Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are rare but serious mucocutaneous disorders primarily caused by medications. Despite their low incidence, both conditions remain associated with high mortality and significant long-term complications. Recent studies have advanced the understanding of their pathogenesis, including the roles of neutrophil extracellular traps and several cell death pathways. However, reliable biomarkers for early diagnosis are lacking, and no internationally standardized diagnostic criteria have been established.

To address these gaps, new diagnostic frameworks have been proposed that incorporate conventional cutaneous and mucosal findings with mandatory histopathological confirmation. These are expected to enhance diagnostic precision and facilitate global comparability. The increasing incidence of SJS/TEN-like reactions associated with immune checkpoint inhibitors and molecular targeted therapies further highlights the importance of accurate histopathological differentiation.

Prognostic tools are essential for therapeutic planning. Although the Severity-of-Illness Score for Toxic Epidermal Necrolysis (SCORTEN) score remains widely used, newer systems offer improved risk stratification and practical utility in diverse clinical settings.

However, the optimal use of immunomodulatory therapies remains uncertain owing to limited consensus and evidence. Corticosteroids continue to serve as first-line treatment, but more selective agents are gaining attention for their potential efficacy and reduced toxicity.

This review summarizes recent progress in SJS/TEN diagnosis, severity assessment, and management. It discusses the utility and limitations of novel scoring systems and emerging therapies while highlighting persistent challenges, including high mortality, regional practice variation, and delayed standardization. International collaboration and high-quality evidence generation remain essential for improving patient outcomes.

Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are acute inflammatory disorders that affect the skin and mucous membranes, and in 40-84 % of SJS/TEN cases, the ocular complications that are often overlooked due to severe systemic symptoms. Specific ocular findings at the acute-phase include conjunctival hyperemia, pseudomembrane formation, and epithelial defects, and severe acute-phase ocular involvement strongly correlates with long-term visual impairment. Thus, it is vital to diagnose ocular involvement early at the acute stage and suppress inflammation on the ocular surface to protect corneal epithelial stem cells. As outlined in the official Japanese treatment guidelines for SJS/TEN cases with ocular involvement, corticosteroid pulse therapy and topical application of 0.1 % betamethasone eye-drops within four days of disease onset significantly reduces ocular sequelae. Early intervention with amniotic membrane transplantation helps reduce scarring and potential loss of vision. As for genetic-related factors, NSAIDs (nonsteroidal anti-inflammatory drugs) and cold medications are major triggers for SJS/TEN with severe ocular complications, with genetic predispositions involving TLR3 and prostaglandin E receptor 3 (subtype EP3) contributing to disease susceptibility. These genetic-environment interactions influence disease onset and progression. At chronic phase, severe dry eye and visual impairment are major long-term sequelae, and both surgical and non-surgical interventions have been applied to obtain favorable long-term treatment outcomes. In summary, early ophthalmic intervention is critical in preventing SJS/TEN-related ocular sequelae, and further research into genetic and immunological mechanisms is essential for better diagnosis and treatment.

Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are severe cutaneous adverse reactions across a spectrum of severity characterized by widespread epidermal detachment and keratinocyte apoptosis. SJS/TEN develops due to a complex immunologic response after exposure to an associated drug antigen and/or its metabolite, and it results in significant morbidity and mortality. Complex immune mechanisms contribute to keratinocyte death. Drug-induced SJS/TEN has been shown to be strongly HLA class I restricted which has contributed to our understanding of mechanisms and has the potential to shape prevention and diagnosis. There is currently no evidence-based treatment outside of aggressive supportive care, and understanding the complete immunopathogenesis of SJS/TEN will be key for the development of efficacious and safe treatments that significantly reduce morbidity and mortality. This article focuses on what is new in the pathogenesis of SJS/TEN, including recent research on the mechanisms of T-cell activation, apoptotic and necroptotic mediators, other related molecules, genetic associations, and possible targeted treatment options.

Drug-induced hypersensitivity syndrome (DIHS) or drug reaction with eosinophilia and systemic symptoms (DRESS) is a severe drug reaction characterized by a range of clinical manifestations. These range from mild cases resolving upon cessation of the causative drug to severe cases involving complex disease progression and potential fatality. A hallmark of DIHS/DRESS is the sequential reactivation of herpesviruses, particularly human herpesvirus 6 (HHV-6), during the disease course, contributing to recurrent symptoms. Viral reactivation can lead to critical complications, including infectious DIHS/DRESS-associated complications (iDACs) and autoimmune sequelae (aDACs). Managing DIHS/DRESS remains challenging due to its complexity, requiring precise prediction and tailored treatment strategies. Recent studies suggest that early-stage classification using the DIHS/DRESS Severity (DDS) score may help identify refractory cases, including DACs. Furthermore, early intervention with anti-cytomegalovirus (anti-CMV) therapy can mitigate iDACs caused by CMV reactivation, preventing progression to severe CMV-related diseases. Long-term follow-up is crucial, as aDACs can manifest even 3 years postonset. Serial monitoring is recommended, particularly in patients treated with intravenous immunoglobulin or corticosteroid pulse therapy, which are recognized risk factors for aDAC development. This review highlights DIHS/DRESS management strategies, focusing on its clinical features, the role of viral reactivation, and therapeutic interventions.

