Journal of Dermatology最新文献

Ritlecitinib is an oral Janus kinase 3/tyrosine kinase expressed in hepatocellular carcinoma (JAK3/TEC) family kinase inhibitor approved for the treatment of severe alopecia areata (AA). Benefit–risk profiles of two doses of ritlecitinib (50 mg vs 30 mg once daily) were evaluated by integrating patient preferences and clinical efficacy and safety estimates for ritlecitinib. A discrete-choice experiment (DCE) was utilized to elicit preferences for benefit and safety attributes of systemic AA treatments. Benefits included probabilities of ≥80% scalp hair coverage and achieving moderate to normal eyebrows and eyelashes. Potential risks included 3-year probabilities of serious infection, cancer, and blood clots. Preference estimates were used to calculate the maximum acceptable risk (MAR) that patients would accept for expected increases in benefit from choosing a higher ritlecitinib dose over a lower dose. Ritlecitinib benefits were calculated from the ALLEGRO-2b/3 clinical trial. MARs were calculated separately for each risk and jointly for all possible combinations. Adults (n = 201) with physician-confirmed ≥50% scalp hair loss from AA participated. To achieve expected increases in the probabilities of ≥80% scalp hair coverage or moderate to normal eyebrows and eyelashes when choosing 50 mg over 30 mg of ritlecitinib, patients would be willing to accept increases in each 3-year risk up to a mean of 3.88 absolute percentage points (95% confidence interval [CI], 2.86–4.90) for serious infection, 1.63 (95% CI, 1.08–2.18) for cancer, and 5.30 (95% CI, 3.60–7.00) for blood clots. These results, combined with the estimated differences in risks between the two doses, indicate that patients with AA value increases in the probabilities of scalp, eyebrow, and eyelash hair regrowth, with the average patient accepting increases in potential treatment-related risks for the 50-mg dose in exchange for higher efficacy than 30 mg. The DCE approach to measuring risk tolerance, combined with comparisons to expected benefit and risk differences, can be used to optimize AA treatment dose selection.

Itch is a prominent symptom in many cutaneous disorders, including atopic dermatitis (AD), prurigo nodularis, and psoriasis. Itch is also a common but overlooked concern in patients with hidradenitis suppurativa (HS). Currently, the mechanisms underlying itch in HS remain unclear. To gain a better understanding, we reviewed the literature on pruritus in HS and other itch-predominant disorders, AD, and psoriasis. In HS, psoriasis, and AD, we found that itch often co-localized with pain and occurred more frequently at night. Furthermore, itch was found to negatively affect sleep and increase the risk for comorbid psychiatric disorders in HS, psoriasis, and AD. However, HS-, psoriasis-, and AD-related itch differ in temporality. Itch in AD is often described as chronic, while itch in HS and psoriasis is often described as episodic. HS-associated itch is likely multifactorial, and several mechanisms have been proposed including peripheral sensitization, central sensitization, and neuroinflammation. Prior studies in HS highlight enhanced IgE production and a dense infiltration of mast cells, along with a variety of cytokines and chemokines. Furthermore, alterations in the skin microbiome may contribute to itch in HS. To date, few therapies have been studied to treat itch in HS. Given the efficacy of several biologics and small molecules in treating itch in AD and psoriasis, similar agents may be explored in future HS studies. Alternative therapies to target neurological and psychiatric contributions to itch may include anticonvulsants, cannabinoids, and nonpharmacological treatments. In conclusion, pathomechanisms of itch in HS remain to be fully elucidated. However, we can draw on lessons from other pruritic disorders to begin addressing the symptom of it and identify important questions for future study.

