The febrile episodes in HIDS typically last 3-7 days, intermediate in duration between those of FMF and TRAPS. The fever episodes are accompanied by the maculopapular rash, abdominal pain, and arthralgias. Onset is almost always within the first year of life. Episodes are often triggered by childhood immunizations. HIDS is seen mainly in people of northern European ancestry, particularly the Dutch. Renal amyloidosis occurs only rarely.
HIDS is caused by recessive mutations in the mevalonate kinase gene, resulting in reduced production of geranylgeranyl pyrophosphate. HIDS is something of a misnomer in that some affected patients with mevalonate kinase mutations have normal IgD levels.
As yet there's no consensus on the treatment of HIDS, Dr. Kastner said.
CAPS. The cryopyrin-associated periodic syndromes consist of three diseases caused by dominant mutations in one gene, NLRP3, which encodes the cryopyrin protein involved in interleukin-1beta activation. The three cryopyrinopathies are neonatal-onset multisystem inflammatory disease (NOMID), Muckle-Wells syndrome, and familial cold autoinflammatory syndrome (FCAS).
What these three diseases have in common is fever, urticarial rash, and excessive production of IL-1beta. Patients with NOMID experience fever nearly every day, while in those with FCAS the fever and hives-like rash develop within a couple of hours after exposure to cold.
Cryopyrin is a central component of the inflammasome, a macromolecular scaffold promoting activation of caspase-1.
"The inflammasome is something that if you were taking a recertification exam or the boards for the first time, you might very well need to know about," the rheumatologist said. "You need to know that cryopyrin is part of the inflammasome, and the inflammasome activates IL-1beta. Patients with these three diseases have activating mutations in cryopyrin, which activates the inflammasome. You need to know that if you’re going to take tests."
NOMID is characterized by bony overgrowth, conjunctivitis, and aseptic meningitis, in addition to fever and urticarial rash. Roughly 40% of NOMID patients lack the cryopyrin mutations and have an as-yet unknown cause for their disease.
Dr. Kastner and his coworkers pioneered anti-IL-1 therapy with anakinra in CAPS patients. "I's quite a dramatic and remarkable response," he said. Other investigators have subsequently reported treatment success using canakinumab and rilonacept.
Dr. Kastner declared having no relevant financial interests.