-
American Journal of Human Genetics May 2024Porokeratosis is a clonal keratinization disorder characterized by solitary, linearly arranged, or generally distributed multiple skin lesions. Previous studies showed...
Porokeratosis is a clonal keratinization disorder characterized by solitary, linearly arranged, or generally distributed multiple skin lesions. Previous studies showed that genetic alterations in MVK, PMVK, MVD, or FDPS-genes in the mevalonate pathway-cause hereditary porokeratosis, with skin lesions harboring germline and lesion-specific somatic variants on opposite alleles. Here, we identified non-hereditary porokeratosis associated with epigenetic silencing of FDFT1, another gene in the mevalonate pathway. Skin lesions of the generalized form had germline and lesion-specific somatic variants on opposite alleles in FDFT1, representing FDFT1-associated hereditary porokeratosis identified in this study. Conversely, lesions of the solitary or linearly arranged localized form had somatic bi-allelic promoter hypermethylation or mono-allelic promoter hypermethylation with somatic genetic alterations on opposite alleles in FDFT1, indicating non-hereditary porokeratosis. FDFT1 localization was uniformly diminished within the lesions, and lesion-derived keratinocytes showed cholesterol dependence for cell growth and altered expression of genes related to cell-cycle and epidermal development, confirming that lesions form by clonal expansion of FDFT1-deficient keratinocytes. In some individuals with the localized form, gene-specific promoter hypermethylation of FDFT1 was detected in morphologically normal epidermis adjacent to methylation-related lesions but not distal to these lesions, suggesting that asymptomatic somatic epigenetic mosaicism of FDFT1 predisposes certain skin areas to the disease. Finally, consistent with its genetic etiology, topical statin treatment ameliorated lesions in FDFT1-deficient porokeratosis. In conclusion, we identified bi-allelic genetic and/or epigenetic alterations of FDFT1 as a cause of porokeratosis and shed light on the pathogenesis of skin mosaicism involving clonal expansion of epigenetically altered cells.
Topics: Porokeratosis; Humans; Mosaicism; Epigenesis, Genetic; DNA Methylation; Keratinocytes; Promoter Regions, Genetic; Male; Alleles; Female
PubMed: 38653249
DOI: 10.1016/j.ajhg.2024.03.017 -
Dermatology Online Journal Mar 2019Epidermodysplasia verruciformis (EV) is an autosomal recessive genodermatosis characterized by susceptibility to beta-genus human papillomavirus (HPV) infection. Owing...
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.
Topics: Adult; Darier Disease; Diagnosis, Differential; Epidermodysplasia Verruciformis; Humans; Male; Membrane Proteins; Papilloma; Papillomavirus Infections; Porokeratosis
PubMed: 30982308
DOI: No ID Found -
Archives of Dermatological Research Dec 2023
Topics: Humans; Porokeratosis; Retrospective Studies; Biopsy; Diagnosis, Differential
PubMed: 37642699
DOI: 10.1007/s00403-023-02694-3 -
The British Journal of Dermatology Oct 2023
Topics: Humans; Porokeratosis; Interleukin-17
PubMed: 37406221
DOI: 10.1093/bjd/ljad223 -
JAAD Case Reports Nov 2022
PubMed: 36186413
DOI: 10.1016/j.jdcr.2022.08.044 -
Clinical and Experimental Dermatology Dec 2017Porokeratosis, a disorder of keratinisation, is clinically characterized by the presence of annular plaques with a surrounding keratotic ridge. Clinical variants include...
Porokeratosis, a disorder of keratinisation, is clinically characterized by the presence of annular plaques with a surrounding keratotic ridge. Clinical variants include linear, disseminated superficial actinic, verrucous/hypertrophic, disseminated eruptive, palmoplantar and porokeratosis of Mibelli (one or two typical plaques with atrophic centre and guttered keratotic rim). All of these subtypes share the histological feature of a cornoid lamella, characterized by a column of 'stacked' parakeratosis with focal absence of the granular layer, and dysmaturation (prematurely keratinised cells in the upper spinous layer). In recent years, a proposed new subtype, follicular porokeratosis (FP_, has been described, in which the cornoid lamella are exclusively located in the follicular ostia. We present four new cases that showed typical histological features of FP.
Topics: Aged; Aged, 80 and over; Female; Hair Follicle; Humans; Lentigo; Male; Middle Aged; Porokeratosis; Skin
PubMed: 28748571
DOI: 10.1111/ced.13195 -
Journal of the European Academy of... Jan 2024The 31 European Academy of Dermatology and Venereology (EADV) Congress took place between 7 and 10 of September 2022 in Milan, Italy.
