Journal of Dermatology最新文献

Antimicrobial use among children in Japan has declined substantially; however, tetracycline use has increased among adolescents, particularly after 2017 and during the COVID-19 period, and the underlying clinical indications remain unclear. We aimed to characterize long-term trends in oral tetracycline use, changes in clinical indications, and treatment patterns among individuals aged < 20 years in Japan. We conducted a time-series analysis using a nationwide administrative claims database of Japan Health Insurance Association from 2015 to 2023, including 24 million individuals aged < 20 years. Oral tetracycline use was measured as days of therapy (DOTs) per 1000 inhabitants per day, and clinical indications were identified using ICD-10 codes. We assessed trends in tetracycline use and indications over time and described treatment patterns, including concomitant therapies, among patients with acne vulgaris. Oral tetracycline use increased from 0.95 to 1.76 DOTs per 1000 inhabitants per day between 2015 and 2023, primarily driven by doxycycline, with a marked rise after 2020 and highest use among adolescents. The clinical indications shifted substantially, with the proportion of acne vulgaris increasing from 34.1% to 73.6% while respiratory infections decreased, and the mean treatment duration for acne was 37.9 days. Among patients with acne, concomitant use of adapalene- and benzoyl peroxide–based therapies was limited, whereas topical antibiotics were commonly used. Oral tetracycline use among individuals aged < 20 years in Japan increased substantially, with a marked shift in clinical indications toward acne vulgaris. These findings provide a basis for further evaluation of acne treatment patterns, including the use of oral tetracyclines and non-antibiotic topical therapies, in Japan.

Postzygotic somatic variants affecting the Ras/MAPK signaling pathway can cause mosaic RASopathies, characterized by craniofacial abnormalities, cardiac defects, growth impairment, and various cutaneous manifestations in localized areas of the body. Herein, we present a rare case of mosaic RASopathy caused by a somatic HRAS variant. A 52-year-old Japanese patient visited our department because of skin metastasis of malignant melanoma. Besides, he had a sebaceous nevus on the forehead, linear epidermal nevus on the trunk along with the Blaschko line, and focal and linear non-epidermolytic palmoplantar keratoderma since he was young. Genetic testing revealed an HRAS missense variant c.34G>A (p.Gly12Ser) in the cells of sebaceous nevus, pigmented skin lesion, palmoplantar keratoderma, and metastatic skin lesion of melanoma. In contrast, no pathogenic HRAS variant was detected in peripheral blood leukocytes or in clinically normal skin. Somatic mutations in HRAS can cause mosaic Costello syndrome, Schimmelpenning syndrome, and woolly hair nevus. However, there is some overlap in clinical manifestations among these diseases, and no clear diagnostic criteria have been established. Therefore, we diagnosed this case as HRAS-mutant mosaic RASopathy. In addition, this is the first reported case of mosaic RASopathy concomitant with malignant melanoma. Although the occurrence of concurrent melanoma would be coincidental in this case, further investigation is necessary to evaluate the precise association between HRAS-mutant mosaic RASopathy and melanoma. The melanoma cells showed a high proportion of mutant alleles, possibly due to loss of heterozygosity. Further investigation is necessary to evaluate the precise association between HRAS-mutant mosaic RASopathy and melanoma.

