Pathogenesis-directed treatment of linear porokeratosis with topical cholesterol-lovastatin.

A 2-year-old boy presented with an extensive, asymptomatic, photosensitive eruption refractory to topical steroids and tretinoin; examination and biopsies were consistent with generalized linear porokeratosis involving the face, limbs, and trunk. Treatment with topical cholesterol-lovastatin was initiated, and it successfully improved early erythematous lesions. Whole exome sequencing that targeted mevalonate pathway genes crucial in cholesterol synthesis later revealed a pathogenic, paternally inherited, porokeratosis-associated MVD, c.70+5 G>A, mutation. Topical cholesterol-lovastatin is a safe and effective empiric treatment for porokeratosis when used in the early, erythematous phase, and its success is likely mediated through its role in targeting mevalonate pathway mutations.

Porokeratosis on the lip: A Case Series.

Porokeratosis is a skin condition that involves the formation of plaques, characterized by a hyperkeratotic ridge with an atrophic center. There is a histological presence of a cornoid lamella, which is a parakeratotic column that traverses through the stratum corneum. The plaques are mostly benign but have the potential to become squamous cell carcinomas if left untreated. Porokeratosis lesions typically occur on the extremities, but they can develop anywhere. The occurrence of porokeratosis on the lip is exceedingly rare. We report three cases of porokeratosis on the lip. Each incidence was treated with cryotherapy, which was unsuccessful in two. One of these two patients did not elect for topical treatment and is being monitored for lesion changes. The second patient was successfully treated via shave biopsy. The third patient was lost to follow-up post-cryotherapy.

Possible Association of Interleukin-31/-31RA Signalling and Basophils with Itch in Porokeratosis.

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Porokeratosis is one of the most common genodermatoses and is associated with an increased risk of keratinocyte cancer and melanoma.

BACKGROUND: Porokeratosis is a clinically heterogeneous group of keratinization disorders with a genetic background mainly affecting the mevalonate pathway, which is involved in the synthesis of cholesterol, an essential component for the formation of the extracellular lipid lamellae in the stratum corneum. Porokeratosis is reportedly associated with an increased risk of keratinocyte cancer, but to date, no large epidemiological studies have been conducted to further address this association. OBJECTIVES: The first objective was to characterize a cohort of patients diagnosed with porokeratosis at the Department of Dermatology and Venereology, Sahlgrenska University Hospital (SU), Gothenburg, Sweden. The second objective was to conduct a nationwide registry-based cohort study to investigate the association, if any, between porokeratosis and the cutaneous malignancies squamous cell carcinoma (SCC), basal cell carcinoma (BCC) and melanoma. METHODS: For the SU cohort, the hospital registry was searched for patients with a diagnosis of porokeratosis recorded between 2016 and 2020. Clinical data were extracted from the records of the identified patients. For the nationwide cohort, national registries were searched to identify patients with a diagnosis of porokeratosis between 2001 and 2020. A tenfold control cohort was formed by Statistics Sweden. The data was cross-referenced with the Swedish Cancer Register to study the associations between porokeratosis and SCC, BCC and melanoma. RESULTS: Disseminated superficial actinic porokeratosis was the most common clinical type among the 108 patients in the SU cohort. In the nationwide search, 2277 patients with porokeratosis were identified (prevalence 1/4132). Porokeratosis was associated with an increased risk for SCC, BCC and melanoma with hazard ratios (95% CI) of 4.3 (3.4-5.4), 2.42 (1.97-2.98) and 1.83 (1.18-2.82), respectively, in the patient cohort, compared to the matched control group. CONCLUSION: Porokeratosis is a common genodermatosis, and it is associated with an enhanced risk of skin cancer.

Efficacy of Topical Cholesterol and Statin Combination Therapy in the Treatment of Porokeratosis: A Systematic Review and Meta-Analysis.

BACKGROUND: Porokeratosis is a group of disorders characterized by aberrant skin keratinization secondary to genetic alterations in the mevalonate pathway, which participates in cholesterol synthesis. While a rare disorder, malignant transformation to squamous cell carcinoma is seen in up to 11% of cases. Recently, topical cholesterol and topical statin therapy have been suggested as a pathogenesis-directed treatment for porokeratosis. METHODS: A PubMed/MEDLINE and Embase literature search was performed using the search terms: "porokeratosis" AND "cholesterol" OR "lovastatin" OR "simvastatin" OR "atorvastatin" OR "fluvastatin" OR "pitavastatin" OR "pravastatin" OR "rosuvastatin" OR "statin." Peer-reviewed clinical trials, case series, and case reports of all porokeratosis subtypes were included. RESULTS: Eleven articles were included in the systematic review and 9 articles in the meta-analysis. The systematic review consisted of an aggregate of 33 patients, most of whom (n=31, 93.9%) applied the treatment twice daily for an average of 9.4 weeks (median=8 weeks), with 93.9% (n=31) experiencing improvement or resolution of porokeratosis. Sixteen patients (48.5%) used lovastatin and 16 (48.5%) used simvastatin with concurrent cholesterol therapy. Mild adverse events including erythema and contact dermatitis were experienced by 12.1% of patients. Our meta-analysis yielded a random effects model supporting a robust reduction in porokeratosis severity (OR = .076, 95% CI [0.022, 0.262]). CONCLUSION: This underpowered meta-analysis provides limited, preliminary evidence supporting the efficacy of topical cholesterol/statin therapy. Overall, quality studies and aggregated sample size are limited; future large clinical trials are needed to further elucidate the role of topical cholesterol/statin therapy in the treatment of porokeratosis. J Drugs Dermatol. 2023;22(12):1160-1165. doi:10.36849/JDD.7775.

