Transcript Factor VIII Inhibitor

Periodic Fever
Syndromes
Periodic Fevers
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Rare group of disorders, four known categories
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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
Clinical Manifestations
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Familial Mediterranean Fever
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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
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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
Diagnosis
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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:
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MEFV gene mutation
TNFRSF1A missense
mutations
Treatment
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Familial Mediterranean
Fever
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Daily colchicine reduces
attacks by 60% and
significantly reduces the risk
of developing systemic
amyloid
TRAPS
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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