Küçükali Batuhan, Bayraktar Elif Özlem, Yıldız Çisem, Gönen Sevim, Kutlar Merve, Karaçayır Nihal, Belder Nuran, Acun Büşra, Esmeray Şenol Pelin, Sunar Yayla Emine Nur, Gezgin Yıldırım Deniz, Bakkaloğlu Sevcan A
From the Department of Pediatric Rheumatology, Gazi University Faculty of Medicine, Ankara, Turkey.
Department of Pediatrics, Gazi University Faculty of Medicine, Ankara, Turkey.
J Clin Rheumatol. 2024 Sep 1;30(6):229-234. doi: 10.1097/RHU.0000000000002119. Epub 2024 Aug 2.
The exact effects of MEFV variants on inflammation are still under investigation, and reports on variants of unknown significance, particularly the E148Q variant, have been conflicting. Therefore, this study aims to investigate patients exhibiting E148Q heterozygosity, focusing on diagnoses and disease courses to assist physicians in interpreting the variant.
Data of pediatric patients presenting to the Pediatric Rheumatology clinic between November 2016 and September 2023, exhibiting only E148Q heterozygosity in MEFV gene analysis, were extracted. Patients who were lost before 9 months of follow-up have been excluded to ensure the completion of initial diagnostic tests and evaluations.
Among the 119 patients with E148Q variant, the diagnoses were as follows: healthy, 51.3%; IgA vasculitis, 10.1%; Familial Mediterranean Fever (FMF), 7.6%; Periodic fever, Aphtous stomatitis, Pharyngitis, Adenitis (PFAPA), 6.7%; and other diagnoses, 19.3%. IgA vasculitis patients experienced articular, gastrointestinal, and renal involvement at rates of 91.7%, 58.3%, and 16.7%, respectively. Complete response, partial response, and no response to colchicine were 37.5%, 12.5%, and 50%, respectively, in PFAPA patients. All FMF patients responded to colchicine treatment resulting in reduced mean FMF episode counts in 6 months from 3.22 ± 0.92 to 0.56 ± 0.52.
The E148Q variant may amplify inflammation and modify disease courses. Patients with the E148Q variant experiencing typical FMF episodes should receive colchicine, but clinicians should exercise caution regarding alternative diagnoses. Additionally, the E148Q variant may increase acute phase reactants and disease severity in IgA vasculitis. However, to reach definitive conclusions on its treatment-modifying role in PFAPA, universal diagnosis and treatment response criteria should be adopted.
MEFV基因变异对炎症的确切影响仍在研究中，关于意义不明的变异，尤其是E148Q变异的报道相互矛盾。因此，本研究旨在调查表现为E148Q杂合性的患者，重点关注诊断和病程，以协助医生解读该变异。
提取2016年11月至2023年9月期间到儿科风湿病诊所就诊的儿科患者的数据，这些患者在MEFV基因分析中仅表现为E148Q杂合性。已排除在随访9个月前失访的患者，以确保完成初始诊断检查和评估。
在119例携带E148Q变异的患者中，诊断结果如下：健康，51.3%；IgA血管炎，10.1%；家族性地中海热（FMF），7.6%；周期性发热、阿弗他口炎、咽炎、腺炎（PFAPA），6.7%；其他诊断，19.3%。IgA血管炎患者关节、胃肠道和肾脏受累率分别为91.7%、58.3%和16.7%。PFAPA患者对秋水仙碱的完全缓解、部分缓解和无反应率分别为37.5%、12.5%和50%。所有FMF患者对秋水仙碱治疗均有反应，6个月内FMF发作平均次数从3.22±0.92降至0.56±0.52。
E148Q变异可能会放大炎症并改变病程。出现典型FMF发作的E148Q变异患者应接受秋水仙碱治疗，但临床医生在考虑其他诊断时应谨慎。此外，E148Q变异可能会增加IgA血管炎患者的急性期反应物和疾病严重程度。然而，要就其在PFAPA中的治疗调节作用得出明确结论，应采用通用的诊断和治疗反应标准。
