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Effisayil 1 was a multicentre, randomized, double‐blind, placebo‐controlled study of the anti‐interleukin (IL)‐36 receptor monoclonal antibody, spesolimab, in patients presenting with a generalized pustular psoriasis (GPP) flare. Previously published data from this study revealed that within 1 week, rapid pustular and skin clearance were observed in patients receiving spesolimab versus placebo. In this pre‐specified subgroup analysis, the efficacy of spesolimab was evaluated according to patient demographic and clinical characteristics at baseline in patients receiving spesolimab (n = 35) or placebo (n = 18) on Day 1. Efficacy was by assessed by achievement of primary endpoint (Generalized Pustular Psoriasis Physician Global Assessment [GPPGA] pustulation subscore of 0 at Week 1) and key secondary endpoint (GPPGA total score of 0 or 1 at Week 1). Safety was assessed at Week 1. Spesolimab was found to be efficacious and had a consistent and favourable safety profile in patients presenting with a GPP flare, regardless of patient demographics and clinical characteristics at baseline. [ABSTRACT FROM AUTHOR]

Background: Erythrodermic and generalized pustular psoriasis are rare, difficult to treat forms of psoriasis. In previous reports, we documented 24‐ and 52‐week findings of an open‐label, phase 3 trial (UNCOVER‐J) of ixekizumab in Japanese patients with erythrodermic or generalized pustular psoriasis; most patients responded to treatment and maintained response through 52 weeks. Objective: To assess the long‐term (>3 years) efficacy and safety of ixekizumab in Japanese patients with erythrodermic or generalized pustular psoriasis. Methods: These subgroup analyses were of a partial population of patients from UNCOVER‐J (NCT01624233; Sponsored by Eli Lilly and Company), specifically those with erythrodermic psoriasis (N = 8) or generalized pustular psoriasis (N = 5). These patients received 160 mg ixekizumab at Week 0, ixekizumab 80 mg every 2 weeks through Week 12, and ixekizumab 80 mg every 4 weeks thereafter up to Week 244. This regimen is consistent with the regimen approved in Japan for plaque, erythrodermic, and generalized pustular psoriasis and psoriatic arthritis. Efficacy assessments included Global Improvement Score (GIS), Psoriasis Area and Severity Index (PASI), dermal symptoms (for patients with generalized pustular psoriasis), Dermatology Life Quality Index (DLQI) and Itch Numeric Rating Scale (NRS). Safety assessments included treatment‐emergent adverse events and adverse events of special interest. Results: Most patients had a GIS of resolved or improved from Week 12 onwards, and all patients had early and sustained improvement in PASI and dermal symptom (generalized pustular psoriasis only) scores. Mean improvements in DLQI and Itch NRS at Week 12 were sustained through Week 244. Ixekizumab was well tolerated over 3 years of treatment in patients with erythrodermic psoriasis or generalized pustular psoriasis, and no new safety concerns were identified. Conclusion: These findings suggest that ixekizumab can be an effective long‐term treatment option for erythrodermic or generalized pustular psoriasis. Linked article: This article is commented on G. Egawa et al., p. 259 in this issue. To view this article visit https://doi.org/10.1111/jdv.15416 [ABSTRACT FROM AUTHOR]

SUMMARY: NTMobile (Network Traversal with Mobility) has been proposed to achieve end‐to‐end encryption communication supporting IP mobility in environments where IPv4/IPv6 networks coexist. However, since NTMobile unconditionally establishes an encrypted User Datagram Protocol (UDP) tunnel between NTMobile‐ready nodes (NTM nodes), a malicious NTM node can attack a target NTM node through the encrypted UDP tunnel without being detected by a firewall. Moreover, since communication with a general server always passes through a relay server (RS), the route becomes redundant even when IP mobility is not needed, and the communication delay increases. In order to solve these problems, this paper proposes an access control function using the name of the correspondent node and a “Route option” that can select whether the RS is used or not. As a result of implementation of the prototype system and evaluation of its performance, it was confirmed that the increase of the start‐up time and that of the overhead at the beginning of the communication were quite small, and there was little influence on practical use. [ABSTRACT FROM AUTHOR]

