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First degree relatives of patients with PFAPA may have undetected disease

WASHINGTON — Twenty percent of patients with periodic fever, aphthous stomatitis, pharyngitis and cervical adenitis syndrome, or PFAPA, had at least one family member who also met the criteria for the disorder, indicating a genetic predisposition, according to data presented at the 2015 AAP National Conference and Exhibition.

“Relatives of children with PFAPA have a higher prevalence of recurrent pharyngitis and/or aphthous ulcers compared with healthy controls,” Kalpana Manthiram, MD, from the division of pediatric infectious diseases at Vanderbilt University School of Medicine, told Infectious Diseases in Children. “Therefore, family histories of these disorders may support a diagnosis of PFAPA.”

Kalpana Manthiram

Although sporadic familial cases of PFAPA have been reported in the past, there has been no systematic evaluation of family history in larger groups of patients. To determine whether there was a correlation between familial history of PFAPA and instances of recurrent pharyngitis, tonsillitis or tonsillectomy, Manthiram and colleagues evaluated medical records of patients with ICD-9 diagnosis of recurrent fever to identify patients with a diagnosis of PFAPA.

Using a structured questionnaire, the researchers then contacted patients (n = 83) and their parents/guardians by phone and inquired whether any first- and second-degree family members had exhibited recurrent periodic fever, recurrent pharyngitis and/or tonsillectomy.

After identification of relatives who had at least five episodes of stereotypical fever or pharyngitis in a year or tonsillectomy for unknown reasons, researchers contacted and questioned these individuals regarding their symptoms. Manthiram and colleagues used the chi-square test to compare characteristics of patients with or without familial history of recurrent oropharyngeal disorders.

According to study results, among the patients diagnosed with PFAPA, 20% had at least one family member who met the criteria for PFAPA; most notably, 4% of parents of these patients had PFAPA, 31% had recurrent pharyngitis but not PFAPA and 18% had tonsillectomy but not PFAPA.

Additionally, 28% of siblings, 14% of grandparents and 19% of aunts and uncles of PFAPA exhibited PFAPA, recurrent pharyngitis or tonsillectomy.

“Many family members were not diagnosed with PFAPA because they were thought to have ‘recurrent pharyngitis,’ but on close history, they meet the diagnostic criteria for PFAPA,” Manthiram said. “We believe such a family history may support the diagnosis.”

The researchers noted that although first- and second-degree relatives of patients with PFAPA exhibited a high prevalence of recurrent pharyngitis and tonsillectomy, they lacked classic PFAPA, suggesting that many family members may have reduced penetrance. In addition, the researchers asserted that patients with PFAPA and their family members with recurrent pharyngitis may have an underlying predisposition to inflammation in their pharyngeal lymphoid tissue.

“Clinicians should carefully ask about these conditions in the family history, which may also be referred to as recurrent pharyngitis, tonsillitis or ‘strep’ throat by patients and their families,” Manthiram said. – by Bob Stott

Reference:
Manthiram K, et al. Abstract 30093. Presented at: AAP National Conference and Exhibition; Oct. 23-27, 2015; Washington, D.C.

Disclosure: The researchers report no relevant financial disclosures.