Cochard M, Clet J, Le L et al. Rheumatology (Oxford) 2010;49:1984–7.
While most periodic fever syndromes are clearly heritable, PFAPA (periodic fevers with aphthous stomatitis, pharyngitis, and adenopathy) has been considered the exception. However, these authors found that almost half of PFAPA patients have a family history of recurrent fevers, strengthening the case that PFAPA may be another autoinflammatory disease.
PFAPA (periodic fevers with aphthous stomatitis, pharyngitis, and adenopathy) is by far the most common diagnosis for recurrent unexplained fevers in childhood. It is characterized principally by onset in early childhood (but not infancy) and most characteristically by episodes of fevers lasting 3–6 days that occur at intervals so regular that families can almost plan on them. Such “clockwork” fevers are almost never seen in other periodic fever syndromes, and the abrupt resolution of fevers with a single dose of corticosteroids essentially seals the diagnosis and portends a benign course with spontaneous resolution over time (or, alternately, cure with tonsillectomy if recurrent fevers and steroid dosing becomes intolerable). Classically, PFAPA has been regarded as a sporadic disorder, and therefore distinct from other periodic fever syndromes, such as familial Mediterranean fever (FMF), which are monogenic heritable disorders. In fact, this assessment of PFAPA rather flies in the face of clinical experience, where a family history of fevers and miraculous cures with tonsillectomy seems far from rare.