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nologic marker for Langerhans cells. N Engl J Med 304:791-792, 1981. 25. Harrist TJ, Bhan AK, Murphy CF, et al: Histiocytosis X: In situ characterization of cutaneous lesions. J Invest Dermatol 78:354-355A, 1982. 26. OvertonJ: The fate of desmosomes in trypsinized tissue. J Exp Zool 168:203-206, 1968.

27. Caputo R, Gianotti F: Junctions between histiocytes: Role of coated vesicles. J Ultrastruct Res 68:256-264, 1979. 28. Caputo R, Gianotti F: Cytoplasmic markers and ultrastructural features in histiocytic proliferations of the skin. G Ital Derm Venereol 115:107-120, 1980.

Porokeratosis plantaris palmaris et disseminata James C. Shaw, M . D . , * and Clifton R. White, Jr., M.D.*,** Portland, OR Porokeratosis plantaris palmaris et disseminata (PPPD) is a rare variant of porokeratosis. We report a second kinship with PPPD that typically appears first on the palms and soles and then gradually progresses to the extremities and trunk. We discuss clinical, histologic, pathogenetic, and therapeutic aspects of PPPD and review the literature concerning the histogenesis of comoid lamella formation. (J AM ACAD DERMATOL 11:454-460, 1984.)

Porokeratosis plantaris palmaris et disseminata (PPPD), one of several distinct variants of porokeratosis, exhibits a unique clinical presentation and biologic behavior. Unlike other types of porokeratosis, lesions o f PPPD typically first appear on palms and soles of patients in their early twenties. Gradually and insidiously, the eruption spreads until virtually the entire trunk and extremities are involved. The previous description o f PPPD by Guss et al! in 1971 reported eight affected members from four generations of a family. Although their report established PPPD as a distinct entity, there have been no subsequent reports o f similarly affected families. We present a second family with PPPD, discuss its clinical and histologic aspects, and review the From the Departmentof Dermatology,* Oregon Health Sciences University, and the Dermatology Service,** Portland Veterans AdministrationMedical Center. Accepted for publicationFeb. 16, 1984. Reprint requests to: Dr. James C. Shaw, Departmentof Dermatology, OregonHealthSciences University,3181 S.W. Sam Jackson Park Rd., Portland,OR 97201. 454

literature concerning the enigmatic histogenesis of cornoid lamellae. CASE REPORT A 57-year-old white man presented to the dermatology clinic in October, 1982, with a 35-year history of multiple dry, hyperkeratotic lesions on his palms, soles, extremities, and trunk. The lesions had been present since his early twenties. They had begun on the palms and soles but had gradually progressed to involve the arms, legs, and chest. Dryness and moderate pruritus during the summer months, his only symptoms, had been present for only 5 to 10 years. He had lived in Oregon his entire life, where he worked in farming. His general health had been excellent. A family history revealed that the patient's deceased mother had had similar lesions on her hands and feet since before she was 40 years old. It is of interest that the patient's mother was reported 20 years ago by Saunders, 2 some 10 years before PPPD was characterized. The patient's sister (37 years old), son (23 years), and daughter (21 years) were not affected.* Examination revealed markedly hyperkeratotic dis*Daughterexamined;son and sister contacted.

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Fig. 1. A, Lesions of porokeratosis on pahn. B, Close-up view showing furrow in peripheral borders. crete papules and plaques on the palms and fingers and annular hyperkeratotic lesions on the proximal palms, soles, ankles, extremities, and chest (Figs. 1 to 3). The lesions measured 0.5-1.0 cm and demonstrated a hyperkeratotic ridge at the border. Many acral lesions showed a furrow within the hyperkeratotic ridge (Figs. 1, B, and 2, B). The face and mucous membranes were not involved, and the remainder of the examination had normal results. Histologic findings. Biopsy specimens were taken from three lesions, two from the hand (Figs. 4-7) and one from the anterior chest (Figs. 8 and 9). All showed characteristic changes of pomkeratosis, including cornoid lamellae composed of columns of parakeratosis overlying a slight " d e l l " in the epidermis, beneath which the granular layer was thinned to absent, with a f e w surrounding dyskeratotic keratinocytes. In addition, the two palmm" lesions (Figs. 4 to 7) showed prominent hyperkeratosis surrounding the eomoid larnellae, as would be expected from the clinical appearance of the lesions. Two of the biopsy specimens (Figs. 6-9) had multiple cornoid lamellae in one punch biopsy. In one of the palmar biopsy specimens (Figs. 4 and 5), the cornoid lamella was not associated with an adnexal structure. The second palmar lesion (Figs. 6 and 7) had two lamellae, one of which surmounted an obvious eccrine acrosyringium, but the other did not do so. In the chest biopsy specimen (Figs. 8 and 9), both cornoid lamellae emerged from infundibula of hair follicles. Thus the full histologic spectrum of cornoid la-

