Disseminated and hyperlrophic porokeratosis Case reporl POROKERATOSIS HYPERTROPHICA ET DISSEMINATA J. Miljkovič, M. Berčič and R. Kavalar ABSTRACT We report on a 54-year-old man with an unusual variant of porokeratosis that has been confirmed histologically. Nearly the whole skin surface was involved. On the heels and on the low extremities there were lesions of porokeratosis Mibelli of hypertrophic type with bizarre polycyclic configuration. On the upper extremities and on the trunk the skin lesions resembled an exaggerated variant of disseminated actinic porokeratosis. The lesions on the face were typical of the common type of the latter. Patient 's father and elder brother have the same lesions but less pronounced. A systemic etretinate therapy during a period or 5 months was relatively successful. Because of the unusual clinical pattern the possibility of a new variant of porokeratosis is discussed. KEY WORDS porokeratosis Mibelli, hypertrophic and disseminated variant, systemic, etretinate therapy INTRODUCTION Porokeratosis was first described by Mibelli in 1893 (1). It is an inherited disorder of the skin, characterized by solitary or multiple lesions with hypertrophic border and an atrophic centre, most commonly located on the extremities. The cause of the disease is unknown. Reed and Leone in 1970 suggested that abnormal clones of keratinocytes are responsible for the development of porokeratotic lesions (2). Porokeratosis is probably an autosomal dominant condition with variable penetrance, where the acta dennatovenerologica A.P.A. Vol 4, 95, No 1 predisposition to it is inherited but the predisposition to the type of porokeratosic lesions may be not. What determines the type of morphologic expression of the disease is not yet clarified (2). A wide variety of clinical manifestations include small ring-like lesions, hypertrophic verrucous lesions, then lesions of the superficial disseminated type, lesions in zosteriform distribution, lesions occurring over the buccal mucosa and finally linear lesions that resemble linear verrucous epidermal n~vus (3,4,5,6,). Development of squamous celi carcinoma or of Bowen's disease within features of porokeratosis had been reported in patients with solitary, disse- 21 Disseminated and hypertrophic porokeratosis Fig. l. Porokeratosis Mibelli. Verrucous hypertrophic reddish-brown plaques on the calf minated and linear lesions (7,3,9,10) . Cornoid lamellae formation is a consistent histopathologic finding of any type of porokeratosis (11). CASE REPORT A 54-year-old man was admitted to our department for evaluation of skin lesions that appeared at the age of 12. The first lesion developed on the left heel representing a verrucous papule that gradually transformed into a thick hyperkeratotic plaque of some centimeters in diameter. In subsequent years new similar lesions constantly developed on the other heel, on the feet, on the extensor sides of the extremities and later on also on the trunk and the face. Some of the lesions were large firm plaques, others were arranged as grouped fiat verrucous papules. Changes once manifested never disappeared. Because of hyperkeratotic plaques on the heels the patient had difficulties walking, but no other subjective symptoms. He therefore never applied any ointments or other therapy. Patient's father and elder brother have 22 Fig. 2. Atrophic macules with red, slightly elevated keratotic rim, resembling disseminated superficial actinic porokeratosis. Fig. 3. Acanthotic epidennis with severa! parakeratotic plugs in epidennal invaginations. HE 1 0x4 Fig. 4. Higher magnification of f eatures in fig. 3 showing the comoid lamella. HE lOxl 6 acta dennatovenerologica A.P.A. Vol 4, 95, No 1 Disseminated and hypertrophic porokeratosis Table I. Pedigree of tbe patient witb porokeratosis III • affected similar, but less pronounced skin lesions. Tbe 32- year-old patient's son bas no skin lesions (Pedigree - Tab. I). Except for skin lesions tbe patient bad tuberculosis of the left bip-joint at tbe age of 7. Since tben be is limping. Later on be got diabetes. CLINICAL SYMPTOMS On admission in June 1994 skin lesions of an extraordinary variegated pattern were found. Nearly tbe wbole skin surface was involved. On botb beels well demarcated verrucous lesions witb severa! centimeters tbick, crateriform borny masses were present. On tbe dorsa of tbe feet and on tbe extensor sides of the lower extremities tbere wbere numerous reddisb-brown plaques of different size from 1 to 10 centimeters in diameter and more (Fig. 1) Tbe borders of the plaques were elevated and byperkeratotic, tbe centre of tbe lesions was sligbtly atropbic. A confluence or some plaques into large areas witb polycyclic shape was evident. On botb tbighs and on tbe extensor sides on the upper extremities tbere were also numerous sucb lesions, but less verrucous. These lesions sbowed sligbt atropbic macules witb a brigbt-red, only slightly elevated keratotic rim (Fig. 2). Similar lesions were also present on tbe trunk. On tbe face, in tbe frontal regions and on tbe cbeeks tbere were very fiat atrophic macules resembling disseminated superficial actinic porokeratosis. Palms and soles were not involved. Histopathology sbowed an irregular acantbotic epidermis witb enormous ortbokeratosis intermingled witb parakeratosis. In some deep invaginations of tbe epidermis tbere