Periodic fever syndrome

Periodic fever syndromes are a group of conditions marked by recurring bouts of inflammation that affect the whole body and specific organs. They differ from autoimmune disorders like lupus, which stem from problems in the adaptive immune system. Instead, these syndromes arise from defects in the innate immune system, and people with them do not produce autoantibodies or T or B cells that target specific antigens.

Although the syndromes vary widely, they commonly trigger episodes of fever, joint pain, skin rashes, and abdominal pain. Over time, they can lead to chronic issues such as amyloidosis. Most of these conditions are genetic and first appear in childhood. The most common inherited form is familial Mediterranean fever, which brings short fever episodes, abdominal pain, and serositis that typically resolve within 72 hours. This syndrome is linked to mutations in the MEFV gene, which provides instructions for making a protein called pyrin.

Pyrin normally resides in the inflammasome, a part of the immune system. When mutated, pyrin is thought to cause the inflammasome to become inappropriately active, leading to the release of the pro-inflammatory cytokine IL-1β. Many other autoinflammatory diseases also involve excessive IL-1β release, making this cytokine a key target for treatment. Drugs such as anakinra, rilonacept, and canakinumab have transformed how these conditions are managed.

Not all autoinflammatory diseases have a clear genetic cause. PFAPA, the most common such condition in children, is one example. It features episodes of fever, aphthous stomatitis, pharyngitis, and cervical adenitis. Other autoinflammatory diseases without known genetic triggers include adult-onset Still's disease, systemic-onset juvenile idiopathic arthritis, Schnitzler syndrome, and chronic recurrent multifocal osteomyelitis. These are likely multifactorial, meaning genetic susceptibility exists but an environmental trigger is also needed for the disease to appear.