What Have We Learned about the Prevention of NMSC from Albino Patients from Malawi? Secondary Prevention Maintained over Time.

BACKGROUND: We have conducted cooperative campaigns focusing on albino patients in a rural area of Malawi. What have we learned? METHODS: Three surgical campaigns were performed in Nkhotakota district (2019-2023). Albino clinical and tumor characteristics were collected. RESULTS: Between 22 and 75 albinos were evaluated in each campaign (mean age < 28 years old). Most patients did not use sunscreen in a way that provided optimal photoprotection. Regarding tumors, the proportion of basal and squamous cell carcinomas ranged from 1:1 to almost 2:1. Of 156 albino patients, 34 attended more than once. However, of the 19 patients with 30 tumors operated on in 2021, only seven were assessed the following year (12 were lost to follow-up). At least 14 albinos with locally advanced tumors were evaluated. CONCLUSIONS: Distributing photoprotective clothing could be more efficient or perhaps an earlier measure of sunscreen in rural Africa as it does not require permanent repositioning. Very-high-risk patients (previous interventions with positive margins or high-risk tumors, intense actinic damage, and new tumors constantly appearing, especially those presenting SCCs) require close follow-up and treatment and represent our main target. Secondary prevention with Malawian collaboration and the use of teledermatology is essential for patient tracking, as they are able to offer curative treatments.

A novel rapamycin cream formulation improves facial angiofibromas associated with tuberous sclerosis complex: a double-blind randomized placebo-controlled trial.

BACKGROUND: Facial angiofibromas (FAs) are a major feature of tuberous sclerosis complex (TSC). Topical rapamycin can successfully treat FAs. A new stabilized cream formulation that protects rapamycin from oxidation has been developed in 0.5% and 1% concentrations. OBJECTIVES: To assess the efficacy and safety of a novel, stabilized topical rapamycin cream formulation. METHODS: This multicentre double-blind randomized placebo-controlled dose-response phase II/III study with a parallel design included participants aged 6-65 years with FAs of mild or moderate severity according to the Investigator's Global Assessment (IGA) scale. Participants were randomized to one of three treatment arms: topical rapamycin 0.5%, topical rapamycin 1% or placebo. Treatment was applied once daily for 26 weeks. Safety and efficacy measures were assessed at days 14, 56, 98, 140 and 182. The primary endpoint was the percentage of participants achieving IGA scores of 'clear' or 'almost clear' after 26 weeks of treatment. Secondary measures included Facial Angiofibroma Severity Index (FASI) and participant- and clinician-reported percentage-based improvement. Safety measures included the incidence of treatment-emergent adverse events and blood rapamycin concentration changes over time. RESULTS: Participants (n = 107) were randomized to receive either rapamycin 1% (n = 33), rapamycin 0.5% (n = 36) or placebo (n = 38). All treated participants were included in the final analysis. The percentage of participants with a two-grade IGA improvement was greater in the rapamycin 0.5% treatment group (11%) and rapamycin 1% group (9%) than in the placebo group (5%). However, this was not statistically significant [rapamycin 0.5%: odds ratio (OR) 1.71, 95% confidence interval (CI) 0.36-8.18 (P = 0.50); rapamycin 1%: OR 1.68, 95% CI 0.33-8.40 (P = 0.53)]. There was a statistically significant difference in the proportion of participants treated with rapamycin cream that achieved at least a one-grade improvement in IGA [rapamycin 0.5%: 56% (OR 4.73, 95% CI 1.59-14.10; P = 0.005); rapamycin 1%: 61% (OR 5.14, 95% CI 1.70-15.57; P = 0.004); placebo: 24%]. Skin adverse reactions were more common in patients following rapamycin application (64%) vs. placebo (29%). CONCLUSIONS: Both rapamycin cream formulations (0.5% and 1%) were well tolerated, and either strength could lead to clinical benefit in the treatment of FA.

Cutaneous lesions and mitochondrial hearing loss: A case report.

Pathogenic sequence changes in mitochondrial DNA (mtDNA) are one of the most common causes of genetic hearing loss. We report an infant with palmoplantar hyperkeratosis, extrapalmoplantar cutaneous features and mitochondrial sensorineural hearing loss caused by the previously reported pathogenic NC_012920:m.7445A > G sequence change in the mitochondrial gene COX1 (COX1, MT-CO1). Next generation sequencing- based technology was key for the diagnosis and management of this patient.

Recalcitrant granulomatous periorificial dermatitis with good response to low-dose oral isotretinoin.

Granulomatous periorificial dermatitis is a clinical variant of periorificial dermatitis. We present the case of an 18-year-old girl with several reddish papular lesions in the perioral, perinasal, and periorbital regions unresponsive to conventional therapy. After 6 months of therapy with low-dose oral isotretinoin, the lesions fully remitted.

ATP6V0A2-related cutis laxa in 10 novel patients: Focus on clinical variability and expansion of the phenotype.

In ATP6V0A2-related cutis laxa, the skin phenotype varies from a wrinkly skin to prominent cutis laxa and typically associates with skeletal and neurological manifestations. The phenotype remains incompletely characterized, especially in adult patients. Glycosylation defects and reduced acidification of secretory vesicles contribute to the pathogenesis, but the consequences at the clinical level remain to be determined. Moreover, the morphology of the elastic fibres has not been studied in ATP6V0A2-related cutis laxa, nor its relation with potential clinical risks. We report on the extreme variability in ATP6V0A2-related cutis laxa in 10 novel patients, expand the phenotype with emphysema and von Willebrand disease and hypothesize on the pathogenesis that might link both with deficiency of glycosylation and with elastic fibre anomalies. Our data will affect clinical management of patients with ATP6V0A2-related cutis laxa.

Facial solitary morphea profunda presenting with painful trigeminal neuropathy: A case report.

BACKGROUND: Localized facial scleroderma usually presents as frontal linear morphea or progressive hemifacial atrophy. Only isolated cases of trigeminal painful neuropathy have been described. CASE REPORT: A 43-year-old woman developed an oval lesion on the right cheek. After 1 year, she noticed constant "pulling" pain and episodes of lancinating pain, both spontaneous and triggered by chewing and cold drinks. She was diagnosed with solitary morphea profunda and CT scan, ultrasonography, cranial MRI and biopsy were completed. Methylprednisolone (1 gr/day for 3 days) was prescribed. For pain, gabapentin, oxcarbazepine, amitryptiline, pregabalin and eslicarbacepine were all ineffective. A capsaicin patch was placed with prolonged benefit. Later on, the pain slightly worsened; occipital blockade was effective and methotrexate was recommended. CONCLUSION: This is the first case of solitary morphea profunda associated with painful trigeminal neuropathy. Treatment should include immunosuppressants and treatment of neuropathic pain, in which local therapies seem particularly beneficial.