bulla on nonerythematous skin of the prox-
`imal medial portion of the thigh.
`
`.. . ... ..
`
`scars, and a nonscarring form . Only thirty-nine of
`the fifty-eight reported cases of persistent, local-
`ized bullous pemphigoid provide adequate data to
`draw conclusions as to sex distribution, anatomic
`site, and presence of scarring. Of the well-docu-
`mented cases, two thirds were the Brunsting-Perry
`type; male patients predominated in this group
`3: 1. Also called localized chronic pemphigoid,
`this entity presents with one or several discrete
`erythematous plaques that eventually heal with
`atrophic scars. 5•8•10 Brunsting-Perry pemphigoid
`shares several histologic and immunofluorescent
`characteristics with both generalized bullous pem-
`phigoid and cicatricial pemphigoid, which will be
`noted below. 16-20 A recent report documented the
`coexistence of this entity with generalized bullous
`pemphigoid in one patient.
`The nonscarring form of persistent, localized
`bullous pemphigoid is characterized by recurrent
`crops of multiple pruritic, vesiculobullous, and in-
`flammatory lesions usually localized to the pretib-
`
`/
`
`ial surfaces. They tend to be symmetrical when
`distributed bilaterally and to heal without scarring.
`The lesions commonly resolve with postinflam-
`matory hyperpigmentation. Only two of th~ four-
`teen reported cases with nonscarring persts~e~t,
`localized bullous pemphigoid spared the pretibial
`area. One patient had lesions only on the forear~s
`and periumbilical area; the second had a dyshi-
`11 Re-
`drosiform eruption of the palms and soleS.4
`cently a patient was reported with pretibial .no~­
`scarring persistent, localized bullous pemphigOid
`and concurrent subcomeal pustulosis and mor-
`phea. 2 1 Except for the man with pal~ and s~le
`lesions, all the patients with nonscarrmg pers.ts-
`tent, localized bullous pemphigoid reported pnor
`to
`this communication were postmenopausal
`women. In patients with generalized bullous pem-
`phigoid, both ultraviolet light and scratching are
`known to induce bullae identical to the lesions of
`the disease . 23-25 A relative increase of exposure to
`these insults by women who usually wear skirts
`
`'
`
`Exh. 1061
`
`

`
`308 Thornfeldt and Menkes
`
`4'
`
`Journal of th~
`. A adelllY 0
`Amencan c
`]ogY
`Derrnato
`
`... • •
`
`. sirl'lj]ar
`.
`)ljgold IS
`'d
`pernpbig01 ·
`persistent, localized bullous pernp
`u0us
`1. d bullous
`to that found in genera 1ze
`11· zed bll
`· t nt Joca
`1·near
`' d. d )lad 1
`In two recent series of persiS e
`ses stu te
`.
`rtler!l'
`h basernent
`. ·ve
`pemphigoid, all th1rteen ca
`deposition of IgG and/or C3 at t e
`)lad posttl.
`I
`tWO
`. t!l'
`brane zone.IO·'' However, on y
`nee. 'fbtS
`fluoresce
`·de!ICe
`.
`.
`.
`.
`zOo/o IJICI
`·Jig
`findings on mdtrect trnrnuno
`rr!
`· h th 10-;o to
`.
`Jatl
`cidence correlates wtt
`e
`of c1rcu
`.
`rninatwns
`'d z6
`d
`. .
`of postttve results on ete~ .
`ernphigot ·. cult
`antibodies found in cicatnctal P.
`uailY dtffi
`5
`h.
`id ts us
`case
`Brunsting-Perry pernp Ig?
`teroidS. rwo?O "'be
`.
`rucos
`s.-
`~
`to control with systerntc co
`uJfones.
`nt
`d to s
`·ste
`'
`rring perst ·cal
`have been reported to respon
`· h toP'
`· th nonsca
`.
`skin of ten patients Wl
`.-0ur
`1 red wtt
`id c ea
`)lefl'
`h.
`localized bullous pernp tgo
`rne ot
`)fa-
`su
`presses.
`1 sulfone,
`corticosteroids and wet corn . .
`e~-
`ddtttona
`thOtf
`. h
`.d or rne
`patients required ett er a
`· sterol s,
`.
`ci!l all
`pyridine, systerntc c~ruco
`d rt~tbrornY
`ate to clear the eruptiOn·
`tbe
`.
`J' e an e,;
`· g tO
`Tetracycline, mmocyc 10 '
`. bY bindtn . 11,·bit-
`.
`·
`nthests
`. 1 111
`petiuve Y (0 ... tA)
`block bactena1 protem sy
`·
`thus corn
`· d ~,P
`cJeic act
`..,.,v-
`ribosome 30s subumt,
`t
`tbrowJ
`ibonu
`ing the binding of trans er r r e and erY
`.1 cne-
`to messenger RNA. Tetrac~cht~bt't neutr0P111 also
`are
`b th 1n 1
`.