Abstract: Background: Appropriate goal‐oriented treatment strategies are important for optimal treatment outcomes and may prevent under‐treatment. As treatment goals vary by patient, a study to examine treatment goals is more meaningful when patients and their physicians are paired. There has not been any study that examines alignment between paired psoriasis patients and physicians in real‐world clinical practice using skin clearance as a treatment goal indicator. Objectives: To evaluate treatment goal alignment between psoriasis patients and their paired physicians, and to quantitatively identify factors associated with goal misalignment. Methods: The study was a nationwide multicenter cross‐sectional observational study. Subjects were physician‐reported moderate‐to‐severe psoriasis patients with a history of systemic treatments, directly paired with their treating physicians. Subjects completed surveys independently. Treatment goals included seven categories, and patient–physician pairs were grouped as ‘aligned’ or ‘misaligned’ when the answers were the same or different, respectively. Results: A total of 425 pairs (mean response rate, 94.7%) of responses were collected from 54 sites (64.8% general practitioners or clinics; 35.2% university or large hospitals). Treatment goal misalignment was found in 67.9% of the patient–physician pairs. The misalignment was mainly ‘patient predominant’ (60.9%) indicating that patients had higher goals (‘complete clearance’) than physicians. In the multivariate logistic regression analyses, patients’ treatment expectation for ‘complete clearance’ [odds ratio (OR): 1.927; 95% confidential interval (CI): 1.232–3.016] and physician rating of ‘level of understanding on treatment options’ being low (OR: 1.552, 95% CI; 1.082–2.227) were significant factors for treatment goal misalignment. Conclusions: The majority of treatment goal misalignment was found between paired psoriasis patients and their treating physicians in Japan. The most important contributing factors to misalignment were patients’ treatment expectation for ‘complete clearance’ and physicians’ rating of their patients’ ‘level of understanding on treatment options’ being low. [ABSTRACT FROM AUTHOR]

Background Palmoplantar psoriasis has significant physical and emotional impact on patients and can be difficult to treat. Objective To evaluate the efficacy of ixekizumab in the treatment of patients with moderate-to-severe plaque psoriasis and moderate-to-severe non-pustular palmoplantar involvement. Methods In three phase 3, double-blind, placebo-controlled trials, patients with moderate-to-severe non-pustular plaque psoriasis [ UNCOVER-1 ( N = 1296), UNCOVER-2 ( N = 1224), UNCOVER-3 ( N = 1346)] were randomized to subcutaneous 80 mg ixekizumab every 2 or 4 weeks (Q2W, Q4W), after a 160-mg starting dose, or placebo through week 12. Additional UNCOVER-2 and UNCOVER-3 cohorts were randomized to 50 mg etanercept biweekly. Patients entering the open-label long-term extension ( UNCOVER-3) received ixekizumab Q4W weeks 12-60. Moderate-to-severe palmoplantar involvement was defined as Palmoplantar Psoriasis Area and Severity Index ( PPASI) ≥8. Results Twenty-eight percent of UNCOVER-1, UNCOVER-2 and UNCOVER-3 patients had baseline palmoplantar involvement ( PPASI ≥0, n = 1092) and 9.1% ( n = 350) had moderate-to-severe involvement, with mean baseline PPASI ~20, PASI ~24, and most (>60%) had static Physician's Global Assessment ≥4. Higher percentages of patients treated with ixekizumab vs. placebo or etanercept achieved PPASI 50 (approximately 80% vs. 32.9%, 67.8%; ixekizumab, placebo, etanercept, respectively) and PPASI 75 (approximately 70% vs. 18.8%, 44.1%; ixekizumab, placebo, etanercept, respectively) at week 12 (all P < 0.05). PPASI 100 was achieved by higher percentages of ixekizumab-treated patients vs. placebo (approximately 50% vs. 8.2%, P < 0.001) and ixekizumab Q2W-treated patients vs. etanercept (51.8% vs. 32.2%, P < 0.05). Outcomes were maintained or improved in patients continuing on ixekizumab Q4W through week 60. Differences between ixekizumab and placebo or etanercept were statistically significant as early as week 1. Conclusion In a subpopulation analysis of patients from phase 3 trials with moderate-to-severe non-pustular palmoplantar involvement and moderate-to-severe plaque psoriasis, ixekizumab treatment resulted in greater and more rapid improvements than placebo and etanercept at week 12; improvements were sustained with continued treatment. [ABSTRACT FROM AUTHOR]

In the present case, the mealworm allergy was thought to have resulted from skin sensitization to the allergen in the course of handling mealworms as pet feed. Mealworms ( I Tenebrio molitor i ), the larvae of the Darkling beetle, are commonly bred as food for pets, including herpetiles, guinea pigs and hamsters. [Extracted from the article]

Deals with a study which carried out linkage analysis on unreported families segregating for autosomal-dominant familial exudative vitreoretinopathy (FEVR). Gene mutation analysis; Results of the two-point linkage analysis of FEVR families.