Bullous pemphigoid (BP) is an autoimmune blistering disorder predominantly affecting the elderly. Recently, many studies have shed light on the effect of specific drug intake and comorbidities on the development of BP. The purpose of this study was to investigate the association of specific drug class intake and comorbidities with the development of BP in the Cretan population. Significant associations with BP were found for statins (odds ratio [OR] = 4.06, 95% confidence interval [CI] 1.99–8.27, P < 0.001), gliptins (OR = 4.27, 95% CI 2.33–7.83, P < 0.001), and antipsychotics (OR = 3.33, 95% CI 1.36–8.11, P = 0.006). Higher proportions of use in the BP group vs. control group were found for atorvastatin (OR = 1.86, 95% CI 1.04–3.32, P = 0.035), linagliptin (OR = 6.63, 95% CI 2.17–20.23, P < 0.001), vildagliptin (OR = 3.20, 95% CI 1.73–5.91, P < 0.001), alogliptin (OR = 5.11, 95% CI 1.19–22.04, P = 0.016), and quetiapine (OR = 4.21, 95% CI 1.5–11.85, P = 0.004). The presence of diabetes mellitus in the absence of gliptins did not show any significant effect on BP (OR = 1.60, 95% CI 0.79–3.23, P = 0.188). Metformin intake showed no significant association with BP (OR = 0.48, 95% CI 0.18–1.28, P = 0.143). Our findings confirm and extend previous studies reporting the association of gliptins and antipsychotics on BP in other European populations. The association found for statins is new, thus more studies are needed to corroborate its validity.

Erythropoietic protoporphyria (EPP) and X-linked protoporphyria (XLP) are rare genetic disorders. There are limited data regarding how these disorders are managed in real-world settings. The aim of this study was to document the characteristics and treatment patterns among patients diagnosed with EPP or XLP in general real-world settings in the United States. We, therefore, conducted a retrospective medical record review of patients diagnosed with EPP or XLP on or before July 1, 2020. Data were analyzed for patients with EPP (n = 299) and XLP (n = 91). Outcomes included demographic and clinical characteristics, diagnostic testing, therapy recommendations, office visits, emergency department visits, and hospitalizations. Costs were assigned to healthcare resources. Mean (standard deviation [SD]; median) time between the first symptom documented in the medical records and diagnosis was 2.9 (5.1; 1.3) years. The most common pre-diagnostic tests were liver function, total plasma and erythrocyte protoporphyrin, genetic tests, and renal function. Patients were advised to use sunscreen (85%) or modify their lifestyle (83%). Within 12 months of diagnosis, the mean (SD; median) number of office visits, emergency department visits, and inpatient hospitalizations related to EPP or XLP were 4.0 (3.5; 3.0), 0.8 (1.6; 0), and 0.4 (1.3; 0), respectively. Patients with EPP or XLP have several unmet needs, including timely and accurate diagnosis, symptom relief, and efficacious prevention of phototoxic reactions.

MPOX is an orthopoxvirus whose infection has been declared a Public Health Emergency of International Concern in 2022 and 2024. It proved to be a virus with markedly heterogeneous and varied clinical presentation. We performed a systematic PubMed review of articles reporting cases of different clinical manifestations of MPOX until October 2024. The infection has mainly affected men who have sex with men. After 4 to 10 days of incubation, it presents with mucocutaneus lesions and systemic symptoms. Some anatomical sites have shown clinical particularities. Genital edema is a potentially serious complication. The ocular and ear/nose/throat area are other infrequent sites with specific manifestations. MPOX whitlow affects the third finger of the dominant hand and may be associated with extensive inflammation and proximal lymphangitis. Bacterial superinfection is a common complication in the genital area with good response to antibiotic treatment. Immunosuppressed patients may develop severe inflammation and necrosis resulting in poor prognosis. Some authors propose ulceronecrotic MPOX as a defining condition of AIDS. The involvement of women has been exceptional in the current outbreak and has predominantly affected the vulva. Some patients such as healthcare workers, atopics, and people who get tattoos are at risk of developing specific lesions via nonsexual routes. Other atypical manifestations include maculopapular rash and inguinal patch. MPOX is a highly relevant and ongoing infection that can present with multiple atypical manifestations, and the knowledge of which is of great importance to the clinician. We present a unique systematic review of atypical presentations of this infection that may be associated with significant morbidity and mortality, especially in the immunocompromised population.

