Makindo Medical Notes

🔥 During attacks, levels of C-reactive protein (CRP), serum amyloid A (SAA), and the absolute neutrophil count often rise — reflecting systemic inflammation.

🌍 About

• A rare autoinflammatory disorder belonging to the cryopyrin-associated periodic syndromes (CAPS).
• Part of a spectrum that also includes familial cold autoinflammatory syndrome and chronic infantile neurological cutaneous articular syndrome (CINCA).
• First described in the 1960s by Dr. Thomas J. Muckle and Dr. Michael A. Wells.

🧬 Aetiology & Pathophysiology

• Caused by mutations in the NLRP3 gene on chromosome 1q44.
• This results in uncontrolled activation of the NLRP3 inflammasome → excessive caspase-1 activity → overproduction of interleukin-1β (IL-1β).
• IL-1β drives fever, neutrophilia, and tissue inflammation → leading to systemic and organ-specific manifestations.

🩺 Clinical Features

• 🌡️ Recurrent fever and flu-like malaise.
• 🌿 Urticarial rash (non-pruritic, migratory, unlike typical allergy).
• 👁️ Conjunctivitis and sometimes episcleritis.
• 🦴 Arthralgia and fatigue, often worsening with cold exposure.
• 👂 Progressive sensorineural hearing loss (a hallmark feature).
• ⚠️ AA amyloidosis — due to persistent high SAA, leading to nephrotic syndrome and renal failure.
• Occasional: oral ulcers, folliculitis, erythema nodosum.

🔬 Investigations

• 📈 Raised inflammatory markers (CRP, SAA, ESR) during flares.
• 🧪 Urine protein: screen for amyloidosis-related proteinuria.
• 🧬 Genetic testing: confirmation of NLRP3 mutation.
• 👂 Audiometry: monitor hearing loss progression.

💊 Management

The mainstay of treatment is IL-1 blockade, which transforms prognosis by preventing attacks and protecting against amyloidosis:

• 💉 Anakinra: recombinant IL-1 receptor antagonist (daily subcutaneous injection). Produces rapid relief and normalisation of CRP/SAA.
• 💉 Rilonacept: a fusion protein “IL-1 trap” (weekly injection).
• 💉 Canakinumab: fully human monoclonal antibody targeting IL-1β (monthly injection) — increasingly preferred for long-term disease control.

⚠️ Complications

• 🧏 Irreversible sensorineural hearing loss.
• 💧 Renal amyloidosis → proteinuria, nephrotic syndrome, chronic kidney disease.
• 🧠 CNS involvement (rare): headache, papilloedema, chronic meningitis.

📚 Teaching Pearls

• CAPS are autoinflammatory (innate immune dysregulation) not autoimmune (no autoantibodies) — a key exam distinction.
• UK renal clinics often pick up Muckle–Wells late, when patients present with unexplained proteinuria/amyloidosis.
• Early recognition + IL-1 blockade prevents renal failure and disability.

🔗 References

• Muckle–Wells syndrome – review article (NCBI)