Porokeratosis

Updated: Dec 19, 2024
  • 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. [1] The term porokeratosis is actually a misnomer; it was erroneously coined on the assumption that the cornoid lamella emerged from pores of the sweat glands. [2] Multiple clinical variants of porokeratosis are recognized, the most common of which are the following:

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

A patient may develop more than one type of porokeratosis simultaneously or consecutively. [4]  Malignancy (typically squamous cell carcinoma [SCC]) may develop within lesions of porokeratosis.

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

  • Porokeratosis ptychotropica, a verrucous variant typically localized to the genitogluteal area [5, 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 [6]
  • 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) [7]
  • Pruritic papular porokeratosis, in which intensely pruritic papules and plaques arise fairly abruptly in a patient with or without preexisting DSP [8]
  • Pigmented porokeratosis, a newer possible variant - A 2016 report described a case of porokeratosis with prominent melanocytic hyperplasia, which was considered to represent a distinct variant of porokeratosis [9] ; the authors suggested that increased recognition of this entity could help avoid an erroneous diagnosis of melanoma in situ
  • Punctate follicular porokeratosis - The description of this entity in two separate reports supports the contention that it is a unique form rather than just a variation in histology [10] ; in both cases, the cornoid lamella 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 its low prevalence in the population or perhaps by a low biopsy rate of lesions that appear to represent a localized form of keratosis pilaris

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. [2] 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 (UV) radiation, and immunosuppression.

Inherited or sporadic genetic defects, possibly affecting immune function 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 DSAP, DSP, and PPPD. [13, 14, 15, 16, 17, 18, 19] The focal variants of porokeratosis (PM and linear porokeratosis) may occur through mosaicism, in which somatic mutations cause focal loss of heterozygosity. [20]

Genetic mutations in SART3MVK genes have been found in DSAP pedigrees. [21]  DSAP has been shown to originate from a postnatal keratinocyte clone with a different second-hit genetic event in the wild-type allele of the corresponding gene. [22, 23]

A somatic mutation in GJB2 associated with keratosis-ichthyosis-deafness syndrome has been found to cause porokeratotic eccrine ostial and dermal duct nevus. [24]

Natural or artificial UV 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, though the sparing of facial skin in most patients remains to be explained.

Immunosuppression associated with porokeratosis may be secondary to a disease process or medications. Diseases reported in association with porokeratosis include the following:

  • HIV infection [25]
  • Diabetes mellitus [26]
  • Liver disease [27]
  • Hematologic or solid organ malignancy [28, 29]

Immunomodulating drugs used to treat autoimmune diseases or to prevent organ transplant rejection may also trigger porokeratosis. [30, 31] Localized cutaneous immunosuppression due to long-term application of a potent topical steroid has been reported to induce PM. [32] The reported incidence of porokeratosis in organ transplant recipients has been in the range of 1-11%. [33, 34]

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

Trauma (eg, thermal injury) may also trigger porokeratosis.

Etiology

Risk factors for porokeratosis include genetic inheritance, UV light exposure, and immunosuppression. One study found that approximately 10% of patients who had undergone renal transplantation developed porokeratosis. [33]

Classic porokeratosis of Mibelli

Autosomal dominant inheritance and immunosuppression are the usual causes of PM. This form has been seen after radiation therapy, at burn wounds, and at hemodialysis sites.

Disseminated superficial (actinic or nonactinic) porokeratosis

Exposure to natural or artificial UV radiation in a patient who is genetically predisposed causes 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 UV radiation may lead to spontaneous resolution. Additionally, immunosuppression predisposes patients to both DSAP and its nonactinic equivalent, 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 with other forms of porokeratosis.

Porokeratosis palmaris et plantaris disseminata

Familial 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

Hepatitis C virus (HCV) infection has been suggested as a link between the immunosuppressed state and development of acquired porokeratosis. A case of a hyperkeratotic variant of porokeratosis was described in a patient with known HIV and HCV infections and a coexisting therapy-related immunosuppressed state. [36]

Epidemiology

DSAP and PM are the most commonly seen forms of porokeratosis; the other forms are rare.

PPPD and linear porokeratosis may be seen at any age, from birth to adulthood. PM usually develops in childhood. DSP generally develops in the third or fourth decade of life.

PM and PPPD affect men twice as often as women. DSAP is twice as likely to develop in women as compared with men. [31]  Linear porokeratosis is seen with equal frequency in men and women.

Porokeratosis most commonly occurs in lighter-skinned individuals; it is rare in darker-skinned populations.

Prognosis

The prognosis is generally excellent, especially for DSP.

Large lesions of porokeratosis, linear porokeratosis, or porokeratosis in an immunocompromised patient should be monitored carefully for the development of cutaneous malignancies within the lesions. Malignant transformation may occur in about 7.5% of patients. [37, 38] Lesions that are large, longstanding, or linear carry the greatest risk for the development of an associated malignancy. [39] Chromosomal instability and reduced immune surveillance with overexpression of p53 are hypothesized to play a role in the development of cutaneous malignancies within porokeratosis. [40]

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.

Very rarely, porokeratosis-associated SCC may metastasize and cause death. [41]

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.

Given the need for careful sun avoidance and protection, it is advisable to consider vitamin D3 supplementation.

Patients should periodically examine their skin for lesions suggestive of malignancy. Any change in a porokeratosis lesion should be promptly evaluated by a qualified physician.

If familial porokeratosis is suspected, family members should be examined for porokeratosis.

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