Efficacy and safety of tirbanibulin 1% ointment in actinic keratoses: Data from two phase-III trials and the real-life clinical practice presented at the European Academy of Dermatology and Venereology Congress 2022.
BACKGROUND
The 31 European Academy of Dermatology and Venereology (EADV) Congress took place between 7 and 10 of September 2022 in Milan, Italy.
OBJECTIVES
We report presented clinical data on the efficacy/effectiveness, safety and tolerability of tirbanibulin 1% ointment that has recently been licensed for actinic keratosis (AK) of the face or scalp in adults.
METHODS
Summary of presentations given at the EADV Congress.
RESULTS
Prof. Pellacani presented two post hoc analyses from two phase-III trials with AK patients (NCT03285477 [N = 351] and NCT03285490 [N = 351]): A descriptive analysis of medical history, concomitant medications, and safety results confirming a favourable profile for tirbanibulin showing that number of baseline AK lesions was not correlated to severity of local skin reactions. The latter analysis showed that cases of tirbanibulin application site pain or pruritus were few, and most were found to be mild. Prof. Kunstfeld reported six real-life clinical cases in Austria showing good tirbanibulin effectiveness, safety and tolerability for the treatment of new or recurring AK lesions. Results demonstrated that after 2- to 4-month follow-up, tirbanibulin was well tolerated and effective in AK patients. Presentations by Dr. Patel confirmed good outcomes and tolerability of tirbanibulin in Olsen grade 1-2 AK (N = 12) and porokeratosis patients (N = 4) treated once daily for 5 consecutive days in the United Kingdom. Furthermore, real-world experience in solid organ transplant recipients (N = 2) demonstrated effectiveness of tirbanibulin in skin field cancerization treatment. A symposium sponsored by Almirall was conducted during the congress in which Dr. Hadshiew and Dr. Lear brought together their clinical experience in Germany and the United Kingdom respectively. Interesting clinical cases of 5 consecutive days of tirbanibulin treatment compared to other treatments were discussed with attendees, as well as current treatment needs of AK patients.
CONCLUSIONS
This article provides an overview of presentations and symposium discussions, summarizing key phase-III results and real-life clinical experience with tirbanibulin shared by dermatologists across Europe.
Topics: Adult; Humans; Keratosis, Actinic; Dermatology; Ointments; Venereology; Neoplasm Recurrence, Local; Treatment Outcome
PubMed: 38116638
DOI: 10.1111/jdv.19636 -
Lasers in Medical Science May 2017Treatment of disseminated superficial actinic porokeratosis (DSAP) is poorly standardized. The present review seeks to comprehensively discuss the potential for laser... (Meta-Analysis)
Meta-Analysis Review
Treatment of disseminated superficial actinic porokeratosis (DSAP) is poorly standardized. The present review seeks to comprehensively discuss the potential for laser and light modalities in the treatment of DSAP. A systematic review of light and laser treatment modalities was conducted to include 26 cases of patients with DSAP. Systematic review resulted in 14 articles to be included. Photodynamic therapy (PDT) overall was the least successful treatment modality, with clinical improvement seen in a minority of patients (MAL-PDT: N = 9 patients, 33.3% showed improvement; ALA-PDT: N = 3 patients, 0% improvement; hypericin-PDT: N = 2 patients, 0% improvement) after numerous post-procedural side effects of hyperpigmentation, inflammation, erythema, and discomfort. Overall, in the available reports, PDT demonstrates poor outcomes with greater incidence of side effects. The response rates of DSAP lesions treated with lasers were as follows: (Q-switched ruby lasers: N = 2, 100%; CO laser: N = 1, 100%; PDT and CO combination therapy: N = 2, 0-50%; erbium and neodymium YAG lasers: N = 2, 100%; fractional 1927-nm thulium fiber lasers: N = 2, 100%; Grenz rays: N = 1, 100%; and fractional photothermolysis: N = 2, 100%). The side effects of laser therapy were minimal and included mild erythema, slight hyperpigmentation, and moderate edema. Laser therapy is a promising treatment option for DSAP with an excellent side effect profile. However, higher power studies are required to determine optimal guidelines for laser treatment of DSAP.
Topics: Adult; Aged; Aged, 80 and over; Female; Humans; Laser Therapy; Lasers, Gas; Lasers, Solid-State; Male; Middle Aged; Photochemotherapy; Phototherapy; Porokeratosis; Treatment Outcome
PubMed: 28239750
DOI: 10.1007/s10103-017-2179-9 -
Dermatology Practical & Conceptual Apr 2024
PubMed: 38810068
DOI: 10.5826/dpc.1402a111 -
Annales de Dermatologie Et de... Dec 2020
Topics: Fingers; Humans; Porokeratosis
PubMed: 32680711
DOI: 10.1016/j.annder.2020.06.010