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ImportanceCurrent topical treatment options for seborrheic dermatitis are limited by efficacy and/or safety.ObjectiveTo assess safety and efficacy of roflumilast foam, 0.3%, in adult patients with seborrheic dermatitis affecting the scalp, face, and/or trunk.Design, Setting, and ParticipantsThis multicenter (24 sites in the US and Canada) phase 2a, parallel group, double-blind, vehicle-controlled clinical trial was conducted between November 12, 2019, and August 21, 2020. Participants were adult (aged ≥18 years) patients with a clinical diagnosis of seborrheic dermatitis for a 3-month or longer duration and Investigator Global Assessment (IGA) score of 3 or greater (at least moderate), affecting 20% or less body surface area, including scalp, face, trunk, and/or intertriginous areas. Data analysis was performed from September to October 2020.InterventionsOnce-daily roflumilast foam, 0.3% (n = 154), or vehicle foam (n = 72) for 8 weeks.Main Outcomes and MeasuresThe main outcome was IGA success, defined as achievement of IGA score of clear or almost clear plus 2-grade improvement from baseline, at week 8. Secondary outcomes included IGA success at weeks 2 and 4; achievement of erythema score of 0 or 1 plus 2-grade improvement from baseline at weeks 2, 4, and 8; achievement of scaling score of 0 or 1 plus 2-grade improvement from baseline at weeks 2, 4, and 8; change in Worst Itch Numeric Rating Scale (WI-NRS) score from baseline; and WI-NRS success, defined as achievement of 4-point or greater WI-NRS score improvement in patients with baseline WI-NRS score of 4 or greater. Safety and tolerability were also assessed.ResultsA total of 226 patients (mean [SD] age, 44.9 [16.8] years; 116 men, 110 women) were randomized to roflumilast foam (n = 154) or vehicle foam (n = 72). At week 8, 104 (73.8%) roflumilast-treated patients achieved IGA success compared with 27 (40.9%) in the vehicle group (P P Conclusions and RelevanceThe results from this phase 2a randomized clinical trial of once-daily roflumilast foam, 0.3%, demonstrated favorable efficacy, safety, and local tolerability in the treatment of erythema, scaling, and itch caused by seborrheic dermatitis, supporting further investigation as a nonsteroidal topical treatment.Trial RegistrationClinicalTrials.gov Identifier: NCT04091646

To compare the safety and efficacy of a novel hyaluronic acid injectable gel with 0.3% lidocaine (test device) with that of a commercially available injectable hyaluronic acid gel with 0.3% lidocaine (comparator) for lip augmentation.Eligible patients (n = 158) with an overall score of very thin (n = 0) or thin (n = 1) on a 5-point Lip Fullness Grading Scale (LFGS) participated in the double-blind, randomized, multicenter study. Efficacy was assessed periodically over 6 months on a per protocol (PP) population (definitive) and a modified intent-to-treat (mITT) population (supportive).In the PP population, the mean change from baseline (day 56) in LFGS score was 1.52 for the test device and 1.53 for the comparator. This 56-day change was the primary efficacy endpoint. The 95% confidence interval (CI) limits for the mean difference in scores (test device minus comparator) were -0.33 and 0.31. In the mITT population, the corresponding 95% CI limits were -0.26 and 0.31. In both populations, the lower limits, -0.33 and -0.26, were higher than the prespecified -0.50, indicating that the test device was non-inferior to comparator. The adverse event profile was similar between the treatment groups. Ninety-three percent of patients treated with test device considered themselves improved, much improved, or very much improved at day 168 compared to 82% of those treated with comparator. The corresponding investigator improvement ratings were 100% and 76%, respectively.For lip augmentation, the efficacy and safety of the test device is non-inferior to comparator. J Drugs Dermatol. 2022;21(1):13-20 doi:10.36849/JDD.6548.

Itch is the most bothersome symptom reported by patients with psoriasis. Safe and effective treatments for psoriasis that also address itch are needed.To report effects of roflumilast cream on itch-related outcomes from a Phase 2b trial.Adults with chronic plaque psoriasis were randomized to roflumilast 0.3%, roflumilast 0.15%, or vehicle once-daily for 12 weeks. Psoriasis severity was assessed via the Investigator Global Assessment (IGA; a 5-point scale assessing plaque thickening, scaling, and erythema ranging from 0 [clear] to 4 [severe]) and ≥ 2 on a modified Psoriasis Area and Severity Index (PASI-HD, which combines severity of lesions and area affected, ranging from 0 [no disease] to 72 [maximal disease], with the actual percentage of the anatomical area involved in those patients with 10% of anatomical area involved [e.g., 0.1 for 1% to 0.9 for 9%]). Itch was evaluated via Worst Itch Numeric Rating Scale (WI-NRS), Psoriasis Symptom Diary (PSD) Items 1 (severity of itch) and 2 (bother of itch), and itch-related sleep loss NRS scores. Post hoc correlation analyses between WI-NRS and PASI, WI-NRS and itch-related sleep loss, and WI-NRS and DLQI were also performed.Roflumilast-treated patients had significantly greater improvements than vehicle-treated patients in WI-NRS and PSD Items 1 and 2 beginning at Week 2 and in itch-related sleep loss Weeks 6 through 12. Among patients with baseline WI-NRS ≥ 6, significantly more patients achieved ≥ 4-point improvement with roflumilast than with vehicle as early as Week 2. Itch severity had low correlation with PASI while WI-NRS and IGA were not always aligned.The first assessment was at 2 weeks, limiting the ability to assess early onset of itch response.Roflumilast cream improved itch and itch-related sleep loss associated with chronic plaque psoriasis.NCT03638258.

