家族性地中海熱

BACKGROUND: Colchicine-resistant familial Mediterranean fever (cr-FMF) represents a therapeutic challenge, and anakinra, a recombinant interleukin-1 receptor antagonist, is widely used in clinical practice. Our aim was to describe real-world practices of pediatric rheumatologists regarding anakinra use in patients with cr-FMF, with a focus on treatment initiation, tapering strategies, and discontinuation approaches. RESEARCH DESIGN AND METHODS: This survey-based study included pediatric rheumatologists with at least one year of clinical experience in managing cr-FMF. The survey assessed physician characteristics, treatment practices including initiation, tapering, and discontinuation strategies. Data were collected via an online survey platform between September and November 2025. RESULTS: A total of 81 pediatric rheumatologists participated, mostly practicing in Türkiye (92.6%). Most respondents preferred once-daily anakinra at 1-2 mg/kg/day and assessed response within the first month. Among tapering strategies, 90.1% favored interval extension, most commonly every 3 days or weekly. 79.0% considered discontinuation after sustained remission (median 6 months). During tapering-related flares, clinicians preferred interval shortening (43.2%) or dose escalation (37.0%), while 19.8% switched to an alternative biologic. After discontinuation-related relapse, 81.5% restarted anakinra at the previous effective dose. CONCLUSION: While anakinra initiation and relapse management appear relatively consistent, tapering and discontinuation strategies remain highly variable, underscoring the need for evidence-based guidance.

INTRODUCTION: Protracted febrile myalgia syndrome is a rare vasculitic manifestation of familial Mediterranean fever that presents as the initial familial Mediterranean fever manifestation in one-third of cases. While familial Mediterranean fever is classically autosomal recessive and associated with Mediterranean ancestry, the p.Met694del variant demonstrates autosomal dominant inheritance with a Northern European founder effect. MEFV-related enterocolitis can produce histologic features indistinguishable from inflammatory bowel disease. CASE DESCRIPTION: A 24-year-old European American man with no Mediterranean, Middle Eastern or Armenian ancestry, with biopsy-confirmed ulcerative colitis on upadacitinib, presented with six weeks of high-grade fevers, incapacitating myalgias, a 30-pound weight loss and pericardial effusion. Faecal calprotectin was markedly elevated (>8,000 μg/g) without gastrointestinal symptoms. Inflammatory markers were noticeably elevated with normal creatine kinase; extensive infectious and malignancy workup was negative. Bone marrow biopsy demonstrated focal haemophagocytosis without malignancy. Dramatic improvement occurred within 24-48 hours of corticosteroid initiation. Genetic testing revealed heterozygous p.Met694del, confirming autosomal dominant familial Mediterranean fever. At six-month follow-up on colchicine monotherapy without inflammatory bowel disease-directed therapy, inflammatory markers, faecal calprotectin and pericardial effusion had completely normalised, fulfilling Tel Hashomer criteria. CONCLUSION: This case highlights protracted febrile myalgia syndrome as an under-recognised initial presentation of autosomal dominant familial Mediterranean fever in non-Mediterranean populations. Colchicine-responsive normalisation of faecal calprotectin raises the possibility that MEFV-mediated enterocolitis contributed to intestinal inflammation initially attributed to ulcerative colitis. Early recognition enables amyloidosis prevention and essential genetic counselling for first-degree relatives. LEARNING POINTS: Protracted febrile myalgia syndrome - prolonged fever, incapacitating myalgia and normal creatine kinase, should prompt consideration of familial Mediterranean fever regardless of ancestry, as the p.Met694del variant follows autosomal dominant inheritance with a Northern European founder effect.Colchicine-responsive normalisation of faecal calprotectin (>8,000 to normal) without inflammatory bowel disease-directed therapy in a patient with biopsy-confirmed ulcerative colitis and a pathogenic MEFV variant, raises the possibility that MEFV-mediated enterocolitis contributed to intestinal inflammation initially attributed to inflammatory bowel disease, a distinction with direct therapeutic implications.Autosomal dominant MEFV variants carry critical implications for family counselling: first-degree relatives have a 50% risk of inheriting the variant and developing familial Mediterranean fever, including phenotype II amyloidosis (renal amyloidosis without preceding typical attacks).

INTODUCTION: Persistent subclinical inflammation is a hallmark of familial Mediterranean fever (FMF), the most common autoinflammatory disease. Among the key mediators implicated in this chronic inflammatory state are tumor necrosis factor-alpha (TNF-α), oxidized low-density lipoprotein (OxLDL), and apolipoprotein C-II (APOC2), which contribute to the dysregulated immune response characteristic of FMF. The present study aims to evaluate the potential role of TNF-α, OxLDL, and APOC2 as diagnostic biomarkers of disease severity in patients with FMF. METHODS: The study enrolled 66 patients diagnosed with FMF and 60 age- and gender-matched healthy controls. Serum levels of tumor necrosis factor-alpha (TNF-α) and oxidized low-density lipoprotein (OxLDL) were quantified using the enzyme-linked immunosorbent assay (ELISA) technique. However, the apolipoprotein C-II (APOC2) concentrations were measured using an automated biochemistry analyzer. Furthermore, the Carotid intima media was assessed. RESULTS: Serum TNF-α levels were significantly higher in FMF patients than in the control group, emphasizing the protein's role as an important marker of chronic inflammation. Levels of low-density lipoprotein (OxLDL) and apolipoprotein C-II (APOC2) were also notably altered in the FMF cohort. Notably, OxLDL, APOC2 and TNF-α demonstrated strong positive correlation with attack frequency, multiple linear regressions analysis showed that OxLDL (β=1.53, p=0.002) and TNF-α (β=1.38, p=0.003) were significant predictors for higher number of attacks, suggesting their potential role involvement in the inflammatory cascade and their utility as complementary biomarkers in FMF. The carotid intima-media thickness (CIMT) of patients and control subjects did not differ statistically significantly. CONCLUSIONS: TNF-α, oxidized LDL, and APOC2 are key pro-inflammatory mediators that may serve as novel biomarkers for assessing chronic inflammatory status in FMF patients. Their elevated levels could provide valuable insights into disease progression and help guide personalized treatment strategies.