An Oral Interleukin-23-Receptor Antagonist Peptide for Plaque Psoriasis.

BACKGROUND: The use of monoclonal antibodies has changed the treatment of several immune-mediated inflammatory diseases, including psoriasis. However, these large proteins must be administered by injection. JNJ-77242113 is a novel, orally administered interleukin-23-receptor antagonist peptide that selectively blocks interleukin-23 signaling and downstream cytokine production. METHODS: In this phase 2 dose-finding trial, we randomly assigned patients with moderate-to-severe plaque psoriasis to receive JNJ-77242113 at a dose of 25 mg once daily, 25 mg twice daily, 50 mg once daily, 100 mg once daily, or 100 mg twice daily or placebo for 16 weeks. The primary end point was a reduction from baseline of at least 75% in the Psoriasis Area and Severity Index (PASI) score (PASI 75 response; PASI scores range from 0 to 72, with higher scores indicating greater extent or severity of psoriasis) at week 16. RESULTS: A total of 255 patients underwent randomization. The mean PASI score at baseline was 19.1. The mean duration of psoriasis was 18.2 years, and 78% of the patients across all the trial groups had previously received systemic treatments. At week 16, the percentages of patients with a PASI 75 response were higher among those in the JNJ-77242113 groups (37%, 51%, 58%, 65%, and 79% in the 25-mg once-daily, 25-mg twice-daily, 50-mg once-daily, 100-mg once-daily, and 100-mg twice-daily groups, respectively) than among those in the placebo group (9%), a finding that showed a significant dose-response relationship (P<0.001). The most common adverse events included coronavirus disease 2019 (in 12% of the patients in the placebo group and in 11% of those across the JNJ-77242113 dose groups) and nasopharyngitis (in 5% and 7%, respectively). The percentages of patients who had at least one adverse event were similar in the combined JNJ-77242113 dose group (52%) and the placebo group (51%). There was no evidence of a dose-related increase in adverse events across the JNJ-77242113 dose groups. CONCLUSIONS: After 16 weeks of once- or twice-daily oral administration, treatment with the interleukin-23-receptor antagonist peptide JNJ-77242113 showed greater efficacy than placebo in patients with moderate-to-severe plaque psoriasis. (Funded by Janssen Research and Development; FRONTIER 1 ClinicalTrials.gov number, NCT05223868.).

Topical sirolimus: Difference between compounded preparations and commercial oral solution.

Topical sirolimus has become a crucial treatment option for many dermatologic disorders. Because an FDA-approved topical formulation is not commercially available, sirolimus creams, ointments, and gels are professionally prepared by compounding pharmacies. Also, the topical use of a commercially available sirolimus solution approved for oral administration is described regularly. To better guide providers in their decision-making when topical sirolimus is being considered, this article highlights the substantial pharmaceutical and clinical differences between commercial oral solution and compounded preparations specifically designed for topical therapy.

Topical rapamycin for acanthosis nigricans in the Fitzpatrick IV/V adolescent population.

Dermatologically, FGFR3 mutations can lead to acanthosis nigricans (AN), epidermal nevi, and seborrheic keratosis. A recent case report found that topical rapamycin (sirolimus) can improve FGFR3-induced epidermal nevi with AN features in children, specifically with Fitzpatrick skin type (FST) I/II, and we would like to expand these findings to skin plaques with extensive AN-like features in the FST IV/V adolescent population. An 18-year-old female with FST IV/V and FGFR3-induced hypochondroplasia presented to our clinic with extensive AN-like plaques. Significant improvement with lightening and thinning of the plaques was observed after applying 1% topical rapamycin cream twice daily. Topical rapamycin should be considered as a treatment option for AN, particularly in FST IV/V adolescents with FGFR3-induced AN.

Analysis of lesional color to differentiate infantile hemangiomas from port-wine birthmarks in infants less than 3 months old: A pilot study.

BACKGROUND: In their early phase, infantile hemangiomas (IH) can sometimes be difficult to differentiate from port-wine birthmarks (PWB). Until recently, inexpensive diagnostic tools have not been readily available. OBJECTIVE: To determine the diagnostic utility of widely available colorimetric technology when differentiating PWB from IH in photographs of infants less than 3 months old. METHODS: Multi-center, retrospective analysis of RGB (red, green, and blue) and HSL (hue, saturation, lightness) values collected using electronic colorimeters from images of clinically confirmed untreated IH or PWB. Subgroup analysis of flat vascular birthmarks was subsequently performed. RESULTS: Images of 119 IH (specifically, 45 flat IH) and 59 PWB were identified. PWB had significantly (P < .001) higher RGB values of all primary colors, most notably for blue and green (mean difference: >50), irrespective of thickness. RGB or RGB with HSL values had an excellent accuracy (90%), sensitivity (92%), specificity (98%), and positive predictive value (98%) when discriminating PWB from flat IH. IH could be distinctly clustered from PWB when combining their RGB with HSL values. CONCLUSION: Electronic colorimeters with emphasis on blue and green values, are able to differentiate PWB from IH, irrespective of thickness, with a high degree of accuracy. A larger scale evaluation is now required.

