The Journal of dermatology最新文献

Secukinumab is one of the human monoclonal antibodies recommended in the Japanese guidelines for patients with psoriasis, but few case reports and clinical studies on secukinumab for pustular psoriasis are available because of the rarity of the disease. This was an open-label, multicenter, uncontrolled, single-arm, prospective observational surveillance conducted in a clinical practice setting to evaluate the safety and effectiveness of secukinumab in Japanese patients with generalized pustular psoriasis (GPP). Patients were monitored for 1 year after starting secukinumab and followed up for an additional 2 years. Of 99 patients from 71 sites, 95 were included in safety and 82 in effectiveness analysis. The mean (standard deviation) observation period was 346.2 (64.87) days, and 91.58% of patients were observed over 52 weeks. Adverse events, serious adverse events, and adverse reactions were reported in 51.58%, 12.63%, and 35.79% of patients, respectively. Safety evaluations showed no significant difference in the incidence of events based on the history of biologics The proportion of patients with either "complete response" or "partial response" was ~90% from week 2 and remained stable until week 52. The proportion of patients with "remission (no symptom)" in the Japanese Dermatological Association total score increased from week 4 (22.22%) to week 52 (47.83%). The mean Psoriasis Area and Severity Index score decreased from week 1 (17.26) to week 16 (1.18), with the mean percentage change decreasing from -28.07% to -90.18%. The mean Dermatology Life Quality Index (DLQI) total score decreased from 8.7 at the start of secukinumab treatment to 1.9 at week 52. At week 52, the proportion of patients with DLQI total score of 0/1 was 57.14%. No new safety signals for secukinumab in long-term treatment were observed from this surveillance, and no additional measures needed to be taken. Moreover, secukinumab showed sustained effectiveness in patients with GPP in Japan.

Palmoplantar pustulosis (PPP) is a chronic skin disease characterized by erythema, pustules, and desquamation of the palms and soles. PPP epidemiological data are scarce. Understanding disease characteristic is essential for effective management and to reduce burden. The objective of the study was to describe disease characteristics of PPP in Korea, including demographics, disease burden, and current clinical practice. This was a cross-sectional, multicenter, noninterventional study conducted among 20 sites in Korea. Patients (aged ≥19 years) with a confirmed PPP diagnosis were examined and interviewed, collecting clinical and patient-reported outcomes in 1 day. A total of 379 patients with PPP (mean age, 51.4 years; 39.3% male) were enrolled. The mean age at diagnosis was 47.9 years, and the mean duration of PPP was 3.2 years. Mean±standard deviation of Palmoplantar Pustulosis Area and Severity Index (PPPASI) score was 10.3±9.0; 33.8% of patients scored ≥12. PPPASI score was significantly higher with younger age (p = 0.0001) and nail involvement (p = 0.0002). Mean Dermatology Life Quality Index (DLQI) score was 12.0, and mean EuroQoL 5-Dimension Health Questionnaire (EQ-5D) score was 62.4 ± 19. Patients with PPPASI ≥12 had significantly higher DLQI (14.1 ± 7.3 vs 10.9 ± 7.6; p < 0.0001) and lower EQ-5D (57.9 ± 18.1 vs 64.7 ± 19.2; p = 0.002) scores. The most common treatments in patients with PPPASI <12 were topicals (50.6%), conventional therapies (34.7%), and retinoids (32.7%); the most common treatments with PPPASI ≥12 were conventional therapies (37.5%), topicals (34.4%), and retinoids (29.7%). Conventional therapy users were "more satisfied" than nonusers (49.6% vs 39.0%; p = 0.05), with a numerical difference observed for biologics (41.8% vs 63.1%; p = 0.07). PPP is a debilitating disease that significantly diminishes overall quality of life. Despite most patients receiving treatment, PPP burden persists. Developing treatment guidelines and identifying more targeted and effective treatments would help alleviate symptoms, reduce severity, and improve overall quality of life.

In this study, we investigated whether circulating S100A7 and S100A15 DNA copies in cell-free DNA (cfDNA) are elevated in patients with psoriasis and atopic dermatitis (AD) and their levels are correlated with clinical findings. Serum cfDNA was obtained from 124 psoriasis patients and 45 AD patients. Circulating S100A7 and S100A15 DNA copies in psoriasis and AD patients were significantly higher than in healthy controls. Although circulating S100A7 and S100A15 DNA copies showed a significant positive correlation with the Psoriasis Severity and Area Index (PASI) scores in patients with severe psoriasis (PASI ≥ 10), in AD patients there was no significant correlation between their levels and disease severity. Furthermore, in psoriasis patients, circulating S100A15 DNA copies were significantly decreased in patients after treatment compared with patients before treatment.

