1. Periodic Fever Syndromes

2. Periodic Fevers Rare group of disorders, four known categories
Familial Mediterranean Fever
TNF Receptor-Associated Periodic Syndrome (TRAPS), previously known as Hibernian Fever
Muckle-Wells Syndrome
Hyper-IgD Syndrome
Age of onset anytime during lifespan, 90% appear before the age of 20
These are disorders of autoinflammation, distinct from autoimmunity and/or immunodeficiencies as there are no specific immunoglobulins associated with these diseases

3. Clinical Manifestations
Familial Mediterranean Fever
Peritonitis, Pleuritis, Pericarditis
Attack is sudden in onset, may present as acute abdomen
Autosomal recessive inheritence, mutation in pyrin gene (MEFV = leukocyte scaffolding protein)
Monoarthritis of the knees, ankles, wrists, and elbows
Attacks last 2-3 days
Most common complication in 60% of affected individuals = systemic amyloidosis
TRAPS
Most common manifestations are periodic low grade fevers lasting ~1-3 weeks, usually unprovoked
“Painful Erythema” of erysipelas like lesions
Monoarthritis of the knees, ankles, wrists and elbows
Due to chronic activation of innate immune system from mutations in TNF receptor gene (TNFRSF1A missense mutations)
Systemic amyloidosis is a common long-term complication

4. Diagnosis Mostly from history and physical exam findings such as
After exhaustive workup for occult malignany, infection, and connective tissue disorders returns negative, blood samples can be sent to specific labs at the NIH for:
MEFV gene mutation
TNFRSF1A missense mutations

5. Treatment Familial Mediterranean Fever TRAPS
Daily colchicine reduces attacks by 60% and significantly reduces the risk of developing systemic amyloid
TRAPS
Colchicine is not as effective
Responsive to corticosteroids and intermittent use of NSAIDS. These do not address risk and complications from amyloid
TNF blockers are now being evaluated with promising results in reduction of amyloid deposits