`·
`cin to a lesser degree, 0
`..,.,vct!l
`and tbUS
`.
`'
`.
`d
`igratwn
`tbrowJ
`motaxts and ran orn rn
` e and erY
`11·velY'
`. .
`M' ocyc m
`pee
`10
`antt-mflammatory.
`t1·0ns, res
`. h
`ncentra
`at moderate and htg co
`
`1.
`
`or dresses may account for the predominance of
`the pretibial site of nonscarring persistent, local-
`ized bullous pemphigoid in female patients.
`The histologic changes in nonscarring persis-
`tent, localized bullous pemphigoid closely resem-
`ble those of generalized bullous pemphigoid. As
`found in our case, in the blisters on nonerythema-
`tous skin, there is a nonacantholytic, subepidermal
`bulla with a rare eosinophil in the cavity associated
`with a mild papillary dermal and perivascular in-
`filtrate or mononuclear cells and a few eosinophils.
`Bullae on erythematous skin of nonscarring per-
`sistent, localized bullous pemphigoid and in the
`plaques of the Brunsting-Perry type have a much
`denser infiltrate usually composed of mononuclear
`cells and eosinophils but sometimes composed
`largely of neutrophils. 25 The scarring form also has
`a significant amount of fibrosis, which is absent
`in all lesions of nonscarring persistent, localized
`bullous pemphigoid but present in cicatricial pem-
`phigoid.8
`In all types of pemphigoid, there is no corre-
`lation between the extent of the skin lesions and
`antibody titers. 3 The immunofluorescent findings
`in both forms of persistent, localized bullous pem-
`phigoid are identical. Contrary to early reports,
`current evidence indicates that the incidence of
`positive findings on direct immunofluorescence in
`
`Exh. 1061
`
`

`
`Volume 16
`Number 2, Part I
`February 1987
`
`Bullous pemphigoid controlled by tetracycline 309
`
`localized bullous pemphigoid, morphea and subcorneal
`pustulosis. Arch Dermatoll981;117:725-7.
`12. MacVicar DN, Graham HJ. Localized chronic pemphi-
`goid: a clinicopathologic histochemical study. Am J Pa-
`thol 1 966;48:52.
`13 . Sparrow GP. Localized pemphigoid. Br J Dermatol
`1976;95(suppl 14):26-8.
`14. Trepanier Y. Localized bullous dermatitis herpetiformis.
`Arch Dermatol 1970;101:98-9.
`15. Weedon D, Robertson E . Localized chronic pemphigoid.
`J Cutan Pathol 1976;3:41-4.
`16. Jacoby WD Jr, Bartholome CW, Ramchand SC, et al.
`Cicatricial pemphigoid (Brunsting-Perry type); case re-
`port of immunofluorescent findings. Arch Dermatol
`1978;1 14:779-8 1.
`17. Nieboer C, Roeleve1d CG, Kalsbeek GL. Localized
`chronic pemphigoid. Dermato1ogica 1978; i 56:24-33.
`18. Graham JH , Mac Vicar DH. Bullous dermatoses. In: Gra-
`ham JF, Johnson WC, Helwig EB, eds. Dermatopath-
`ology. Philadelphia: Harper & Row, 1972:301-22.
`19. Perret WJ. Localized pemphigoid. lnt J Dermatol 1980;
`19:47-8 .
`20. Hanno R, Foster DR, Bean SF. Brunsting-Perry cicatri-
`cial pemphigoid with bullous pemphigoid. 1 AM ACAD
`DERMATOL 1980;3:470-3 .
`21. Levine N, Freilich A , Harland P. Localized pemphigoid
`simulating dyshidrosiform dermatitis. Arch Dermatol
`1979;115:320-1.
`22. Person JR , Rogers RS. Bullous and cicatricial pemphi-
`goid. Mayo Clinic Proc 1977;52:54-66.
`23. Cram DL, Fukuyama K . Immunohistochemistry of ul-
`traviolet-induced pemphigus and pemphigoid lesions.
`Arch Dermatol 1972;106:819-24.
`24. Dahl MGC, Cook LJ. Lesions induced by trauma in
`pemphigoid. Br J Dermatol 1979;101:469-73 .
`25 . Lever WF, Schaumburg-Lever G. Histopathology of the
`skin , 6th ed. Philadelphia: JB Lippincott, 1983: I 14, 116.
`26. Perry HO. Cicatricial pemphigoid . In: Demis DJ, Dobson
`RL, McGuire J, eds. Clinical dermatology. Philadelphia:
`Harper & Row, 1982:3 (sections 6- I 3).
