Journal of Dermatology最新文献

Eczema is the most common category of inflammatory skin disorders as dermatologists see many patients with eczematous diseases in daily practice. It is characterized by the three major morphological features: multiple-pinpoint condition, polymorphism, and itch. To describe polymorphism, “eczema triangle” has been used in German/Japanese dermatology. The multiple pinpoints correspond to numerous tiny foci from which individual papules/vesicles arise. The polymorphism betrays composition of erythema, papule, seropapule, vesicle, pustule, scale, and crust, which are seen in acute eczema. Meanwhile, chronic eczema is represented by lichenification and hyperpigmentation, and possibly by hypopigmentation. In acute eczema, spongiosis is associated with overproduction of hyaluronic acid, secretion of self-protective galectin-7, and decreased expression of E-cadherin. In the upper dermis, Th1/Tc1 or Th2/Tc2, and additional Th17, Th22, and/or Tc22 infiltrate, depending on each eczematous disease. Innate lymphoid cells are also involved in the formation of eczema. In chronic eczema, periostin contributes to remodeling of inflammatory skin with dermal fibrosis, and epidermal melanogenesis and dermal pigment deposition result in hyperpigmentation. Finally, eczematous diseases are potentially associated with increased risk of comorbidities, including not only other allergic diseases but also coronary heart disease and mental problems such as depression. Although the original word for eczema is derived from old Greek “ekzein,” eczema remains a major target of modern science and novel therapies.

A 42-year-old Vietnamese egg factory worker in Ishikawa prefecture, Japan, presented with itchy concentric erythema on the trunk and left calf. The lesions tested positive by direct potassium hydroxide examination, and two fungal strains were isolated. The isolates produced conidia abundantly and were morphologically indistinguishable from Trichophyton mentagrophytes/interdigitale, but were identified as Trichophyton indotineae by internal transcribed spacer sequence of ribosomal DNA. The lesions were refractory to treatment with topical luliconazole (LLCZ) cream for 4 weeks but subsided with oral itraconazole (ITCZ) 100 mg/day for 4 weeks in combination with topical lanoconazole (LCZ) cream. The lesions recurred 6 weeks after discontinuation of oral ITCZ, and an additional isolate was cultured. The minimum inhibitory concentrations of antimycotics for the isolate cultured at the first visit were: terbinafine (TBF) 0.03 μg/mL, ITCZ 0.015 μg/mL, LLCZ 0.0005 μg/mL, and LCZ 0.002 μg/mL. No TBF-resistant mutation in the amino acid sequence of squalene epoxidase, i.e., Leu 393 Ser/Phe or Phe 397 Leu, was detected in the isolate. The reason for recalcitrance in this case, despite the isolate's sensitivity to antimycotics, was unclear. Possible factors include insufficient use of the antimycotics, incomplete removal of abundantly produced conidia from the lesions, the patient's environment, and a language gap between the patient and physician hindering communication.

The advent of biologics has greatly improved patient outcomes, yet some patients are compelled to switch therapies. Predicting these therapeutic failures is important; however, the factors associated with switching biologics have not been fully explored. This study examined patterns and determinants of biologics switching in psoriasis treatment retrospectively over 13 years. We focused on the association between clinical characteristics, basal laboratory data, and frequency of biologics switching. The findings revealed that elevated Psoriasis Area Severity Index scores and the presence of arthritis were observed in patients who experienced two or more treatment switches compared with those without treatment switches. Moreover, neutrophil to lymphocyte ratio was associated with higher biologics switching rates, indicating that systemic inflammation significantly impacts treatment adherence. A treatment approach, taking into account both the clinical presentation and inflammatory biomarkers, may be important for optimizing patient management in psoriasis.

Tapinarof is a nonsteroidal, topical, aryl hydrocarbon receptor agonist. We evaluated the efficacy and safety of tapinarof cream 1% in Japanese patients aged ≥12 years with atopic dermatitis (AD) in two phase 3 trials, ZBB4-1 and ZBB4-2. ZBB4-1 (N = 216) consisted of an 8-week, double-blind, vehicle-controlled treatment period (period 1) and a 16-week extension treatment period (period 2). Patients were randomized 2:1 to tapinarof or vehicle in period 1; subsequently, all patients who enrolled in period 2 received tapinarof. ZBB4-2 (N = 291) was a 52-week, open-label, uncontrolled trial in which all patients received tapinarof. In period 1 of ZBB4-1, the proportion of patients who achieved an Investigator's Global Assessment (IGA) score of 0 (clear) or 1 (almost clear) with ≥2-grade improvement from baseline at week 8 (IGA treatment success, the primary end point) was 20.24% in the tapinarof group and 2.24% in the vehicle group (p = 0.0007). The proportion of patients with ≥75% improvement from baseline in Eczema Area and Severity Index (EASI) score at week 8 (EASI-75 response, the key secondary end point) was 40.3% in the tapinarof group and 4.3% in the vehicle group (p < 0.0001). In ZBB4-2, IGA treatment success rate was 28.1% at week 16, 32.3% at week 24, and 41.3% at week 52, and EASI-75 response rate was 53.3% at week 16, 63.7% at week 24, and 76.6% at week 52, indicating that efficacy responses improved over time and were maintained over 52 weeks. Across the two trials, most adverse events (AEs) were mild or moderate; common AEs included folliculitis, acne, and headache. In summary, tapinarof cream 1% was effective and generally safe for up to 52 weeks of treatment in Japanese patients with AD.

Mucosal malignant melanoma (MMM) is a rare subtype of malignant melanoma with a more aggressive biological behavior than cutaneous melanoma (CM). Owing to its rarity, it is necessary to accumulate information on treatments, especially in Asians, in whom MMM occurs more frequently than in Caucasians. In this study, we investigated the efficacy and adverse events (AEs) of nivolumab plus ipilimumab therapy (NIVO+IPI) versus immune checkpoint inhibitor (ICI) monotherapy (PD-1) in Japanese patients with MMM. We reviewed patients with advanced or recurrent MMM who received ICIs as first-line systematic therapy between February 2012 and February 2024 at the Shizuoka Cancer Center. We enrolled a total of 57 patients: 10 (17.5%) were treated with NIVO+IPI, and 47 (82.5%) were treated with PD-1 as first-line systemic therapy. Objective response rates (ORR) did not differ significantly between the NIVO+IPI and PD-1 groups (40.0% vs 27.7%; p = 0.176). There was also no statistically significant difference in progression-free survival (PFS) (median PFS time: 4.3 months vs 9.9 months, log-rank test, p = 0.578) or overall survival (OS) (median OS time: 33.1 months vs. 22.8 months, log-rank test, p = 0.697) between the two groups. However, regarding AEs, grade ≥3 AEs leading to discontinuation of first-line treatment occurred in 80% of patients in the NIVO+IPI group and in 22.6% of patients in the PD-1 group (p = 0.002). No difference was found in the efficacy of NIVO+IPI therapy and anti-PD-1 antibody monotherapy as the first-line treatment for MMM in Japanese patients, but an increase in AEs was observed with combination therapy. This study suggests that patients with MMM may receive less benefit from NIVO+IPI than from PD-1.