Enhanced dendritic cells and regulatory T cells in the dermis of porokeratosis.

Porokeratosis is characterized clinically by annular lesions and histologically by the presence of a cornoid lamella (CL) in the epidermis. The underlying mechanism of porokeratosis development remains unclear. We performed immunohistochemical staining of CD1a, langerin, Ki67, CD3, CD4, CD8, FOXP3, and RANKL (receptor activator of nuclear factor κB ligand) in samples from 17 porokeratosis lesions and analyzed the differences in staining patterns among the CL, the inner part of the annular ridge (IC), and the adjacent normal skin (ANS). Numbers of CD1a+ Langerhans cells in the epidermis were reduced and numbers of CD1a+ dermal dendritic cells were significantly increased in the CL and IC compared to those in the ANS. In addition, there was also an increase in FOXP3+ cells in the dermis below the CL and IC. Our findings suggest that Langerhans cells are downregulated in the epidermis in CL and that regulatory T cells and dendritic cells are upregulated in the dermis below the CL. This alteration in the distribution of immune cells, such as various lymphocyte subsets, Langerhans cells, and dermal dendritic cells, may play a key role in the pathomechanisms of porokeratosis.

Hyperkeratotic variant of porokeratosis in a patient with Hepatitis C virus infection and a concomitant immunosuppressed state.

Porokeratoses are acquired and hereditary disorders of keratinization that share a distinctive lesion characterized by raised keratotic borders corresponding histologically to an angled column of parakeratotic cells, called a cornoid lamella. Although a precise mechanistic explanation is lacking, ultraviolet radiation and immunosuppressed states are considered causally-associated with most cases of acquired porokeratosis. Hepatitis C virus (HCV) infection has been proposed as a link between the immunosuppressed states and development of acquired porokeratosis. Among the various recognized clinical entities that constitute this group, rare cases of hyperkeratotic variants have been described that may pose a diagnostic challenge. Herein we describe a remarkable case of the hyperkeratotic variant of porokeratosis that occurred in a patient with known HIV and HCV infections and a coexisting therapy-related immunosuppressed state. We also provide a review of the relevant literature.

[Porokeratosis in a patient with dermatomyositis]. / Poroqueratosis en una paciente con dermatomiositis.

There are several reports of porokeratosis in the context of immmunosuppressive diseases. These mainly include organ transplant, HIV infection, lymphomas and some inflammatory and autoimmune diseases commonly treated with immunosuppresive drugs or chemotherapy. Disseminated superficial actinic porokeratosis is the clinical variant of porokeratosis that most frequently develops in immunosuppressive states. We report a case of porokeratosis in a woman with dermatomyositis.

Fatal squamous cell carcinoma arising from transplant-associated porokeratosis.

Porokeratosis is a disorder of epidermal keratinization characterized by variably sized plaques with central depression and a well-demarcated keratotic border. Associations of porokeratosis with immunosuppression and of porokeratosis with malignancy have been observed. The authors report a case of fatal metastatic squamous cell carcinoma arising from porokeratosis in an immunosuppressed patient.

Disseminated epidermolytic acanthoma with disseminated superficial porokeratosis and verruca vulgaris in an immunosuppressed patient.

A 40-year-old man who had received long term immunosuppressive treatment for 14 years following kidney transplantation developed multiple skin lesions on both antecubital fossae, scalp, and both lower extremities. Histopathologic findings from three skin regions revealed characteristic features of epidermolytic hyperkeratosis, verruca vulgaris, and disseminated superficial porokeratosis, respectively. Although immunocompromised individuals may demonstrate verruca vulgaris or porokeratosis, disseminated epidermolytic acanthoma (DEA) has not been reported to be associated with immunosuppressed status. We suggest that immunosuppression may play a role in the pathogenesis of DEA, as shown in our case.

Rapid development of disseminated superficial porokeratosis after transplant induction therapy.

Disseminated superficial actinic porokeratosis (DSAP) is a cutaneous disorder, usually inherited in an autosomal dominant fashion, characterized by numerous annular papules with subtle raised hyperkeratotic borders and slightly atrophic centers. While the precise pathophysiologic mechanisms underlying the development of DSAP are unknown, one hypothesis is multifocal expansion of atypical clones of keratinocytes, perhaps unmasked by actinic damage, as implied by its name. Although primarily of cosmetic concern, there is an increased risk of squamous cell carcinoma of the skin developing within DSAP lesions, which often show histologic keratinocytic atypia centrally. Immunosuppression, which is a significant risk factor for secondary malignancies including cutaneous squamous cell carcinoma, is also a well-documented precipitant of porokeratosis. We report a 62-year-old man who developed DSAP in a widely and rapidly progressive manner within days of receiving total body radiation and high-dose induction chemotherapy as planned preparative therapy for an autologous peripheral blood stem cell transplant for relapsed high grade lymphoma. Our patient's eruption of DSAP highlights a little recognized cutaneous manifestation of aggressive bone marrow transplant induction therapy.

Porokeratosis and immunosuppression.

Immunosuppression may favour the development of disseminated superficial porokeratosis (DSP). We report the clinical features and the outcome of DSP in 24 patients receiving immunosuppressive treatment (group A), and compare the characteristics of the disease with those of 13 immunocompetent patients with DSP (group B). The two groups were similar with regard to age, sex, area of skin involvement and mean follow-up. There was a family history of DSP in only two patients in group A, compared with five patients in group B (P = 0.03). The skin type, based on the tanning response to sunlight, was not significantly different between the two groups. Two of the 24 patients in group A had high sun exposure, compared with five of the 13 patients in group B (P = 0.03). Moreover, 10 patients in group A and 11 in group B (P = 0.01) exhibited worsening of the disease after exposure to sunlight, usually during the summertime. These observations appear to support the hypothesis that sun exposure is not always essential for the development of porokeratosis in immunosuppressed patients. None of our patients developed skin cancer in porokeratotic lesions during the follow-up period.

Porokeratosis in immunosuppressed and nonimmunosuppressed patients.

Porokeratosis is an uncommon, inherited, autosomally dominant disorder. In the last decade association of porokeratosis and immunosuppression has been observed. In this study we carried out a comparative study between immunosuppressed and nonimmunosuppressed porokeratosis cases. We found that 9 out of 20 cases of porokeratosis were associated with organ transplantation/immunosuppression. Clinicopathologic study revealed that the pattern of disease is alike both in immunosuppressed and nonimmunosuppressed patients. Our observations indicate that immune modulation could be a factor in the genesis of porokeratosis.