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Periodic fever with aphthous stomatitis, pharyngitis and adenitis (PFAPA syndrome)

Author
Shai Padeh, MD
Section Editors
E Richard Stiehm, MD
Robert Sundel, MD
Sheldon L Kaplan, MD
Deputy Editor
Elizabeth TePas, MD, MS

INTRODUCTION

The recurrent fever syndromes are autoinflammatory diseases that are characterized by attacks of seemingly unprovoked inflammation without significant levels of either autoantibodies or autoreactive T cells [1,2]. The known genetic causes of these syndromes derive from defects in proteins of the innate immune system. More than 10 hereditary autoinflammatory syndromes caused by over 770 different mutations have been identified. In addition, 30 to 70 percent of cases referred to the United States National Institute of Health (NIH) Translational Autoinflammatory Disease Section do not have mutations diagnostic of known genetic autoinflammatory disorders [3]. The most common such condition is periodic fever, aphthous stomatitis, pharyngitis, and adenopathy (PFAPA) syndrome.

PFAPA was first described by Drs. Gary Marshall, Alexander Lawton, and colleagues in 1987 [4]. It is one of two truly predictably periodic fever syndromes. The other is cyclic hematopoiesis, which has indistinguishable clinical features. PFAPA is a sporadic syndrome, unlike most hereditary autoimmune fevers, and second cases in siblings are rare. Two large registries, one in the United States and one in Israel, form the basis for the following description [5-8]. An overview of the periodic fevers and other autoinflammatory diseases is presented separately. (See "Periodic fever syndromes and other autoinflammatory diseases: An overview".)

The pediatrician is generally the first clinician to evaluate the child with recurrent fever, since these disorders often become clinically apparent in childhood. The approach to a child with unexplained fever is presented separately. (See "Fever of unknown origin in children: Evaluation" and "Fever of unknown origin in children: Etiology".)

EPIDEMIOLOGY

Periodic fever in children diagnosed with PFAPA generally begins between the ages of two and five years (3.7 ± 3.8 years of age in the Israeli cohort of >500 patients) [7,9,10], although a younger median age of onset (11 months) was seen in a smaller Norwegian cohort [11]. There is a slight male predominance (55 to 71 percent). There is no predilection for a particular ethnic or racial group. Familial cases are rare [12-15].

Attacks cease before 10 years of age in most patients. However, this syndrome has been described in adults. The first cases in adults were reported in 2008 [8], with over 30 cases diagnosed within two years of that report [16].

                    

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Literature review current through: Nov 2016. | This topic last updated: Tue Nov 04 00:00:00 GMT 2014.
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