Yuehua Liu

The increasing use of JAK inhibitors in clinical practice is raising concerns regarding the potential risk of cutaneous lymphoma. This study aimed to conduct a comprehensive search for cases of cutaneous lymphoma associated with JAK inhibitors in the Food and Drug Administration’s Adverse Event Reporting System. The clinical characteristics of cases from January 2004 to September 2023 were retrieved from the FAERS database. Disproportionality and Bayesian analyses were performed to detect signals for cutaneous lymphoma associated with JAK inhibitors. In total, 24 cases of cutaneous lymphoma were identified associated with JAK inhibitors, including tofacitinib, ruxolitinib, baricitinib, upadacitinib, and abrocitinib. The majority of patients (64%) were aged 60 or older, with no significant difference in incidence between genders. The average onset time was 8.64 months. One patient with ruxolitinib experienced a fatal outcome, and 1 patient with tofacitinib had a life-threatening event. Cutaneous lymphoma associated with baricitinib has the highest reporting odds ratio (23.91, 95% confidence interval 10.71–53.4), proportional reporting ratio (23.88, χ2 = 103.67), information component (4.57, IC025 = 2.05), and empirical Bayes geometric mean (23.73, EBGM05 = 12.12). The occurrence of cutaneous lymphoma associated with JAK inhibitors highlights the importance of pharmacovigilance studies to deepen our understanding of both the medications and associated conditions.

Vitiligo is a complex, multifactorial disorder characterized by acquired skin pigment loss that strongly influences the physical and mental well-being of patients with vitiligo. The precise pathogenesis remains incompletely elucidated, but recent studies emphasize the significant roles of both innate and adaptive immunity. Pattern recognition receptors (PRRs), essential for innate immune sensing, significantly contribute to melanocyte destruction in vitiligo. In vitiligo patients, melanocytes and keratinocytes secrete substances like heat shock protein 70 (HSP70), high-mobility group box 1 protein (HMGB1), calreticulin (CRT), and S100 calcium-binding protein B (S100B) due to various internal and external influences. PRRs are capable of recognizing these “danger signals”. This recognition activates the immune response by stimulating innate immune cells, like plasmacytoid dendritic cells (pDCs) and natural killer cells (NK cells). The activation of innate immune cells leads to the release of cytokines and the presentation of melanocyte antigens to T cells, triggering the adaptive immune response. Activated CD8⁺ T cells release cytotoxic substances such as perforin and granzyme, which directly target and kill melanocytes. Cytokines like IFN-γ can concurrently stimulate keratinocytes to produce chemokines such as CXCL9 and CXCL10, which further recruit additional T cells, establishing an inflammatory amplification loop. This loop leads to continuous damage of melanocytes and ultimately results in the development of vitiligo. PRR inhibitors target the initial phase of the immune response cascade in vitiligo, offering a more fundamental and precise therapeutic approach with potential advantages in controlling disease activity and preventing recurrence. This review provides an overview of current research regarding PRRs and their ligands in vitiligo pathogenesis, with a focus on potential therapeutic strategies.

Vitiligo is a chronic autoimmune disease, and current treatments for vitiligo have limited efficacy. Janus kinase (JAK) inhibitors could offer new therapeutic options. To evaluate the efficacy and safety of baricitinib, an oral JAK1/2 inhibitor, combined with narrow‐band ultraviolet B (NB‐UVB) in vitiligo treatment. This prospective, controlled, open‐label study included adults with progressive non‐segmental vitiligo (NSV). Patients were assigned to combination therapy with baricitinib 2 mg daily and NB‐UVB three times a week or NB‐UVB alone three times a week (control). The primary endpoint was the proportion of patients achieving 50% or greater improvement from baseline in the total Vitiligo Area Scoring Index (T‐VASI50) at week 16. Of the 33 patients (mean age, 34.1 years; 27.3% women) who completed the study, 12 of 17 (70.6%) patients in the combination group and 2 of 16 (12.5%) in the control group had a T‐VASI50 response at week 16 (relative risk [RR] = 5.6; 95% CI = 1.5–21.4; p = 0.001). Adverse events were minor, including erythema, mild blister after phototherapy and acne. Combination therapy with low‐dose baricitinib and NB‐UVB was effective and well tolerated in adults with progressive NSV.

