Berdazimer gel for molluscum contagiosum: An integrated analysis of 3 randomized controlled trials.

BACKGROUND: An out-of-office therapeutic agent indicated for molluscum contagiosum is needed. OBJECTIVE: To assess the efficacy and safety of berdazimer gel, 10.3% (a topical, antiviral, nitric oxide-releasing medication) versus vehicle. METHODS: Berdazimer gel, 10.3% or vehicle was applied once daily to all molluscum contagiosum lesions for 12 weeks in patients ≥6 months with 3-70 mollusca. Efficacy assessment: complete lesion clearance and partial clearance at week 12. Safety and tolerability assessment: adverse events through week 24 and local skin reactions through week 12. RESULTS: There were 1598 patients enrolled (n = 917 berdazimer, n = 681 vehicle). Berdazimer was superior to vehicle at week 12 in complete clearance rates, 30.0% versus 19.8% (odds ratio, 1.75; 95% CI, 1.38-2.23, P < .001). Subgroup analyses of primary efficacy showed consistent favorable efficacy for berdazimer across most subgroups, including age, sex, baseline lesion count, and disease duration. Berdazimer provided favorable outcome for partial clearance. Application-site pain (18.7% vs 4.8% in berdazimer vs vehicle) and erythema (11.7% vs 1.3%), mostly mild to moderate, were the most common local skin reactions. LIMITATIONS: Berdazimer sodium in molluscum patients with lesions (B-SIMPLE) trials enrolled only US patients; no efficacy assessments beyond week 12. CONCLUSIONS: Berdazimer gel, 10.3% showed favorable efficacy and safety across subgroups.

Characterization of wound microbes in epidermolysis bullosa: A focus on Pseudomonas aeruginosa.

The most common bacteria isolated from wound cultures in patients recorded in the Epidermolysis Bullosa Clinical Characterization and Outcomes Database (EBCCOD) are Staphylococcus aureus and Pseudomonas aeruginosa. Given the prevalence of P. aeruginosa in this patient population and prior research implicating P. aeruginosa's potential role in carcinogenesis, we sought to further analyze patients with recorded wound cultures positive for Pseudomonas aeruginosa in the EBCCOD. We provide a descriptive analysis of this subset of patients and highlight potential avenues for future longitudinal studies that may have significant implications in our wound care management for patients with epidermolysis bullosa.

The use of Janus kinase inhibitors and narrowband ultraviolet B combination therapy in non-segmental vitiligo.

Vitiligo is a depigmentation disorder of the skin that occurs secondary to the destruction of melanocytes by an immune-mediated process. Vitiligo clinically presents with depigmented macules and patches, most commonly on the face, acral sites, and genitalia. It can be characterized as generalized or localized based on distribution. The localized form can be further divided into segmental (linear, band-like, or Blaschkoid) and non-segmental vitiligo. The classical treatment of vitiligo includes topical steroids, pulsed oral steroids in unstable vitiligo, phototherapy, a combination of steroid therapy and phototherapy, surgical grafting, as well as intentional depigmentation therapy in severe cases. However, recent advances in understanding the immune mechanisms implicated in the pathogenesis of vitiligo have led to the use of an FDA-approved topical Janus kinase (JAK) inhibitors for vitiligo. Despite this novel therapy advancement, we recommend the addition of narrowband ultraviolet B (NB-UVB) to JAK inhibitors in patients with extensive and progressive lesions, or those not fully responsive to JAK inhibitor monotherapy.

Efficacy and Safety of Topical Nitric Oxide-Releasing Berdazimer Gel in Patients With Molluscum Contagiosum: A Phase 3 Randomized Clinical Trial.