A Review of the Efficacy of Topical Statins for Treating Disseminated Superficial Actinic Porokeratosis.

Porokeratosis is a rare group of acquired or hereditary dermatoses characterized by linear or annular plaques with a keratotic border. DSAP is the most common porokeratosis, and lesions range from asymptomatic to pruritic circular pink to brown macules, papules, or plaques surrounded by a raised border. DSAP carries about 7.5-10% risk of malignant transformation to SCC or BCC. While in the past DSAP has been widely treated with topical diclofenac, ingenol mebutate, topical vitamin D analog, 5-fluorouracil, imiquimod, photodynamic therapy, retinoids, cryotherapy, and laser therapy, these therapies have shown limited efficacy and have caused adverse effects including inflammatory reactions, hyperpigmentation, pain, and erythema. Recently, a formulation of topical statin and cholesterol has surfaced as a new and promising treatment for DSAP which has shown clinical improvement with a tolerable adverse effect profile when compared to the current therapies. Of the 8 case studies with a total of 20 patients with DSAP, 90% (18/20) reported clinical improvement with various forms of topical statin therapy. While promising, larger randomized controlled trials are needed to evaluate the long-term use of topical statins for DSAP. J Drugs Dermatol. 2023;22(10):     doi:10.36849/JDD.7540.

Drugs associated with development of porokeratosis: A systematic review.

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.

Porokeratosis Plantaris, Palmaris et Disseminata Caused by Con- genital Pathogenic Variants in the MVD Gene and Loss of Hetero-zygosity in Affected Skin.

Porokeratoses are a heterogeneous group of keratinization disorders. For linear porokeratosis and disseminated superficial actinic porokeratosis, a heterozygous pathogenic germline variant in a mevalonate pathway gene and a postzygotic second hit mutation present in affected skin have been shown to be the patho-genetic mechanism for the development of the lesions. However, the molecular mechanism leading to development of porokeratosis plantaris, palmaris et disseminata is not known. This study analysed a cohort of 4 patients with linear porokeratosis and 3 patients with porokeratosis plantaris, palmaris et disseminata, and performed mutation analyses of DNA extracted from blood samples and skin biopsies. All of the study patients carried the heterozygous germline variant c.70+5G>A in the MVD gene. Loss of heterozygosity due to a second hit mutation was found in affected skin of 3 patients with linear porokeratosis and 2 patients with porokeratosis plantaris, palmaris et disseminata. These results suggest that porokeratosis plantaris, palmaris et disseminata shares the same pathogenetic mechanism as other porokeratosis subtypes and belongs to the phenotypic spectrum of MVD-associated porokeratosis.

Localized eruptive porokeratosis in pediatric patients following treatment of acute leukemia.

Porokeratosis is a rare diagnosis in the pediatric population, and eruptive disease has been documented prior in patients with history of stem cell transplantation. Comparing various porokeratosis eruptions between patients can be difficult due to limitations in current classification and nomenclature. Here, we discuss a single-institution case series of three children who developed porokeratosis following hematopoietic stem cell transplantation for acute leukemia, and we propose that this presentation be termed localized eruptive porokeratosis (LEP). We present the distinguishing features of this variant by discussing the shortcomings in current nomenclature and also examine the association between porokeratosis and hematopoietic stem cell transplantation in the pediatric population.

Linear porokeratosis with bone abnormalities treated with compounded topical 2% cholesterol/2% lovastatin ointment.

We describe a case of linear porokeratosis with associated bone resorption in a 17-year-old female with marked improvement after 2% cholesterol/2% lovastatin ointment application. Porokeratosis is a heterogenous group of keratinization disorders characterized by a cornoid lamella, consisting of focal dyskeratotic cells in the granular layer and columns of parakeratosis. The pathogenesis of porokeratosis is not fully elucidated; however, germline mutations have recently been identified in the mevalonate pathway which can lead to a buildup of metabolites that could play a role in dysmaturation. There has only been one prior report of an affected distal digit with underlying bone resorption in association with linear porokeratosis.

