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. Five clinical variants of porokeratosis are recognized: classic porokeratosis of Mibelli (PM), disseminated superficial actinic porokeratosis (DSAP), porokeratosis palmaris et plantaris disseminata (PPPD), linear porokeratosis, and punctate porokeratosis. Several other variants have been described, including hyperkeratosis types, a pruritic papular variant, and a verrucous variant that is localized to the buttocks and mimics psoriasis.[1]
A related disorder is porokeratotic adnexal ostial nevus (PAON). This is a rare 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).[2]
Occasionally, a patient may develop more than one type of porokeratosis simultaneously or consecutively.
Pathophysiology
Clonal hyperproliferation of atypical keratinocytes leads to the formation of the cornoid lamella, which expands peripherally and forms the raised boundary between abnormal and normal keratinocytes. Local or systemic changes in immune function may allow the development of atypical clones of keratinocytes. Loss of heterozygosity has been proposed as a mechanism for linear porokeratosis associated with a personal or family history of DSAP.
Several risk factors for the development of porokeratosis have been identified; these factors include genetic inheritance, ultraviolet radiation, and immunosuppression. Immunosuppression associated with porokeratosis may be secondary to a disease process such as HIV infection or lymphoma or an iatrogenic suppression such as with immune-modulating drugs used to prevent organ transplant rejection or to treat autoimmune diseases.[3, 4] An autosomal dominant mode of inheritance has been established for familial cases of all forms of porokeratosis. Extensive sun exposure is thought to cause DSAP, although the typical sparing of facial skin is unexplained. Excessive natural or artificial ultraviolet radiation, electron beam therapy, and extensive radiation therapy are well-established trigger factors. Immunosuppression may induce new lesions or cause preexisting lesions to flare.
The formation of squamous or basal cell carcinomas has been reported in all forms of porokeratosis.[5, 6, 7] Chromosomal instability and reduced immune surveillance with overexpression of p53 are hypothesized to play a role in the development of cutaneous malignancies within porokeratosis.[8, 9, 10, 11, 12]
Epidemiology
Frequency
United States
DSAP is relatively common. The other forms of porokeratosis are rare.
Mortality/Morbidity
- 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.[13]
- Malignant degeneration has been reported in all forms of porokeratosis, with risks of 7.5% and 11% determined from 2 published reviews of the literature. Large lesions, lesions of long-standing duration, and the linear type of porokeratosis were found to be at greatest risk. Extensive metastases of a squamous cell carcinoma developing within a large PM lesion has been reported.[14]
Race
- Porokeratosis most commonly occurs in fair-skinned individuals. Porokeratosis is rare in darker-skinned populations.
Sex
- PM and PPPD affect men twice as often as women.
- DSAP is 3 times as likely to develop in women compared with men.
- 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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