Severe infection is associated with increased mortality in patients receiving systemic corticosteroid therapy, including those with bullous pemphigoid (BP). Cytomegalovirus (CMV) reactivation represents a highly probable and underrecognized cause of death in immunosuppressive individuals. The aim of this study was to evaluate the association between CMV reactivation and disease course in patients with BP, and to develop a clinical scoring system for the prediction and early detection of CMV reactivation. A retrospective analysis of 41 patients with BP who received systemic corticosteroid therapy in our institution was conducted. Clinical and laboratory data were evaluated to identify factors associated with CMV reactivation, and a scoring system was developed to support both prediction and detection. Compared with CMV-negative BP patients, CMV-positive patients exhibited a more severe and protracted course, characterized by a higher incidence of complications. In addition, CMV-positive patients had more extensive areas of blistering and erosion than CMV-negative patients. Neutrophil-lymphocyte ratio, platelet count, eosinophil count, serum sodium concentration level, and systemic corticosteroid dose were identified as key indicators for predicting and early detection of CMV reactivation. The proposed scoring system demonstrated high sensitivity (95.5%) and specificity (89.5%) for detecting CMV reactivation. Timely initiation of anti-CMV therapy following the detection of CMV reactivation was crucial for preventing fatal complications. A newly-invented scoring system may serve as a useful tool for predicting and detecting CMV reactivation in BP. Early identification of high-risk cases may enable timely anti-CMV therapy to prevent CMV disease leading to better outcomes.

Multicentric reticulohistiocytosis (MRH) is a rare non-Langerhans cell histiocytosis characterized by destructive polyarthritis and papulonodular cutaneous lesions. We describe a woman who developed erythroderma 20 years after MRH diagnosis—to our knowledge, a previously unreported manifestation of this disease. The patient initially presented at age 50 with arthralgia, and MRH was diagnosed one year later based on distal interphalangeal (DIP) joint deformities, erythematous papules on the lower legs, and a skin biopsy showing dermal infiltration of CD68-positive, S-100– and CD1a–negative histiocyte-like cells with ground-glass eosinophilic cytoplasm. Despite long-term treatment with methotrexate (MTX), prednisolone (PSL), infliximab (year 11), and bone-modifying agents (alendronate, later denosumab), the disease progressed, with development of pulmonary arterial hypertension (PAH) attributable to lesions around the upper pulmonary veins. At age 71, twenty years after diagnosis, pruritic erythema appeared on the back and evolved into erythroderma despite topical corticosteroids. Biopsies from erythematous areas demonstrated CD68-positive histiocytic infiltrate identical to that of the original MRH lesions, whereas biopsies from clinically uninvolved skin showed no such infiltration, supporting a direct association with the MRH disease process. Comprehensive evaluation excluded eczematous/atopic erythroderma (normal eosinophils and IgE), drug-induced erythroderma (no new medications; infliximab discontinued 9 years previously), dermatophytosis (negative PAS staining), granulomatous mycosis fungoides (absent characteristic histological features), sarcoidosis (normal sIL-2R; no granulomas on biopsy), dermatomyositis (absent characteristic features; normal creatine kinase), and internal malignancy (contrast-enhanced CT and 2-year follow-up). MTX was discontinued because of MTX-induced interstitial pneumonia, and oral PSL was increased to 30 mg/day, with rapid improvement; the patient is currently maintained on PSL 10 mg/day without relapse. The cumulative inflammatory burden of long-standing MRH may have culminated in this erythrodermic phenotype.

Cytokine release syndrome (CRS) induced by immune checkpoint inhibitors (ICIs) is a potentially life-threatening immune-related adverse event (irAE). CRS has been recognized as a complication of chimeric antigen receptor T-cell (CAR-T) therapy and bispecific T-cell engager (BiTE) therapy, but remains exceedingly rare as a complication of ICI therapy. Here, we report a case of CRS that developed after combination therapy with nivolumab and ipilimumab in a woman in her 60s with advanced conjunctival melanoma. The diagnosis was based on the clinical course and imaging findings together with characteristic laboratory abnormalities, including systemic inflammation, hepatic dysfunction, coagulopathy, and marked hyperferritinemia. This case highlights the importance of careful exclusion of infectious and neoplastic diseases for early diagnosis, demonstrates that ICI-related CRS can relapse after initial control, and shows that it may overlap with hemophagocytic lymphohistiocytosis (HLH)–like syndromes. Given the central role of interleukin-6 (IL-6) in CRS, early administration of tocilizumab may contribute to rapid control of inflammation and reduction of steroid exposure.