were typical cornoid lamellae. acta dermatovenerologica A.P.A. Vol 4, 95, No 1 DO non-affected Beneatb tbe cornoid lamellae tbe stratum granulosum was absent. In tbe papillary dermis a sligbt perivascular lympbohistiocytic infiltrate was noted (Fig. 3 and 4). Routine laboratory finding were normal. A systemic etretinate tberapy and keratolytics were administered. Tbe dose of 75 mg etretinate daily was given for one montb; then tbe dose was reduced to 50 mg daily during tbe next 5 montbs. Tbe effect of this therapy was relatively good; ali lesions flattened. DISCUSSION In recent years severa! clinical manifestations of porokeratosis have been described and some classi- fication scbemes bave been suggested (12,13,14). The most recent classification was proposed by Kopera et al in 1992. Tbey systemized ali described clinical variants of porokeratosis, mainly characterized by distribution of tbe lesions (15), (Tab. II). Tbe coexistence of two variants of porokeratosis bas been reported in a few cases (16,17). In our case we have observed typical lesions of porokeratosis Mibelli namely bypertropbic verrucous plaques and also lesions of superficial actinic porokeratosis. Our case obviously does not fit into any of tbe proposed classifications. Concerning tbe interpretation of tbis case tbere are tberefore two possibilities. Eitber tbe case is presenting a coexistence of two different variants of porokeratosis or it sbould be considered a new variant of tbe disease. In our opinion, tbe coexistence of different variants of tbe same disease is more probable. So we support tbe view, tbat many areas of tbe skin. can be affected by porokeratosis and tbat tbese areas may express different clinical variants (17). 23 Disseminated and hypertrophic porokeratosis Tab. 2. Types of porokeratosis and their features; cit m (15). AUTHOR TYPE CLINICAL FEATURES LOCALIZATION Mibelli single or few annular limbs, face, 1893 lesions with hyperkeratotic genitalia border and atrophic centre Freund :inear linear configurated small unilateral 1934 papules Rhabari punctate pin-point sized follicular disseminated 1977 keratotic papules Chernosky disseminated multiple uniformly sized sun exposed areas, Freeman superficial (5 mm) lesions with slightly especially extremities 1967 actinic raised border in symmetrical distribution porokeratosis Guss porokeratosis multiple annular lesions with palmoplantar et al. palmaris hyperkeratotic border and 1971 plantaris et central atrophy disseminata Coldner zosteriform multiple annular lesions with corresponding to 1971 hyperkeratotic border and a nervous territory central atrophy McMillan linear with small circular plaques, sharply 1976 giant cornoid rising edges, central keratinous lamella horn Schramm neviform (=syn. for zosteriform) Bork 1982 Strani zoniform ( =syn. for zosteriform) et al. 1983 REFERENCES l. Mibelli V. Contributo allo studio ipercheratosi dei canali sudoripari (porokeratosis). G Ital Mal Ven Pel 1893; 28:313-355. superficial actm1c porokeratosis (DSAP). Arch Dermatol 1967; 96: 611-624. 4. Rhabari H, Cordero AA, Mehregan AH. Linear porokeratosis. Arch Dermatol 1974; 109:526-528. 2. Reed RJ, Leolle P. Porokeratosis: A mutant clonal keratosis of the epidermis. Arch Dermatol 1970; 101; 340-347. 3. Chernosky ME, Freeman RG. Disseminated 24 5. Schramm P, Bork K. Naeviform Porokeratosis- kein distinktes Krankheitsbild, sondern morphologische Variante der Porokeratosis Mibelli. Z Hautkr 1982; acta dermatovenerologica A.P.A. Vol 4, 95, No 1 Disseminated and hypertrophic porokeratosis 57: 963-970. 6. Goldner MR. Zosteriform Porokeratosis of Mibelli, Arch Dermatol 1971; 104:425-426. 7. Gray MH, Smoller BS, McNutt NS. Carcinogenesis in porokeratosis. Evidence for a role relating to chronic growth activation of keratinocytes. Am J Dermatopathol 1991; 13(5): 438-444. 8. Coskey JR, Mehregan A. Bowen's disease associated with porokeratosis of Mibelli. Arch Dermatol 1975; 111: 1480-1481. 9. Brodkin RH, Rickert RR, Fuller FW, Saporito C. Malignant disseminated porokeratosis. Arch Dermatol 1987; 123: 1521-1526. 10. Shrum JR, Cooper PH, Greer KE, et al. Sqamous cell carcinoama in disseminated superficial actinic porokeratosis, J Am Acad Dermatol 1982; 6: 58-62. 11. W ade TR, Ackerman AB. Cornoid lamellation. Am J Dermatopathol 1980; 2: 5-15. 12. Virgili A, Strumia R. Annular hyperkeratosis. Arch Dermatol 1986; 122: 585-590. 13. Walter F Lewer. Histopathology of the skin. 7th ed. Philadelphia: J B Lippincot Company, 1990; 70- 72. 14. Moshella and Hurley. Dermatology /3rd ed./ Philadelphia: W B Saunders Company, 1992: 1406- 1407. 15. Kopera D, Cerroni L, Soyer HP, Hodi S. Porokeratosis linearis. A variant of Iinear epidermal nevus with cornoid Iamellae? Acta Dermatovene- rologica A.P.A 1992; 2;49-53. 16. Guss SB, Osbourn RA, Lutzner MA. Porokeratosis plantaris palmaris et disseminata. A third type of parakeratosis of Mibelli. Arch Dermatol 1971; 104: 366-373. 17. Dover JS, Miller JA, Levene GM. Linear poro- keratosis of Mibelli and DSAP. Clinical and Experimental Dermatology 1986; II 79-83. AUTHORS' ADDRESSES Jovan Miljkovič MD, dermatologist, Dpt. of Dermatology, General Hospital Maribor, Ljubljanska 5, 62000 Maribor, Slovenia Marija Berčič MD, PhD, dermatologist, same address Rajko Kavalar MD, pathologist, Dpt. of Pathology, same address acta dermatovenerologica A.P.A. Vol 4, 95, No 1 25