mellation was present in the three biopsy specimens-comoid lamellae associated with eccrine acrosyringia, with follicular infundibula, and with nonadnexal epidermis. Treatment was limited to a trial of retinoic acid (Retin-A) gel, 0.025%, applied daily to the left arm only. Examination in 2 months showed no significant improvement on the treated arm but some reduction in the hyperkeratotic palmar lesions, which the patient attributed to "not Working so hard." For the past 8 months he has had some symptomatic improvement with the use of emollient creams. DISCUSSION PPPD is one of a group of diseases known collectively as porokeratosis. The number of distinct variants in this group has increased to at least five since Mibelli described the solitary form in 1893. Chernosky and Freeman 3 characterized disseminated superficial actinic porokeratosis (DSAP) in 1967, and PPPD was described in 197! by Guss et al. 1 Since then, linear porokeratosis 4 and a punctate porokeratosis 5 have been described. PPPD is a genoderrnatosis that usually appears first in the patient's late teens or early twenties. The inheritance pattern is consistent with an autosomal dominant mode of transmission. Our patient's children were not affected but may still be too young for the expression of the gene. Lesions in PPPD classically begin on the palms

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Fig. 2. A, Porokeratotic lesions on ankle. B, Close-up view showing furrow in hyperkeratotic borders.

Journal of the American Academyof Dermatology

Fig. 3. A, Porokeratotic lesions of chest. B, Close-up view demonstrating fine hyperkeratotic borders.

Fig. 4. One of two palmar biopsy specimens showing hyperkeratosis surrounding prominent cornoid lamella situated in typical epidermal "dell." (Original magnification, x 100.)

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Fig. 5. Higher-power view of Fig. 4, demonstrating detail at base of cornoid lamella, including decreased granular layer and a few scattered dyskeratotic keratinocytes. (Original magnification, ×250.)

or soles and, over several years, gradually spread to involve the arms, legs, and trunk. Individual lesions are usually less than 1.0 cm in diameter and demonstrate a typical elevated margin. Although the original report characterizes the lesions as lacking a furrow at the peripheral border, t many o f our patient's pahnar lesions demonstrated the classic " d i k e , " or furrow, as seen in the Mibelli type (Figs. 1, B, and 2, B). Xerosis and slight hyperpigmentation in the lesions are common. The clinical course of the lesions is persistent, slow progression throughout the life of the patient. Symptoms are variable and can include itching, pain, and dryness. Guss et al ~ reported symptoms in only three of their eight patients. Our patient complained of mild dryness and pruritus in the summer. At first glance the disseminated array of lesions in PPPD could easily be misdiagnosed as DSAP. However, several unique clinical and historical features distinguish the two types of pomkeratosis. First, involvement of the palms and soles does not occur in DSAP. Second, lesions of PPPD have no predilection for areas subjected to prolonged sun exposure, whereas those in DSAP characteristically appear on the exposed arms and lower legs. Finally, the age of onset in PPPD is earlier

Fig. 6. Second palmar biopsy specimen, in this case with two closely situated cornoid lamellae, one (left) overlying intraepidermal portion of ecerine duct. (Original magnification, × 25.)

