Division of Pediatric Allergy/Immunology, Faculty of Medicine, Pediatric Allergy and Immunology, Marmara University, Fevzi Çakmak Mah. No: 41, Pendik, Istanbul, Turkey.
Istanbul Jeffrey Modell Diagnostic and Research Center for Primary Immunodeficiencies, Istanbul, Turkey.
J Clin Immunol. 2023 Nov;43(8):1882-1890. doi: 10.1007/s10875-023-01554-z. Epub 2023 Jul 29.
Autosomal recessive dedicator of cytokinesis 8 (DOCK8) and autosomal dominant signal transducer and activator of transcription 3 (STAT3) deficiencies are inborn errors of immunity (IEI) disorders present with the classic features of eczema and create a dilemma during differentiation from atopic dermatitis (AD). Therefore, an appropriate approach is required for eczema to diagnose DOCK8 and STAT3 early. Here, we described a set of clinical and immunological variables, including atypical AD localizations and lymphocyte subsets, to differentiate DOCK8 or STAT3 from AD.
This multicenter study involved 100 patients with DOCK8 and STAT3 and moderate/severe AD. We recruited disease manifestations, including detailed localizations of eczema, infections, and allergy. Principle component analysis (PCA) was used to discriminate DOCK8 or STAT3 from AD.
There were 43 patients with DOCK8, 23 with STAT3, and 34 with AD. Pneumonia, severe infections, mucocutaneous candidiasis, and skin abscesses were commonly observed in DOCK8 and STAT3 deficiencies. Atypical skin involvement with neonatal rash, retro auricular, axillary, sacral, and genital eczema discriminate DOCK8 and STAT3 from AD with high specificity ranges between 73.5 and 94.1% and positive predictive index ranges between 55 and 93.1%. Together with using absolute numbers of CD3, CD4, and CD8 T cells, the combined clinical and laboratory features showed perfect differentiation between DOCK8 or STAT3 and AD via PCA.
The described features can be easily implemented by physicians providing early diagnosis of DOCK8 and STAT3 deficiencies.
常染色体隐性细胞分裂定向因子 8（DOCK8）和常染色体显性信号转导和转录激活因子 3（STAT3）缺陷是先天性免疫缺陷（IEI）疾病，具有特应性皮炎（AD）的典型特征，并在与 AD 区分时带来困境。因此，需要一种合适的方法来早期诊断 DOCK8 和 STAT3 引起的特应性皮炎。在此，我们描述了一组临床和免疫学变量，包括非典型 AD 定位和淋巴细胞亚群，以区分 DOCK8 或 STAT3 与 AD。
这项多中心研究纳入了 100 例 DOCK8 和 STAT3 及中重度 AD 患者。我们收集了疾病表现，包括特应性皮炎的详细定位、感染和过敏情况。主成分分析（PCA）用于区分 DOCK8 或 STAT3 与 AD。
有 43 例 DOCK8、23 例 STAT3 和 34 例 AD 患者。DOCK8 和 STAT3 缺陷患者常出现肺炎、严重感染、黏膜皮肤念珠菌病和皮肤脓肿。具有新生儿皮疹、耳后、腋窝、骶部和生殖器特应性皮炎的非典型皮肤受累，具有 73.5%至 94.1%的高特异性范围和 55%至 93.1%的阳性预测指数，可将 DOCK8 和 STAT3 与 AD 区分开来。结合使用 CD3、CD4 和 CD8 T 细胞的绝对值，这些联合的临床和实验室特征通过 PCA 可实现 DOCK8 或 STAT3 与 AD 的完美区分。
所描述的特征可由医生轻松实施，从而可实现 DOCK8 和 STAT3 缺陷的早期诊断。
