Drugs associated with development of porokeratosis: A systematic review

Abstract

Porokeratosis is a rare disorder characterized by atrophic macules or patches, with a well‐defined ridge‐like hyperkeratotic border called cornoid lamella. Although the exact pathogenesis is unknown, drug associated cases have recently been reported in the literature. As such, we systematically reviewed and identified drugs associated with drug‐induced porokeratosis, their resultant effects, and whether there was a casual relationship between the use of a drug and the development of porokeratosis. We searched for articles which reported drug‐induced porokeratosis in MEDLINE and Embase in June 2020. After full‐text review, 25 studies were included for analysis. We identified 26 patients with drug‐induced porokeratosis. The most common therapies associated with development of porokeratosis is biologic use, phototherapy, and radiotherapy. The most common clinical variants were the disseminated superficial or actinic types (60%), which occurred in psoriasis patients undergoing phototherapy, and eruptive disseminated type (24%) which occurred in the context of biologic therapies. The Naranjo score ranged from possible to probable for the identified treatments. Clinicians should consider drug reactions as possible triggering events for porokeratosis, especially for patients taking biologics, phototherapy, and radiotherapy. Large‐scale studies are required to confirm our findings and further explore the pathogenesis for drug‐induced porokeratosis.

Pembrolizumab associated Stevens–Johnson syndrome with porokeratosis in a patient in the setting of primary hepatocellular carcinoma

“…Patients with pembrolizumab and other PD-1/PD-L1 inhibitors usually have nonspecific morbilliform or lichenoid drug reactions. However, the emergence of rare and specific clinical manifestations of skin diseases includes psoriasis, bullous pemphigoid, vitiligo, sarcoidosis, porokeratosis 4 and Stevens-Johnson syndrome/toxic epidermal necrolysis. 5 SJS/TEN is a grade 4 reaction of the Common Terminology Criteria for Adverse Events (CTCAE), which occurs in less than 1% of patients during anti-PD-1 therapy.…”

“…2 Porokeratosis is a rare epidermal keratinisation disorder, which may be a rare complication of biological therapy 6 and phototherapy especially in individuals with underlying malignancies. 4 However, the pathway that leads to this process remains unknown. SJS and porokeratosis co-occur in a patient, which has not been reported so far.…”

Disseminated superficial actinic porokeratosis following hydroxyurea treatment: A case report

“…Porokeratosis encompass a group of keratinization disorders hallmarked by the presence of dysplastic keratinocytes with the formation of a thin column of parakeratotic cells which invaginates into the epidermis -the cornoid lamella -representing the thread-like active border of the lesions, pathognomonic in all PK forms. 1 Genetic predisposition seems to play a pivotal role in all clinical variants of PK; to date, heterozygous germline mutations of four mevalonate kinase (MVK) pathway genes (MVK, MVD, PMVK and FDPS) have been reported as causative of PK. 2 In DSAP, it has been hypothesized that mitochondrial dysfunction induced by MVK pathway mutations could be an important contributory mechanism, since MVK pathway play a role in regulating calcium-induced keratinocyte differentiation and could have a protective effect on apoptosis of keratinocytes induced by UV-A spectrum light.…”

“…Porokeratosis encompass a group of keratinization disorders hallmarked by the presence of dysplastic keratinocytes with the formation of a thin column of parakeratotic cells which invaginates into the epidermis – the cornoid lamella – representing the thread‐like active border of the lesions, pathognomonic in all PK forms 1 …”

“…The relationship between PK onset and drugs has been recently evaluated in a systematic review, which mentioned HU as a possible trigger drug (mean Naranjo score of 3.3) 1 . HU is an anti‐metabolite drug which inhibits ribonucleotide reductase, thus affecting the production of deoxyribonucleotides and finally altering DNA repair 6 .…”