A 2-Year-Old Patient Has Had Recurrent Fevers For The Last Year. He Often Has A Red Throat, Adenopathy, And Stomatitis With His Fevers. I Am Concerned About Periodic Fever, Aphthous Stomatitis, Pharyngitis And Cervical Adenitis Syndrome. What Are The Treatment Options For This Diagnosis?
Erica
Lawson,
MD
Aimee
Hersh,
MD
PFAPA, or Periodic Fever, Aphthous stomatitis, Pharyngitis, and cervical Adenitis syndrome, is the most common periodic fever syndrome of childhood. The diagnosis of a periodic fever syndrome should be considered in a child who has a history of recurrent episodes of fever, occurring at predictable (periodic) time intervals, and when more common causes of fever, such as recurrent or chronic infection, have been excluded.
There are several clues in the history that can help distinguish a periodic fever syndrome from recurrent or chronic infection. First, the febrile episodes of periodic fever syndromes tend to be predictable, occurring at regular intervals. Symptoms that accompany the fevers are generally the same from episode to episode. In the case of PFAPA, the most common symptoms are aphthous stomatitis (painful oral ulcers), pharyngitis (red and painful posterior oropharynx with tonsillar enlargement), and cervical adenitis (tender anterior cervical lymphadenopathy). Secondly, one of the hallmarks of a periodic fever syndrome is a complete lack of symptoms and a normal physical examination between episodes of fever, which is generally not true in the case of an underlying chronic infectious or inflammatory process. Similarly, inflammatory markers erythrocyte sedimentation rate (ESR), C-reactive protein (CRP) tend to rise during the fever episodes and then normalize once the fever resolves. If the inflammatory markers remain elevated between fever episodes, then a diagnosis other than a periodic fever syndrome should be considered.
Once the fever pattern is felt to be consistent with a periodic fever syndrome, other elements of the history and physical examination may help pinpoint a specific syndrome. The interval between fevers, duration of the fever episodes, typical symptoms (eg, mouth sores, rash, arthritis) family history and ethnicity are all potentially important clues to identifying the specific periodic fever syndrome (Table 49-1).2
The various periodic fever syndromes have overlapping symptoms; therefore, a definitive diagnosis of PFAPA cannot be made until other periodic fever syndromes have been excluded via genetic testing, which can be done via GeneDx (www.genedx.com).
PFAPA typically presents in children younger than 5 years. The typical patient has 3 to 6 days of high fevers (38.9°C to 41.1°C), which on average occurs every 30 days. Criteria for diagnosis include the presence of recurrent, predictable episodes of high fever accompa- nied by at least 1 of the 3 major clinical findings associated with PFAPA (aphthous stoma- titis, pharyngitis, or lymphadenitis), a well interval between episodes, and the exclusion of another cause of recurrent fever.1
In general, PFAPA is felt to be a benign and self-limited disease. Patients with PFAPA have normal growth and development, and there does not appear to be any residual sequelae from PFAPA after symptoms resolve. Most patients with PFAPA will outgrow the condition by 10 years of age; however, the mean duration of symptoms is approximately 4.5 years. The frequency and severity of the fever episodes vary from patient to patient, but for many the episodes can be disruptive and impair their ability to participate in regular activities, including school. For this reason, many families chose to pursue treatment for PFAPA.
There are several treatment options for PFAPA. For symptomatic management, regular dosing of ibuprofen and acetaminophen during fever episodes can reduce the height of the fever and also lessen the pain associated with aphthous stomatitis and pharyngitis.
Another treatment option is corticosteroids. The majority of patients will experience a dramatic resolution of fever within 2 to 24 hours with a single dose of prednisone or prednisolone (1 to 2 mg/kg, maximum dose of 60 mg) at the start of a fever episode. This dose can be repeated every 12 hours for up to 3 total doses if the fever persists. Families should be aware that approximately 25% to 50% of patients will experience a shortening by 1 to 2 weeks of the interval between fever episodes when prednisone is used.
Cimetidine is used as a prophylactic medication to prevent fever episodes. The typical dose is 20 to 40 mg/kg/d, with a maximum dose of 150 mg twice daily. Approximately 25% of patients will experience a remission of PFAPA symptoms with cimetidine; some patients who respond to cimetidine will experience a recurrence of symptoms once the cimetidine is discontinued.
Tonsillectomy has emerged as a potentially curative treatment for PFAPA. Although the cause of PFAPA is unknown, the high rate of pharyngitis suggests that chronically inflamed lymphoid tissue may be the stimulus for recurrent inflammatory episodes. The theory is that surgical removal of this tissue eliminates the inflammatory stimulus and prevents further fever episodes. There have been 2 recent randomized control trials and several observational studies that support the use of tonsillectomy for treatment of PFAPA. If a patient is considering tonsillectomy, the risks and benefits of surgery, balanced with the natural history of PFAPA and the medical options for treatment, need to be considered carefully.3
References
1. Caorsi R, Pelagatti MA, Federici S, Finetti M, Martini A, Gattorno M. Periodic fever, apthous stomatitis, pharyngitis and adenitis syndrome. Curr Opin Rheumatol. 2010;22(5):579-584.
2. Feder HM, Salazar JC. A clinical review of 105 patients with PFAPA (a periodic fever syndrome). Acta Paediatr. 2010;99(2):178-184.
3. Burton MJ, Pollard AJ, Ramsden JD. Tonsillectomy for periodic fever, aphthous stomatitis, pharyngitis and cervi- cal adenitis syndrome (PFAPA). The Cochrane Collaboration. Cochrane Database Syst Rev. 2010;(9):CD008669.