Relapsing periodic fever syndrome

Specialty: Pediatrics.

• Childhood relapsing fever
• suspected autoinflammation
• PFAPA syndrome

Why it occurs

• PFAPA syndrome (Periodic Fever, Aphthous Stomatitis, Pharyngitis and Cervical Adenitis, the most common autoinflammatory syndrome in childhood, with a benign cause and self-limiting in adolescence)
• Familial Mediterranean Fever or FMF (monogenic recessive autoinflammatory disease due to a mutation of the MEFV gene, which presents with episodic fever accompanied by painful abdominal or thoracic polyserositis)
• Hyper-IgD syndrome or mevalonate kinase deficiency (autosomal recessive genetic disorder that produces febrile attacks associated with generalized lymphadenopathy, splenomegaly and diarrhea)
• TNF receptor-associated periodic syndrome or TRAPS (mutation of the TNFRSF1A gene with prolonged febrile outbreaks lasting more than a week with myalgia and periorbital edema)
• Cyclic neutropenia (hematological defect that occurs with oscillations of neutrophils every 21 days, leading to recurrent febrile infections).

Initial workup

Comprehensive daily recording of temperature and associated symptoms for at least 6 months. Analysis during the febrile outbreak and in the afebrile phase: blood count with neutrophil count, acute phase reactants (CRP, ESR, serum amyloid A, which should completely normalize in the afebrile periods in PFAPA, but may remain elevated in monogenic pathologies). Serum immunoglobulins (IgD, IgA). Genetic panel of periodic fever/autoinflammatory diseases using massive sequencing (NGS) to detect mutations in MEFV, MVK, TNFRSF1A, NLRP3.

Standard management

• Prednisone or Prednisolone — oral corticosteroid indicated of choice when PFAPA is suspected; A single dose of 1 to 2 mg/kg administered at the beginning of the febrile episode dramatically reduces fever within a few hours, although it may shorten the seizure-free interval in some patients.
• Colchicine — continuous daily treatment of choice for the prevention of outbreaks of Familial Mediterranean Fever and the prevention of secondary amyloidosis; dose of 0.5 to 1.5 mg/day orally adjusted according to gastrointestinal tolerance and renal function
• Anakinra or Canakinumab (interleukin-1 antagonist monoclonal antibodies, reserved for the treatment of refractory forms of severe autoinflammatory syndromes, under pediatric rheumatological supervision).