Drabko Katarzyna, Zarychta Julia, Kowalczyk Adrian, Cienkusz Magdalena
Department of Pediatric Hematology, Oncology and Transplantology, Medical University of Lublin, Lublin, Poland.
Student Scientific Society of Department of Pediatric Hematology, Oncology and Transplantology, Medical University of Lublin, Lublin, Poland.
Front Immunol. 2024 Nov 18;15:1484467. doi: 10.3389/fimmu.2024.1484467. eCollection 2024.
Cytotoxic T lymphocyte-associated antigen-4 (CTLA-4) insufficiency is a rare disease belonging to inborn errors of immunity. Most cases of patients with CTLA-4 insufficiency are diagnosed in adults, therefore it is not a common problem in the clinical practice of pediatricians. However, it is worth noticing that most cases described in the literature show the first symptoms of the disease before the age of 18, but the phenotypic variability of patients complicates and delays the diagnostic process.
Herein, we report a case of an almost 4-year-old patient whose first symptom of CTLA-4 insufficiency was thrombocytopenia after an upper respiratory tract infection, suggesting the diagnosis of primary immune thrombocytopenia, often occurring in pediatric patients. Due to the addition of symptoms suggesting a proliferative disease in this patient (pancytopenia, enlargement of lymph nodes, liver and spleen), a bone marrow biopsy was performed 11 months later, which did not confirm a hematopoietic tumor. Two years after the first symptoms appeared, the patient was referred for next-generation sequencing genetic testing, which confirmed the presence of a pathological CTLA-4 variant (c.356T>C). Due to the patient's lack of response to the pharmacological treatment and the intensification of autoimmune symptoms that threatened the patient's life, the patient underwent hematopoietic stem cell transplantation (HSCT) 34 months after the first occurrence of symptoms. After HSCT, the patient is alive and does not present any symptoms of autoimmunity.
The first symptoms of some diseases classified as inborn errors of immunity are non-specific and may delay the final diagnosis. Therefore, it seems extremely important that practicing pediatricians should take into account inborn errors of immunity in the differential diagnosis of autoimmune diseases.
细胞毒性T淋巴细胞相关抗原4（CTLA-4）功能不全是一种罕见的免疫缺陷病。大多数CTLA-4功能不全患者在成年期被诊断出来，因此这在儿科医生的临床实践中并非常见问题。然而，值得注意的是，文献中描述的大多数病例在18岁之前就出现了该疾病的首发症状，但患者的表型变异性使诊断过程变得复杂并延迟。
在此，我们报告一例近4岁的患者，其CTLA-4功能不全的首发症状是上呼吸道感染后出现血小板减少，提示原发性免疫性血小板减少症的诊断，这在儿科患者中较为常见。由于该患者出现了提示增殖性疾病的附加症状（全血细胞减少、淋巴结、肝脏和脾脏肿大），11个月后进行了骨髓活检，结果未证实存在造血肿瘤。首发症状出现两年后，患者接受了下一代测序基因检测，结果证实存在病理性CTLA-4变异（c.356T>C）。由于患者对药物治疗无反应且自身免疫症状加重，威胁到患者生命，在首发症状出现34个月后，患者接受了造血干细胞移植（HSCT）。HSCT后，患者存活且未出现任何自身免疫症状。
一些被归类为免疫缺陷病的疾病首发症状不具有特异性，可能会延迟最终诊断。因此，执业儿科医生在自身免疫性疾病的鉴别诊断中考虑免疫缺陷病似乎极为重要。
