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Actas Dermo-sifiliograficas Sep 2020Porokeratosis comprises a group of heterogeneous and uncommon acquired or congenital skin diseases of unknown origin characterized by a keratinization disorder resulting... (Review)
Review
Porokeratosis comprises a group of heterogeneous and uncommon acquired or congenital skin diseases of unknown origin characterized by a keratinization disorder resulting from abnormal clonal expansion of keratinocytes. Numerous genetic mutations are thought to be involved. These conditions are characterized histologically by the presence of a cornoid lamella. Clinical manifestations are variable, with localized, disseminated, and even eruptive forms. Porokeratosis has been associated with immunosuppression, ultraviolet radiation, and systemic, infectious, and neoplastic diseases. Many authors consider it to be a premalignant condition because of the potential for malignant transformation to squamous cell or basal cell carcinoma. Therefore, long-term follow-up is a key component of treatment, which is usually complex and often unsatisfactory. We review the latest advances in our understanding of the pathogenesis, diagnosis, and treatment and propose a treatment algorithm.
Topics: Cell Transformation, Neoplastic; Humans; Porokeratosis; Precancerous Conditions; Skin Neoplasms; Ultraviolet Rays
PubMed: 32401728
DOI: 10.1016/j.ad.2020.03.005 -
Journal of the American Academy of... Jan 2020Porokeratosis is associated with mevalonate pathway gene mutations. Therapeutic options are few and often limited in efficacy. We hypothesized that topical therapy that...
BACKGROUND
Porokeratosis is associated with mevalonate pathway gene mutations. Therapeutic options are few and often limited in efficacy. We hypothesized that topical therapy that aims to replenish cholesterol, an essential mevalonate pathway end-product, and block the accumulation of mevalonate pathway toxic metabolites could alleviate porokeratosis.
OBJECTIVE
To study the efficacy of topical cholesterol/lovastatin in different variants of porokeratosis.
METHODS
We enrolled a series of 5 porokeratosis patients,1 with disseminated superficial actinic porokeratosis, 2 with porokeratosis palmaris et plantaris disseminata, and 2 with linear porokeratosis. Patients were genotyped before initiation of therapy. Patients then applied topical cholesterol/lovastatin twice daily to a unilaterally defined treatment area for up to 3 months. The response was evaluated and patients photographed at every visit.
RESULTS
Three patients had MVD mutations, and 2 patients had PMVK mutations. Treatment with topical cholesterol/lovastatin (but not cholesterol alone) resulted in near complete clearance of disseminated superficial actinic porokeratosis lesions after 4 weeks of therapy and moderate improvement of porokeratosis palmaris et plantaris disseminata lesions and linear porokeratosis lesions. There were no adverse events.
LIMITATIONS
Case series design with a small number of patients.
CONCLUSION
Topical cholesterol/lovastatin is an effective and well-tolerated therapy for porokeratosis that underscores the utility of a pathogenesis-based therapy that replaces deficient end products and prevents accumulation of potentially toxic precursors.
Topics: Administration, Cutaneous; Adult; Anticholesteremic Agents; Carboxy-Lyases; Child, Preschool; Cholesterol; Drug Combinations; Genotype; Humans; Lovastatin; Middle Aged; Mutation; Ointments; Phosphotransferases (Phosphate Group Acceptor); Porokeratosis; Young Adult
PubMed: 31449901
DOI: 10.1016/j.jaad.2019.08.043 -
Clinical and Experimental Dermatology May 2024
PubMed: 38747355
DOI: 10.1093/ced/llae192 -
JAMA Dermatology Feb 2023
Topics: Humans; Porokeratosis
PubMed: 36515921
DOI: 10.1001/jamadermatol.2022.5108 -
Pediatric Dermatology Nov 2022Inflammatory linear verrucous epidermal nevus (ILVEN) is a rare skin disease characterized by pruritic erythematous scaly plaques distributed along the lines of...
BACKGROUND
Inflammatory linear verrucous epidermal nevus (ILVEN) is a rare skin disease characterized by pruritic erythematous scaly plaques distributed along the lines of Blaschko. Two cases of ILVEN with CARD14 mutations and one case with a GJA1 mutation have been previously reported.
OBJECTIVE
To elucidate the genetic cause of a cohort of patients diagnosed based on clinical and histopathological evaluation with ILVEN.
METHODS
We recruited patients diagnosed with ILVEN based on clinical and histopathological criteria. Exome sequencing of affected skin with or without blood/saliva was performed and germline and somatic pathogenic variants were identified.
RESULTS
Five patients were enrolled. All had skin lesions from birth or early childhood. Two patients developed psoriasis vulgaris after the diagnosis of ILVEN. The first had a germline heterozygous CARD14 mutation and a post-zygotic hotspot mutation in KRT10. The histopathologic evaluation did not show epidermolytic hyperkeratosis. The second had a post-zygotic hotspot mutation in HRAS. Her ILVEN became itchy once psoriasis developed. One patient was re-diagnosed with linear porokeratosis based on a germline mutation in PMVK and a post-zygotic second-hit mutation. Two patients were re-diagnosed with congenital hemidysplasia with ichthyosiform nevus and limb defect nevus based on germline NSDHL mutations.
CONCLUSION
ILVEN is a clinical descriptor for a heterogenous group of mosaic inflammatory disorders. Genetic analysis has the potential to more precisely categorize ILVEN and permits pathogenesis-directed therapies in some cases.