`27 . Esterly NB , Furey NL, Flanagan LE. The effect of an-
`timicrobial agents on leukocyte chemotaxis. J Invest Der-
`matol 1978;70:51-5.
`28 . Plewig G, Schopf E. Anti-inflammatory effects of anti-
`microbial agents: an in vivo study. J Invest Dermatol
`I 975;65:532-6.
`29. Martin RR , Warr GA , Counch RB , et al. Effect of tet-
`racycline on Jeukotaxis. J Infect Dis 1974;129:110-6.
`30. Forsgren A, Schmeling D . Effect of antibiotics on che-
`motaxis of human leukocytes. Antimicrob Agents Che-
`mother I 977; 1 I :580-4.
`31. Banck G , Forsgren A . Antibiotics and suppression of
`lymphocyte function in vitro. Antimicrob Agents Che-
`mother 1979;16:554-60.
`32. Thong TG, Ferrante A. Inhibition of mitogen-induced
`human lymphocyte proliferative responses to tetracycline
`analogues. Clin Exp lmmunol 1979;35:443-6.
`33 . Elewski BE, Lamb BAJ , Sams W Jr, Gammon WR.
`In vivo suppression of neutrophil chemotaxis by systemi-
`cally and topically administered tetracycline. JAM AcAo
`DERMATOL 1983;8:807-12.
`34. Lynch WS , Bergfeld WE. Pyoderma gangrenosum re-
`
`.
`.
`inhibit the
`tetracy r mttogemc response of lymphocytes, but
`been c Ine does not. n-33 These observations have
`confirm d ·
`·
`.
`e m vitro by two cases of mycosis
`fungo·d
`five 1 es that cleared with the use of tetracycline,
`cases of
`sponded to
`. pyod.erma gangrenosum that re-
`Phigoid th mino~yclme, two cases of bullous pem-
`and fo
`at remitted with the use of erythromycin,
`With thur cases of bullous pemphigoid that cleared
`I.
`e use of tetracycline and niacinamide. 7 ·34' 38
`n summ
`scarn
`a~y, the cases of two men with non-
`are ng persistent, localized bullous pemphigoid
`presented
`'T'
`•
`man
`· .tO our knowledge , one IS the first
`Preti~~~orted to have the lesions localized to the
`With ala area. The two men are the first patients
`tion . ny form of bullous pemphigoid whose erup-
`Is com 1 1
`Poss·bl
`PeteY controlled by oral tetracycline,
`clear1
`1 Y because of its effects on polymorphonu-
`cases . eu~ocytes, including eosinophils. These
`locar IndiCate that this antibiotic may be used in
`agen:Zed bullous pemphigoid as a sole therapeutic
`Furth or ~s a systemic corticosteroid-sparing one.
`Pern ~~ tn.als of tetracycline in generalized bullous
`spaligoid may reveal a systemic corticosteroid-
`ng effect.
`~FERENCES
`.
`I
`.
`.
`.
`.d
`h.
`1. Sams W Jr Bull
`ous pemp 1g01 ; IS 1t an 1mmuno og1c
`·
`dis
`2. Do~se? Arch Dermatol 1970; I 02:485-7.
`lous ~~kos AAN, Arnold HL, Odom RB. Chronic ~ul­
`de! h ' sease. In: Andrews' d1seases of the skm. Ph!la-
`3. Sn~da: WB Saunders, 1981 :590.
`Ds Eon IB. Bullous eruptions. In: Rook A , Wilkinson
`B!a~k blmg F!G, eds. Textbook of dermatology. Oxford:
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`B/~0~ lR, Rogers RS, Perry HO. Localized pemphigoid .
`5. Br
`ermatol I 976;95:531-4.
`Ph~~erma~ IM. Skin signs of systemic disease, 2nd ed.
`6. Dow delph1a: WB Saunders, 1981 :498-9.
`De nham TF, Chapel TA. Bullous pemphigoid. Arch
`7 R rmatol 1978·114·1639-42
`· ox B
`'
`·
`·
`in b J , Odom RB , Findlay RF. Erythromycin therapy
`fe t ullous pemphigoid: possible anti-inflammatory ef-
`8. B c s. JAM ACAD DERMATOL 1982;7:504-10.
`ofrunstmg LA, Perry HO. Benign pemphigoid? A report
`ab seven cases with chronic, scarring herpetiform plaques
`SO~ut the head and neck. Arch Dermatol 1957;75:489-
`.
`~~med AR. Bullous pemphigoid: clinical and immu-
`ogic follow-up after successful therapy. Arch Der-
`IO ~~to! 1977;113:1043-6.
