Adam Jones, MD,
Resident, Department of Emergency Medicine
Medical College of Georgia, Augusta

Larry B. Mellick, MD, MS, FAAP, FACEP
Professor of Emergency Medicine and Pediatrics
Medical College of Georgia, Augusta.  

Pearl: Parents often think that their child’s frequent febrile illnesses are part of a rare syndrome and have nothing to do with being exposed to other infected children in the daycare setting. In the case of PFAPA, the parent may be right on target.

Case: A 9-year-old boy presented with recurrent fevers and tongue pain. On further examination, he also had glossitis, pharyngitis, malaise, and cervical lymphadenopathy. (Figure 1) His mother reported that he had previously been diagnosed with a chronic condition called PFAPA (periodic fever, cervical adenopathy, pharyngitis, aphthous stomatitis), and she believed his current illness likely was a recurrence. The emergency medicine team was in agreement and treated with the patient with a single 30-mg-dose of prednisone.

Discussion: PFAPA (periodic fever, aphthous stomatitis, pharyngitis, cervical adenitis) is part of the family of periodic fevers. These disorders are thought to be autoimmune in nature and include cyclic neutropenia, familial Mediterranean fever, and periodic fever.¹ They are generally suspected in cases where infection and neoplastic processes have been ruled out, but the patient continues to have cyclic (or periodic) fever. PFAPA was first described in 1987 and is characterized by glossitis (or aphthous stomatitis), recurrent and cyclic fever, pharyngitis and cervical lymphadenopathy (in the absence of obvious infection or neoplasm).² It was initially thought to be a pediatric disorder, but has recently been described in adults as well.³ The natural history of the illness in adults and children is similar and consists of being healthy for 4-8 weeks between attacks and then ill for approximately 5 days. New research suggests that abdominal pain could be added to the diagnostic criteria for PFAPA because 65% of those diagnosed with PFAPA had this complaint as well. Only 35% of patients diagnosed with PFAPA had aphthous stomatitis at the time of their illness.⁴ Relief of symptoms occurs promptly if 1-2 mg/kg of oral prednisone is administered at the beginning of the attack.³ Besides using prednisone for abortive therapy, many curative and/or preventative therapies have been tried. Cimetidine has been shown to be promising for prevention. Daily doses of 20-40 mg/kg/day helped one third of a study group to be symptom-free for greater than 6 months.⁵ Another touted cure is tonsillectomy. Multiple case reports (ranging from 10-40 patients in each) exist that document complete resolution of symptoms following surgery, but others report eventual spontaneous resolution and recommend against surgery.^6,7,8 

Summary: It is not uncommon for parents of children presenting with a series of febrile illnesses to express concerns that their child might have a serious illness or a syndrome of some kind. Thankfully, the vast majority of the time, simple reassurance with a discussion about herd immunity and the spread of diseases in daycare centers is sufficient. However, the next time you slide into your reassurance spiel hesitate long enough to consider whether your patient might be demonstrating the recurrent constellation of signs and symptoms consistent with PFAPA.

References: 

1. Rigante D. Autoinflammatory syndromes behind the scenes of recurrent fevers in children. Med Sci Monit 2009;15:RA179-87.
2. Thomas KT, Feder HM Jr, Lawton AR, et al. Periodic fever syndrome in children. J Pediatr 1999;135:15-21.
3. Padeh S, Stoffman N, Berkun Y. Periodic fever accompanied by aphthous stomatitis, pharyngitis and cervical adenitis syndrome (PFAPA syndrome) in adults. Isr Med Assoc J 2008;10:358-60.
4. Tasher D, Somekh E, Dalal I. PFAPA syndrome: New clinical aspects disclosed. Arch Dis Child 2006;91:981-4. Epub 2006 Apr 4.
5. Pinto A, Lindemeyer RG, Sollecito TP. The PFAPA syndrome in oral medicine: Differential diagnosis and treatment. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 2006;102:35-9. Epub 2006 Apr 24.
6. Leong SC, Karkos PD, Apostolidou MT. Is there a role for the otolaryngologist in PFAPA syndrome? A systematic review. Int J Pediatr Otorhinolaryngol 2006;70:1841-5. Epub 2006 Aug 14.
7. Galanakis E, Papadakis CE, Giannoussi E, et al. PFAPA syndrome in children evaluated for tonsillectomy. Arch Dis Child 2002;86:434-5.
8. Berlucchi M, Meini A, Plebani A, et al. Update on treatment of Marshall’s syndrome (PFAPA syndrome): Report of five cases with review of the literature. Ann Otol Rhinol Laryngol2003;112:365-9.