Importance: Molluscum contagiosum (MC) is a highly contagious skin condition. Lesions may persist for months to years, and no US Food and Drug Administration-approved medications are currently available in the US. Objective: To assess the efficacy and safety of berdazimer gel, 10.3%, a novel topical nitric oxide-releasing medication, in the treatment of MC. Design, Setting, and Participants: This was a multicenter, vehicle-controlled, double-blind, phase 3 randomized clinical trial (B-SIMPLE4) conducted in 55 clinics (mostly dermatology and pediatric) in the US from September 1, 2020, to July 21, 2021. Eligible participants were 6 months or older and had from 3 to 70 raised MC lesions. Patients with sexually transmitted MC or with MC only in the periocular area were excluded. Interventions: Patients were randomized to treatment with berdazimer gel, 10.3%, or vehicle gel, applied as a thin layer to all lesions once daily for 12 weeks. Main Outcomes and Measures: The primary efficacy end point was complete clearance of all MC lesions at week 12. Safety and tolerability measures included adverse event frequency and severity, and assessment of local skin reactions and scarring. Data analyses were performed from August 31, 2021, to September 14, 2021. Results: A total of 891 participants were randomized, 444 to berdazimer, 10.3% (mean [range] age, 6.6 [0.9-47.5] years; 228 [51.4%] male; 387 [87.2%] White individuals), and 447 to vehicle (mean [range] age, 6.5 [1.3-49.0] years; 234 [52.3%] female; 382 [85.5%] White individuals). In the intention-to-treat population, 88.5% (393 patients) in the berdazimer group and 88.8% (397 patients) in the vehicle group had a lesion count performed at week 12. At week 12, 32.4% (144 patients) in the berdazimer group achieved complete clearance of MC lesions compared with 19.7% (88 patients) in the vehicle group (absolute difference, 12.7%; odds ratio, 2.0; 95% CI, 1.5-2.8; P < .001) with 14.4% (64 patients) of the berdazimer group discontinuing treatment because of MC clearance compared with 8.9% (40 patients) of the vehicle group. Adverse event rates were low. The most common adverse events were application-site pain and erythema, mostly mild in severity. Adverse events leading to discontinuation affected 4.1% (18 patients) of the berdazimer group and 0.7% (3 patients) of the vehicle group. The most common local skin reaction was mild to moderate erythema. Conclusions and Relevance: Use of berdazimer gel, 10.3%, for MC appears to demonstrate favorable efficacy and safety with low adverse event rates. Trial Registration: ClinicalTrials.gov Identifier: NCT04535531.

A retrospective analysis of diagnostic testing in a large North American cohort of patients with epidermolysis bullosa.

BACKGROUND: Accurate diagnosis of epidermolysis bullosa (EB) has significant implications for prognosis, management, and genetic counseling. OBJECTIVE: To describe diagnostic testing patterns and assess diagnostic concordance of transmission electron microscopy (TEM), immunofluorescence mapping (IFM), and genetic analysis for EB. METHODS: A retrospective cohort included patients enrolled in the Epidermolysis Bullosa Clinical Characterization and Outcomes Database from January 1, 2004, to July 8, 2019. Tests concluding the same EB type (EB simplex, junctional EB, dominant dystrophic EB, and recessive dystrophic EB) were considered concordant; those concluding different EB types were considered discordant; and those with nonspecific/nondefinitive results were equivocal. RESULTS: A total of 970 diagnostic tests were conducted from 1984 to 2018 in 771 patients. Genetic analyses were performed chronologically later than IFM or TEM (P < .001). The likelihood of undergoing genetic analysis was greater for junctional EB and recessive dystrophic EB, and the same for dominant dystrophic EB as compared with EB simplex. TEM results in 163 patients were equivocal (55%), concordant (42%), and discordant (3%). IFM results in 185 patients were equivocal (54%), concordant (42%), and discordant (4%). LIMITATIONS: Retrospective design. CONCLUSIONS: Diagnostic testing has shifted in favor of genetic analysis. TEM and IFM frequently offer equivocal findings when compared to the specificity afforded by genetic analysis.

Pediatric Subungual Exostosis.

Exostosis is a type of benign bone tumor in which trabecular (spongy) bone overgrows its normal border in a nodular pattern. When the growth occurs under the nail bed, it is termed subungual exostosis or Dupuytren exostosis. This condition may mimic other bony abnormalities such as an osteochondroma and may present with nail deformities with or without pain. For this reason, a biopsy of the lesion is necessary to rule out a precancerous growth. In rare cases, pediatric patients may have subungual exostosis, as demonstrated in our case.

Characterization of wound microbes in epidermolysis bullosa: Results from the epidermolysis bullosa clinical characterization and outcomes database.

