The Enigma of PFAPA Syndrome
The "periodic fever, aphthous stomatitis, pharyngitis and adenitis" (PFAPA) syndrome is a clinical entity that was first recognized by Marshall in 1987 and is characterized by (1) an onset before the age of 5 years; (2) quite regularly recurring episodes of fever, with at least 1 of the 3 associated constitutional signs of aphthous stomatitis, pharyngitis or cervical adenitis without any signs of upper respiratory tract infection; (3) completely asymptomatic interfebrile periods with normal growth and development and (4) the exclusion of cyclic neutropenia, immunodeficiency and autoinflammatory syndromes. Fever peaks of up to 39–40°C periodically recur every 3–8 weeks for a period of 3–4 years, after which they usually spontaneously disappear; however, there are an increasing number of reports of adult-onset forms. Various authors have also observed that the syndrome can be associated with different combinations of other nonspecific symptoms, such as nausea, vomiting, headache, abdominal pain, malaise and arthralgia, which may complicate differential diagnosis. This review considers how to diagnose PFAPA syndrome, describes the debate concerning its pathogenesis and describes the suggested therapeutic approaches.
Abstract and Introduction
Introduction
The "periodic fever, aphthous stomatitis, pharyngitis and adenitis" (PFAPA) syndrome is a clinical entity that was first recognized by Marshall in 1987 and is characterized by (1) an onset before the age of 5 years; (2) quite regularly recurring episodes of fever, with at least 1 of the 3 associated constitutional signs of aphthous stomatitis, pharyngitis or cervical adenitis without any signs of upper respiratory tract infection; (3) completely asymptomatic interfebrile periods with normal growth and development and (4) the exclusion of cyclic neutropenia, immunodeficiency and autoinflammatory syndromes. Fever peaks of up to 39–40°C periodically recur every 3–8 weeks for a period of 3–4 years, after which they usually spontaneously disappear; however, there are an increasing number of reports of adult-onset forms. Various authors have also observed that the syndrome can be associated with different combinations of other nonspecific symptoms, such as nausea, vomiting, headache, abdominal pain, malaise and arthralgia, which may complicate differential diagnosis. This review considers how to diagnose PFAPA syndrome, describes the debate concerning its pathogenesis and describes the suggested therapeutic approaches.