The association of human leukocyte antigen (HLA) with the risk of drug-induced skin eruptions has been extensively studied. The sensitivity of the association of specific HLA alleles with drug eruptions ranges from approximately 50 to 100%, indicating a significant influence of HLA alleles on the risk of developing such reactions. Consequently, HLA testing holds substantial clinical potential as a genetic diagnostic tool to avoid drug eruptions. For instance, when prescribing drugs like carbamazepine and lamotrigine, which are known to cause severe drug eruptions, preemptive HLA genetic testing can help predict an individual's risk. This approach enables clinicians to reduce the overall incidence of drug eruptions by selecting alternative therapeutic agents or adjusting dosages based on the results of HLA genetic testing.

Food allergy (FA) is a growing global concern, which contributes significantly to anaphylaxis and severe allergic reactions. Despite advancements in treatments like allergen immunotherapy and biologics, current approaches have notable limitations and there is a pressing need for new therapeutic strategies. Recent research into taste receptors has unveiled their potential role in FA, offering fresh perspectives for understanding and managing this condition. Taste receptors, particularly type 1 taste receptors (TAS1Rs/T1Rs, sweet taste receptors) and type 2 taste receptors (TAS2Rs/T2Rs, bitter taste receptors), are distributed not only in the oral cavity but also in various extra-oral tissues, and their interactions with immune responses are increasingly recognized. This review highlights the connections between taste receptors and FA, exploring how taste receptor mechanisms might contribute to FA pathogenesis and treatment. Taste receptors, especially TAS2Rs, which include multiple subtypes with varying ligand specificities, have been implicated in modulating allergic responses and could serve as targets for novel FA therapies. Additionally, compounds such as bitter agents and sweeteners that interact with taste receptors show promise in influencing FA outcomes. This review emphasizes the need for further research into the mechanisms of taste receptor involvement in FA and suggests that targeting these receptors could provide new avenues for therapeutic intervention in the future.

Alpha-gal syndrome (AGS) is a unique allergic condition triggered by IgE antibody production against the mammalian oligosaccharide galactose-α-1,3-galactose (α-gal). The syndrome, acquired by bites from multiple tick species, leads to delayed allergic reactions after consuming mammalian-derived products containing α-gal, including red meat, dairy, and select medications. AGS is especially prevalent in regions with high tick exposure and has become a global public health concern, with rising cases across continents. Despite growing research, including recent findings suggesting that asymptomatic α-gal sensitization may contribute to coronary artery disease, the precise immune mechanisms—particularly B cell-mediated IgE production following tick bites—remain poorly understood. Additionally, the tick saliva components that trigger sensitization and the role of the skin-gut axis in food allergy development are knowledge gaps. AGS research has benefited from animal models like mice, zebrafish, and pigs, which replicate key syndrome features, though have limitations. Humanized mouse models and human organoid systems now offer promising tools for investigating AGS pathogenesis and testing potential therapies. This review explores current pre-clinical methodologies, challenges, and the future of AGS research, emphasizing innovative models that may bridge knowledge gaps and advance therapeutic development.

Background: Identification of predictive biomarkers is crucial for formulating preventive interventions and halting the progression of atopic march. Although controversial, the use of accessible markers to predict or detect early onset of atopic diseases is highly desirable. Therefore, this study aimed to investigate whether corneal squamous cell carcinoma antigen-1 (SCCA1) collected from infants can predict the development of atopic dermatitis and food allergy.

Methods: This prospective study enrolled 117 infants aged 2 months (55 female and 62 male infants). The participants were monitored to evaluate the occurrence of eczematous changes at several time points, and stratum corneum samples were obtained. The association of corneal SCCA1 with the development of atopic dermatitis and food allergy in the first 3 years of life was evaluated using univariate and multivariate logistic regression.

