Dermatology Online Journal

Porokeratosis plantaris, palmaris, et disseminata
Rachael Hartman MD, Rajni Mandal MD, Miguel Sanchez MD, Jennifer A Stein MD PhD
Dermatology Online Journal 16 (11): 22

Department of Dermatology, New York University, New York, New York

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Abstract

We describe a 73-year-old woman with a long-standing history of annular, hyperkeratotic papules that began on the palms and soles and gradually spread to her trunk, extremities, and face. The clinical presentation and biopsy findings were consistent with PPPD, which is a rare subtype of porokeratosis that begins on the palms and soles and gradually spreads to the trunk and extremities. Owing to the risk of malignant degeneration in porokeratosis, patients should be closely monitored with total body skin examinations. There is no definitive treatment for PPPD. Oral retinoids are sometimes helpful although relapses are common after discontinuation of therapy.

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History

Figure 1	Figure 2

Figure 3

A 73-year-old woman was referred to the Disorders of Keratinization Clinic at Bellevue Hospital Center 27 years ago with scaly lesions that began on her soles and progressively spread to her palms, legs, thighs, upper extremities, trunk, neck, and face. Her mucous membranes were spared. The papules on the palms and soles became increasingly hyperkeratotic and confluent into thick plaques. The palmoplantar lesions are painful due to pressure and interfere with ambulation and manual dexterity. Some of the other lesions are pruritic, especially in the summer and on exposure to heat.

The patient has a history of atrial fibrillation that is treated with warfarin, dofetilide, and propranolol. She also has hyperlipidemia that is treated with atorvastatin. After an evaluation of bone density for retinoid-associated osteoporosis, treatment with alendronate was initiated. She has no known allergies to medications or family history of dermatologic diseases. She worked in a factory sewing cases for cosmetic products for more than 20 years although she retired in 2001.

Histopathologic examination of a biopsy speciman from a lesion on her right upper thigh at the time of presentation confirmed the suspected clinical diagnosis. A biopsy specimen obtained in 2002 disclosed the same diagnosis. She was initially treated with isotretinoin 60 to 80 mg daily, which resulted in a decrease in the number of lesions on the body and in the hyperkeratosis of the papules on the palms and soles. In 1985, the medication was changed to etretinate in doses that ranged from 25 to 50 mg and this medication was even more effective in decreasing the number of lesions and the palmoplantar hyperkeratosis. In 1998, after removal of etretinate from the market, acitretin was initiated at a dose of 25 mg daily, with similar clinical efficacy as the parent compound. Attempts to discontinue or decrease systemic retinoids have resulted in pain and pruritus that interfere with her quality of life. Conversely, attempts to increase the dose of acitretin have been limited by both cheilitis and systemic adverse effects, which include blackouts. Numerous adjunctive treatments to diminish hyperkeratosis have been tried; these include salicylic acid 6 percent gel, salicylic acid in 10 to 40 percent concentrations, and urea 20 to 50 percent with and without occlusion. These agents have facilitated debridement of the palms and soles, which has been routinely performed by the patient and periodically in the office. Prolonged treatments with topical imiquimod and fluorouracil neither produced improvement nor prevented formation of new lesions. Topical tretinoin had to be discontinued because of erythema and pruritus. Destructive modalities, which included 90 percent trichloracetic acid, cryotherapy, and electrodesiccation have been successful in treating individual lesions.

Physical examination

Innumerable 2-3 mm, grey, annular papules with well-demarcated, slightly raised, hyperkeratotic borders covered her face, chest, back, abdomen, and extremities. Lesions were present in both sun-exposed and sun-protected areas. On the palms and soles, there were numerous, dicrete, non-punctate lesions as well as a confluence of papules, some with elevated borders. Her mucous membranes were spared.

Laboratory data

A complete blood count with differential analysis and comprehensive metabolic panel were normal.

Histopathology

There is focal thinning of the epidermis, with loss of the granular layer, and a discrete column of parakeratosis.

Comment

Porokeratosis is a clonal disorder of epidermal keratinization, which is characterized by hyperkeratotic papules or plaques that are surrounded by a thread-like elevated border [1, 2, 3]. The histopathologic hallmark of porokeratosis is the cornoid lamella, which is a thin column of parakeratosis that overlies a thin or absent granular layer and that corresponds to the raised, hyperkeratotic border that is observed clinically. The underlying dermis often shows a lymphohistiocytic infiltrate [1].

At least five distinct clinical variants of porokeratosis have been recognized: porokeratosis of Mibelli; disseminated superficial (actinic) porokeratosis (DSP or DSAP); linear porokeratosis; punctate porokeratosis, which may be limited to the palms and soles; and porokeratosis plantaris, palmaris, et disseminata (PPPD) [2, 3, 4]. There are reports of more than one type of porokeratosis developing in the same patient [5].

