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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 -
Clinical Reviews in Allergy & Immunology Dec 2023Recent advances in medical genetics elucidated the background of diseases characterized by superficial dermal and epidermal inflammation with resultant aberrant... (Review)
Review
Recent advances in medical genetics elucidated the background of diseases characterized by superficial dermal and epidermal inflammation with resultant aberrant keratosis. This led to introducing the term autoinflammatory keratinization diseases encompassing entities in which monogenic mutations cause spontaneous activation of the innate immunity and subsequent disruption of the keratinization process. Originally, autoinflammatory keratinization diseases were attributed to pathogenic variants of CARD14 (generalized pustular psoriasis with concomitant psoriasis vulgaris, palmoplantar pustulosis, type V pityriasis rubra pilaris), IL36RN (generalized pustular psoriasis without concomitant psoriasis vulgaris, impetigo herpetiformis, acrodermatitis continua of Hallopeau), NLRP1 (familial forms of keratosis lichenoides chronica), and genes of the mevalonate pathway, i.e., MVK, PMVK, MVD, and FDPS (porokeratosis). Since then, endotypes underlying novel entities matching the concept of autoinflammatory keratinization diseases have been discovered (mutations of JAK1, POMP, and EGFR). This review describes the concept and pathophysiology of autoinflammatory keratinization diseases and outlines the characteristic clinical features of the associated entities. Furthermore, a novel term for NLRP1-associated autoinflammatory disease with epithelial dyskeratosis (NADED) describing the spectrum of autoinflammatory keratinization diseases secondary to NLRP1 mutations is proposed.
Topics: Humans; Psoriasis; Inflammation; Mutation; Immunity, Innate; Keratosis; Guanylate Cyclase; Membrane Proteins; CARD Signaling Adaptor Proteins; Interleukins
PubMed: 38103162
DOI: 10.1007/s12016-023-08971-3 -
Journal of Drugs in Dermatology : JDD Dec 2023Porokeratosis is a group of disorders characterized by aberrant skin keratinization secondary to genetic alterations in the mevalonate pathway, which participates in... (Meta-Analysis)
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.
Topics: Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Porokeratosis; Lovastatin; Simvastatin; Cholesterol
PubMed: 38051843
DOI: 10.36849/JDD.7775 -
Actas Dermo-sifiliograficas Feb 2024
Review
Topics: Male; Humans; Porokeratosis; Scrotum; Buttocks
PubMed: 38048959
DOI: 10.1016/j.ad.2023.11.005 -
Clinical Genetics Mar 2024The evolutionarily conserved mevalonate pathway plays an important role in the synthesis of cholesterol and isoprenoid compounds. Mevalonate kinase (MVK) and...
The evolutionarily conserved mevalonate pathway plays an important role in the synthesis of cholesterol and isoprenoid compounds. Mevalonate kinase (MVK) and phosphomevalonate kinase (PMVK) enzymes regulate key rate-limiting steps in this pathway by sequentially phosphorylating mevalonic acid to yield downstream metabolites that regulate protein prenylation and cell signaling. Biallelic pathogenic variants in MVK cause a spectrum of rare autoinflammatory disorders that encompass milder forms of hyper-IgD syndrome (HIDS) at one end and the more severe mevalonic aciduria on the other. In contrast, pathogenic variants reported in PMVK are heterozygous and associated with porokeratosis, a skin disorder with no systemic manifestations. Recently, biallelic variants in PMVK were reported as a cause for an autoinflammatory disorder for the first time in two unrelated patients. In this study, we describe a child with recurrent arthritis and a HIDS-like phenotype harboring a novel homozygous variant c.398 C>T (p.Ala133Val) in PMVK. Mononuclear cells isolated from the patient showed significantly elevated production of interleukin 1β, a key cytokine that shapes the inflammatory response in HIDS. Protein modeling studies suggested potential defects in PMVK enzyme activity. These results posit a further expanding of the genotypic spectrum of autoinflammatory disease to include biallelic PMVK variants.
Topics: Child; Humans; Genotype; Mevalonate Kinase Deficiency; Phenotype; Phosphotransferases (Alcohol Group Acceptor); Phosphotransferases (Phosphate Group Acceptor)
PubMed: 38018277
DOI: 10.1111/cge.14451 -
Journal Der Deutschen Dermatologischen... Jan 2024
Topics: Humans; Follow-Up Studies; Mutation; Porokeratosis; Skin
PubMed: 37940570
DOI: 10.1111/ddg.15268 -
Case Reports in Dermatology 2023Porokeratosis is a group of well-known clinically distinct entities, characterised by different clinical aspects, but sharing a single common histological aspect, namely...
Porokeratosis is a group of well-known clinically distinct entities, characterised by different clinical aspects, but sharing a single common histological aspect, namely the cornoid lamella. Usually, porokeratosis occurs in the limbs and trunk, while it rarely involves the face, especially as an exclusive, single, and solitary lesion. We report the case of a 52-year-old Caucasian woman, with an 11-month history of a 2-cm slowly growing solitary, keratotic lesion on her left cheekbone. The patient did not present other cutaneous lesions on the face, as well as in other body sites. A cutaneous biopsy showed epidermal hyperplasia with multiple, sharply defined cornoid lamella, associated with an underlying attenuation of the granular layer and scattered dyskeratotic cells in the spinous layer. The superficial dermis underneath showed a mild lymphocytic infiltrate and fibrosis with remodelled collagen bundles. A final diagnosis of solitary facial porokeratosis was made.
PubMed: 37899946
DOI: 10.1159/000530936 -
Acta Dermato-venereologica Oct 2023is missing (Short communication).
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Topics: Humans; Porokeratosis; Basophils; Interleukins; Pruritus
PubMed: 37815092
DOI: 10.2340/actadv.v103.6560 -
Journal of Drugs in Dermatology : JDD Oct 2023Porokeratosis is a rare group of acquired or hereditary dermatoses characterized by linear or annular plaques with a keratotic border. DSAP is the most common... (Review)
Review
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.
Topics: Humans; Porokeratosis; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Photochemotherapy; Imiquimod; Retinoids
PubMed: 37801522
DOI: 10.36849/JDD.7540 -
Pediatric Dermatology 2024A 2-year-old boy presented with an extensive, asymptomatic, photosensitive eruption refractory to topical steroids and tretinoin; examination and biopsies were...
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.
Topics: Child, Preschool; Humans; Male; Cholesterol; Lovastatin; Mevalonic Acid; Porokeratosis; Treatment Outcome
PubMed: 37726979
DOI: 10.1111/pde.15427