BACKGROUND/OBJECTIVES: Patients with epidermolysis bullosa (EB) require care of wounds that are colonized or infected with bacteria. A subset of EB patients are at risk for squamous cell carcinoma, and bacterial-host interactions have been considered in this risk. The EB Clinical Characterization and Outcomes Database serves as a repository of information from EB patients at multiple centers in the United States and Canada. Access to this resource enabled broad-scale analysis of wound cultures. METHODS: A retrospective analysis of 739 wound cultures from 158 patients from 13 centers between 2001 and 2018. RESULTS: Of 152 patients with a positive culture, Staphylococcus aureus (SA) was recovered from 131 patients (86%), Pseudomonas aeruginosa (PA) from 56 (37%), and Streptococcus pyogenes (GAS) from 34 (22%). Sixty-eight percent of patients had cultures positive for methicillin-sensitive SA, and 47%, methicillin-resistant SA (18 patients had cultures that grew both methicillin-susceptible and methicillin-resistant SA at different points in time). Of 15 patients with SA-positive cultures with recorded mupirocin susceptibility testing, 11 had mupirocin-susceptible SA and 6 patients mupirocin-resistant SA (2 patients grew both mupirocin-susceptible and mupirocin-resistant SA). SCC was reported in 23 patients in the entire database, of whom 10 had documented wound cultures positive for SA, PA, and Proteus species in 90%, 50%, and 20% of cases, respectively. CONCLUSIONS: SA and PA were the most commonly isolated bacteria from wounds. Methicillin resistance and mupirocin resistance were reported in 47% and 40% of patients tested, respectively, highlighting the importance of ongoing antimicrobial strategies to limit antibiotic resistance.

Skin cleansing and topical product use in patients with epidermolysis bullosa: Results from a multicenter database.

BACKGROUND/OBJECTIVES: Epidermolysis bullosa (EB) comprises a group of inherited skin blistering diseases. There is currently no cure, and management includes skin protection and prevention of infection. To date, there has been no systematic investigation of home skin care practices among EB patients on a multicenter scale. METHODS: This cross-sectional, observational study included data collected from patients with EB enrolled in the Epidermolysis Bullosa Characterization and Clinical Outcomes Database (EBCCOD) who provided answers to a patient-directed questionnaire between January 1, 2017, and December 31, 2017. RESULTS: Of 202 respondents, 130 (64.4%) had dystrophic EB, 51 (25.2%) had EB simplex, 21 (7.4%) had junctional EB, 3 (1.5%) had Kindler syndrome, and 3 (1.5%) had an unspecified subtype. Seventy-eight patients reported cleansing in plain water only (39%). Of those who used an additive in their cleansing water, 75 (57%) added salt, 71 (54%) added bleach, 36 (27%) added vinegar, and 34 (26%) endorsed the use of an "other" additive (multiple additives possible). Reported concentrations of additives ranged widely from 0.002% sodium hypochlorite and 0.002% acetic acid solutions, which are thought to have negligible effects on microbes, to 0.09% sodium hypochlorite and 0.156% acetic acid, concentrations shown to be cytotoxic. One hundred eighty-eight patients answered questions regarding topical product use (93%). Of those, 131 reported topical antimicrobial use (70%). Mupirocin and bacitracin were the most commonly reported topical antibiotics (59, 58 [31.4%, 30.9%], respectively). CONCLUSIONS: These findings highlight the variety of skin care routines and frequent use of topical antimicrobials among EB patients and have potential implications for antibiotic resistance. The reported range of bleach and vinegar additives to cleansing water, including cytotoxic concentrations, emphasizes the need for clear and optimized skin cleansing recommendations.

Assessment of the Timing of Milestone Clinical Events in Patients With Epidermolysis Bullosa From North America.

Importance: Children with epidermolysis bullosa (EB) comprise a rare population with high morbidity and mortality. An improved understanding of the clinical trajectory of patients with EB, including age at time of clinical diagnosis and major clinical events, is needed to refine best practices and improve quality of life and clinical outcomes for patients with EB. Objectives: To describe demographics, clinical characteristics, milestone diagnostic and clinical events (such as initial esophageal dilation), and outcomes in patients with EB using the Epidermolysis Bullosa Clinical Characterization and Outcomes Database and to determine what characteristics may be associated with overall EB severity and/or disease progression. Design, Setting, and Participants: This cohort study included data on patients with EB who were enrolled in the Epidermolysis Bullosa Clinical Characterization and Outcomes Database from January 1, 2011, to June 30, 2017; 17 participating EB centers in the United States and Canada contributed data to this study. Exposures: Type of EB, including recessive dystrophic epidermolysis bullosa (RDEB), junctional epidermolysis bullosa (JEB), dominant dystrophic epidermolysis bullosa (DDEB), and epidermolysis bullosa simplex (EBS). Main Outcomes and Measures: Demographic information, clinical characteristics (including age at onset of signs of EB and subsequent clinical diagnosis), types of diagnostic testing performed, and milestone clinical events for patients with RDEB. Results: Of 644 enrolled patients from 17 sites included in this study, 323 were male (50.2%), with a mean (SD) age of 14.4 (11.7) years; 283 (43.9%) had RDEB, 194 (30.1%) had EBS, 104 (16.2%) had DDEB, and 63 (9.8%) had JEB. Signs of disease were present at birth in 202 patients with RDEB (71.4%), 39 with JEB (61.9%), 60 with DDEB (57.7%), and 74 with EBS (38.1%). For those with signs of disease at birth, a clinical diagnosis was made at the time of birth in 135 patients with RDEB (67.0%), 31 with DDEB (52.6%), 35 with EBS, (47.3%) and 18 with JEB (46.2%). Patients with JEB had the highest rate of any confirmatory testing (51 of 63 [81.0%]), followed by RDEB (218 of 283 [77.0%]), DDEB (71 of 104 [68.3%]), and EBS (100 of 194 [51.5%]). For all types of EB, both electron microscopy and immunofluorescence microscopy were performed at younger ages than genetic analysis. Among 283 patients with RDEB, 157 (55.5%) had esophageal dilation, 104 (36.7%) had gastrostomy tube placement, 62 (21.9%) had hand surgery, 18 (6.4%) developed squamous cell carcinoma, and 19 (6.7%) died. Conclusions and Relevance: The findings suggest that diagnostic testing for EB is more common for patients with severe phenotypes. Earlier diagnostic testing may enable improved characterizations of patients so that appropriate counseling and clinical care may be offered, especially pertaining to milestone events for those with RDEB.

