Periodic fever and autoinflammatory syndromes — formative SAQs

SAQ 1 (10)

A six-year-old boy of Lebanese background has had fevers every four to five weeks for two years. Each attack lasts two days, with severe central abdominal pain and a tender right knee that swells for a day. Between attacks he is completely well and grows along the fiftieth centile. His father had a renal transplant at thirty-two for amyloidosis. ^[3]

1. Give the most likely diagnosis and the clinical criteria you would apply. (3) ^[3]
2. Outline your definitive management, naming the first-line agent, its purpose, and the long-term complication you must prevent. (4) ^[4]
3. Explain why this disease is classified as autoinflammatory rather than autoimmune, and how that distinction guides the treatment. (3) ^[1]

Model answer

Diagnosis and criteria. The most likely diagnosis is familial Mediterranean fever. The one-to-two-day attacks of fever with serositis (abdominal pain from peritonitis and a transient monoarthritis), the Mediterranean ethnic background, the family history of amyloidosis leading to a renal transplant, and the complete wellness with normal growth between attacks, are the classical phenotype. I would apply the Livneh 1997 clinical criteria, which combine the typical attack pattern with the ethnic predisposition and the family history, and a response to colchicine supports the diagnosis. I would confirm with MEFV gene testing and exclude the surgical abdomen at the first presentation. ^[3]

Definitive management. The first-line treatment is colchicine, taken orally, lifelong. Colchicine reduces both the frequency and the severity of the attacks, and it is the only treatment proven to prevent the AA amyloidosis that caused his father's renal failure. I would start it at a low dose and titrate to the response, and I would build the adherence and the surveillance from the outset. The long-term complication I must prevent is the AA amyloidosis, monitored with a regular urinalysis for proteinuria and a serum creatinine, and the serum amyloid A can guide the titration. For the colchicine-resistant disease I would add an interleukin-one blockade such as canakinumab. ^[4]

Autoinflammatory versus autoimmune. Familial Mediterranean fever is autoinflammatory because it is driven by the innate immune system, the pyrin inflammasome and the interleukin-one-beta, in an antigen-independent manner, with no autoantibodies. Autoimmune disease, by contrast, is adaptive and self-antigen-driven. The distinction guides the treatment: the disease responds to the colchicine and the interleukin-one blockade, which target the innate pathway, rather than to the autoantibody-directed immunosuppression that governs the autoimmune diseases. ^[1]