Background Psoriasis vulgaris is commonly treated with topical corticosteroids and vitamin D analogues. Although potent and super-potent topical corticosteroids are very effective at clearing psoriasis, with short-term reactive treatment durations, symptoms usually recur after treatment discontinuation, necessitating long-term disease management strategies. A foam formulation of calcipotriol and betamethasone dipropionate (Cal/BD foam), consisting of calcipotriol 50 μg/g and betamethasone dipropionate 0.5 mg/g, is approved for the daily treatment of psoriasis for up to 4 weeks. Here, we describe a clinical trial protocol for evaluating the long-term safety and efficacy of twice-weekly Cal/BD foam as a proactive topical maintenance therapy for plaque psoriasis for up to 52 weeks. Objective The aim of this trial was to evaluate the safety and efficacy of Cal/BD foam when applied twice weekly for up to 52 weeks as proactive maintenance therapy, with the goal of preventing or delaying disease relapse as long as possible while minimizing adverse effects. Methods Once-daily Cal/BD foam treatment responders from an initial 4-week open-label period were randomized to receive Cal/BD foam or foam vehicle applied to previously cleared plaques twice weekly for up to 52 weeks. In case of relapse, affected subjects in either group received rescue therapy with once-daily Cal/BD foam for 4 weeks on active areas. Thus, the trial (NCT02899962) compared the long-term use of Cal/BD foam in a proactive approach with a conventional, reactive approach. Planned Outcomes Efficacy endpoints included the time to first relapse, the number of relapse-free days, and the number of relapses during the maintenance phase. Safety assessments included adverse events, incidence of rebound, local safety and tolerability scores, and effects on calcium metabolism and hypothalamic–pituitary–adrenal axis function. Trial registration ClinicalTrials.gov identifier, NCT02899962. Electronic supplementary material The online version of this article (10.1007/s12325-020-01497-6) contains supplementary material, which is available to authorized users.

Introduction: Seborrheic dermatitis (SD) is a common, chronic, inflammatory dermatosis that affects patients of all ages with a global prevalence ≥5%. Treatments usually consist of topical therapies, including antifungals and low potency corticosteroids; however, current treatments have limitations such as side effects with long-term use and/or vehicles that can be difficult to use on both hair-bearing and non-hair-bearing areas. Roflumilast is a selective, nonsteroidal, highly potent phosphodiesterase-4 inhibitor once-daily foam under investigation for the treatment of SD. Efficacy, safety, and local tolerability of roflumilast foam 0.3% in patients with SD were demonstrated in a phase 2a and subsequent open-label trial (NCT04091646 and NCT04445987, respectively). Here, we present efficacy, safety, and local tolerability in a phase 3 trial of roflumilast foam 0.3% in patients with SD (NCT04973228). Methods: This phase 3 randomized, parallel group, double blind, vehicle-controlled trial was conducted in patients ≥9 years old with at least moderate SD affecting scalp and/or non-scalp areas. Patients were randomized 2:1 to apply once-daily roflumilast foam 0.3% (n=304) or vehicle (n=153) for 8 weeks. The primary efficacy endpoint was Investigator Global Assessment (IGA) Success (IGA of Clear or Almost Clear plus ≥2-grade improvement from baseline) at Week 8. Secondary efficacy endpoints included IGA score of Clear at Week 8, achievement of ≥4-point improvement from baseline in Worst Itch Numeric Rating Score (WI-NRS) among patients with baseline score ≥4 (WI-NRS Success), Overall Assessment of Erythema score of 0, and Overall Assessment of Scaling score of 0. Safety and local tolerability were also evaluated. Results: Overall, significantly more roflumilast-treated patients than vehicle-treated patients achieved the primary efficacy endpoint of IGA Success (79.5% vs. 58.0%; P

Calcipotriene 0.005% plus betamethasone dipropionate 0.064% (Cal/BD) aerosol foam is a topical agent indicated for the treatment of plaque psoriasis. While topical treatments are typically reserved for milder disease, in clinical trials with Cal/BD foam, the vast majority of patients had beyond-mild psoriasis at baseline, and multiple studies (including subgroup analyses from randomized controlled trials and other small-scale studies) have demonstrated favorable outcomes with the use of Cal/BD foam in this population. The objective of this article is to review existing data on the efficacy, safety, and cost-effectiveness of Cal/BD foam used in patients with beyond-mild psoriasis, either alone as topical monotherapy or as adjunctive therapy. Practical recommendations for managing beyond-mild psoriasis with Cal/BD foam are also provided. J Drugs Dermatol. 2020;19(8): doi:10.36849/JDD.2020.5300.