Vitiligo is a chronic dermatological condition marked by the loss of skin pigmentation. Its complex etiology involves multiple factors and has not been completely elucidated. Protein post-translational modification pathways have been proven to play a significant role in inflammatory skin diseases, yet research in the context of vitiligo remains limited. This review focuses on the role of post-translational modifications in vitiligo pathogenesis, especially their impact on cellular signaling pathways related to immune response and melanocyte survival. Current therapeutic strategies targeting these pathways are discussed, emphasizing the potential for novel treatments in vitiligo management.

Mycosis fungoides (MF) is the most common type of cutaneous T cell lymphoma. As the early clinical manifestations of MF are non-specific (e.g., erythema or plaques), it is often misdiagnosed as inflammatory skin conditions (e.g., atopic dermatitis, psoriasis, and pityriasis rosea), resulting in delayed treatment. As there are no effective biological markers for the early detection and management of MF, the aim of the present study was to perform a proteomic analysis of urine samples (as a non-invasive protein source) to identify reliable MF biomarkers. Thirteen patients with early-stage MF were administered a subcutaneous injection of interferon α-2a in combination with phototherapy for 6 months. The urine proteome of patients with early-stage MF before and after treatment was compared against that of healthy controls by liquid chromatography-tandem mass spectrometry. The differentially expressed proteins were subjected to Gene Ontology, Kyoto Encyclopedia of Genes and Genomes, and Clusters of Orthologous Groups analyses. For validation, the levels of the selected proteins were evaluated by enzyme-linked immunosorbent assay (ELISA). We identified 41 differentially expressed proteins (11 overexpressed and 30 underexpressed) between untreated MF patients and healthy control subjects. The proteins were mainly enriched in focal adhesion, endocytosis, and the PI3K-Akt, phospholipase D, MAPK, and calcium signaling pathways. The ELISA results confirmed that the urine levels of Serpin B5, epidermal growth factor (EGF), and Ras homologous gene family member A (RhoA) of untreated MF patients were significantly lower than those of healthy controls. After 6 months of treatment, however, there was no significant difference in the urine levels of Serpin B5, EGF, and RhoA between MF patients and healthy control subjects. The area under the receiver operating characteristic curve values for Serpin B5, EGF, and RhoA were 0.817, 0.900, and 0.933, respectively. This study showed that urine proteomics represents a valuable tool for the study of MF, as well as identified potential new biomarkers (Serpin B5, EGF, and RhoA), which could be used in its diagnosis and management.

Background: Mycosis fungoides (MF) is the most common type of cutaneous T-cell lymphoma. Objectives: This study was conducted to evaluate efficacy and safety of interferon (IFN) α-2a combined with phototherapy for early-stage MF. Methods: Thirteen patients with early-stage MF received subcutaneous injections of IFN α-2a at 3 million IU combined with phototherapy three times per week for 6 months. Treatment efficacy was measured by changes in body surface area (BSA) score and modified severity-weighted assessment tool (mSWAT) score at 1, 3, and 6 months after treatment. Histopathologic examinations of skin lesions were performed before and after treatment. Results: After 3 months of treatment, all 13 patients achieved a partial response, and BSA and mSWAT scores were significantly lower than those at baseline (p < 0.001). After 6 months, BSA and mSWAT scores were significantly lower than those at baseline (p < 0.001) and after 3 months (p < 0.05). Eleven patients achieved complete remission and two patients achieved a partial response (overall response rate, 100%). Histopathologic examination showed a significant decrease in the number of atypical lymphocytes in both epidermis and dermis. No severe adverse effects occurred. Conclusion: IFN α-2a in combination with phototherapy may be an effective and safe alternative modality for early-stage MF.

Hypopigmented mycosis fungoides is a rare form of mycosis fungoides that is characterized by achromic lesions, early onset of disease, a predilection for darker skinned populations, and a predominance of CD8+ T cells. Due to the rarity and heterogeneous presentation of hypopigmented mycosis fungoides, there are no criteria that clearly define the clinical characteristics and treatment regimens for this condition. This retrospective study of 44 paediatric patients with hypopigmented mycosis fungoides aimed to summarize their epidemiological and clinical characteristics and assess the effectiveness and safety of different treatment regimens. Clinical manifestations were further classified into 3 morphological groups: hypopigmented lesions, papules overlying hypopigmented lesions, and erythematous plaques overlying hypopigmented lesions. In addition, the results of this study suggest that interferon alpha might be an effective and well-tolerated therapy that could shorten the treatment time to complete response compared with other treatments. Maintenance therapy and long-term follow-up reduced the recurrence rate.