Our patient’s clinical presentation is most consistent with PPPD, which is a rare variant of porokeratosis that begins on the palms and soles and then subsequently spreads to the trunk and extremities. The acral lesions are usually more keratotic than are the trunk lesions, which are more superficial and morphologically similar to DSAP. Both PPPD and DSAP exhibit numerous, widely disseminated lesions; however, unlike DSAP, PPPD is not limited to sun-exposed areas. In addition, DSAP spares the palms and soles [6, 7, 8]. As is the case in our patient, 25 percent of patients with PPPD report severe pain from plantar keratoses and another 25 percent experience exacerbations of the lesions during the summer [6]. The onset of PPPD is usually in adolescence or early adulthood, although there are reports of cases that begin in the fourth decade, as was the case with our patient [7, 9, 10]. Although some report a male predominance in PPPD, others have found the opposite [6, 7].

The classic lesions of PPPD are annular rather than punctate. However, there have been reports of punctate lesions in PPPD [3]. In fact, in the original description of PPPD described some early punctate lesions that then enlarged centrifugally to form the classic gyrate and annular plaques of PPPD [6]. In contrast, the entity known as punctate porokeratosis describes patients with purely punctate lesions, which may be restricted to the palms and soles. However, there may be some overlap between PPPD and punctate prokeratosis. It has been suggested that punctate porokeratosis may be a forme fruste of PPPD [3].

The etiology of porokeratosis remains unclear. PPPD usually occurs as an autosomal dominant condition although there have been reports of sporadic cases of PPPD, as in our patient who has no family history of PPPD [4, 6, 8, 9]. Sporadic cases may result from spontaneous gene mutations [9]. A locus for PPPD has been identified based on a genotyping performed in a five-generation, Chinese family with autosomal dominant PPPD. The locus was identified within a 6·9-cM region at chromosome 12q24·1-24·2 using polymorphic markers on 12q, which contains the DSAP1 locus on chromosomal region 12q23·2-24·1. Thus, there is an overlap region between the loci for PPPD and DSAP1, which may explain the morphologic similarities of these two variants of porokeratosis [4]. The genetic defect in PPPD may result in abnormal clones of epidermal cells that proliferate spontaneously or in response to triggers, such as immunosuppression or radiation [7]. Porokeratosis has been reported in association with immunosuppression related to systemic diseases (leukemia, human immunodeficiency virus infection, liver disease, diabetes mellitus, Crohn disease, ulcerative colitis, pemphigus vulgaris, pemphigus foliaceus, lupus erythematosus, dermatomyositis, rheumatoid arthritis), organ transplantation (kidney, liver, heart, lung, bone marrow), and medications [11]. However, our patient does not have any known form of immunosuppression.

Malignant degeneration has been reported in all forms of porokeratosis, with a reported incidence of 7.5 to 11 percent [10, 12]. Over-expression of p53 in lesional epidermis may play a role in malignant transformation [13]. In addition, DNA flow cytometry analysis has demonstrated abnormal DNA ploidy in the lesional epidermis of patients with different types of porokeratosis, which includes PPPD and may suggest an increased oncogenic potential [14]. The most commonly associated malignant conditions with porokeratosis are Bowen disease, squamous-cell carcinoma (SCC), and, rarely, basal cell carcinoma. The greatest risk is attributed to large lesions, lesions of long-standing duration, and linear-type lesions [12]. Although more common in other types of porokeratosis, malignant conditions have been reported in PPPD. In the original description of PPPD, one patient developed two SCCs in lesional skin [6]. A case of PPPD has been described in which multiple SCCs arose within lesional sites [15].

There is no definitive treatment for PPPD and treatments generally have been disappointing. Attempts to treat PPPD with topical, systemic, and intralesional glucocorticoids; topical 5-fluorouracil; phototherapy; and keratolytics have yielded only marginal benefits. Surgical modalities, such as cryotherapy, shave excision, curettage, linear excision, and dermabrasion have been used to treat small lesions with variable success, but are often impractical for more disseminated lesions [7]. The use of oral retinoids has yielded conflicting results. Substantial improvement has been reported in a patient with PPPD after three weeks of etretinate therapy. However, others have reported exacerbations of PPPD lesions in patients treated with etretinate [10, 16]. Successful treatment of PPPD with isotretinoin, with marked reduction in the number of lesions and abolition of plantar pain and disability has been reported [7]. A combination of oral retinoids and topical 5-fluorouracil has been beneficial [17]. It has been suggested that oral retinoids may reduce the risk of malignant transformation because the SCCs have occurred after cessation of treatment with etretinate. Relapses are common within weeks to months after cessation of oral retinoid therapy [15].

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