BACKGROUND Onychomycosis is a fungal disease that affects the fingernails and toenails and is predominantly caused by dermatophytes. VT-1161 is a novel inhibitor of fungal CYP51 through the inhibition of lanosterol demethylase, and has demonstrated potent activity against Trichophyton rubrum and Trichophyton mentagrophytes. OBJECTIVES To evaluate the safety and efficacy of four dosing regimens of orally administered VT-1161 compared with placebo in patients with moderate-to-severe distal and lateral subungual onychomycosis of the toenail. METHODS This was a phase II, randomized, double-blind, placebo-controlled, multicentre study (ClinicalTrials.gov identifier NCT02267356). Patients aged 18-70 years (n = 259) who had 25-75% mycotic involvement were randomized to five treatment groups. They received 300 mg VT-1161 as a 2-week daily dose, followed by a once-weekly dose for either 10 or 22 weeks, or 600 mg VT-1161 as a 2-week daily dose, followed by a once-weekly dose for either 10 or 22 weeks. All treatments were followed by a nontreatment period of 36 weeks. A matching placebo arm was included. RESULTS In the intent-to-treat population, at week 48 the complete cure rates were 0% in the placebo group and ranged from 32% to 42% in the VT-1161 treatment groups (P < 0·001 vs. placebo). VT-1161 was well tolerated, with no evidence of an adverse effect on liver function or QT intervals. CONCLUSIONS VT-1161 treatment led to high nail clearance rates and a favourable safety profile. VT-1161 exhibits characteristics that appear promising for the treatment of this chronic and difficult-to-treat condition and warrants further evaluation in larger studies.

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A 46-year-old white male with a history of HIV (CD4 245), acquired epidermodysplasia verruciformis, anal carcinoma in situ, hepatitis B and C presented with 3 asymptomatic, nontender, firm pink/skin-colored nodules involving the arm, left lateral leg, and right third finger. One year later, he developed a similar lesion on his right medial lower leg. Excisional biopsy of one of the lesions showed an atypical spindle cell neoplasm of the dermis compatible with a low-grade sarcoma of fibroblastic origin. Testing for human herpes virus-8, 23 human papillomavirus types, Epstein-Barr virus, and FUS fusion protein were negative. The patient underwent diagnostic imaging with computed tomography scans of the chest, abdomen, and pelvis along with positron emission tomography scan to ensure that there was no other occult primary tumor, all of which were negative. The lesions were excised and have not recurred with 3 years of follow-up. The best histopathologic term for these lesions is multiple low-grade sarcomas of fibroblastic phenotype. They have been proven to be nonaggressive, with little or no metastatic potential. This is a neoplastic process that has not been well defined in the literature. To our knowledge, there are no previous reports of these lesions occurring in multiple sites or in an HIV-positive patient.

Objective: To evaluate the efficacy of fixed combination aerosol foam calcipotriene 0.005% (Cal) plus betamethasone dipropionate 0.064% (BD). Design: Patients were randomized (100:101:101) to receive Cal/BD foam, Cal foam, or BD foam once daily for four weeks. Setting: Twenty-eight United States centers. Participants: 302 patients (≥18 years) with Psoriasis vulgaris (plaque Psoriasis; ≥mild disease severity by physicians global assessment). Measurements: Treatment success of the body (“clear”/”almost clear” from baseline moderate/severe disease; “clear” from baseline mild disease). Involved scalp treatment success was an additional endpoint. Results: Most patients (76%) had moderate Psoriasis of the body (66% for scalp). At Week 4, 45 percent of Cal/BD foam patients achieved treatment success, significantly more than Cal foam (14.9%; OR 4.34 [95%CI 2.16,8.72] P

