Case Presentation: Here we present a case of a 22-year-old female with a history of periodic fever who presented to our hospital with the chief complaint of cyclical fever. For four months prior to presentation, the patient had experienced fevers every four weeks, nearly to the date, that each lasted for two to three days, self-resolved, and were associated with sore throat; waxing and waning, non-tender cervical lymphadenopathy; and oral ulcers. The patient reported having had similar symptoms in her childhood that ultimately required tonsillectomy, and she had been symptom-free for years since. On presentation to our hospital, the patient was febrile to 39.2 C but overall well appearing, with a physical exam only notable for palpable cervical lymphadenopathy. Imaging of her chest, abdomen, and pelvis revealed non-specific, enlarged cervical lymph nodes, but otherwise no other evidence of an acute infectious, inflammatory, or neoplastic process to explain her fever. An infectious workup was unrevealing, including negative testing for HIV, sexually transmitted infections, SARS COV-2, influenza, and tuberculosis. Blood and urine cultures showed no growth. Rheumatologic workup was also unrevealing, with a negative ANA, anti-CCP, anti-SS-A/B, and RF. Peripheral flow cytometry revealed no monoclonal cell populations. She was subsequently discharged from the hospital and underwent a lymph-node biopsy as an outpatient, flow cytometry of which revealed no abnormal cell populations. She was subsequently diagnosed with Periodic Fever, Aphthous Stomatitis, Pharyngitis, and Cervical Adenitis (PFAPA) Syndrome, which was believed to be a recurrence of her childhood condition. She was managed supportively without the use of steroids.
Discussion: PFAPA Syndrome, the most common periodic fever syndrome in children, is thought to affect 2.3 per 10000 children annually, but evidence has emerged in recent years of PFAPA Syndrome being diagnosed in adults. Very few cases in the literature report on patients who experienced years of complete symptom resolution in childhood later experiencing recurrence in adulthood, as most affected children have no long-term sequelae from the condition. This case represents a rare example of a patient who, as a child, likely had PFAPA Syndrome, which became inactive for many years after tonsillectomy and subsequently recurred in adulthood.
Conclusions: PFAPA Syndrome should be considered in adults presenting with cyclical fevers of unknown origin, but it represents a diagnostic challenge for clinicians as no universally accepted diagnostic criteria exist for PFAPA Syndrome in adults, and it is likely less rare than currently believed. Additionally, our case raises a question for future research to identify a trigger to predict recurrence of PFAPA Syndrome and other cyclical fever syndromes alike. Identifying predisposing risk factors could greatly help clinicians identify this condition early, therefore expediting the appropriate therapy, improving patient quality of life, and potentially avoiding unnecessary testing.