Systemic Autoinflammatory Syndromes — Written Clinical Reasoning

SAQ 1 — Familial Mediterranean fever complicated by AA amyloidosis (20 marks, 30 minutes)

Model answer

Diagnosis and pathophysiology (4 marks) ^[1]

This patient has familial Mediterranean fever (FMF) complicated by AA amyloidosis. The combination of Mediterranean ancestry, recurrent brief attacks (one to two days) of fever and serositis (abdominal pain mimicking an acute abdomen), a previous negative laparotomy or appendicectomy, complete wellness between attacks, and new proteinuria is classic. The Tel Hashomer criteria — one major criterion (typical abdominal attack) or two minor criteria — establish the diagnosis with a sensitivity above 95 per cent ^[1].

FMF is caused by autosomal recessive mutations in MEFV, encoding pyrin, which regulates the pyrin inflammasome. Mutant pyrin constitutively activates the inflammasome, driving interleukin-1 beta and interleukin-18 release and neutrophil-mediated serositis. The peritonitis reflects neutrophil infiltration of the peritoneum during an attack. The new proteinuria reflects AA amyloid deposition in the kidney from years of persistent subclinical inflammation — the feared and preventable complication of inadequately treated FMF. ^[1]

Immediate management (5 marks) ^[1]

1. Confirm the diagnosis with MEFV genetic testing (targeted autoinflammatory gene panel), a serum amyloid A level (elevated, indicating ongoing inflammation), and a renal biopsy to confirm AA amyloidosis if the diagnosis is uncertain.
2. Start colchicine immediately — 1.5 mg orally daily (commonly 0.5 mg three times daily), titrated to the maximum tolerated dose that completely prevents attacks. The goal is complete attack prevention, not attack reduction, because colchicine prevents further AA amyloid deposition ^[2].
3. Do NOT perform laparotomy for an acute abdominal attack — a careful history of recurrent self-limiting attacks prevents unnecessary surgery. NSAIDs manage the acute pain.
4. Assess renal function — full renal workup with creatinine, eGFR, urinary albumin-to-creatinine ratio, and nephrology referral given the proteinuria.
5. Screen for amyloidosis complications — renal function, liver function and, if indicated, an echocardiogram for cardiac amyloid.

Long-term management and surveillance (5 marks) ^[1]

• Lifelong colchicine is the cornerstone. The dose is titrated to complete attack prevention, monitored by attack diary and serum amyloid A. Gastrointestinal intolerance (diarrhoea) is the main adverse effect; reduce the dose in renal impairment and monitor full blood count for myelosuppression.
• Canakinumab for colchicine-resistant FMF — for patients who do not achieve complete attack control on the maximum tolerated colchicine dose, canakinumab 150 mg subcutaneously every 4 weeks is the evidence-based IL-1 blocker, approved on the basis of the CLUSTER trial ^[3].
• AA amyloidosis surveillance — urinalysis for proteinuria and serum amyloid A at every follow-up visit (every 3 to 6 months). Any new proteinuria or rising serum amyloid A mandates intensification of therapy.
• Cascade family testing — siblings should be screened with a careful attack history, urinalysis and serum amyloid A, with genetic counselling and MEFV testing where indicated.
• Monitor colchicine toxicity — full blood count, liver function and renal function every 3 to 6 months. Counsel the patient on the danger of colchicine overdose (multi-organ failure) and the need for dose reduction in renal impairment.

Key differentials to exclude (3 marks) ^[1]

Communication and follow-up (3 marks) ^[1]

• Frame the diagnosis as a genuine lifelong condition with effective treatment — the shift from recurrent unexplained attacks to a named, treatable diagnosis is therapeutic for a patient who has often been dismissed for years.
• Explain the colchicine contract: the goal is complete attack prevention and amyloidosis prevention, not just fewer attacks; adherence is the single biggest determinant of long-term renal outcome.
• Address the psychosocial impact of a delayed diagnosis and a preventable complication, and the implications for siblings and future children. Genetic counselling should be offered before cascade family testing. ^[1]