The Journal of dermatology最新文献

Combination therapy with nivolumab and ipilimumab (NIVO+IPI) is highly effective in treating advanced malignant melanoma (MM) but it is associated with a high incidence of treatment-related adverse events (TRAEs). This retrospective, cohort study evaluated the efficacy and TRAEs of NIVO+IPI in Japanese patients with unresectable stage III and IV MM, comparing outcomes based on the number of treatment cycles and the IPI dose. We reviewed data from 57 patients with advanced or recurrent MM who received NIVO+IPI at the Shizuoka Cancer Center between August 2015 and July 2024. Patients who received two or fewer NIVO + IPI cycles (NIVO+IPI ≤2 cycles) generally had worse Eastern Cooperative Oncology Group performance status and more advanced stages compared to those who received three or more cycles (NIVO+IPI ≥3 cycles). The analysis revealed that the NIVO+IPI ≥3 cycles group had significantly better overall survival compared to the NIVO+IPI ≤2 cycles group, although receiving three or more cycles was not an independent prognostic factor in multivariate analysis. There was no significant difference in the frequency or severity of TRAEs between the two groups, but the incidence of grade ≥3 TRAEs increased significantly between the first and second cycles of NIVO+IPI. Additionally, reducing the IPI dose from 3 mg/kg to 2 mg/kg appeared to lower the risk of grade ≥3 TRAEs. In conclusion, further research is needed to determine the optimal number of NIVO+IPI cycles for Japanese patients with advanced MM. However, assessing efficacy after the second cycle may help avoid unnecessary NIVO+IPI administration. Reducing the IPI dose to 2 mg/kg may also offer a safer treatment approach for these patients.

The efficacy, safety, and optimal concentration of topical sirolimus gel for treatment of cutaneous lesions of vascular anomalies requires evaluation. This study was a multicenter, double-blind, placebo-controlled, parallel-group, phase II randomized clinical trial. We enrolled patients with venous malformation (n = 27), lymphatic malformation (n = 14), tufted angioma (n = 8), or kaposiform hemangioendothelioma (n = 1). Patients applied either placebo or 0.2% or 0.4% topical sirolimus gel to the target lesion twice per day for 12 weeks. The primary endpoint was the overall improvement score in the target lesion assessed from photographs by the independent review committee at Week 12. There was no statistically significant difference in the mean improvement score in the 0.2% group (p = 0.410) or the 0.4% group (p = 0.549) compared with in the placebo group. Thus, we could not prove the efficacy of topical sirolimus for cutaneous vascular anomalies in this protocol. Conversely, the improvement in target lesion size at Week 12 assessed by the committee as one of the 16 secondary endpoints was significantly higher in the 0.4% sirolimus gel group than in the placebo group (p = 0.031). In the post-hoc analysis outside the protocol tracing the contour of the lesion, the percentages of patients with ≥20% reduction in the lesion area increased dose-dependently (0%, 37.5%, and 65.0% in the placebo, 0.2%, and 0.4% group, respectively). Regarding safety, irritation and dermatitis at the application site occurred in the 0.4% gel group. Sirolimus gel reduced lesion size in our cohort. The safety data demonstrated topical sirolimus to have an acceptable safety profile.

Juvenile-onset morphea can severely impact activities of daily living by causing functional disability. This study was performed to clarify the epidemiological and clinical characteristics of juvenile-onset morphea in Japan. We conducted a nationwide, two-part postal survey. The first survey aimed to estimate the number of patients with juvenile-onset morphea, while the second survey aimed to elucidate the epidemiological and clinical characteristics of juvenile-onset morphea. This study included patients of all ages with juvenile-onset morphea whose age at disease onset was <18 years and who visited a medical institution from 1 January, 2016 to 31 December, 2020. The first survey identified 371 patients with juvenile-onset morphea. The second survey collected detailed clinical information for 315 patients with juvenile-onset morphea. We estimated that the number of patients diagnosed with juvenile-onset morphea from 2016 to 2020 was 591 (95% confidence interval 479-702) among children aged <18 years. The estimated annual incidence rate of juvenile-onset morphea ranged from 2.11 to 2.87 per 1 000 000 children aged <18 years from 2016 to 2019. The mean age at onset was 7.7 years. Regarding subtypes, linear morphea was the most common, followed by circumscribed morphea. Complications and treatments varied widely by subtype, with local treatment primarily used for circumscribed morphea. By contrast, patients with linear morphea, generalized morphea, pansclerotic morphea, and mixed morphea had severe complications affecting daily life, and they received systemic immunosuppressive therapy more frequently. The prognosis of juvenile-onset morphea was generally favorable. The results of this study are expected to help in the development of appropriate diagnostic and therapeutic approaches for juvenile-onset morphea.

