PERIODIC FEVER, APHTHOUS STOMATITIS, PHARYNGITIS, ADENOPATHY SYNDROME

Periodic fever, aphthous stomatitis, pharyngitis, adenopathy (PFAPA) syndrome is a common cause of recurrent fever in children but has also been reported in adults. In this condition, patients develop stereotypical attacks on a predictable schedule. This predictability is unique to PFAPA syndrome and separates it from the hereditary autoinflammatory syndromes, which all occur with irregular and unpredictable frequencies. No single genetic mutation has been associated with PFAPA syndrome.

Age at onset for PFAPA syndrome is typically prior to age 3 years. Febrile attacks on average last 5 days and occur every 4 weeks. During these attacks, PFAPA syndrome patients may experience aphthous stomatitis, nonspecific exudative or nonexudative pharyngitis, and/or enlarged and tender cervical lymph nodes. Between attacks, patients are healthy and exhibit normal growth.

Owing to the self-limited nature of the syndrome, treatment is reserved for those patients with severe disease or those patients whose condition creates difficult socioeconomic circumstances for the family. In patients requiring therapy, one or two doses of systemic prednisone (1 mg/kg) within 6 hours of fever onset is effective in aborting fever in 90% of patients. However, up to 50% of patients may experience an increased frequency of attacks after treatment with systemic corticosteroids. Additional options include daily colchicine or cimetidine, both effective in preventing attacks of PFAPA syndrome in one third of patients. Tonsillectomy represents curative therapy. The prognosis of PFAPA syndrome is favorable. Without intervention, 40% of patients experience a significant reduction in the severity and frequency of fever attacks within 5 years of diagnosis. To date, there have been no reports of amyloidosis or hearing loss in PFAPA syndrome patients.

DIAGNOSTIC EVALUATION OF PATIENTS WITH SUSPECTED AUTOINFLAMMATORY DISEASE

Fundamental historical information and careful physical examination will often lead to the proper diagnosis in patients with autoinflammatory syndromes. Critical historical elements include age at onset of attacks, duration of attacks, presence of serositis, adenopathy, myalgias, arthralgias/arthritis, ocular symptoms, CNS symptoms, orchitis, rash characteristics, family members with similar symptoms, and ethnic background. Malignancy and infection should be considered in all patients; however, the repetitive and stereotypical nature of the attacks will differentiate the autoinflammatory conditions. The utility of acute phase reactant assessment in the diagnostic evaluation of patients is limited because all conditions will result in abnormal values. Patients with CNS symptoms should undergo a thorough examination that includes a formal ophthalmologic evaluation, imaging, and possibly lumbar puncture for assessment of intracranial pressure and inflammatory changes in the cerebrospinal fluid (CSF). Dermatologic manifestations should be examined first hand and imaging for fascial inflammation as well as full-thickness biopsy considered at the time of rash occurrence. Gross bony abnormalities should be evaluated with plain radiography, and audiologic testing may also be indicated in the diagnostic evaluation of patients with recurrent fevers. Finally, genetic testing is available commercially for patients with suspected hereditary autoinflammatory syndromes; however, up to 30% of patients with phenotypic manifestations characteristic of a given autoinflammatory syndrome have a normal genetic testing. Genetic testing may ultimately be indicated for proper counseling of reproductive risk.