Background Tufted angioma (TA) is a benign cutaneous vascular tumor that most commonly occurs in young children. TAs have rarely been reported in adults and/or arising within port-wine stains (PWS). Kasabach–Merritt phenomenon (KMP) is a life-threatening consumptive coagulopathy hypothesized to occur specifically in young children who develop either a TA or kaposiform hemangioendothelioma. Methods Here we present a 52-year-old man with hepatitis C cirrhosis who presented with an extensive, painful vascular tumor involving the right side of his head, neck, and back that initially arose within a PWS. Results He developed petechiae, severe thrombocytopenia, and a consumptive coagulopathy consistent with KMP. An incisional biopsy of his vascular tumor was compatible with a TA. Numerous treatments aimed at halting proliferation of his TA were attempted, with sustained improvement in his vascular tumor and platelet count achieved only after several courses of electron beam radiation therapy in association with corticosteroids and bevacizumab. Conclusion To our knowledge, this represents the first report of KMP in an adult man associated with TA and challenges previous hypotheses arguing that KMP occurs only in children. We offer our own hypothesis concerning how, in extremely rare circumstances, this life-threatening consumptive coagulopathy may occur in adults. Electron beam radiation therapy in association with corticosteroids can be an effective treatment in these rare patients.

Several unusual clinical presentations of bullous pemphigoid have been described such as localized, vesicular, vegetating, nodular, and sine bulla pemphigoid. Patients with erythroderma who fulfill diagnostic criteria for bullous pemphigoid and in whom bullae develop have been reported. We describe a patient with exfoliative erythroderma without any blistering in whom a diagnosis of bullous pemphigoid was based on examination of a biopsy specimen. Circulating antibodies to the basement membrane zone, with an epidermal pattern on salt split skin, and the presence of eosinophilic spongiosis in the skin biopsy specimen supported the diagnosis.

Background Psoriasis is a common, nonulcerative skin disorder. Observations We describe 3 men recently referred to our institution for evaluation and treatment of severe, ulcerative psoriasis that ultimately was determined to be aggressive, cytotoxic, cutaneous lymphoma. Each had a history of relatively indolent, nonulcerative patches and plaques (duration, 2-45 years) that changed to ulcerated lesions; these rapidly progressed and eventuated in death. Conclusions The clinical characteristics of the skin lesions and the histopathologic findings form a distinct and rare presentation of cutaneous lymphoma. The initial course is similar to that of mycosis fungoides but eventuates in a highly aggressive disease with fatal outcome.

Background Dermatitis herpetiformis (DH) is a cutaneous manifestation of gluten sensitivity, occasionally associated with other autoimmune disorders, and reportedly associated with an increased risk of lymphoproliferative disorders. We describe a series of patients with DH, focusing on associated disorders (particularly celiac disease), incidence of lymphoma, histopathology, and sensitivity of direct immunofluorescence (DIF) testing and serologic testing with antiendomysium antibodies for the diagnosis of DH. Methods The medical records of 264 patients with DH diagnosed between 1970 and 1996 were reviewed retrospectively. In addition, the records of six patients evaluated before the advent of DIF testing between 1932 and 1969 were reviewed. Results Established celiac disease was present in 12.6% of patients with DH, autoimmune systemic disorders in 22.2%, malignant neoplasms in 10.4%, sarcoidosis in four patients, and ulcerative colitis in six patients. Lymphoproliferative disorders were found in seven patients. The histopathologic examinations showed a marked predominance of neutrophils in the inflammatory infiltrate. DIF testing was positive in 92.4% of the patients tested. Indirect immunofluorescence assay indicated circulating antiendomysial antibodies in the sera of 40 of the 63 patients tested (63.5%). Conclusions In this large series of patients with DH from a single institution, patients had a low incidence of symptomatic gluten-sensitive enteropathy, low risk of lymphoproliferative disorders, and associations with other systemic autoimmune disorders. The value of DIF testing in the diagnosis of DH was confirmed. The detection of antiendomysial antibodies by indirect immunofluorescence was less sensitive than indicated by other reports.

An elderly woman of Bahamian heritage with Fitzpatrick VI skin type presented with a 1-week history of indolent papules all over her body. She was otherwise asymptomatic. Findings from physical examination were notable for discrete skin-colored to pink papules coalescing into plaques on her face, trunk (Figure, A and B), and all 4 extremities. There was no scale or other epidermal change. A punch biopsy for hematoxylin-eosin staining was performed (Figure, C). The patient returned 1 week later with worsening cutaneous eruptions and new complaints of fever, weakness, and malaise. Repeat physical examination revealed splenomegaly and axillary lymphadenopathy. A peripheral blood smear (Figure, D) and other diagnostic tests were performed. A B

We describe a 45-year-old white man in whom distinctive clinical and histologic features of localized scleroderma developed at sites of injection of vitamin K 1 (phytonadione). A direct immunofluorescence test demonstrated prominent linear deposition of IgA along the basement membrane zone. No circulating antibasement membrane zone IgA antibodies were identified on indirect immunofluorescence testing. We believe that the unusual immunofluorescence finding in our patient is nonspecific and represents an epiphenomenon caused by cutaneous injury. (J Am Acad Dermatol 1998;38:322-4.)