Search

Summary: Background: Palmoplantar pustulosis (PPP) is a rare, debilitating, chronic inflammatory skin disease that affects the hands and feet. Clinical, immunological and genetic findings suggest a pathogenic role for interleukin (IL)‐1. Objectives: To determine whether anakinra (an IL‐1 receptor antagonist) delivers therapeutic benefit in PPP. Methods: This was a randomized (1 : 1), double‐blind, two‐staged, adaptive, UK multicentre, placebo‐controlled trial [ISCRTN13127147 (registered 1 August 2016); EudraCT number: 2015‐003600‐23 (registered 1 April 2016)]. Participants had a diagnosis of PPP (> 6 months) requiring systemic therapy. Treatment was 8 weeks of anakinra or placebo via daily, self‐administered subcutaneous injections. Primary outcome was the Palmoplantar Pustulosis Psoriasis Area and Severity Index (PPPASI) at 8 weeks. Results: A total of 374 patients were screened; 64 were enrolled (31 in the anakinra arm and 33 in the placebo arm) with a mean (SD) baseline PPPASI of 17·8 (10·5) and a PPP investigator's global assessment of severe (50%) or moderate (50%). The baseline adjusted mean difference in PPPASI favoured anakinra but did not demonstrate superiority in the intention‐to‐treat analysis [–1·65, 95% confidence interval (CI) –4·77 to 1·47; P = 0·30]. Similarly, secondary objective measures, including fresh pustule count (2·94, 95% CI –26·44 to 32·33; favouring anakinra), total pustule count (–30·08, 95% CI –83·20 to 23·05; favouring placebo) and patient‐reported outcomes, did not show superiority of anakinra. When modelling the impact of adherence, the PPPASI complier average causal effect for an individual who received ≥ 90% of the total treatment (48% in the anakinra group) was –3·80 (95% CI –10·76 to 3·16; P = 0·285). No serious adverse events occurred. Conclusions: No evidence for the superiority of anakinra was found. IL‐1 blockade is not a useful intervention for the treatment of PPP. What is already known about this topic?Treatment options for palmoplantar pustulosis include superpotent corticosteroids, phototherapy, acitretin, methotrexate and ciclosporin. However, these have poor evidence for benefit and there is a risk of toxicity with long‐term use.Anakinra is a recombinant interleukin (IL)‐1 receptor antagonist that blocks the activity of IL‐1α and IL‐1β, two cytokines repeatedly linked to neutrophil activation and extravasation.A therapeutic benefit of anakinra has been shown in neutrophilic dermatoses and conditions that manifest with skin pustulation. What does this study add?Anakinra was not significantly superior to placebo at 8 weeks in objective investigator‐assessed and patient‐reported measures.A greater proportion of participants in the anakinra group strongly agreed that the treatment was worthwhile.The safety profile of anakinra was consistent with previous studies.This is one of the largest randomized controlled trials for this rare condition, providing important data on its natural history and change in disease severity over time. Linked Comment: S.N. Lo and J.F. Thompson. Br J Dermatol 2022; 186:205–206. Plain language summary available online [ABSTRACT FROM AUTHOR]

Angiolymphoid hyperplasia with eosinophilia is a rare benign vascular lesion most commonly affecting the head and neck region. This article reports a case of a 26-year-old white woman with rapidly enlarging nodules of the upper lip and cheek treated successfully with oral corticosteroids and cetirizine. Morbidity and cosmetic deformity associated with radical surgery to the face and possible consequences of radiation treatment were avoided. There were no long-term complications. [ABSTRACT FROM AUTHOR]

Summary: Background: Bullous pemphigoid (BP) is a subepidermal blistering disease characterized by autoantibodies against the two hemidesmosomal proteins, BP180 (type XVII collagen) and BP230. The multicentre prospective BLISTER (Bullous Pemphigoid Steroids and Tetracyclines) trial randomized 253 patients with BP to compare the benefits and harms between initial treatment with doxycycline or prednisolone. Objectives: To analyse distinct autoantibody profiles for the prediction of the disease course in a well‐characterized cohort of BP sera. Methods: One hundred and forty‐three patients of the BLISTER trial consented to participate in this serological study. Sera taken at baseline were analysed by (i) indirect immunofluorescence, (ii) anti‐BP180 NC16A (16th noncollagenous domain) and anti‐BP230 enzyme‐linked immunosorbent assay and (iii) immunoblotting with various substrates. Results were then linked with clinical parameters including age, Karnofsky score, number of blisters, related adverse events and mortality. Results: Disease activity correlated with immunoglobulin (Ig)G anti‐BP180 levels but not with levels of anti‐BP230 IgG and anti‐BP180 IgE. High levels of both anti‐BP180 IgG and anti‐BP230 IgG were associated with a low Karnofsky score. The presence of anti‐BP230 IgG was more frequent in older patients. Those with higher total IgE serum levels suffered from fewer adverse events. Higher IgG anti‐BP180 levels were associated with an increased 1‐year mortality rate. Conclusions: Analysis of the autoantibody profile is not only of diagnostic relevance but may also be helpful in predicting the course of the disease. What's already known about this topic? Serum levels of immunoglobulin (Ig)G autoantibodies against BP180 correlate with disease activity in bullous pemphigoid (BP).Reports about the correlation of serum anti‐BP180 IgE with disease severity are inconclusive.Karnofsky score is a predictor of death in BP but to date has not been shown to be related to serum autoantibody levels. What does this study add? High serum anti‐BP180 IgG levels are associated with an increased mortality in BP.Patients with BP with a lower Karnofsky score show higher serum levels of anti‐BP180 and anti‐BP230 IgG.High levels of total serum IgE appear to be related to a lower number of treatment‐related adverse events.Patients with BP with high anti‐BP180 IgG may be at risk of fatal outcomes, while in those with high total IgE, fewer adverse events can be expected. Linked Comment: Hashimoto and Tsuruta. Br J Dermatol 2018; 179:820–821. Plain language summary available online Respond to this article [ABSTRACT FROM AUTHOR]