Porokeratosis

Updated: Sep 24, 2018
  • Author: Amarateedha Prak LeCourt, MD; Chief Editor: William D James, MD  more...
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Overview

Background

Porokeratosis is a clonal disorder of keratinization characterized by one or more atrophic patches surrounded by a clinically and histologically distinctive hyperkeratotic ridgelike border called the cornoid lamella. Historically, porokeratosis is a misnomer that was erroneously coined on the assumptions that cornoid lamellae emerged from pores of the sweat glands. [1] Multiple clinical variants of porokeratosis are recognized. Malignancies, typically squamous cell carcinomas, may develop within lesions of porokeratosis.

The most common forms of porokeratosis are as follows:

  • Classic porokeratosis of Mibelli (PM) [2]
  • Disseminated superficial actinic porokeratosis (DSAP) and its nonactinic variant disseminated superficial porokeratosis (DSP)
  • Linear porokeratosis
  • Porokeratosis palmaris et plantaris disseminata (PPPD)
  • Punctate porokeratosis, which might represent a variant of PPPD [3]

A patient may develop more than one type of porokeratosis simultaneously or consecutively. [2]

Less commonly reported clinical entities that share the histopathologic characteristic of cornoid lamellation include the following:

  • Porokeratosis ptychotropica, a verrucous variant localized to the buttocks [4]
  • Porokeratoma, also referred to as porokeratotic acanthoma, an entity arising as a solitary keratotic or verrucous nodule with prominent multiple and confluent cornoid lamellae [5]
  • Porokeratotic adnexal ostial nevus (PAON), a rare congenital disorder of keratinization with eccrine and hair follicle involvement: This name was proposed to incorporate porokeratotic eccrine ostial and dermal duct nevus (PEODDN) and porokeratotic eccrine and hair follicle nevus (PEHFN). [6]
  • Pruritic papular porokeratosis, in which intensely pruritic papules and plaques arise fairly abruptly in a patient with or without preexisting DSP [7, 8]
  • Pigmented porokeratosis: A case published in 2016 showed a new possible variant of porokeratosis. Biopsies showed prominent melanocytic hyperplasia in 8 of 31 patients studied. The case represents a distinct variant of porokeratosis; biopsies were performed to clinically exclude melanoma. An erroneous diagnosis of melanoma in situ can be avoided with increased recognition of this entity. [9]
  • Punctate follicular porokeratosis: This has been described in two separate reports, which supports the contention that this is a unique form rather than just a variation in histology. In both cases, the cornoid lamellae originated exclusively from hair follicles with no associated annular plaque. Diagnosis relies heavily on proper histopathologic sampling, and the rarity of this variant could be explained by the low prevalence of this condition in the population or perhaps low biopsy rate of lesions that appear to represent a localized form of keratosis pilaris to physicians. [10]
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Pathophysiology

Clonal proliferation of atypical keratinocytes showing abnormal terminal keratinocyte differentiation leads to the formation of the cornoid lamella. Cornoid lamellation is typically seen in porokeratosis, where it corresponds to the threadlike scale present at the lesional border. [1] This expands peripherally and forms the raised boundary between abnormal and normal keratinocytes. The atypical keratinocytes show abnormal differentiation but do not show an increased rate of proliferation. [11, 12]

It is not known what triggers this process, and more than one causative factor may be involved. Several risk factors for the development of porokeratosis have been identified, including genetic inheritance, ultraviolet radiation, and immunosuppression.

Inherited or sporadic genetic defects, possibly creating a change in immune function and/or keratinocyte function, are thought to be responsible for several forms of porokeratosis. Familial cases of all forms of porokeratosis have been reported and appear to have an autosomal dominant inheritance pattern with incomplete penetrance. Several chromosomal loci have been identified for disseminated superficial actinic porokeratosis (DSAP), disseminated superficial porokeratosis (DSP), and porokeratosis palmaris et plantaris disseminata (PPPD). [13, 14, 15, 16, 17, 18, 19] The focal variants of porokeratosis (porokeratosis of Mibelli [PM] and linear porokeratosis) may occur through mosaicism, in which somatic mutations cause focal loss of heterozygosity. [20] Genetic mutations in the SART3 and MVK genes have been found in DSAP pedigrees.

A somatic mutation in the GJB2 mutation associated with keratosis-ichthyosis-deafness syndrome was found to cause porokeratotic eccrine ostial and dermal duct nevus. [21]

Natural or artificial ultraviolet radiation, electron beam therapy, and extensive radiation therapy are well-established trigger factors for DSAP and PM. Sun exposure in genetically susceptible individuals is thought to cause DSAP, although the sparing of facial skin in most patients is unexplained.