Nagashima-type palmoplantar keratosis (NPPK) has been shown to represent a form of autosomal recessive palmoplantar keratosis due to biallelic pathological variants of SERPINB7, which encodes a serine protease inhibitor expressed in the epidermis. Approximately 10 years have elapsed since NPPK was demonstrated to be an independent genetic disease, and the most prevalent palmoplantar keratoderma (PPK) in East Asian countries due to a high prevalence of founder mutations in SERPINB7. Since then, it has become evident that biallelic pathological variants of SERPINA12, which encodes a serine protease inhibitor expressed in the epidermis, can also manifest symptoms analogous to those of NPPK. Furthermore, a pathological variant of SERPINB7 was identified as a risk factor for the development of atopic dermatitis in a genome-wide association study (GWAS) of atopic dermatitis, indicating that the frequent co-occurrence of NPPK and atopic dermatitis is not a mere coincidence. Despite the documentation of NPPK cases in Japan since the 1970s, there have been no reports of individuals with similar symptoms from other regions, including Europe and the USA. Consequently, the existence and independence of the disease remained uncertain until its genetic cause was identified. The disease's independence was established through the accumulation of data on affected individuals, including the provision of accurate descriptions of their symptoms, which enabled the identification of the genetic cause. This review presents a comprehensive overview of the history and prospects of NPPK with a particular focus on the history of the process of establishing NPPK as an independent disease.

The long-term complications of coronavirus disease 2019 (COVID-19) continue to cause global concern. This study aimed to estimate the incidence and risk of chronic urticaria, vitiligo, alopecia areata, and herpes zoster following COVID-19 infection. Only participants confirmed by real-time reverse transcription-polymerase chain reaction tests to have COVID-19 were enrolled in the COVID-19 group. The matched cohort without COVID-19 was enrolled randomly at a ratio of 1:1. The incidence and risk of chronic urticaria, vitiligo, alopecia areata, and herpes zoster were assessed in both groups using univariable and multivariable Cox proportional hazard analyses. A total of 4 976 589 COVID-19 patients (9.58% of the total population of South Korea) and an equivalent number of matched non-infected control subjects were analyzed. Chronic urticaria, vitiligo, alopecia areata, and herpes zoster manifested at higher rates within the COVID-19 cohort, even after multivariable adjustment for potential confounders. COVID-19 may increase the risk of developing chronic urticaria, vitiligo, alopecia areata, and herpes zoster.

The rapid aging of the population has led to an increase in the number of cutaneous squamous cell carcinoma (cSCC) cases among the older population. However, the characteristics of these cases remain unclear. In this study, we aimed to identify the problem by analyzing the clinical characteristics of patients with cSCC aged 90 years and over. In this retrospective study, we analyzed the characteristics of patients aged >90 years with regard to gender, risk factors for cSCC, and disease course, using data from 316 patients with cSCC who underwent surgery at the Kagoshima Medical Centre between October 2014 and September 2022. Patients were separated into two groups based on age: those aged ≥90 years (104 patients) and those aged <90 years (212 patients). Regarding the National Comprehensive Cancer Network risk classification, there was no difference between groups. Univariate, multivariate, and Cox analyses of relapse-free survival of patients in both groups indicated that the recurrence risk was significantly high among those aged ≥90 years. Patients aged ≥90 years were at higher risk for recurrence, suggesting a need for closer follow-up than that for patients aged <90 years.

The tyrosine kinase 2 inhibitor deucravacitinib is therapeutically effective for psoriasis. However, predictive factors for high responses to deucravacitinib have not been examined in a real-world clinical study. Our study aimed to identify predictive factors for responders to deucravacitinib. Therefore, a retrospective study was conducted on 74 patients with psoriasis treated with deucravacitinib (6 mg/day) at week 16 of treatment from January 2023 to February 2024. Patients were classified into responders (achievers of a static Physician's Global Assessment [sPGA] of 0 or 1 with ≥2-point improvement from basal sPGA) and non-responders (non-achievers). We compared baseline values of clinical and laboratory indexes between responders and non-responders. Multivariate logistic regression analysis was used to identify variables predicting responders. Forty-one patients (55.4%) were considered as responders at week 16. Multivariate logistic regression analysis revealed that the response to deucravacitinib was associated with higher age (odds ratio [OR] 1.04; 95% confidence interval [CI] 1.01–1.08; p = 0.0222) and lower body mass index (BMI) (OR 0.825; 95% CI 0.713–0.955; p = 0.0101). Higher age and lower BMI may predict a higher response to deucravacitinib (6 mg/day) at week 16 of treatment.