What are the clinical presentations, treatments, and complications of Familial Mediterranean Fever (FMF)?

From the Guidelines

Here are 4 MCQ questions about Familial Mediterranean Fever (FMF) covering clinical presentation, treatment, and complications:

Question 1: Clinical Presentation

Which of the following is the most common clinical presentation of Familial Mediterranean Fever? A) Chronic joint pain with morning stiffness B) Recurrent fevers with peritonitis, pleuritis, or synovitis C) Persistent maculopapular rash with angioedema D) Progressive renal failure with hypertension Answer: B) Recurrent fevers with peritonitis, pleuritis, or synovitis. FMF is characterized by self-limited episodes of fever accompanied by serositis, particularly peritonitis (causing severe abdominal pain), pleuritis (causing chest pain), and synovitis (causing joint pain) 1.

Question 2: First-Line Treatment

What is the first-line treatment for preventing attacks in Familial Mediterranean Fever? A) Prednisone 40mg daily B) Colchicine 0.5-2mg daily C) Anakinra 100mg daily D) Methotrexate 15mg weekly Answer: B) Colchicine 0.5-2mg daily. Colchicine is the mainstay of FMF treatment, typically started at 0.5mg daily and titrated up to 1-2mg daily as needed and tolerated. It prevents attacks in 60-95% of patients and, most importantly, prevents the development of amyloidosis 1.

Question 3: Long-Term Complication

Which is the most serious long-term complication of untreated Familial Mediterranean Fever? A) AA amyloidosis B) Rheumatoid arthritis C) Pulmonary fibrosis D) Hepatocellular carcinoma Answer: A) AA amyloidosis. The most dreaded complication of untreated FMF is AA (secondary) amyloidosis, which primarily affects the kidneys and can lead to proteinuria and eventually end-stage renal disease. Regular colchicine therapy is highly effective in preventing this complication, which is why early diagnosis and treatment are crucial 1.

Question 4: Colchicine-Resistant FMF

Which treatment option is most appropriate for colchicine-resistant FMF? A) Increasing colchicine dose beyond 2mg daily B) IL-1 inhibitors such as anakinra or canakinumab C) TNF inhibitors such as infliximab D) Cyclophosphamide pulse therapy Answer: B) IL-1 inhibitors such as anakinra or canakinumab. For the 5-10% of patients who are resistant to colchicine or cannot tolerate it, IL-1 inhibitors are the treatment of choice. Anakinra (100mg daily subcutaneous injection) or canakinumab (150mg subcutaneous injection every 4-8 weeks) target the IL-1 pathway, which is central to the inflammatory process in FMF. These medications have shown efficacy in reducing attack frequency and severity in colchicine-resistant cases 1.

From the Research

Clinical Presentation of FMF

• The clinical features of FMF include recurrent episodes of fever, leukocitosis, serositis (peritonitis or pleuritis, arthritis), myalgia or erysipelas-like skin lesions, lasting 12-72 hrs 2.
• The continuous inflammation in FMF is associated with increased serum amyloid A (SAA) protein which may lead to secondary amyloidosis and deposition of this insoluble protein in the kidney, gut, spleen, liver, heart etc. 3.

Treatment of FMF

• Colchicine remains the mainstay therapeutic option in FMF, effective in various manifestations of the disease such as fever, peritonitis and pleuritis, and prevents the development of amyloidosis 2, 3.
• Adjunctive symptomatic therapy to colchicine includes nonsteroidal anti-inflammatory drugs and corticosteroids 2, 3.
• In colchicine-resistant or intolerant patients, alternative treatments such as IL-1 inhibitors (anakinra, canakinumab, rilonacept) may be considered 4, 5, 6.

Complications of FMF

• Secondary amyloidosis is a potential complication of FMF, which can lead to renal damage and other organ involvement 2, 3.
• Protracted febrile myalgia or exertional leg pain are also potential complications of FMF, which may not be prevented by colchicine therapy 4.

MCQ Questions

1. What is the primary treatment for Familial Mediterranean Fever (FMF)? A) Colchicine B) Corticosteroids C) Nonsteroidal anti-inflammatory drugs D) IL-1 inhibitors

Answer: A) Colchicine 2, 3

1. What is a potential complication of FMF? A) Secondary amyloidosis B) Rheumatoid arthritis C) Lupus D) Gout

Answer: A) Secondary amyloidosis 2, 3

1. What is the role of IL-1 inhibitors in the treatment of FMF? A) To prevent secondary amyloidosis B) To reduce the frequency of attacks C) To treat colchicine-resistant or intolerant patients D) To diagnose FMF

Answer: C) To treat colchicine-resistant or intolerant patients 4, 5, 6

1. How often should a patient with FMF experiencing more than four attacks a year be considered for colchicine dose adjustment? A) Every 6 months B) Every year C) Immediately D) Only if the patient has a history of amyloidosis

Answer: C) Immediately 6