Immunosuppression associated with porokeratosis may be secondary to a disease process or medications. Diseases reported in association with porokeratosis include HIV infection, [22] diabetes mellitus, [23] liver disease, [24] and hematologic or solid organ malignancy. [25, 26] Immunomodulating drugs used to treat autoimmune diseases or to prevent organ transplant rejection may also trigger porokeratosis. [27, 28, 29, 30, 31, 32, 33, 34, 35] Localized cutaneous immunosuppression due to long-term application of a potent topical steroid was reported to induce PM. [36] The incidence of porokeratosis in organ transplant recipients has been reported to be anywhere from 1-11%. [28, 31]

Immunosuppression may induce new lesions or cause preexisting lesions to flare. New lesions of porokeratosis have occurred as quickly as 4 months after initiation of immunosuppressive therapy, or as long as 14 years [31, 33] and may resolve following cessation of immunosuppressive therapy. [34, 35]

Trauma, such as a burn, may also trigger porokeratosis. [37]

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Etiology

Risk factors for porokeratosis include genetic inheritance, ultraviolet light exposure, and immunosuppression. One study found that approximately 10% of patients who had undergone renal transplantation developed porokeratosis. [28]

Classic porokeratosis (Mibelli)

Autosomal dominant inheritance and immunosuppression are the usual causes. Porokeratosis of Mibelli (PM) has been seen following radiation therapy, at burn wounds, and at hemodialysis sites.

Disseminated superficial (actinic) porokeratosis

Sun exposure and/or artificial ultraviolet radiation exposure in a patient who is genetically predisposed causes disseminated superficial actinic porokeratosis (DSAP). Exacerbations have been reported following prolonged sun exposure, repeated tanning bed exposure, electron beam radiation therapy, and therapeutic phototherapy or photochemotherapy for psoriasis. Drug-induced photosensitivity may play a role. Protection from ultraviolet radiation may lead to spontaneous resolution. Additionally, immunosuppression predisposes patients to both DSAP and nonactinic disseminated superficial porokeratosis (DSP).

Linear porokeratosis

No definite inheritance pattern has been established. Loss of heterozygosity has been proposed as a genetic mechanism and may explain the higher risk of malignant degeneration seen in linear porokeratosis in comparison to other forms of porokeratosis.

Porokeratosis palmaris et plantaris disseminata

Familial porokeratosis palmaris et plantaris disseminata (PPPD) is transmitted in an autosomal dominant mode with variable penetrance. Acquired PPPD may be caused by immunosuppression, or it may be a cutaneous marker of internal malignancy.

Punctate porokeratosis

This condition has no unique inheritance pattern and is usually associated with other forms of porokeratosis.

Hyperkeratotic porokeratosis

A case report on hyperkeratotic porokeratosis describes hepatitis C virus (HCV) infection as a link between the immunosuppressed state and development of acquired porokeratosis. A rare case of a hyperkeratotic variant has been described in a patient with known HIV and HCV infections and a coexisting therapy-related immunosuppressed state. [38]

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Epidemiology

Frequency

Disseminated superficial actinic porokeratosis (DSAP) and porokeratosis of Mibelli (PM) are the most commonly seen variants. The other forms of porokeratosis are rare.

Race

Porokeratosis most commonly occurs in fair-skinned individuals. Porokeratosis is rare in darker-skinned populations.

Sex

PM and porokeratosis palmaris et plantaris disseminata (PPPD) affect men twice as often as women.

DSAP is twice as likely to develop in women compared with men. [33]

Linear porokeratosis is seen with equal incidence in men and women.

Age

PPPD and linear porokeratosis may be seen at any age, from birth to adulthood.

PM usually develops in childhood.

Disseminated superficial porokeratosis (DSP) generally develops in the third or fourth decade of life.

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Prognosis

The prognosis is generally excellent. This is especially true for disseminated superficial porokeratosis (DSP).

Large lesions of porokeratosis, linear porokeratosis, or porokeratosis in an immunocompromised patients should be monitored carefully for the development of cutaneous malignancies within the porokeratosis lesions. Malignant transformation can occur in about 7.5% of patients. [39, 40, 41] Lesions that are large, long-standing, or linear have the greatest risk of developing an associated malignancy. [42] Chromosomal instability and reduced immune surveillance with overexpression of p53 are hypothesized to play a role in the development of cutaneous malignancies within porokeratosis. [43, 44, 45, 46, 47]

Porokeratosis of Mibelli (PM) circumferentially involving the digits may induce pseudoainhum. Most lesions are asymptomatic. Ulcerative lesions have been described. Giant PM in a facial or acral location may cause destruction of underlying soft tissue or pseudoainhum with amputation. [48]

Very rarely, porokeratosis-associated squamous cell carcinomas may metastasize and cause death. [49, 50]

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Patient Education

Patients must practice strict sun precautions. These measures include wearing protective clothing; applying sunblock; avoiding exposure to midday sunlight; and discontinuing exposure to artificial ultraviolet light, such as tanning beds and therapeutic phototherapy.

Consideration for vitamin D3 supplementation should be made given the need for careful sun avoidance and protection.

Patients must periodically examine their skin for lesions suggestive of malignancy. A qualified physician should promptly evaluate any change in a porokeratosis lesion.

Family members should be examined for porokeratosis if familial porokeratosis is suspected.

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