The Molting Man: Anasarca-Induced Full-Body Desquamation.

Blisters and subsequent desquamation of the skin in the presence of acute edema is a well-known clinical phenomenon. In this case report, we describe a new variant that we have termed anasarca-induced desquamation in a 50-year-old man with molting of the entire cutaneous surface after acute edema, in a setting of 40-lb weight gain over 5 days. Laboratory workup for infectious causes and punch biopsies of skin lesions ruled out Stevens-Johnson syndrome and staphylococcal scalded skin syndrome, which have a similar clinical presentation to anasarca-induced desquamation. In patients with diffuse superficial desquamation in the setting of acute edema, anasarca-induced desquamation is worth investigating to avoid the use of corticosteroids and intravenous antibiotics in this inherently benign condition.

Efficacy and Safety of Bimekizumab in Moderate to Severe Hidradenitis Suppurativa: A Phase 2, Double-blind, Placebo-Controlled Randomized Clinical Trial.

IMPORTANCE: Hidradenitis suppurativa (HS) is a chronic inflammatory disease with a high burden for patients and limited existing therapeutic options. OBJECTIVE: To evaluate the efficacy and safety of bimekizumab, a monoclonal IgG1 antibody that selectively inhibits interleukin 17A and 17F in individuals with moderate to severe HS. DESIGN, SETTING, AND PARTICIPANTS: This phase 2, double-blind, placebo-controlled randomized clinical trial with an active reference arm was performed from September 22, 2017, to February 21, 2019. The study included a 2- to 4-week screening period, a 12-week treatment period, and a 20-week safety follow-up. Of 167 participants screened at multiple centers, 90 were enrolled. Eligible participants were 18 to 70 years of age with a diagnosis of moderate to severe HS 12 months or more before baseline. INTERVENTIONS: Participants with HS were randomized 2:1:1 to receive bimekizumab (640 mg at week 0, 320 mg every 2 weeks), placebo, or reference arm adalimumab (160 mg at week 0, 80 mg at week 2, and 40 mg every week for weeks 4-10). MAIN OUTCOMES AND MEASURES: The prespecified primary efficacy variable was the proportion of participants with a 50% or greater reduction from baseline in the total abscess and inflammatory nodule count with no increase in abscess or draining fistula count (Hidradenitis Suppurativa Clinical Response [HiSCR] at week 12. Exploratory variables included proportion achieving a modified HiSCR with 75% reduction of HiSCR criteria (HiSCR75) or a modified HiSCR with 90% reduction of HiSCR criteria (HiSCR90), change in Patient's Global Assessment of Pain, and Dermatology Life Quality Index total scores. RESULTS: Eighty-eight participants received at least 1 dose of study medication (61 [69%] female; median age, 36 years; range, 18-69 years). Seventy-three participants completed the study, including safety follow-up. Bimekizumab demonstrated a higher HiSCR rate vs placebo at week 12 (57.3% vs 26.1%; posterior probability of superiority equaled 0.998, calculated using bayesian analysis). Bimekizumab demonstrated greater clinical improvements compared with placebo. Improvements in the International Hidradenitis Suppurativa Severity Score (IHS4) were seen at week 12 with bimekizumab (mean [SD] IHS4, 16.0 [18.0]) compared with placebo (mean [SD] IHS4, 40.2 [32.6]). More bimekizumab-treated participants achieved positive results on stringent outcome measures compared with placebo. At week 12, 46% of bimekizumab-treated participants achieved HiSCR75 and 32% achieved HiSCR90, whereas 10% of placebo-treated participants achieved HiSCR75 and none achieved HiSCR90; in adalimumab-treated participants, 35% achieved HiSCR75 and 15% achieved HiSCR90. One participant withdrew because of adverse events. Serious adverse events occurred in 2 of 46 bimekizumab-treated participants (4%), 2 of 21 placebo-treated participants (10%), and 1 of 21 adalimumab-treated participants (5%). CONCLUSIONS AND RELEVANCE: In this phase 2 randomized clinical trial, bimekizumab demonstrated clinically meaningful improvements across all outcome measures, including stringent outcomes. Bimekizumab's safety profile was consistent with studies of other indications, supporting further evaluation in participants with HS. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT03248531.

Tolerability and Pharmacokinetics of Ingenol Mebutate 0.05% Gel Applied to Treatment Areas up to 100cm(2) on the Forearm(s) of Patients with Actinic Keratosis.

