PFAPA (Periodic Fever, Aphthous Stomatitis, Pharyngitis, Cervical Adenitis) Syndrome

A 4-year-old girl presented with a history of recurrent fevers for 1 year. The current episode of fever had begun 2 days ago. The febrile episodes were usually sudden in onset, associated with a temperature of 102–103 °F, and typically lasted for 3–5 days. There was a history of sore throat during some of the episodes during which the child was being treated with oral antibiotics. There was no history of rashes, joint pain, or swelling. She was otherwise active in the intervals between episodes, gaining weight and doing well in school. She had an elder brother aged 9 years who was normal. She had no significant medical history till the age of 3 years. She had received all her immunizations according to the national immunization schedule without any adverse reactions. There was no history of previous hospitalization or life -threatening infections. The parents reported that the doctors they had consulted in the past had always found her physical examination to be normal except for throat congestion. Her repeated blood and urine investigations also apparently had been noncontributory. As these episodes were occurring almost every month, the parents wanted to rule out major underlying illnesses. On physical examination, her axillary temperature was 103.2 °F and her other vital signs were normal. She was well grown, and her general condition was good. Throat examination revealed hyperemic, congested pharynx and tonsils. A clinical diagnosis of recurrent tonsillitis was made. Throat cultures were sent and oral amoxicillin was started. She was also investigated for other possible causes of recurrent fever. Her blood tests showed leukocytosis (TLC 15680/cmm) with a shift to the left, C-reactive protein value of 8 mg/dL and erythrocyte sedimentation rate of 24 mm/h. The blood and throat cultures were negative, and serological studies for EBV (Epstein–Barr virus) were also negative. The serum electrolytes and renal and liver function tests were normal. The peripheral blood smear revealed normal findings. She had normal levels of C3 and C4 and serum immunoglobulin (Ig). Rheumatological tests including the antinuclear antibodies (ANA), anti-DNA antibodies, and rheumatoid factor were negative. Chest X-ray and abdominal ultrasonography showed normal findings. On review after 48 h, fever was persisting and the mother also complained that the child was refusing to eat even mildly spicy food. A thorough physical examination was performed again. Repeat oral examination revealed small ulcers in the mucus membrane of the mouth. Based on these clinical features and the exclusion of other causes of recurrent fever, the possibility of periodic fever, aphthous stomatitis, pharyngitis, and adenitis (PFAPA) syndrome was considered. All antibiotics were stopped, and oral corticosteroids were started. The patient had a satisfactory response to a single dose of oral prednisone (2 mg/kg). The fever remitted in 2 h and was symptom-free in 24 h. The episodes continued with the same periodicity, but these episodes also responded well to a single dose of oral prednisolone. As she became older, the frequency of fever decreased and there were no episodes after the age of 8 years.