Inhibition of IL-13: A New Pathway for Atopic Dermatitis [Formula: see text].

Dupilumab, a monoclonal antibody against the common receptor of interleukin (IL)-4 and IL-13, was the first biologic therapy approved in Canada for treatment of moderate-to-severe atopic dermatitis (AD). While it is considered safe and effective, dupilumab is not universally effective and 8%-38% of patients develop conjunctivitis, while some patients develop head and neck dermatitis. Thus, new therapeutic options are warranted. While both IL-4 and IL-13 play important roles in the pathogenesis of AD, it has been recently demonstrated that IL-13 is the primary upregulated cytokine in AD skin biopsy samples. A placebo-controlled phase 2b clinical trial evaluating the efficacy and safety of lebrikizumab, an IL-13 inhibitor, in AD demonstrated that, at 16 weeks, Eczema Area and Severity Index (EASI) 75 and Investigator's Global Assessment (IGA) 0/1 were achieved by 60.6% and 44.6% of patients taking lebrikizumab at its highest dose (vs 24.3% and 15.3% of patients taking placebo, respectively). Moreover, treatment with lebrikizumab was associated with rapid improvement of pruritus and low rates of conjunctivitis (1.4%-3.8%). Another IL-13 monoclonal antibody, tralokinumab, was evaluated for safety and efficacy in moderate-to-severe AD. By week 12, among adults receiving 300 mg tralokinumab, 42.5% achieved EASI-75 and 26.7% achieved IGA 0/1 score (vs 15.5% and 11.8% in the placebo group, respectively). Both lebrikizumab and tralokinumab demonstrated acceptable safety profiles in AD (and non-AD) trials with adverse events often being comparable between treatment and control groups. Thus, IL-13 inhibitors may provide a safe and effective treatment alternative for patients with moderate-to-severe AD.

Safety of Direct Drug Provocation for the Evaluation of Penicillin Allergy in Low-Risk Adults.

BACKGROUND: About 10% of patients have a penicillin allergy label, but less than 5% of them are actually allergic. Unnecessary penicillin avoidance is associated with serious medical consequences. Given the growing number of these labels, it is imperative that our diagnostic strategy for penicillin allergy be as efficient as possible. The validity of traditionally used skin tests (STs) has been questioned, whereas drug provocation testing (DPT), the criterion standard, without previous ST appears very safe in most cases. OBJECTIVE: To evaluate the safety of direct DPT without consideration for ST results and the validity of ST in the diagnosis of penicillin allergy. METHODS: In this prospective cohort study without a control group, we recruited patients consulting an allergist for penicillin allergy. Patients underwent ST followed by DPT regardless of ST results. Patients with anaphylaxis to penicillin within the past 5 years or a severe delayed reaction were excluded, as were those with significant cardiorespiratory comorbidity. RESULTS: None of the 1002 recruited patients had a serious reaction to DPT. Ten (1.0%) had a mild immediate reaction, of whom only 1 (0.1%) was considered likely IgE-mediated. The positive and negative predictive values of ST for an immediate reaction were 3.6% and 99.1%, respectively. CONCLUSIONS: In a low-risk adult population reporting penicillin allergy, ST has very poor positive predictive value. Direct DPT without ST is safe and appears to be an ideal diagnostic strategy to remove penicillin allergy labels that could be implemented in first-line practice.

Adenopathy and extensive skin patch overlying plasmacytoma syndrome-the clue to early diagnosis of polyneuropathy, organomegaly, endocrinopathy, monoclonal gammopathy, and skin changes: A case series and literature review.

Importance: Adenopathy and extensive skin patch overlying plasmacytoma syndrome is a paraneoplastic syndrome characterized by a cutaneous vascular patch overlying a plasmacytoma and systemic manifestations. It is thought to be an early stage of polyneuropathy, organomegaly, endocrinopathy, monoclonal gammopathy, and skin changes syndrome, which is a rare, but potentially fatal multisystemic disease that is associated with plasma cell dyscrasia. Thus, a high index of suspicion is required to identify patients with adenopathy and extensive skin patch overlying plasmacytoma as they may present with early polyneuropathy, organomegaly, endocrinopathy, monoclonal gammopathy, and skin changes, which is curable if detected early. Objective: To report additional cases of adenopathy and extensive skin patch overlying plasmacytoma syndrome, describe dermatoscopic and histologic findings of the cutaneous patch and review all up to date literature on adenopathy and extensive skin patch overlying plasmacytoma syndrome. Design: Case series from a single tertiary care center. Participants: Here, we present the second case series of three patients with adenopathy and extensive skin patch overlying plasmacytoma syndrome who all meet the diagnostic criteria for polyneuropathy, organomegaly, endocrinopathy, monoclonal gammopathy, and skin changes. The diagnosis was suspected based on the presence of the violaceous cutaneous patch along with symptoms of systemic involvement (fatigue, weight loss, weakness). Dermoscopy revealing regular dilated parallel capillaries was suggestive of a benign/reactive vascular process. Histopathology in all three cases showed reactive vascular proliferation with a characteristic 90° branching. To date only 20 cases of adenopathy and extensive skin patch overlying plasmacytoma have been published, including ours. All patients presented with cutaneous lesions (violaceous patch and others) and most, at least 15/20, met the diagnostic criteria for polyneuropathy, organomegaly, endocrinopathy, monoclonal gammopathy, and skin changes. When clinical follow-up was reported, most patients had a favorable prognosis with partial or complete symptom resolution following treatment of the underlying plasmocytoma.

Community Use of Epinephrine for the Treatment of Anaphylaxis: A Review and Meta-Analysis.

BACKGROUND: Community use of epinephrine for the treatment of anaphylaxis is low. Knowledge of rates of epinephrine use in the pre-hospital setting along with identification of barriers to its use will contribute to the development of policies and guidelines. OBJECTIVES: A search was conducted on PubMed and Embase in April 2020. Our systematic review focused on 4 domains: (1) epinephrine use in the pre-hospital setting; (2) barriers to epinephrine use in the pre-hospital setting; (3) cost evaluation and cost-effectiveness of epinephrine use; and (4) programs and strategies to improve epinephrine use during anaphylaxis. METHODS: Two meta-analyses with logit transformation were conducted to: (1) calculate the pooled estimate of the rate of epinephrine use in the pre-hospital setting among cases of anaphylaxis and (2) calculate the pooled estimate of the rate of biphasic reactions among all cases of anaphylaxis. RESULTS: Epinephrine use in the pre-hospital setting was significantly higher for children compared with adults (20.98% [95% confidence interval (CI): 16.38%, 26.46%] vs 7.17% [95% CI: 2.71%, 17.63%], respectively, P = .0027). The pooled estimate of biphasic reactions among all anaphylaxis cases was 3.92% (95% CI: 2.88%, 5.32%). Our main findings indicate that pre-hospital use of epinephrine in anaphylaxis remains suboptimal. Major barriers to the use of epinephrine were identified as low prescription rates of epinephrine autoinjectors and lack of stock epinephrine in schools, which was determined to be cost-effective. Finally, in reviewing programs and strategies, numerous studies have engineered effective methods to promote adequate and timely use of epinephrine. CONCLUSION: The main findings of our study demonstrated that across the globe, prompt epinephrine use in cases of anaphylaxis remains suboptimal. For practical recommendations, we would suggest considering stock epinephrine in schools and food courts to increase the use of epinephrine in the community. We recommend use of pamphlets in public areas (ie, malls, food courts, etc.) to assist in recognizing anaphylaxis and after that with prompt epinephrine administration, to avoid the rare risk of fatality in anaphylaxis cases.