COLUMBUS, Ohio -- A young child with recurrent fevers may have one of the ever-expanding list of autoinflammatory disorders, some of which can be traced to a single mutated gene such as MEFV in familial Mediterranean fever (FMF).
For other recurrent fever syndromes, however, no gene mutation has yet been identified, including the condition referred to as periodic fever, aphthous stomatitis, pharyngitis, and cervical adenitis (PFAPA) syndrome, according to Cagri Toruner, MD, of the Ohio State University College of Medicine here.
As the prototypic autoinflammatory disease, FMF is inherited in an autosomal recessive manner, and the mutations in MEFV, which encodes the protein pyrin, are common in individuals from the Mediterranean region and Middle East. This disorder is usually diagnosed before age 20, Toruner said at the here.
It is characterized by intermittent fevers lasting 1 to 3 days, accompanied by serositis in approximately 30% of patients, abdominal pain in 95%, arthritis in 70%, and rash in 30%. The characteristic rash is an erysipeloid erythema, typically around the ankles.
"Why do we care so much about FMF?" Toruner asked. "Because its complications include amyloidosis and end-stage renal disease," she said.
"Treatment must begin immediately," she said. First-line therapy is with the microtubule inhibitor colchicine, which is thought to act through pyrin's binding to microtubules and effects on granulocytes involved in pyrin expression.
Complete remission with colchicine is seen in approximately two-thirds of patients, and attacks are less frequent and severe in many others. "We sometimes have trouble getting authorization for colchicine because it's so expensive now, but if you mention end-stage renal disease you'll get approval," she said.
The interleukin (IL)-1β inhibitor (Ilaris) can be used for nonresponders, which was approved for FMF in 2016 based on the observation that pyrin plays a role in the regulation of IL-1β.
The most common periodic fever syndrome of childhood is PFAPA, which is characterized by episodes of fever that occur every 3 to 8 weeks and persist for 3 to 6 days. The fevers typically resolve during adolescence, but other symptoms can persist into adulthood.
"As soon as the fever starts, treatment with steroids should begin, with prednisone in doses of 1 mg/kg," Toruner said.
However, many parents don't want to give their child steroids every month, and some children are steroid nonresponders. In those cases, prophylactic therapy can be considered, she explained.
As with FMF, colchicine can be given and in , the intervals between febrile episodes increased significantly with colchicine compared with steroids alone.
Another option for prophylaxis is the H2 antagonist cimetidine. "We do not know exactly how cimetidine works to prevent fever episodes, but it has minimal side effects and you can still add on steroids," she said.
Tonsillectomy is an additional option, which led to disease resolution in 99 out of 102 patients in .
Currently, when PFAPA patients undergo tonsillectomy, the tonsils are being sent to the National Institutes of Health for analysis, she noted.
Disclosures
Toruner had no financial disclosures.
Primary Source
Ohio Association of Rheumatology
Toruner C "Autoinflammatory disorders: Primer for the adult rheumatologist" OAR 2018.