Periodic Fever Syndromes Flashcards
What are the periodic fever syndromes?
These rare disorders are characterised by recurrent episodes of fever and organ inflammation, associated with an elevated acute phase response
What is Familial Mediterranean Fever?
Familial Mediterranean fever (FMF) is the most common of the familial periodic fevers, predominantly affecting Mediterranean people, including Arabs, Turks, Sephardic Jews and Armenians. It results from mutations of the MEFV gene, which encodes a protein called pyrin that regulates neutrophil-mediated inflammation by indirectly suppressing the production of IL-1.
How does FMF present?
FMF is characterised by recurrent painful attacks of fever associated with peritonitis, pleuritis and arthritis, which last for a few hours to 4 days and are associated with markedly increased CRP levels. Symptoms resolve completely between episodes. Most individuals have their first attack before the age of 20. The major complication of FMF is AA amyloidosis. Colchicine significantly reduces the number of febrile episodes in 90% of patients but is ineffective during acute attacks.
What is mevalonic aciduria?
Mevalonate kinase deficiency, previously known as hyper-IgD syndrome, is an autosomal recessive disorder that causes recurrent attacks of fever, abdominal pain, diarrhoea, lymphadenopathy, arthralgia, skin lesions and aphthous ulceration. Most patients are from Western Europe, particularly the Netherlands and northern France. It is caused by loss-of-function mutations in the gene encoding mevalonate kinase, which is involved in the metabolism of cholesterol.
How is mevalonic aciduria managed?
It remains unclear why this causes an inflammatory periodic fever. Serum IgD and IgA levels may be persistently elevated, and CRP levels are increased during acute attacks.
Standard anti-inflammatory drugs, including colchicine and glucocorticoids, are ineffective in suppressing the attacks but IL-1 inhibitors, such as anakinra, and TNF inhibitors, such as etanercept, may improve symptoms and can induce complete remission in some patients.
What is TNF receptor-associated periodic syndrome?
TNF receptor-associated periodic syndrome (TRAPS) also known as Hibernian fever, is an autosomal dominant syndrome caused by mutations in the TNFRSF1A gene.
How does TRAPS present? How is it managed?
The presentation is with recurrent attacks of fever, arthralgia, myalgia, serositis and rashes. Attacks may be prolonged for 1 week or more. During a typical attack, laboratory findings include neutrophilia, increased CRP and elevated IgA levels. The diagnosis can be confirmed by low serum levels of the soluble type 1 TNF receptor and by mutation screening of the TNFRSF1A gene. As in FMF, the major complication is amyloidosis, and regular screening for proteinuria is advised. Acute episodes respond to systemic glucocorticoids. Therapy with IL-1 inhibitors, such as anakinra, can be effective in preventing attacks.