Topics: Female; Humans; Child, Preschool; Nevus, Sebaceous of Jadassohn; Skin Neoplasms; Nevus; Nevus, Pigmented; Psoriasis; Skin Diseases; Guanylate Cyclase; Membrane Proteins; CARD Signaling Adaptor Proteins; 3-Hydroxysteroid Dehydrogenases
PubMed: 35853659
DOI: 10.1111/pde.15094 -
Clinics in Dermatology 2022Annular lichenoid diseases encompass a diverse range of pathologies that present as circular, raised, or flat lesions that may vary in size and number. Examples include...
Annular lichenoid diseases encompass a diverse range of pathologies that present as circular, raised, or flat lesions that may vary in size and number. Examples include annular lichenoid dermatitis of youth, annular lichen planus, erythema dyschromicum perstans, erythema multiforme, fixed drug eruption, lichen sclerosus, neonatal lupus, porokeratosis, subacute cutaneous lupus erythematosus, and lichenoid syphilis. Clinical morphology and histopathology can differentiate these entities.
Topics: Adolescent; Infant, Newborn; Humans; Lichenoid Eruptions; Lichen Planus; Erythema; Lupus Erythematosus, Cutaneous; Erythema Multiforme; Eczema
PubMed: 34979268
DOI: 10.1016/j.clindermatol.2021.12.009 -
JAMA Dermatology May 2023Disseminated superficial actinic porokeratosis (DSAP) is an inherited or sporadic disorder of keratinization associated with germline variations. There is no effective... (Randomized Controlled Trial)
Randomized Controlled Trial
Safety and Efficacy of Topical Lovastatin Plus Cholesterol Cream vs Topical Lovastatin Cream Alone for the Treatment of Disseminated Superficial Actinic Porokeratosis: A Randomized Clinical Trial.
IMPORTANCE
Disseminated superficial actinic porokeratosis (DSAP) is an inherited or sporadic disorder of keratinization associated with germline variations. There is no effective standard of care therapy for DSAP, but treatment with topical lovastatin combined with cholesterol cream has shown promise.
OBJECTIVES
To evaluate and compare the safety and efficacy of topical lovastatin 2% plus cholesterol 2% cream (lovastatin-cholesterol) and topical lovastatin 2% cream (lovastatin) alone in adults diagnosed with DSAP.
DESIGN, SETTING, AND PARTICIPANTS
This patient- and assessor-blinded, randomized clinical trial was conducted at the Medical University of South Carolina between August 3, 2020, and April 28, 2021. Nonpregnant adults with a previous clinical or histological diagnosis of DSAP were eligible. Data were blindly analyzed after study completion.
INTERVENTIONS
Participants were randomized to once- or twice-daily application of either lovastatin-cholesterol cream (n = 17) or lovastatin cream (n = 14) to symptomatic regions for 12 weeks.
MAIN OUTCOMES AND MEASURES
The primary efficacy measure was the effect of the treatment on DSAP at the end of treatment (12 weeks) as measured by the DSAP General Assessment Severity Index (DSAP-GASI; scored from 0-4, with 0 indicating clear and 4 indicating severe). Treatment efficacy was based on investigator-standardized photographs provided by the participants because of the need for evaluation via telehealth during the COVID-19 pandemic. Secondary efficacy measures included patient-reported outcomes, application frequency, and adverse events (AEs).
RESULTS
Of the 87 participants screened, 32 were enrolled. One participant randomized to receive lovastatin-cholesterol did not receive the intervention, leaving 17 participants (mean [range] age, 59.2 [40-83] years; 13 females [76.5%]; all White) allocated to receive lovastatin-cholesterol treatment and 14 participants (13 female [92.9%]; mean (range) age, 53.7 [33-71] years; all White) to receive lovastatin treatment. Twelve participants in each treatment group qualified for the analysis. Disease severity decreased from week 1 to week 12 by 50.0% (from 3.08 [95% CI, 2.57-3.60] to 1.54 (95% CI, 1.04-2.05] points on the DSAP-GASI; P < .001) in the lovastatin-cholesterol group and 51.4% (from 2.92 [95% CI, 2.40-3.43] to 1.50 [95% CI, 0.99-2.01] points; P < .001) in the lovastatin group. There was no significant difference between the treatment groups according to application frequency at the end of 12 weeks. Adverse events reported included myalgia (n = 2), elevation in the creatine kinase level (n = 1), application discomfort (n = 4), and rash (n = 1). No serious AEs occurred, and all participants with an AE were able to complete the study.
CONCLUSIONS AND RELEVANCE
This randomized clinical trial found improvements in DSAP severity in both treatment groups, without serious AEs, indicating a limited benefit with the addition of cholesterol. These results suggest that lovastatin cream may be a new primary treatment option for patients diagnosed with DSAP.
TRIAL REGISTRATION
ClinicalTrials.gov Identifier: NCT04359823.
Topics: Adult; Humans; Female; Middle Aged; Lovastatin; Porokeratosis; Pandemics; COVID-19; Treatment Outcome; Emollients; Cholesterol
PubMed: 36947042
DOI: 10.1001/jamadermatol.2023.0205 -
Frontiers in Immunology 2020
Topics: Animals; Autoimmune Diseases; Autoimmunity; Humans; Inflammation; Inflammation Mediators; Keratins; Signal Transduction; Skin; Skin Diseases
PubMed: 32849625
DOI: 10.3389/fimmu.2020.01753