特应性皮炎（AD）前沿文献精读特辑（Br J Dermatol / Dermatol Ther (Heidelb) / Allergy）

BACKGROUND: Inborn errors of immunity (IEI) with atopy (IEI-A) are a subgroup of IEIs with eczema as a prominent clinical feature that can mimic atopic dermatitis (AD). However, IEI-A-associated eczema can differ from that of classic AD, and its frequency, genotype-specific clinical patterns and temporal relationships with other manifestations of IEI-A (infections, allergic manifestations, autoimmunity) remain poorly defined. OBJECTIVES: To characterize the frequency of eczema, timing and phenotypes in patients with IEI-A, and to explore the relationship of eczema with other clinical manifestations of IEI-A. METHODS: This retrospective study used data from the French National Referral Center for Primary Immunodeficiency Diseases (CEREDIH), focusing on patients with genetically defined IEI-A followed in three large CEREDIH-participating centres and available clinical data. Eczema frequency and onset in relationship to other clinical events, particularly severe-or-unusual infections, was assessed, as were eczema phenotypes, concomitant allergic manifestations, treatments and autoimmunity. Clustering analyses were computed to identify distinct IEI-A eczema-associated clinical phenotypes. RESULTS: Among 373 patients with IEI-A, varying widely by genotype, 50.9% (n = 190) had eczema. All patients deficient in DOCK8 (dedicator of cytokinesis-8) were affected, followed by those deficient in FOXP3 (n = 22/30; 73%) and those with STAT3 loss of function (n = 44/59; 75%). Onset was usually early (median 4 months). Eczema frequency and clinical presentation varied markedly across IEI-A genotypes; four phenotypic clusters were identified, with particular localizations and severe pruritus being strongly associated with pathogenic STAT3 or DOCK8 variants. For children with isolated eczema at 24 months, the risk of developing IEI-related severe or unusual infections was lower than that of persistent isolated eczema until the age of 6.8 years. CONCLUSIONS: Eczema is a common, early feature of IEI-A, often preceding infections by years. While 38.4% (n = 73/190) of patients with IEI-A with eczema fulfilled the UK Working Party diagnostic criteria for AD, some clinical pictures may differ from that of classic AD. At a time when systemic AD treatments are rapidly advancing in paediatrics, recognizing these patterns to identify patients with IEI-A could refine diagnostic strategies, improve IEI detection among children with eczema, shorten the time to IEI-A diagnosis, guide tailored management and ensure patients receive the optimal care.

INTRODUCTION: Biologics have expanded treatment options for moderate-to-severe atopic dermatitis (AD), but practical guidance on how to initiate and manage these therapies in routine care remains limited. The advancing management of atopic dermatitis and eczema (AMAZE ) project examined global clinical practices and developed expert-informed recommendations to support biologic initiation and long-term management. METHODS: An online survey of 150 dermatologists from North America, Europe, and Japan assessed real-world approaches to biologic management. Findings were interpreted by an international global steering committee and further refined through expert discussion meetings. Best practice recommendations were developed on the basis of survey findings, expert consensus, and a narrative literature review. RESULTS: Respondents reported considerable variability in biologic initiation practices. Overall, 47% of dermatologists intended biologic therapy for long-term use, while Japanese clinicians more frequently anticipated shorter treatment durations (4-12 months), reflecting national guideline recommendations. Transition practices from conventional systemic therapies varied substantially between dermatologists: 49% reported overlapping, 33% transitioned directly without overlap, and 18% used a washout period. European clinicians were more likely to discontinue conventional systemic therapies prior to biologic initiation, whereas overlapping strategies were more common in North America and Japan. Early follow-up within 4 weeks was reported by 36% of dermatologists and was most common in Japan, largely owing to healthcare system requirements. Expert-informed recommendations emphasized: establishing patient-centered treatment goals focused on long-term disease control; individualized transition strategies when switching from conventional systemic therapies; structured follow-up with formal assessment of treatment response around 12-16 weeks after treatment initiation; and proactive management of flares through continued use of emollients and topical anti-inflammatory therapies. CONCLUSIONS: The AMAZE project highlights substantial regional variation in biologic initiation practices for AD. These expert-informed recommendations provide practical guidance to support individualized, patient-centered approaches to initiating and managing biologic therapy in routine clinical practice. Graphical plain language summary available for this article at https://doi.org/10.6084/m9.figshare.32991755 .

BACKGROUND: Alopecia areata (AA) frequently co-occurs with atopic dermatitis (AD; AA-AD); however, AA-AD's features remain unclear. OBJECTIVE: To elucidate the clinical and immunological features of AA-AD. METHODS: Retrospective analysis of data from 123 AA-AD patients, 119 non-atopic AA patients, and 126 AD patients (2011-2024). Peripheral blood mononuclear cells (PBMCs), plasma, and scalp tissues from patients and healthy controls (HC) were examined by flow cytometry, multiplex cytokine assays, and immunofluorescence. RESULTS: Clinically, AA-AD patients were younger than non-atopic AA and AD-only patients, showed more severe alopecia and longer duration, but milder eczema, and exhibited higher dust-mite allergy, total IgE (tIgE), and Eos counts/percentages than non-atopic AA, while showing more intrinsic AD and lower tIgE and Eos counts/percentages than AD-only patients. AA severity and duration were positively correlated with those of AD. Compared with AA-AD patients with AA-first onset and AA with intrinsic AD (AA-IAD) patients, AA-AD patients with AD-first onset and AA with extrinsic AD (AA-EAD) patients were younger, had more severe eczema, higher tIgE levels, and dust-mite allergy. Compared with the non-atopic AA group and HC, the AA-AD group showed elevated plasma IL-4/6/10/13 levels and increased Th2 cells and ILC2s (group 2 innate lymphoid cells) proportions in PBMCs, along with their IL-13 production, all of which were positively correlated with AA course. AA-AD scalp also showed that Th2 cells and ILC2s were most abundant. CONCLUSION: AA-AD defines a distinct clinical-immunologic endotype of AA. AA and AD exhibit an asymmetric but bilateral interaction driven by Th2/ILC2s-IL-13-centered pathways, representing key mechanisms and targets for precision therapy.