The concept of immune reconstitution inflammatory syndrome (IRIS) has recently been applied to patients with non-HIV infection with immune fluctuations. However, quantitative criteria to diagnose non-HIV IRIS have not been established. Similarly, immune-related adverse events (irAEs) caused by immune checkpoint inhibitors (ICIs) are also caused by immune fluctuations. No study has directly compared the immunological indicators of non-HIV IRIS and irAEs. Thus, we investigated whether irAEs can be included in non-HIV IRIS. We aimed to search for diagnostic biomarkers for non-HIV IRIS and to compare the immunopathogenesis of non-HIV IRIS and irAEs based on immunological indicators. We selected drug-induced hypersensitivity syndrome/drug reaction with eosinophilia and systemic symptoms (DIHS/DRESS) and dipeptidyl peptidase-4 inhibitor-associated bullous pemphigoid (DPP4i-BP) as underlying diseases of non-HIV IRIS. Blood cell counts, cytokines or chemokines, and herpesvirus-derived DNA in saliva were quantified and compared between IRIS/irAE-positive and -negative as well as non-HIV IRIS and irAEs groups. The DPP4i-BP group had a shorter incubation time to IRIS onset than the DIHS/DRESS group; the irAE group had a longer incubation time than the DIHS/DRESS group. A higher neutrophil-to-lymphocyte ratio and serum interferon gamma inducible protein 10 levels could be potential biomarkers of IRIS and irAEs onset; however, no useful cut-off values for diagnosis were indicated. Meanwhile, the transition of  regulatory T cells (Tregs) from the baseline to the onset of IRIS or irAEs differed between IRIS in DIHS/DRESS and irAEs. Only the DIHS/DRESS group showed an increase of Epstein-Bar virus (EBV) (p < 0.0001) and human herpesvirus 6 (p < 0.05) positivity in saliva at the onset of IRIS compared to that at baseline. Although non-HIV IRIS and irAEs have a small number of common immunological indicators, the dynamics of Tregs, cytokines, or chemokines and positivity of herpesvirus-derived DNA in saliva differ, suggesting that non-HIV IRIS and irAEs should remain as separate entities.

Guselkumab is a monoclonal antibody that binds to the p19 subunit of interleukin-23 and inhibits its downstream signaling. The safety profile of guselkumab and its superior efficacy over placebo and adalimumab for the treatment of patients with moderate-to-severe psoriasis were reported in phase 3 studies conducted within and outside Japan. To assess the real-world safety and effectiveness of guselkumab in Japanese patients with psoriasis, we conducted a multicenter, single-arm, prospective, post-marketing surveillance study. Guselkumab was administered by subcutaneous injection at a dose of 100 mg at weeks 0 and 4, then every following 8 weeks. The patient observation period was 52 weeks after the initial guselkumab dose or until treatment withdrawal. The safety analysis set consisted of 416 patients, including 310 patients with vulgaris (PsV); and the effectiveness analysis set consisted of 251 patients, including 236 patients with PsV or psoriatic arthritis (PsA). There were more men (71.3%, 221/310) than women among the PsV group. The median age among those with PsV was 58 years, the median disease duration was 11.50 years, 50.0% (155/310) had comorbidity, and 41.3% (128/310) had previously been treated with biologic agents. During the observation period, 8.4% (35/416) of patients experienced 49 adverse drug reactions, 2.9% (12/416) experienced 13 serious adverse drug reactions, and 3.4% (14/416) experienced 16 adverse events leading to treatment discontinuation. In the effectiveness analysis set of 236 patients with PsV or PsA, the Psoriasis Area and Severity Index (PASI) 75, 90, and 100 response rates at week 52 were 69.9%, 54.5%, and 32.5%, respectively. Bio-naïve patients consistently had higher PASI 75 and 90 response rates than bio-experienced patients. This post-marketing surveillance study demonstrated that guselkumab was well-tolerated and effective in a real-world setting in Japanese patients with psoriasis.

Antibodies to 3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMGCR) form a newly identified distinct serological marker for necrotizing autoimmune myopathy. Although anti-HMGCR myopathy is currently classified into polymyositis, skin involvement has been reported, with its characteristics only vaguely described. We retrospectively examined the clinical and histological features of non-dermatomyositis-like persistent exanthema in five anti-HMGCR myopathy patients followed up in the neurology and dermatology clinic of Huashan Hospital between December 2020 and September 2024. The exanthema presented as persistent violaceous or erythematous plaques, asymptomatic or itching, mainly distributed on the trunk, whereas dermatomyositis-specific lesions such as Gottron's sign and papules, heliotrope rash, V or shawl signs, and nailfold telangiectasia were all absent. Skin rash in 80% of patients (4/5) appeared earlier than muscle symptoms such as fatigue, proximal limb weakness, and hyperCKemia, with the median advanced time of 3 years (8 months to 7 years). Biopsies revealed scant interface dermatitis, interstitial mucin, and perivascular lymphocytic infiltrate with occasionally plasma cells and/or neutrophils. Notably, the exanthema showed no response to topical or even systemic corticosteroid but relieved after systemic immunosuppressive therapy for myopathy, in accordance with the improvement of muscle symptoms and hyperCKemia. Dermatologists should be aware of this rare entity of "pseudo-dermatomyositis", carefully evaluate muscle syndromes and carry out further investigations, including muscle biopsy and serum anti-HMGCR antibodies assays if present.