Topical sirolimus for treatment of a solitary angiokeratoma.

Angiokeratomas are benign vascular neoplasms that arise as solitary or multiple lesions, most commonly treated with excision, electrodessication, cryotherapy, or laser therapies. This case presents a young female whose solitary angiokeratoma was treated with topical 1% sirolimus cream, improving the appearance, symptoms, and size of the lesion. Topical sirolimus cream may be a noninvasive treatment option for angiokeratomas with fewer risks than standard therapy that may be feasible and preferable for some patients.

Effectiveness of Early Laser Treatment in Surgical Scar Minimization: A Systematic Review and Meta-analysis.

BACKGROUND: Studies investigating the efficacy of lasers to minimize early surgical scars are low powered and report variable results. To further examine the evidence, the authors performed a systemic review and meta-analysis. OBJECTIVE: To present the evidence of randomized controlled trials investigating the efficacy of laser modalities in minimizing surgical scars when applied <1 month after operation. MATERIALS AND METHODS: A literature search of PubMed, EMBASE, Northern Light Life Sciences Conference Abstracts, and Cochrane Library was performed between November 6, 2015, and November 20, 2015. After assessing for inclusion, data extraction used the PRISMA checklist. Assessment for quality, validity, and risk of bias applied a scale devised by Jadad and colleagues, the Oxford Pain Validity Scale, and the RevMan risk of bias assessment tool, respectively. The GRADEpro application graded overall quality, and statistical analysis was performed with RevMan. RESULTS: Approximately 4,373/4,397 abstracts and 16/24 full articles were excluded using predefined criteria, leaving 8 articles in the systematic review and 4 in the meta-analysis. The primary outcome reached statistical significance favoring the intervention group with standardized mean difference 0.39 (95% confidence interval, 0.05-0.74) and p = .03. CONCLUSION: The outcome supports the efficacy of lasers in minimizing primarily closed surgical scars when treated <1 month after surgery.

Unconventional use of ablative fractional photothermolysis in arm contouring.

Brachioplasty, in addition to several nonsurgical interventions (e.g. cryolipolysis, noninvasive radiofrequency, and intense-focused ultrasound) have been described as efficacious in the elimination of excess skin laxity from the upper arms. Recently, fractional CO2 ablation has gained attention for its ability to reduce rhytids and improve skin texture on the face, neck, and hands. In this article, we report the first successful case of fractional CO2 ablation for upper arm contouring.

Severe irritant reaction following sequential waxing and use of a chemical depilatory cream in an adolescent.

A 15-year-old girl presented with leg wounds that were sustained after waxing and subsequent chemical depilation. History revealed prior usage of chemical depilatories without irritation. Given this finding, we suspect that waxing disrupted the epidermal barrier and, therefore, rendered the patient more susceptible to severe irritant contact dermatitis upon depilation. While there are reported cases of irritant contact dermatitis and chemical burns secondary to waxing or depilatory cream use in adults, a literature review found no reported cases of chemical burns in a pediatric patient or adult consequent to using these methods in tandem.

Treatment of benign cephalic histiocytosis with topical 1% rapamycin ointment.

We report a pediatric case of extensive, progressive benign cephalic histiocytosis (BCH) involving the face, trunk, and extremities with response of facial lesions to treatment with topical 1% rapamycin. A split-face model was used to demonstrate improvement on the treated side versus the untreated side. After physician and parental perception of effectiveness, based in part on photodocumentation, subsequently both cheeks were treated with continued improvement.

Topical sirolimus for treatment of a venolymphatic malformation in an adolescent girl.

Sirolimus has emerged as a promising treatment for complex congenital vascular malformations but is limited because of systemic side effects. Topically compounded formulations, which have been found to be successful in the treatment of several other conditions, are a preferred drug delivery system to provide local therapy. We report a case of a venolymphatic malformation in an adolescent girl treated with topical 1% sirolimus cream leading to improvement in appearance and associated symptoms.

Exogenous Cushing syndrome from an unexpected source of systemic steroids.

A 12-year-old Hispanic boy with chronic atopic dermatitis and cushingoid features presented to our institution. He was being treated with an unknown quantity of oral prednisolone 15 mg/5 mL, equivalent to 70 mg/m2 /d of oral prednisone, purchased over the counter in El Salvador. Systemic corticosteroids are not recommended for chronic therapy of atopic dermatitis because of their significant adverse effects. Foreign-sourced pharmaceuticals account for almost half of the drugs consumed in the United States, which means that, to protect our patients, medical providers must inquire about and report unsafe medications deemed legal outside the United States to the Food and Drug Administration.

