464 Analysis of IL36RN and CARD14 gene mutation in Japanese patients with generalized pustular psoriasis and palmoplanter pustulosis

Abstract

IL36RN mutations and CARD14 mutations are reportedly responsible for generalized pustular psoriasis (GPP), palmoplanter pustulosis (PPP) and other pustular diseases. IL36 receptor antagonist deficiency, or DITRA, is thought to stem from the IL36RN gene mutation in GPP. In this study, we discuss a patients background, disease characteristics, and IL36RN and CARD14 gene mutations in patients with GPP and PPP who visited our department after 2013. We assessed the severity of skin lesions using the Psoriasis Area and Severity Index (PASI) or Palmoplanter pustulosis Area and Severity Index (PPPASI). There were 29 patients with GPP (14 males, 15 females) with an average age of 54 years. There were 36 patients with GPP (3 males, 33 females) with an average age of 55 years. As focal infections, Oral infectious lesions (apical lesions, periodontitis, dental caries, and pulpitis), tonsillitis, and sinusitis were observed. In 25 patients with GPP, we identified four cases of IL36RN gene mutation and four cases of CARD14 gene mutation. In 36 patients with PPP, three cases of IL36RN gene mutation and three cases of CARD14 gene mutation. None of the patients had both IL36RN and CARD14 mutations. No novel mutation was found in the exon analyzed at this time. All four GPP patients with IL36RNgene mutations had psoriasis vulgaris before GPP. Among patients with genetic mutation, many presented focal infections which generally responded well to treatment. Screening and treatment of focal infectious were considered to be important for GPP as well as PPP patients with either an IL36RN or CARD 14 gene mutation. 465 A-101 (hydrogen peroxide) topical solution safety and efficacy in patients with seborrheic keratoses: Results from two identical randomized, double-blind, placebo-controlled, phase 3 studies

Efficacy and safety of spesolimab in Asian patients with a generalized pustular psoriasis flare: Results from the randomized, double‐blind, placebo‐controlled Effisayil™ 1 study

“…As such, blockade of the IL-36 pathway could be an effective therapeutic approach for GPP. 1,5,18,[33][34][35][36][37][38] In the Effisayil™ 1 study (NCT03782792), patients with a GPP flare treated with spesolimab, a humanized anti-IL-36 receptor monoclonal antibody and the first targeted treatment for GPP to be studied in a randomized clinical trial, achieved rapid pustular and skin clearance with an acceptable safety profile. 39 At Week 1, the primary endpoint (Generalized Pustular Psoriasis Physician Global Assessment [GPPGA] pustulation subscore of 0, no visible pustules) was achieved by 54% of patients receiving spesolimab compared with 6% receiving placebo (one-sided p < 0.001).…”

“…Evidence suggests that the interleukin (IL)‐36 pathway plays a key role in the pathology of GPP, and several studies have indicated that Asian patients with GPP have high rates (46.8%–81.8%) of mutations in IL36RN , the gene encoding the IL‐36 receptor antagonist. As such, blockade of the IL‐36 pathway could be an effective therapeutic approach for GPP 1,5,18,33–38 …”

“…As such, blockade of the IL‐36 pathway could be an effective therapeutic approach for GPP. 1 , 5 , 18 , 33 , 34 , 35 , 36 , 37 , 38 …”