OBJECTIVE: To determine safety, tolerability, and systemic absorption of ingenol mebutate 0.05% gel applied for two consecutive days to treatment areas up to 100cm(2) on the forearm(s) of patients with actinic keratosis. DESIGN AND SETTING: Two studies are reported: a Phase 1, multicenter, open-label, dose-area escalation cohort study (http://www.clinicaltrials.gov/ct2/show/NCT00659893) and a Phase 2, double-blind, vehicle-controlled pharmacokinetic study (http://clinical trials.gov/ct2/show/NCT00852137). PARTICIPANTS: The Phase 1 study included male patients (n=65), mean age 68.1 years; the Phase 2 study included both male and female patients (n=16), mean age 63.3 years. MEASUREMENTS: In the Phase 1 study, patients assigned to escalating dose-area cohorts were evaluated for local skin responses, adverse events, and any other relevant safety data. In the pharmacokinetic study, blood samples were collected pre-dose and for up to 24 hours after administration on Day 2, and analyzed for ingenol mebutate and its primary metabolites. In both studies, safety assessments were performed on Days 2, 3, 8, 15, 29, and 57 (study end). RESULTS: In the Phase 1 study, most adverse events were mild, and all treatment-related adverse events resolved before the end of the study. The 100cm(2) treatment area showed a small increase in the overall intensity of mean composite local skin response scores. There was no quantifiable systemic exposure to ingenol mebutate or its primary metabolites. CONCLUSION: Ingenol mebutate 0.05% gel has a good safety profile when applied to treatment areas up to 100cm(2) with acceptable tolerability and local skin responses. There is no systemic absorption following application to areas of 100cm(2).

A multicenter, randomized, vehicle-controlled phase 2 study of blue light photodynamic therapy with aminolevulinic acid HCl 20% topical solution for the treatment of actinic keratoses on the upper extremities: the effect of occlusion during the drug incubation period.

BACKGROUND: Photodynamic therapy (PDT) with aminolevulinic acid (ALA) has been shown to be safe and effective in the treatment of actinic keratoses (AKs) of the face and scalp. A recent small study has suggested that ALA-PDT can be effective for AKs of the dorsal hands/forearms. However, studies designed to provide sufficient statistical power to test this hypothesis are lacking in the literature. OBJECTIVES: To determine and compare the safety and efficacy of blue light ALA-PDT vs blue light placebo vehicle (VEH) in the treatment of AKs of the upper extremities and to evaluate the effect of occlusion after application of ALA vs VEH. METHODS: ALA or VEH was applied to both dorsal hands/forearms for the 3-hour incubation period before blue light treatment (10 J/ cm2). One extremity of each subject was covered with occlusive dressing during the incubation period. Treatment was repeated at week 8 if any AK lesions remained. RESULTS: The median AK lesion clearance rate at week 12 was 88.7% for extremities treated with occluded ALA (ALA+OCC), 70.0% for extremities treated with nonoccluded ALA, 16.7% for extremities treated with occluded VEH (VEH+OCC), and 5.6% for extremities treated with nonoccluded VEH (P<.0001). ALA+OCC resulted in a significantly higher clearance rate compared with the nonoccluded extremity at weeks 8 (P=.0006) and 12 (P=.0029). Thirty-four percent (12/35) of extremities treated with ALA+OCC had complete clearance of lesions at week 12 compared with 0% (0/35) of extremities treated with VEH+OCC (P=.0002). The safety pro!le in this study is consistent with previously reported side effects of the therapy. CONCLUSION: Blue light ALA-PDT following a 3-hour incubation appears efficacious for AK clearance of the upper extremities. Incubation using an occlusive dressing significantly increases the efficacy of the procedure and also increases the incidence and severity of some acute inflammatory side effects of PDT.

Randomized, double-blind, double-dummy, vehicle-controlled study of ingenol mebutate gel 0.025% and 0.05% for actinic keratosis.

BACKGROUND: There is a need for improved medical approaches to the treatment of actinic keratosis. Ingenol mebutate, a diterpene ester extracted and purified from the plant Euphorbia peplus, is being evaluated as a topical therapy for actinic keratosis. OBJECTIVE: Assess the efficacy and safety of ingenol mebutate (formerly PEP005) gel at 3 dosing regimens for the treatment of actinic keratosis. METHODS: Patients with non-facial actinic keratoses applied vehicle gel for 3 days, ingenol mebutate gel, 0.025% for 3 days, or ingenol mebutate gel, 0.05% for 2 or 3 days, with an 8-week follow-up period. RESULTS: All 3 active treatments were significantly more effective than vehicle at clearing actinic keratosis lesions, with a dose response observed. The partial clearance rate (primary efficacy end point) for patients treated with ingenol mebutate gel ranged from 56.0% to 75.4% compared with 21.7% for vehicle gel (P = .0002 to P < .0001 vs vehicle). The complete clearance rate was also significantly higher (P < or = .0006) for patients in the ingenol mebutate gel treatment groups (range: 40.0% to 54.4%) compared with vehicle (11.7%), as was the baseline clearance rate (range: 42.0% to 57.9% for ingenol mebutate gel compared with 13.3% for vehicle, P < .0001 to .0007 vs vehicle). The median percentage reduction in baseline actinic keratosis lesions for patients treated with ingenol mebutate gel ranged from 75% to 100% compared with 0% for vehicle gel (P < .0001 vs vehicle). Active treatment was well tolerated at all dosages. The mechanism of action of this agent is the localized induction of necrosis followed by a transient inflammatory response, and this was manifested in most patients as transient local skin responses consisting primarily of erythema, flaking/scaling, and crusting. There was no evidence of treatment-related scarring. LIMITATIONS: Local skin responses may have suggested active treatment to investigators. CONCLUSIONS: Short-course, field-directed therapy with ingenol mebutate gel for actinic keratoses on non-facial sites seems to be effective with a favorable safety profile and potential benefits over topical agents that require a more prolonged course of treatment.