Dipartimento di Scienze Mediche e Chirurgiche, Fondazione Policlinico Universitario A. Gemelli, IRCCS, Rome, Italy.
UOC di Medicina Interna e Gastroenterologia, Dipartimento di Scienze Mediche e Chirurgiche, Fondazione Policlinico Universitario A. Gemelli IRCCS, Rome, Italy.
Front Immunol. 2023 Jan 11;13:995304. doi: 10.3389/fimmu.2022.995304. eCollection 2022.
We described a case of IPEX syndrome successfully controlled with dupilumab, an anti-IL4 receptor alpha subunit inhibitor. IPEX syndrome is a rare and generally fatal genetic disorder characterized by immune dysregulation, polyendocrinopathy and enteropathy, mostly diagnosed in early childhood. Nonetheless, cases reported in the last 20 years demonstrated that IPEX clinical spectrum encompasses more than the classical triad of early-onset intractable diarrhea, type 1 diabetes and eczema. Atypical cases of IPEX include patients with late-onset of symptoms, single-organ involvement, mild disease phenotypes or rare clinical features. A 21-year-old caucasian man presented with immune dysregulation (hypereosinophilia and elevated IgE), protein-losing enteropathy, polyendocrinopathy (thyroiditis, osteoporosis, delayed puberty), weight loss, eczema manifestations and celiac disease. IPEX syndrome was diagnosed because of the presence of a hemizygous mutation in FOXP3 gene (c.543C>T (p.S181S) in the exon 5). During the course of the disease, the patient developed erosive proctitis, pyoderma gangrenosum, and erythema nodosum. Symptoms improved only after enteral and parenteral corticosteroid therapy and the patient soon developed steroid-dependence. Notwithstanding various therapies including azathioprine, sirolimus, tacrolimus, adalimumab, vedolizumab, the patient failed to achieve a good control of symptoms without steroids. Almost exclusive enteral nutrition with a hypoallergenic, milk-protein free, amino acid-based food for special medical purposes. He continued to lose weight (BMI 14.5 kg/m2) with a consequent high limitation of physical activity and a progressive worsening of the quality of life. In consideration of the poor response to conventional immunosuppressants and the presence of type 2 inflammatory manifestations, treatment with dupilumab at an initial dose of 600 mg, followed by a maintenance dose of 300 mg every other week, according to atopic dermatitis labeled dose, was started and combined to oral budesonide 6 mg/day and 6-mercaptopurine 75 mg/day. The patient experienced a rapid improvement in bowel and skin symptoms, leading to a progressive tapering of steroids. By our knowledge, this is the first report of IPEX syndrome successfully treated by antiIL-4/IL-13 therapy. In this case dupilumab demonstrated to be an effective, safe and steroid-sparing option.
我们描述了一例 IPEX 综合征患者，该患者使用抗 IL-4 受体 alpha 亚单位抑制剂（dupilumab）成功得到控制。IPEX 综合征是一种罕见且通常致命的遗传性疾病，其特征为免疫失调、多内分泌腺病和肠病，大多数在婴幼儿早期诊断。尽管如此，过去 20 年报告的病例表明，IPEX 的临床谱不仅仅包括早发性难治性腹泻、1 型糖尿病和湿疹的经典三联征。不典型 IPEX 病例包括症状迟发、单器官受累、疾病表型较轻或罕见临床特征的患者。一名 21 岁的白人男性表现为免疫失调（嗜酸性粒细胞增多和 IgE 升高）、蛋白丢失性肠病、多内分泌腺病（甲状腺炎、骨质疏松症、青春期延迟）、体重减轻、湿疹表现和乳糜泻。由于 FOXP3 基因（外显子 5 中的 c.543C>T（p.S181S））的杂合突变，该患者被诊断为 IPEX 综合征。在疾病过程中，患者出现溃疡性直肠炎、坏疽性脓皮病和结节性红斑。仅在接受肠内和肠外皮质类固醇治疗后症状才有所改善，且患者很快出现了类固醇依赖。尽管进行了各种治疗，包括硫唑嘌呤、西罗莫司、他克莫司、阿达木单抗、vedolizumab，但患者在不使用类固醇的情况下仍无法很好地控制症状。他继续减重（BMI 为 14.5 kg/m2），导致体力活动受到极大限制，生活质量逐渐恶化。鉴于对常规免疫抑制剂反应不佳，以及存在 2 型炎症表现，根据特应性皮炎的标签剂量，开始给予 600mg 初始剂量、随后每两周给予 300mg 维持剂量的 dupilumab 治疗，并联合口服布地奈德 6mg/天和 6-巯基嘌呤 75mg/天。患者的肠道和皮肤症状迅速改善，导致类固醇逐渐减量。据我们所知，这是首例成功使用抗 IL-4/IL-13 治疗的 IPEX 综合征报告。在该病例中，dupilumab 被证明是一种有效、安全且可减少类固醇用量的选择。
