Description
A middle-aged man in his late 50s was admitted in a surgical ward for scrotal enlargement. Ultrasound of the scrotal sac confirmed the diagnosis of bilateral hydrocoele. He was referred to dermatology services for lesions on his skin over the scrotum. He reported that the lesions on his scrotal skin were present since last 10 years. He also revealed that similar lesions were present on his other body areas. He gave no history of metabolic disorder. His laboratory investigations for complete blood haemogram, liver function and renal function were within normal reference range. There was no history of similar skin lesions in the parents or siblings.
Cutaneous examination showed multiple annular plaques with central atrophy and raised keratotic border on scrotum, shaft of penis, left half of back and left arm and forearm (figures 1 and 2). Lesions on the trunk were restricted to left half of back. On the basis of clinical examination, we made a provisional diagnosis of atrophic lichen planus and lichen sclerosus. The distribution of lesions on the back appeared similar to ‘geographical islands’. Polarised contact dermoscopy (Dermlite, DL5) showed a central white atrophic structureless area surrounded by a dark brown thready border, the ‘keratin rim’ (figure 3). Based on the findings on clinical examination and dermoscopic findings, we diagnosed our case as blaschkoid (mosaic pattern) of disseminated superficial porokeratosis (DSP).
Figure 1.
Multiple well-defined geographical shaped plaques (geographical Islands) with central ivory white atrophy on left half of back.
Figure 2.
Lesions of superficial porokeratosis on scrotal skin along the median raphe and few lesion on each side of Scrotum.
Figure 3.
Polarised contact dermoscopy with a Dermlite Dl5 dermoscope showed a central white area with dark brown thready border.
Porokeratosis has been considered as a disorder of keratinisation and traditionally classified into five main variants based on clinical appearance: porokeratosis of Mibelli (PM), disseminated superficial actinic porokeratosis (DSAP), DSP, porokeratosis palmaris et plantaris disseminata and linear porokeratosis. Mosaicism refers to the presence of genetically distinct cells within an organism that result from postzygotic mutation. Recently, genetic defect in the mevalonate pathway has been implicated in the pathogenesis of porokeratosis.1 Sporadic second-hit postzygotic mutation in phosphomevalonate kinase (PMVK), mevalonate diphospho decarboxylase and farnesyl diphosphate synthase after birth may explain the development of porokeratosis in adulthood.2 In our case, lesions of porokeratosis follow the epidermal migration called as ‘lines of Blaschko’.
It has been hypothesised that PMVK-deficient individuals show premature apoptosis and dysregulated keratinisation of lesional keratinocytes and play a crucial role in the pathogenesis of porokeratosis especially PM, DSAP and DSP subtypes.3 The end product of mevalonate pathway such as cholesterol plays as important role in the skin barrier function along with ceramides and free-fatty acid. Defects in cholesterol biosynthesis may lead of apoptosis of lesional keratinocytes. Based on the genetic studies carried out on patients with porokeratosis, topical cholesterol/lovastatin formulation has been recommended for the treatment of porokeratosis as a pathogenesis-directed therapy.4
Learning points.
Porokeratosis is a disorder of keratinisation with underlying defect in mevalonate biosynthetic pathway.
Postzygotic mutation in genes encoding for enzymes in mevalonate pathway has been implicated in the pathogenesis of porokeratosis.
Porokeratosis following the lines of Blaschko has a second-hit postzygotic mutation in lesional keratinocytes for mevalonate biosynthetic pathway.
Footnotes
Twitter: @rashlessdoctor
Contributors: All the authors have contributed in the writing the manuscript, editing and revising.
Funding: The authors have not declared a specific grant for this research from any funding agency in the public, commercial or not-for-profit sectors.
Case reports provide a valuable learning resource for the scientific community and can indicate areas of interest for future research. They should not be used in isolation to guide treatment choices or public health policy.
Competing interests: None declared.
Provenance and peer review: Not commissioned; externally peer reviewed.
Ethics statements
Patient consent for publication
Consent obtained directly from patient(s).
References
- 1. Atzmony L, Khan HM, Lim YH, et al. Second-Hit,Postzygotic PMVK and MVD mutations in linear Porokeratosis. JAMA Dermatol 2019;155:548–55. 10.1001/jamadermatol.2019.0016 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 2. Wang J, Liu Y, Liu F, et al. Loss-of-function Mutation in PMVK causes Autosomal dominant disseminated superficial Porokeratosis. Sci Rep 2016;6:24226. 10.1038/srep24226 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 3. Shen CS, Tabata K, Matsuki M, et al. Premature apoptosis of Keratinocytes and the dysregulation of Keratinization in Porokeratosis. Br J Dermatol 2002;147:498–502. 10.1046/j.1365-2133.2002.04853.x [DOI] [PubMed] [Google Scholar]
- 4. Atzmony L, Lim YH, Hamilton C, et al. Topical cholesterol/lovastatin for the treatment of Porokeratosis: A pathogenesis-directed therapy. J Am Acad Dermatol 2020;82:123–31. 10.1016/j.jaad.2019.08.043 [DOI] [PMC free article] [PubMed] [Google Scholar]