Recurrent Squamous Cell Carcinoma Arising Within a Linear Porokeratosis

Here we report a case of linear porokeratosis with recurrent malignant degeneration to squamous cell carcinoma (SCC) recurring six years after excision of initial SCC. A 79-year-old woman presented with a friable tumor located within a longstanding lesion on her posterior thigh. Six years prior, she was diagnosed with SCC arising within the same lesion, which had been surgically excised with negative margins. Physical examination revealed a 3.5 x 2.7 cm friable tumor on the left proximal posterior thigh. The tumor was located within a hyperpigmented and erythematous scaly linear plaque within a line of Blaschko, extending from the left buttock to the left distal posterior thigh. Two 4 mm punch biopsies were performed: one of the erythematous plaque on the left buttock and one from the friable tumor on the left posteromedial thigh. Histology from the left buttock revealed a cornoid lamella consistent with porokeratosis and the left posteromedial thigh revealed SCC. The patient underwent Mohs micrographic surgery with negative margins, followed by a linear repair. Porokeratosis is a disorder of epidermal keratinization that has been associated with malignant degeneration, although such cases are rare. The risk of recurrence of SCC arising within a porokeratosis is unknown. This case emphasizes the importance of ongoing monitoring for malignant degeneration within these lesions. J Drugs Dermatol. 2020;19(2)205-206. doi:10.36849/JDD.2020.4640

Clinical course of porokeratosis ptychotropica over 7 years in an otherwise healthy child.

Porokeratosis ptychotropica is an unusual variant of porokeratosis characterized by papules and plaques located on the buttocks and gluteal cleft and showing multiple coronoid lamellae on histology. In this case report, we present the longitudinal clinical course of porokeratosis ptychotropica in a pediatric patient with individual red-brown hyperkeratotic lesions that enlarged and became confluent prior to surgical intervention. We also discuss the etiology of porokeratosis ptychotropica and review current as well as future treatment options for the disease.

Porokeratosis ptychotropica: a rare variant that is commonly misdiagnosed.

Porokeratosis ptychotropica (PP) is a rare variant of porokeratosis characterized by pruritic, scaly papules and plaques localized to the perianal and gluteal cleft regions. Clinically, PP resembles other common disorders, resulting in frequent misdiagnosis. The diagnosis of PP often takes several years to make, therefore many reported cases in the literature described the late stages of PP. We report a case of PP diagnosed at an early stage. By presenting our patient, we aim to raise further awareness of PP to avoid a delay in diagnosis, thus preventing long term complications of this rare entity.

Linear porokeratosis associated with Bardet-Biedl syndrome: A case report.

This case report presents a 17-year-old boy with Bardet-Biedl syndrome (BBS) and a long-standing hyperpigmented eruption on the left trunk and upper extremity, clinically and histologically consistent with linear porokeratosis (LP). BBS patients frequently require solid organ transplant, and subsequent immunosuppression places them at especially high risk for malignant transformation of premalignant skin lesions such as LP. Although BBS affects multiple organ systems, there are only a handful of case reports detailing associated cutaneous involvement, and, to our knowledge, this is the first reported case of linear porokeratosis occurring in patient with BBS.

Pink verrucous plaque in a man with systemic mastocytosis.

Porokeratosis ptychotropica is a rare and commonly misdiagnosed subtype of porokeratosis involving the body folds. We present a 53-year-old man with systemic mastocytosis who presented with a pruritic, verrucous plaque in the gluteal fold that showed multiple cornoid lamellae on histopathologic evaluation, diagnostic of porokeratosis ptychotropica. Various treatments have been reported, including topical corticosteroids, retinoids, vitamin D analogs, calcineurin inhibitors, imiquimod, phototherapy, cryotherapy, or ablative laser therapy, but recurrences are common.

Multiple flat-topped scaly violaceous papules.

Epidermodysplasia verruciformis (EV) is an autosomal recessive genodermatosis characterized by susceptibility to beta-genus human papillomavirus (HPV) infection. Owing to TMC6/EVER1 and TMC8/EVER2 mutations that lead to abnormal transmembrane channels in the endoplasmic reticulum involved in immunological pathways, keratinocytes cannot combat infection from non-pathogenic HPV strains. Mutations involving RHOH, MST-1, CORO1A, and IL-7 have also been associated with EV in patients without TMC6 or TMC8 mutations. We highlight a 27-year-old man with multiple violaceous flat-topped papules with scale and irregular borders distributed on his chest, extremities, abdomen, and back. The striking physical examination and the subsequent biopsy findings of enlarged nests of cells in the granular and spinous layers with blue-gray cytoplasm and keratohyaline granules confirmed the diagnosis. We conclude with a brief discussion on the differential diagnosis, which includes confluent and reticulated papillomatosis, Darier disease, and disseminated superficial actinic porokeratosis.