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Fig. 7. Higher-power view of Fig. 6, showing eccrine acrosyringium, tier of parakeratosis,

diminished granular layer, and dyskeratotic keratinocytes (pale-staining cells), (Original magnification, x 250.)

i iiii~?i ~ ~ 15(~

Fig. 8. Low-power view of chest biopsy specimen. Note presence, again, of two cornoid lamellae at either end of specimen, in this case both situated within follicular infundibula. (Original magnification, x 25.) than in DSAP, which typically begins in the third or fourth decade. Numerous treatments have been attempted for all types of porokeratosis, but the results generally have been poor." For solitary lesions, primary excision or deep dermal destruction with subsequent reepithelialization or scarring is effective. One method utilized to achieve the latter has been aggressive use of topical 5-fluorouracil under occlu-

sion. 7 For the disseminated types of porokeratosis, the only promising therapy has been the use of aromatic retinoid Ro 10-9359 (etretinate). Karinimi et ats treated a patient with DSAP with 100 rag/day for 10 days with a good initial response. The dosage was then lowered to 50 mg/day for 40 days and then to 25 mg/day for 2 months. At that time, repeat biopsy still showed small, shallow cornoid lamellae. A maintenance dose of 25 mg

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e v e r y other day was continued. Bundino and Zina9 treated two patients with widespread porokeratosis o f Mibelli with Ro 10-9359, 75 mg/day for 10 days, 50 mg/day for 3 weeks, and 25 rag/day as a maintenance dose until treatment was stopped. T h e responses were considered good, but both patients relapsed 3 to 4 weeks after treatment was stopped. Similar results have been reported in a c a s e o f linear porokeratosis treated with Ro 109359. ~° Thus, although Ro 10-9359 may be helpful in disseminated types of porokeratosis, responses are i n c o m p l e t e and lesions recur when the medication :is stopped. Aromatic retinoids have not yet been u s e d for PPPD. HISTOGENESIS

The cause of the lesions of PPPD and other types of porokeratosis is not clear. Although several theories exist concerning the origin of cornoid lamellae, confirmation and agreement are lacking. Mibelli's concept, that solitary lesions were the result of a disturbance in the acrosyringia of eccrine sweat ducts, led to his designation "porok e r a t o s i s . " This view was supported by Saunders in 1961. 2 He showed that the cornoid lamellae in his two patients had granules with staining characteristics identical to keratohyaline granules and proposed that they represented the keratohyaline granules o f eccrine sweat units. An opposing viewpoint was offered by Chernosky and Freem a n , a who studied 13 patients with DSAP and f o u n d the granules to contain deoxyribonucleic acid, ribonucleic acid, and diastase-resistant material positive to periodic acid-Schiff staining, all e x p e c t e d components of parakeratotic nuclei. F u r t h e r evidence against the eccrine sweat duct o r i g i n of porokeratosis is the frequent finding of c o r n o i d lamellae within hair folficles and epidermis independent of adnexae. Another view, proposed by Reed and Leone l~ in 1970, is that porokeratosis results from a mutant c l o n e of epidermal cells that, in a fashion similar to that of actinic keratoses, arises either without apparent cause as in the Mibelli type, or following actinic exposure in those patients with the genetic predisposition, as in DSAP. According to this t h e o r y , the cornoid lamella represents the border

Fig. 9. Higher-power view of Fig. 8, showing lamella

on right side emerging from deep within infundibulum and traversing entire follicular orifice to emerge on epidermal surface. Note hair shaft cut in cross section. between the expanding clone of abnormal cells and normal epidermis. The fact that ultraviolet B irradiation can induce new lesions of DSAP lends some support to this theory. 12 However, since most of the patients in the study by Reed and Leone 11 had lesions consistent with DSAP, this "clone hypothesis," if shown to be true, may apply only to that variant. At present, there are no specific markers to identify such clones. A more recent theory presented by Wade and Ackerman 13 in 1980 is that cornoid lamellation is a morphologic expression of disordered epithelial metabolism. As such, this epithelial "reaction pattern" is analogous to focal acantholytic dyskeratosis, epidermolytic hyperkeratosis, and follicular mucinosis. Their view is based on the observation of comoid lamellae in a variety of inflammatory and neoplastic processes, including actinic keratoses, basal cell carcinomas, and seborrheic keratoses. Other investigators have recently de-

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scribed cornoid lamellae in two possibly related congenital disorders: (1) the porokeratotic eccrine ostial and dermal duct nevus 14 and (2) the porokeratotic eccrine duct and hair follicle nevus.15 In summary, cornoid lamellation is present in all cases of porokeratosis, where it is frequently associated with eccrine ducts or hair follicles. It can occasionally be seen as an isolated finding in a variety of seemingly unrelated acquired and congenital skin lesions. The stimulus for this abnormal epidermal expression remains unknown. The presence of a dermal infiltrate, as well as the fact that nearly full-thickness dermal destruction is required to prevent recurrence, suggests that the abnormality may, in part, be in the dermis.