East Indian Sandalwood Oil Is a Phosphodiesterase Inhibitor: A New Therapeutic Option in the Treatment of Inflammatory Skin Disease.

Cyclic adenosine monophosphate phosphodiesterases (PDEs) regulate pro-inflammatory cytokine production. One isoform, PDE4, is overactive in chronic relapsing inflammatory skin diseases: psoriasis and eczema/atopic dermatitis, and in several cancers. East Indian sandalwood oil (EISO) has significant anti-inflammatory properties. Here, we report that 75% of pediatric eczema/atopic dermatitis patients treated with topical EISO formulations achieved a >50% reduction in their Eczema Area and Severity Index score. EISO treatment of a psoriasis model reduced PDE4 expression and reversed histopathology. EISO directly inhibited PDE enzymatic activity in vitro. In lipopolysaccharide-stimulated human dermal fibroblast, BEAS-2B, A549, and THP-1 cells, EISO suppressed total cellular PDE activity, PDE4, and 7 transcript levels, nuclear factor kappa B (NF-κB) activation, and pro-inflammatory cytokines/chemokine production. These results suggest that EISO anti-inflammatory activity is mediated through suppressing PDE activity, thus facilitating cAMP-regulated inhibition of NF-κB and indicate EISO as an attractive natural therapeutic for chronic and acute inflammatory disorders.

A Case of Psoriasis Replaced by Allergic Contact Dermatitis in a 12-Year-Old Boy.

Allergic contact dermatitis is a significant clinical problem in children and one that the use of essential oils and natural remedies probably exacerbates. We report a case of chronic plaque psoriasis replaced by allergic contact dermatitis in a 12-year-old boy. We suspect that the immunologic response to a hapten in lavender oil disrupted the pathogenesis of psoriasis, causing the psoriasis to temporarily "disappear."

Vesicular rash in a newborn girl.

The appearance and pattern of this child's rash led us to suspect a rare diagnosis. The findings of a cutaneous biopsy confirmed it.

Pediatric morphea.

This article outlines the epidemiology, pathogenesis, clinical presentation, diagnosis, and treatment of childhood morphea. Also known as localized scleroderma, morphea is a fibrosing disorder of the skin and subcutaneous tissues. Morphea is differentiated from systemic sclerosis (scleroderma) based on the absence of sclerodactyly, Raynaud phenomenon, and nail-fold capillary changes. Confusion may occur because patients with morphea often have systemic symptoms such as malaise, fatigue, arthralgias, myalgias, and positive autoantibodies. Unlike morphea, systemic sclerosis has organ involvement, particularly gastrointestinal, pulmonary, and renal.

Complications of ichthyosis beyond the skin.

Although ichthyoses are noted for their skin features, like many dermatologic conditions, patients are often impacted in ways beyond the skin. Much has been described in recent years regarding quality of life and skin disorders. This is certainly the case for ichthyosis. For neonates or others with diffuse involvement of their skin, nutritional needs are often exceeding normal requirements. These can often result in growth abnormalities. Lastly, with specific subtypes of ichthyosis, compromise of tissues around the eyes and ears can be of concern to some patients. Certainly, some forms of ichthyosis are routinely complicated by such findings. It is important for practitioners caring for individuals with ichthyosis to have these issues in mind.