Warming up to the idea of wet wraps.

Atopic dermatitis (AD) is a prevalent condition in the pediatric population that can have a significant effect on a child's quality of life. Management is multifactorial, involving topical pharmacotherapy, emollients, and a bathing regimen in conjunction with close supervision from the caregiver and physician. In the case of moderate to severe or refractory AD, wet wraps can be used. As part of our wet wrap regimen, we propose warming damp cotton pajamas in the dryer before application. This makes the wet wraps more comfortable for children, increasing adherence to the prescribed regimen.

Multilineage somatic activating mutations in HRAS and NRAS cause mosaic cutaneous and skeletal lesions, elevated FGF23 and hypophosphatemia.

Pathologically elevated serum levels of fibroblast growth factor-23 (FGF23), a bone-derived hormone that regulates phosphorus homeostasis, result in renal phosphate wasting and lead to rickets or osteomalacia. Rarely, elevated serum FGF23 levels are found in association with mosaic cutaneous disorders that affect large proportions of the skin and appear in patterns corresponding to the migration of ectodermal progenitors. The cause and source of elevated serum FGF23 is unknown. In those conditions, such as epidermal and large congenital melanocytic nevi, skin lesions are variably associated with other abnormalities in the eye, brain and vasculature. The wide distribution of involved tissues and the appearance of multiple segmental skin and bone lesions suggest that these conditions result from early embryonic somatic mutations. We report five such cases with elevated serum FGF23 and bone lesions, four with large epidermal nevi and one with a giant congenital melanocytic nevus. Exome sequencing of blood and affected skin tissue identified somatic activating mutations of HRAS or NRAS in each case without recurrent secondary mutation, and we further found that the same mutation is present in dysplastic bone. Our finding of somatic activating RAS mutation in bone, the endogenous source of FGF23, provides the first evidence that elevated serum FGF23 levels, hypophosphatemia and osteomalacia are associated with pathologic Ras activation and may provide insight in the heretofore limited understanding of the regulation of FGF23.

Characteristics and treatment pathways in pediatric and adult hidradenitis suppurativa: An examination using real world data.

Background: Hidradenitis suppurativa (HS) is a chronic, debilitating, inflammatory disease. Contemporaneous real-world data can be used to elucidate the clinical treatment of pediatric patients and how treatment strategies compare with adult hidradenitis suppurativa patients. Objective: The objective of this study is to evaluate clinical and treatment characteristics of pediatric and adult HS patients. Methods: HS adult and pediatric patients were identified in 3 the United States administrative claims databases during the study period between 2016 to 2021. Patients were required to have 2 diagnostic codes for HS and have at least 365 days of prior observation time to the first HS diagnosis. Results: Pediatric and adult HS treatments were similar. The proportions of subjects treated with topical and oral antibiotic or oral antibiotic alone or topical medication alone or surgery alone covered 90% of the treated pediatric subjects and 91% of treated adult subjects. The remaining proportion of subjects received other treatment combinations. Limitations: The databases represent subjects with commercial or government insurance coverage and thus do not necessarily represent the broader US population. The databases do not capture information about medications obtained without insurance. Conclusions: Although subtle differences exist, this study confirms that topical and systemic therapeutic treatment of HS in adults and adolescents is very similar.

The Epidemiology of Palmoplantar Pustulosis: An Analysis of Multiple Health Insurance Claims and Electronic Health Records Databases.

BACKGROUND: Palmoplantar pustulosis (PPP) is a chronic inflammatory condition characterized by sterile pustules on the palms and soles. This study evaluated the epidemiology of PPP using claims and electronic health record (EHR) databases. METHODS: Patients coded for PPP in the United States (US) and Japan from 2016 to 2020 were identified. Several PPP definitions were evaluated; the specific definition (≥ 2 visits coded for PPP, the second 31-730 days after diagnosis) was chosen for characterizing PPP epidemiology. Baseline characteristics and pre- and post-diagnosis treatments were summarized. Prevalence and incidence rates were analyzed by calendar year, sex, age, and database. RESULTS: Prevalence and incidence of PPP were higher in Japan than the US. PPP prevalence increased over time. PPP occurred predominantly in adulthood and was more common among women. Features of metabolic syndromes, anxiety, and depression were more common among US PPP patients. Consistently high baseline use of anti-bacterial, anti-inflammatory/anti-rheumatic, and obstructive airway disease treatments was observed among PPP patients. Potential miscoding or misclassification of PPP limited this analysis. Prevalence estimates from databases may differ from field- and population-based approaches. CONCLUSIONS: The burden of PPP was greater in Japan than in the US. Additional studies are needed to further elucidate PPP epidemiology worldwide.