`lchel B, Bean SF, Chorzelski T, et a!. Cicatricial
`·
`f~~phigoid of Brunsting-Perry. Arch Dermatol I 977;
`:1403-5.
`Bernstein JE, Medenica M , Soltani K. Coexistence of
`
`9
`
`II.
`
`Exh. 1061
`
`

`
`Thornfeldt and Menkes
`
`Journal of the
`American AcademY of
`DermatologY
`
`sponsive to minocycline hydrochloride. Cutis 1978;
`21 :535-8.
`35. Davies MG , PiperS. Pyoderma gangrenosum: successful
`therapy with minocycline. Clin Exp Dermatol 1980;
`6:219-23.
`36. Shelley WB. Demethylchlortetracycline and griseofulvin
`as examples of specific treatment for mycosis fungoides.
`Br J Dermatol 1981 ; I 04:477 .
`
`d.
`t demethyl-
`37. Thomsen K. Mycosis fungo ides respon mg 0
`1 1981;
`chlortetracycline and griseofulvin. Br J Dermato
`em-
`105:483-4.
`38. Berk MA, Lorincz AL. The treatment ~f bullou~ PDer-
`phigoid with tetracycline and niacinamide . Arc
`matol 1986; 122:670-4.
`
`Syringoma presenting as milia*
`Stephen J. Friedman, Major, MC, USA, and David F. Butler, Major, MC, USA
`El Paso, TX
`
`We present two unrelated patients with numerous infraocular milium-like
`lesions that histologically revealed syringoma with many overlying keratin
`cysts in the papillary dermis. A Fontana-Masson stain revealed no melanin-
`containing cells in the keratin cyst walls, suggesting that they originated
`from eccrine ductal structures. A classification of the clinical variants of
`syringoma is presented. (J AM ACAD DERMATOL 1987; 16:310-4.)
`
`Syringomas are common benign appendageal
`tumors derived from the intraepidermal eccrine
`ducts.t.2 Although sometimes solitary,3 syringo-
`mas usually are multiple and localized, 4
`13 although
`·
`15 Usually the lesions
`they may be generalized. 14
`"
`are small, firm , dermal papules ranging in size
`from a few millimeters to l em . Ordinarily, they
`are flesh-colored but may be in shades of red, tan,
`or brown. Multiple lesions may simulate multiple
`basal cell carcinomas, pigmented nevi, trichoepi-
`theliomas, angiofibromas, cylindromas, and li-
`chen planus- like lesions .Z·7
`14 We found no men-
`•
`tion in the literature of syringoma presenting as
`milium-like lesions. We report two patients with
`multiple clustered infraorbital milium-like lesions
`with typical histologic findings of syringoma.
`
`From the Department of Internal Medicine Dermatology Service,
`William Beaumont Army Medical Center.
`Accepted for publication July 17 , 1986.
`Reprint requests to: Dr. Stephen J. Friedman, Dermatology Service,
`William Beaumont Army Medical Center, El Paso, TX.
`*The opinions or assertions contained herein are the private views
`of the authors and are not to be construed as official or as reflecting
`the views of the Department of Defense.
`310
`
`CASE REPORTS
`Case 1
`h Wi!lia!ll
`A 23-year-old white woman presented tot e Clinic
`Beaumont Army Medical Center Dermatology
`e
`d
`I ppearanc
`.
`m August 1985 complaining of the gra ua a
`r
`'
`.
`d uppe
`of grouped white papules on the lower eyehds .an s were
`aspect of the cheeks for 3 years. The lesiOn
`s
`.
`.
`There wa
`asymptomatic but were of cosmetic concern:
`11 nt
`no history of local trauma. The patient was m excel e
`·
`·1 prob e!ll·
`b .d
`health. No other family members had a s1m1 ar
`glo o1
`.
`.
`.
`.
`fi
`Exammatlon revealed multiple whtte,
`rm,
`er
`papules measuring 1-3 mm in diameter on t~e JoWJ!y
`.
`h k btlatera
`eyelids and upper aspect of the c ee s
`(Fig. 1). No similar lesions were present elsewhere.
`
`Case 2
`t d to the
`f the
`A 20-year-old Latin-American man pres.e~ e
`dermatology clinic in April 1986, cqmplmmng 0
`the
`gradual appearance of grouped white papules on
`f 3 years.
`lower eyelids and upper aspect of the cheeks or
`.
`.
`f osmeuc
`The lesions were asymptomatic but were 0 c
`The
`concern. There was no history of local trauma.
`·1 mern-
`patient was in excellent health. No other famt Y
`.
`bers had a similar problem.
`.
`fi Jll ,
`Physical examination revealed multiple white,
`r h
`globoid papules measuring 1-3 mm in diameter on t e
`
`Exh. 1061