Signal transducer and activator of transcription (STAT)1 heterozygous gain-of-function (GOF) mutations are known to induce immune dysregulation and chronic mucocutaneous candidiasis (CMCC). Previous reports suggest an association between demodicosis and STAT1 GOF. However, immune characterization of these patients is lacking. Here, we present a retrospective analysis of patients with immune dysregulation and STAT1 GOF who presented with facial and ocular demodicosis. In-depth immune phenotyping and functional studies were used to characterize the patients. We identified five patients (three males) from two non-consanguineous Jewish families. The mean age at presentation was 11.11 (range = 0.58–24) years. Clinical presentation included CMCC, chronic demodicosis and immune dysregulation in all patients. Whole-exome and Sanger sequencing revealed a novel heterozygous c.1386C>A; p.S462R STAT1 GOF mutation in four of the five patients. Immunophenotyping demonstrated increased phosphorylated signal transducer and activator of transcription in response to interferon-α stimuli in all patients. The patients also exhibited decreased T cell proliferation capacity and low counts of interleukin-17-producing T cells, as well as low forkhead box protein 3⁺ regulatory T cells. Specific antibody deficiency was noted in one patient. Treatment for demodicosis included topical ivermectin and metronidazole. Demodicosis may indicate an underlying primary immune deficiency and can be found in patients with STAT1 GOF. Thus, the management of patients with chronic demodicosis should include an immunogenetic evaluation.

中文翻译：

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免疫失调患者的慢性蠕形螨病：信号转导和转录激活因子 (STAT)1 功能获得的意外感染表现

已知信号转导和转录激活因子 (STAT)1杂合功能获得 (GOF) 突变可诱导免疫失调和慢性皮肤黏膜念珠菌病 (CMCC)。以前的报告表明蠕形螨病与STAT1 GOF 之间存在关联。然而，缺乏这些患者的免疫特征。在这里，我们对免疫失调和STAT1患者进行回顾性分析。患有面部和眼部蠕形螨病的 GOF。深入的免疫表型和功能研究用于描述患者的特征。我们确定了来自两个非血缘犹太家庭的五名患者（三名男性）。就诊时的平均年龄为 11.11（范围 = 0.58-24）岁。临床表现包括所有患者的 CMCC、慢性蠕形螨病和免疫失调。全外显子组和 Sanger 测序揭示了一种新的杂合 c.1386C>A；p.S462R STAT1五名患者中有四名发生了 GOF 突变。免疫表型显示所有患者对干扰素-α 刺激的磷酸化信号转导和转录激活因子增加。患者还表现出 T 细胞增殖能力下降和产生白介素 17 的 T 细胞数量减少，以及叉头盒蛋白 3 ⁺调节性 T 细胞数量减少。一名患者出现特异性抗体缺乏。蠕形螨病的治疗包括局部伊维菌素和甲硝唑。蠕形螨病可能表明潜在的原发性免疫缺陷，并且可以在STAT1 GOF 患者中发现。因此，慢性蠕形螨病患者的管理应包括免疫遗传学评估。