References 1 Schmid-Grendelmeier P, Guillet C. Reply to "A case of anaphylactic shock induced by mealworm antigen in the bite of a Japanese flying squirrel" by Seshimo et al. Response to 'Reply to "A case of anaphylactic shock induced by mealworm antigen in the bite of a Japanese flying squirrel" by Seshimo et al'. by Schmid-Grendelmeier and Guillet A case of anaphylactic shock induced by mealworm antigen in the bite of a Japanese flying squirrel. [Extracted from the article]

Emotional and behavioural problems in primary school children were investigated with Renter's questionnaires, in Japan (N = 2638), China (N = 2432) and Korea (N = 1975). The prevalence rates of children with deviant scores on the teachers' and parents scales were 3.9 and 12.0% in Japan, 8.3 and 7.0% in China and 14.1 and 19.1 Korea respectively. Deviance of the antisocial type was more frequent than the neurotic type in Japan and China. Both types were almost equally frequent in Korea. The prevalence of deviance was higher in boys, and also higher in those children with poor school achievement. In China and Korea, the prevalence was higher in children from one-parent families. Although other family background factors had major effects on deviant behaviour in these two countries, the number of siblings and birth order had only a limited effect on the deviant behaviour of children in Japan, China and Korea. [ABSTRACT FROM AUTHOR]

We examined the hypothesis that one of the pro-inflammatory cytokines, tumour necrosis factor-α (TNF-α), could induce expression of the adhesion molecule CD4 on human eosinophils. We further examined the effector function of CD4 and the mechanisms regulating CD4 expression. Human eosinophils were cultured with various concentrations of recombinant human TNF-α (rhTNF-α) with or without various drugs for 24 hr. After culture, eosinophils were stained for CD4 using a monoclonal antibody and then analysed by flow cytometry. Eosinophil-derived neurotoxin (EDN) release as eosinophil degranulation was examined by cross-linking of CD4 on eosinophils. The rhTNF-α induced CD4 expression on human eosinophils in a dose- and time-dependent fashion; rhTNF-α-induced CD4 expression was significantly inhibited by 10-6M cycloheximide, 10-8M dexamethasone, or 10-6M herbimycin A. Recombinant human interferon-γ inhibited rhTNF-α-induced CD4 expression in a dose-dependent manner. However, cross-linking of CD4 on eosinophils did not evoke EDN release, suggesting that newly expressed CD4 molecules on human eosinophils do not play any role in triggering degranulation. Our data indicate that TNF-α- induced CD4 expression on human eosinophils is dependent on protein synthesis and may be dependent on tyrosine kinase activity. [ABSTRACT FROM AUTHOR]

Activation of human natural killer (NK) cells involves sequential events including cytokine production and induction of cell surface molecules, resulting in the enhancement of cytolytic activity. To delineate the activation process of NK cells, we generated murine monoclonal antibodies (mAbs) against YT, a human large granular lymphocyte/natural killer (LGL/NK) cell line. Among the mAbs reactive with YT cells, one mAb, termed 2B9, was noted because of the lack of reactivity with most of the human T- and B-cell lines tested. In fresh peripheral blood mononuclear cells (PBMC), however, the majority of cells expressing this antigen (Ag) were T cells but not CD16+ nor CD56+ NK cells. Since YT cells showed an activated phenotype expressing interleukin-2 (IL-2) receptor α chain, we examined whether 2B9 Ag could be induced on normal human peripheral blood NK cells by cytokines known to activate NK cells. The 2B9 Ag was induced on NK cells by IL-2, IL-12 or IL-15 while no induction was observed by interferon-γ (IFN-γ). Biochemical analysis showed that anti-2B9 mAb recognized a 115 kDa molecule in YT cells. A cDNA clone encoding the 2B9 Ag was isolated from a cDNA expression library of YT cells and its sequence was identical to CD26 cDNA although it was not of full length. Transient expression of the 2B9 cDNA on COS-7 cells revealed that this cDNA encodes the antigenic epitope(s) recognized by anti-2B9 mAb as well as Ta1, an anti-CD26 mAb. These results showed that the 2B9 Ag is identical to CD26, and demonstrated that CD26 is an activation antigen on CD16+ CD56+ NK cells inducible by IL-2, IL-12 or IL-15. [ABSTRACT FROM AUTHOR]

Examines the decay-accelerating factor (DAF, CD55), a glycoprotein that expresses the cromer-system blood group antigens. Characteristics of DAF, CD55; Representation of mixture of antibodies to four DAF short consensus repeat domains; Loss of a TaqI restriction site from DAF exon five.

