What is the pathophysiology of porokeratosis?

Updated: Oct 09, 2020
  • Author: Amarateedha Prak LeCourt, MD; Chief Editor: William D James, MD  more...
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Answer

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. [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 the GJB2 mutation associated with keratosis-ichthyosis-deafness syndrome was found to cause porokeratotic eccrine ostial and dermal duct nevus. [24]


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