Yusho, a dioxin poisoning incident in Japan, has resulted in patients experiencing persistent symptoms, including sensory disturbances, decades after the initial exposure. This study investigated the potential involvement of the descending pain inhibitory system in Yusho patients. Serum serotonin, dopamine, and norepinephrine levels were measured in 29 Yusho patients and 29 age-matched healthy controls. No significant differences in these neurotransmitters were observed between the two groups. However, weak correlations were found between polychlorinated biphenyl levels and dopamine (r = 0.4310, p = 0.0315) in Yusho patients. This study provides new insights into the pathophysiology of cutaneous sensory disorders and highlights the need for further research to clarify the long-term effects of dioxin exposure on Yusho patients.

A 60-year-old Japanese woman had a history of acneiform rashes and pruritus from age 20. She had sought medical attention at the age of 49 due to the progressive enlargement of the lesions. Despite various therapeutic interventions, including topical steroids and oral cyclosporine, the condition continued to worsen. Upon examination at age 60, erythematous areas with hyperkeratotic nodules were noted, and a dermoscopic evaluation revealed keratin plugs within the hair follicles. A histopathological analysis showed suprabasal acantholysis, with grains and corps ronds dispersed throughout the lesions. Genetic testing identified a non-pathogenic variant in ATP2A2, which effectively excluded Darier's disease. We made the final diagnosis of warty dyskeratomas (WD). Human papillomavirus was not implicated. Notably, immunohistochemical analyses revealed the overexpression of SERCA2, which further supported the diagnosis of WD rather than Darier's disease. WD is a rare, benign, dermatological condition that typically affects middle-aged women and is often localized to the scalp. While histologically similar to Darier's disease, WD lacks the pathogenic mutations in ATP2A2. Ultimately, the diagnosis of WD was confirmed in our patient through a comprehensive assessment of clinical, histopathological, and genetic findings.

Generalized pustular psoriasis is a rare but severe form of psoriasis, accounting for 7.5% of all psoriasis cases. We investigated whether the disease burden and quality of life of patients with generalized pustular psoriasis were lower than those of patients with psoriasis vulgaris in Japan. Patients registered in the Western Japan Psoriasis Registry, a prospective cohort of patients with psoriasis treated at 31 facilities specializing in psoriasis medicine, were surveyed using the SF-36v2 and other patient-reported outcomes. We enrolled patients with generalized pustular psoriasis (n = 97) and psoriasis vulgaris (n = 1065). The generalized pustular psoriasis group had fewer males, were younger at onset, had fewer smokers and habitual drinkers, and were more frequently treated with biologics than patients with psoriasis vulgaris. Questions on disease burden revealed that patients with generalized pustular psoriasis experienced sores, blisters, skin pain, and systemic symptoms more frequently than patients with psoriasis vulgaris. A higher proportion of patients with generalized pustular psoriasis had joint pain and fatigue than those with psoriasis vulgaris, although patient satisfaction with treatment did not differ significantly between the two groups. The Short Form-36 evaluation revealed that patients with generalized pustular psoriasis had significantly lower physical component summary scores than patients with psoriasis vulgaris. These findings indicate that patients with generalized pustular psoriasis have a higher burden and more impaired quality of life than patients with psoriasis vulgaris.

Palmoplantar pustulosis (PPP) is a chronic, debilitating skin disease of the palms and/or soles. We report the efficacy and safety of risankizumab (RZB), an interleukin 23 p19 inhibitor, from the JumPPP study (a phase 3, multicenter, randomized, placebo-controlled, double-blind study to evaluate RZB in adult Japanese sUbjects with Moderate-to-severe PalmoPlantar Pustulosis; NCT04451720). Patients were randomized 1:1 to receive RZB (150 mg) or placebo at weeks 0 and 4; all patients received RZB from week 16 to week 52 (patients initially randomized to RZB) or week 56 (patients initially randomized to placebo). The primary end point was a Palmoplantar Pustulosis Area and Severity Index (PPPASI) change from baseline; secondary end points were ≥50%/≥75% improvement in PPPASI (PPPASI 50/75) at week 16. Efficacy and safety were evaluated to 68 and 76 weeks, respectively. In total, 119 patients (RZB, n = 61; placebo, n = 58) were enrolled. Greater improvement with RZB versus placebo was demonstrated by the significant difference in PPPASI change from baseline at week 16 (least squares mean treatment difference, -3.48; p < 0.05). At week 16, a greater proportion of patients receiving RZB vs placebo achieved PPPASI 50 (41.0% vs 24.1%; nominal p < 0.05) but not PPPASI 75 (13.1% vs 15.5%; nominal p = 0.74). Improvements generally continued through to week 68. The safety profile was generally consistent with previous studies of RZB in psoriasis. RZB demonstrated efficacy over placebo at week 16 in Japanese patients with PPP, with improvements sustained through to week 68, and was well tolerated with no unexpected safety findings.