Results: The corneal SCCA1 level was significantly higher in children who developed atopic dermatitis than in children who did not (cheek at 2 months: 1653.06 ± 178.48 ng/mg vs. 786.95 ± 101.59 ng/mg, P = 0.0033). The corneal SCCA1 level was also significantly higher in children who developed food allergy than in children who did not (perioral skin at 2 months: 2567.31 ± 408.09 ng/mg vs. 1120.85 ± 188.49 ng/mg, P = 0.0018).

Conclusions: The findings suggest that non-invasive measurements of corneal SCCA1 at 2 months of age is useful for predicting atopic dermatitis and food allergy in infants at risk for atopic dermatitis and subsequent food allergy.

Background: The detection of drug-specific activation of T cells in the lymphocyte transformation test (LTT) is mainly based on cell proliferation or cytokine secretion. However, the LTT presents with a varying sensitivity and specificity. The aim of our study was to analyse the genome wide gene expression of PBMC to identify drug allergy-specific gene regulation patterns. Additionally, gene expression differences related to the allergy-inducing drug or the type of allergy (immediate/delayed) were investigated.

Methods: Blood samples from 40 patients with allergy to different drugs and from 40 non-drug-allergic controls were recruited. PBMC were isolated and stimulated with the culprit drug (“LTT-platform”). Transcriptome analyses of PBMC were conducted after 3.5 days. The concentration of IFN-γ and IL-5 in the culture supernatants was measured by ELISA after 6 days.

Results: The transcriptome analyses revealed an allergy type and drug-specific gene regulation in PBMC from patients. Importantly, in the corresponding control groups these genes were barely or even opposingly regulated. It was also shown that in particular cefuroxime exerted a strong effect on the gene regulation in PBMC. Quantitative RT-PCR of selected genes identified by the transcriptome analyses revealed that CCL17, CISH and CD25 were specifically upregulated in patients. Notably, a strong upregulation of CCL17, CISH or CD25 did not necessarily correlate with the ELISA outcome of the patients and controls.

Conclusions: Our results could be helpful for the identification of one or a panel of regulated genes considering patient specific parameters like the type of the allergy-inducing drug.

Background: In recent years, several targeted therapeutic options have become available for the management of atopic dermatitis in children. In this systematic review and meta-analysis, we assessed the efficacy and safety of systemic targeted therapies for atopic dermatitis in children.

Methods: A systematic review of literature available in CENTRAL, MEDLINE, Embase, and ICHUSHI databases until January 7, 2023, was performed. Randomized controlled trials of systemic targeted therapies (biologics and small molecules) on children aged 18 years or younger with atopic dermatitis were included. The primary outcomes were the eczema area and severity index (EASI) and adverse events. Other efficacy and safety outcomes were also used for meta-analysis and risk of bias analysis.

Results: We included 10 studies reported in 11 articles involving three agents (dupilumab, abrocitinib, and upadacitinib) and 1760 children. Systemic targeted therapies significantly improved eczema severity with an EASI-75 response (risk ratio, 2.99; 95 % confidence interval [CI], 2.66-3.37). However, systemic targeted therapies were associated with treatment-emergent adverse events (risk difference, 0.05; 95 % CI, 0.01-0.09), particularly among small molecules in subgroup analysis, while no such trend was observed with biologics. Systemic targeted therapy also significantly improved other efficacy outcomes, and no significant association was found in the other safety outcomes. There was no risk of bias in any of the outcomes.

Conclusions: Our findings indicate that systemic targeted therapies are effective and relatively safe for treating atopic dermatitis in children, although small molecules may pose a slightly higher risk of adverse events.

Background: Although randomized controlled trials (RCT) have demonstrated the efficacy of mepolizumab for asthma, they have excluded certain patient subgroups. To bridge the gap between RCT and real-world practice, the effectiveness of mepolizumab in a diverse population, including those potentially excluded from RCT, was assessed. Its effects on imaging findings and symptoms of chronic rhinosinusitis (CRS) with asthma were also assessed.

Methods: This retrospective observational study of patients in Japan (J-Real-Mepo: UMIN000045021) evaluated multiple endpoints and analyzed the relationship between clinical background and treatment outcomes.

Results: Mepolizumab significantly reduced exacerbations, improved Asthma Control Test (ACT) scores, and forced expiratory volume in 1 s, and reduced oral corticosteroid (OCS) dose, regardless of patient characteristics, including age, body mass index, smoking history, and comorbidities. Regarding RCT exclusion criteria, 29.4 % of patients had no history of exacerbations. Although 25.4 % of these patients required continuous OCS, the OCS dose was reduced similar to those with a history of exacerbations. Disease control and mepolizumab effectiveness in patients with a smoking history ≥10 pack-years was similar to that of never-smokers. Patients with eosinophil counts <150/μL had lower ACT scores and higher OCS use compared with patients with eosinophilia and comparable effectiveness regarding exacerbation and OCS reduction. Significant improvements in Lund-Mackay scores and CRS symptoms were observed.