3. 4. 5. 6. 7. 8.

9.

CONCLUSION PPPD is a rare type of porokeratosis with morphologic, genetic, and histologic features typical o f the porokeratoses. The distribution and clinical evolution of this variant allow its clear distinction from other types. The pathophysiologic features of PPPD may be similar to those o f D S A P and the Mibelli forms, with differences in presentation and course because o f genetic o r other factors as yet unidentified.

REFERENCES 1. Guss SB, Osbourn RA, Lutzner MA: Porokeratosis plantaris palmaris et disseminata: A third type of porokeratosis. Arch Dermatol 104:366-373, 1971. 2. Saunders TS: Porokeratosis: A disease of epidermal

10. 11.

eccrine-sweat-duct units. Arch Dermatol 84:980-988, 1961. Chemosky ME, Freeman RG: Disseminated superficial actinic porokeratosis (DSAP), Arch Dermatol 96:611624, 1967. Rahbari H, Cordero AA, Mehregan AH: Linear porokeratosis: A distinct clinical variant of porokeratosis of Mibelli. Arch Dermatol 109:526-528, 1974. Herman PS: Punctate porokeratotic keratoderma. Dermatologica 147:206-213, 1973. Hazelrigg DE, Fan'ell WF: Disseminated superficiaI actinic porokeratosis. Cutis 26(1):102-105, 1980. McDonald SG, Peterka ES: Porokeratosis (Mibe[li): Treatment with topicaI 5-fluorouricil. J AM ACAo DERMATOL8: 107-110, 1983. Kariniemi A, Stubb S, Lassus A: Treatment of disseminated superficial actinic porokeratosis with a new aromatic retinoid (RO 10-9359). Br J Dermatol 102:213214, 1980. Bundino S, Zina AM: Disseminated porokeratosis Mibelli treated with RO 10-9359. Dermatologica 160: 328-336, 1980. Pehamberger H, Konrad K: Treatment with an oral aromatic retinoid in linear porokeratosis. Dermatologica 160:270-274, 1980. Reed RJ, Leone P: Porokeratosis: A mutant clonal keratosis of the epidermis. Arch Dermatol 101:340-347,

1970. 12. Chernosky ME, Anderson DE: Disseminated superficial actinic porokeratosis: Clinical studies and experimental production of lesions. Arch Dermatol 99:401-407, 1969, 13. Wade TR, Ackerman AB: Cornoid lamellation: A histologic reaction pattern. Am J Dermatopathol 2:5-15, 198O. 14. Abel E, Read SI: Porokeratotic eccrine ostial and dermal duct naevus. Br J Dermatol 103:435-441, 1980. 15. Coskey RJ, Mehregan AH, Hashimoto K: Porokeratotic eccfine duct and hair follicle nevus. J AM ACADDERraA'roL 6:940-943, 1982.

ABSTRACTS Topical idoxuridine for genital condyioma acuminatum

Hypocalcemia-induced pustular psoriasis of yon Zumbusch

Hamsumi K, Kobayashi T, Ata M: Lancet 1:968, 1984

Stewart AF, Battaglini-Sabetta J, Milstone L: Ann Intern Med 100:677-680, 1984

Idoxuridine ointment 0.25% was used in a study of eleven female patients, age 19 to 32, with widespread condyloma acuminatum in a randomized, double-blind placebo-controlled trial. Condylomas in the six patients treated with idoxuridine ointment cleared, both macroscopically and colposcopically. Three monthfollow-uprevealed no recurrences. In the placebo group, one patient progressed and the other four showed no change.

A patignt who had hypocalcemia-precipitated pustular psoriasis of yon Zumbusch with surgical hypoparathyroidism is reported. The patient cleared on two occasions when serum calcium levels were brought to normal by therapy with oral calcium and vitamin D or its analogues.

J. G . S.

J.G.S.