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Indian Journal of Dermatology,... 2023
Topics: Humans; Porokeratosis; Buttocks; Biopsy
PubMed: 34245530
DOI: 10.25259/IJDVL_122_2021 -
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 -
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 -
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 -
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 -
SAGE Open Medical Case Reports 2022Genitogluteal porokeratosis is a rare localized disorder of keratinization. Due to the rarity of the case and non-specific keratotic lesion, it is often misdiagnosed...
Genitogluteal porokeratosis is a rare localized disorder of keratinization. Due to the rarity of the case and non-specific keratotic lesion, it is often misdiagnosed until a histological examination is performed. Treatment of this condition can be challenging, which comprises various topical and systemic drugs, lasers, cryotherapy, phototherapy, and also surgical intervention. Regular follow-up is necessary in the view of this disorder being a premalignant condition.
PubMed: 36467011
DOI: 10.1177/2050313X221139559 -
Biological Research May 2021The MVD gene mutations are identified in porokeratosis, which is considered a skin-specific autoinflammatory keratinization disease. However, the biological function of...
BACKGROUND
The MVD gene mutations are identified in porokeratosis, which is considered a skin-specific autoinflammatory keratinization disease. However, the biological function of MVD gene remains largely unknown. Therefore, we analyzed the function of mvda gene, orthologous to the human MVD gene, in developing zebrafish.
METHODS
Morpholino antisense oligonucleotide technique was used to generate mvda loss-of-function phenotypes. Knockdown of mvda was confirmed by RT-PCR and Sanger sequencing. Scanning and transmission electron microscopy were performed to analyze the morphology of the epidermis. Angiogenesis study was presented using the Tg(fli1a:EGFP) transgenic strain. In addition, acridine orange staining was used to examine the apoptotic cells in vivo.
RESULTS
As expected, the mvda morphants showed abnormal morphology of the epidermis. Moreover, we observed ectopic sprouts in trunk angiogenesis and impaired formation of the caudal vein plexus in the mvda-deficient zebrafish. Besides, increased apoptosis was found throughout the tail, heart, and eyes in mvda zebrafish morphants.
CONCLUSIONS
These findings indicated the essential role of mvda in the early development of zebrafish. This was the first in vivo knockdown study of the zebrafish mvda gene, which might offer insight into the biological function of the human MVD gene.
Topics: Animals; Animals, Genetically Modified; Cell Differentiation; Humans; Morphogenesis; Phenotype; Zebrafish
PubMed: 34051853
DOI: 10.1186/s40659-021-00341-7