Conclusions: Mepolizumab effectiveness was demonstrated in a broad range of patients including those with RCT exclusion criteria, who had significant disease or OCS burden. These findings may explain the consistent results between RCT and real-world studies of mepolizumab.

Background: Allergic rhinitis may impair work productivity. This study aimed to assess (i) the differential impact of allergic rhinitis symptoms on work performance, assessed by means of Visual Analogue Scale (VAS) work; and (ii) the effect of asthma comorbidity on work productivity.

Methods: We assessed data from the MASK-air mHealth app of patients with allergic rhinitis. We identified factors associated with the impact of allergic symptoms on work productivity through multivariable linear mixed effects models.

Results: We studied 260,378 days from 20,724 patients. In multivariable regression models, nasal symptoms showed the strongest association with VAS work (regression coefficient = 0.38 [95%CI = 0.38; 0.38]). Poor rhinitis control, measured by the combined symptom-medication score, was associated with worse VAS work (regression coefficient = 0.96 [95%CI = 0.96; 0.97]). The median VAS work in patients with probable or possible asthma (median = 9, interquartile range = 22 for probable and 23 for possible asthma) was greater than for patients with no evidence of asthma (median = 3, interquartile range = 12) (Cohen's d = 0.60). In patients with probable asthma, nasal and asthma symptoms showed a similar impact on work productivity (regression coefficient for VAS nose = 0.32 [95%CI = 0.31; 0.32]; regression coefficient for VAS asthma = 0.30 [95%CI = 0.29; 0.31]).

Conclusions: Allergy symptoms, especially nasal symptoms, are associated with worse work productivity. In addition, patients with allergic rhinitis and asthma display more impairment in work productivity than patients with allergic rhinitis alone.

Background: Elderly asthma has distinct pathophysiologic and phenotypic characteristics compared with asthma in younger patients. However, a potential relationship between sex hormones and the severity of asthma remains unknown in the elderly population. The aim of the present study was to elucidate the relationship between the level of circulating free testosterone and severity of asthma among Japanese with elderly asthma.

Methods: The level of free testosterone was measured using sera from elderly patients with asthma aged ≥60 years (n = 192), and its association with the severity of asthma was examined after stratification by sex.

Results: Based on previous literature and our preliminary analysis showing that current oral corticosteroid (OCS) use might be a risk factor for a lower free testosterone level regardless of severity of asthma, analyzed patients were limited to those who were not currently using OCS (n = 164). Regarding elderly men who were not currently using OCS (n = 62), there was no significant association between free testosterone level and severity of asthma. However, in female counterparts (n = 102), a low free testosterone level was significantly associated with severe asthma even after adjustment for age (p for trend, 0.03).

Conclusions: The present study showed a significant association between the serum free testosterone level and severity of asthma among elderly women who were not currently using OCS. Although the causal relationship is unclear, this finding may provide a clue to understand the sex difference in the mechanisms of severe asthma in elderly populations.

Background: The increasing prevalence of allergic rhinitis may be attributed to lifestyle changes such as dietary habits. Regarding dietary factors, n-3 and n-6 polyunsaturated fatty acids (PUFAs) are considered to be involved in the pathogenesis. Therefore, we examined whether the intake and serum concentrations of fatty acids affect inhaled allergen sensitization and the development of allergic rhinitis.

Methods: In total, 571 participants (20-69 years) from the Iwaki Health Promotion Project, a community-based project in 2022, were surveyed. Based on the results of PUFA intake and serum fatty acid concentrations obtained using a self-administered diet-history questionnaire, we examined whether n-3 or n-6 PUFAs were involved in reducing or increasing the risk of sensitization, respectively, and developing the disease. We also analyzed whether monounsaturated fatty acids—palmitoleic acid and oleic acid—were risk factors for sensitization and development. Univariate dietary intake, serum concentration, and logistic regression analyses were performed to identify the risk factors.

Results: Our study revealed that higher serum concentrations of n-3 PUFAs were associated with a decreased risk of developing rhinitis, but had no effect on allergen sensitization in younger age group <50 years. Furthermore, palmitoleic acid had increased sensitization, and oleic acid may also increase the risk of the allergen sensitization.

Conclusions: n-3 PUFAs may reduce the risk of developing allergic rhinitis. Notably, palmitoleic acid may be a new risk factor that increases the risk of inhalant allergen sensitization and allergic rhinitis. These findings are significant in understanding the role of dietary factors in allergic rhinitis.