(a) Esophagogastroduodenoscopy (EGD) showed a diffuse erythematous and ulcerated mucosa with hemorrhage involving entire remnant stomach. Gastrointestinal: Recurrence of pembrolizumab-induced severe gastritis after tapering steroid therapy Esophagogastroduodenoscopy (EGD) demonstrated a diffuse erythematous and ulcerated gastric mucosa with hemorrhage involving the entire remnant stomach (Fig. [Extracted from the article]

Two promoter polymorphisms of the high-affinity IgE receptor α-subunit (FcεRIα) gene ( FCER1A), −66T>C (rs2251746) and −315C>T (rs2427827), were analysed in Japanese atopic dermatitis subjects. Patients with the −315CT/TT genotype tended to have higher total serum IgE levels, while the proportion of −315CT/TT genotype or the −315T allele was significantly higher in those with highly elevated total serum IgE concentrations. [ABSTRACT FROM AUTHOR]

The main World Health Organization (WHO) activities of the Tokyo Center are as follows: (1) It performed the research project entitled 'A Bio-Psycho-Social Study on Children with Emotional and Behavioral Problems' in cooperation with the Beijing and Seoul Centers from 1985 to 1987. These results suggested that the deviant behavior of children in the general population had no biological background, but presumably stemmed from psychosocial disadvantages. (2) It has participated in a field trial for the proposed draft for chapter V of the ICD-10 as the Field Trial Coordinating Center in Japan since 1986 and the first Japanese edition of the ICD-10 Classification of Mental and Behavioral Disorders: Clinical Descriptions and Diagnostic Guidelines were published in 1993. (3) It proposed the collaborative project exploratory eye movements in patients with schizophrenia in 1989 and has promoted the project with the cooperation of six centers that included Beijing, Casablanca, Montreal, Munich, Prague and Sapporo. The findings of the present project indicated that exploratory eye movements may be specific to schizophrenia and can be practically used to discriminate schizophrenia without significantly depending on language. [ABSTRACT FROM AUTHOR]

Inflammatory diseases that are driven by several pro-inflammatory cytokines has resulted in in the development of targeted therapies across different disease settings. Interleukin (IL)-36 cytokines have been implicated in several inflammatory diseases. In this review we describe the scientific evidence surrounding the use of the IL-36 receptor (IL-36R)-targeting antibody, spesolimab, in IL-36-mediated skin diseases: generalized pustular psoriasis (GPP), palmoplantar pustulosis (PPP), hidradenitis suppurativa, and Netherton syndrome (NS). Spesolimab, a high affinity, specific, humanized, antagonistic immunoglobulin G1 antibody, targets the IL-36R at a binding site distinct from its agonists, IL-36α/β/γ, and at least one endogenous antagonist, IL-36R antagonist. In vitro and in vivo data for spesolimab show effective inhibition of IL-36R-mediated signaling pathways, and six Phase I studies in healthy volunteers presented a favorable safety and pharmacokinetic (PK) profile, leading to the development of a clinical trial program to evaluate spesolimab in the treatment of IL-36R-mediated diseases. Six studies (including an expanded access program) have evaluated the efficacy, safety, PKs, and pharmacogenomics of spesolimab in patients with GPP flares. Spesolimab treatment of GPP flares resulted in rapid and sustained improvements in pustular and skin clearance, and clinically significant improvements in patient-reported symptoms and quality of life. Spesolimab also significantly reduces the risk of GPP flares and flare occurrence, preventing disease worsening and has a favorable safety profile. There have been three trials of spesolimab in PPP; further evaluation is needed to better define those patients who might benefit from the treatment. A trial of spesolimab in NS is ongoing, while other spesolimab trials suggest that IL-36 may only play a secondary role in the pathogenesis of atopic dermatitis. In conclusion, research into spesolimab has provided much needed insight into the role of IL-36 in the human immune system and the mechanism behind IL-36-mediated inflammatory diseases. Spesolimab provides an efficacious targeted treatment for GPP, a disease with a high unmet medical need., (© 2024 The Author(s). The Journal of Dermatology published by John Wiley & Sons Australia, Ltd on behalf of Japanese Dermatological Association.)