Evaluating the Genetics and Immunology of Periodic Fever, Aphthous Stomatitis, Pharyngitis, and Cervical Adenitis (PFAPA) Syndrome and Other Tonsil Disorders

Study Description:

The purpose of this multisite study is to collect specimens and data from patients with periodic fever, aphthous stomatitis, pharyngitis, and cervical adenitis (PFAPA) syndrome and other tonsil disorders for genetic, immunologic, cellular, molecular, and microbial research into the pathogenesis of these conditions. Specimens include blood, saliva, buccal swabs, oropharyngeal swabs, nasopharyngeal swabs, nasopharyngeal wash, and/or stool. If a participant is scheduled to undergo a clinically indicated tonsillectomy and/or adenoidectomy, then leftover clinical specimens will also be collected for research. Participants may either be seen in person at the study sites or may be seen remotely via telehealth and provide send-in samples collected locally.

Primary Objective:

To collect samples to understand the immunologic mechanisms and genetic and microbial risk factors for PFAPA and other tonsil disorders.

Primary Endpoints:

• Identify genetic risk variants for PFAPA and other tonsil disorders.
• Characterize immune cell populations, gene expression (including at the single-cell level), epigenetic features, and protein expression ex vivo in blood, tissue, washes, or swabs from people with PFAPA and other tonsil disorders.
• Characterize the tonsillar/adenoid, oral, nasal and/or stool microbiota in people with PFAPA and other tonsil disorders.
• Characterize clinical outcomes following tonsillectomy and other clinically indicated treatments.

Secondary Objective: To understand the characteristics and function of unique cell populations in the pharyngeal lymphoid tissues (tonsils and adenoids) and how immune responses to antigens are generated in these tissues.

Secondary Endpoints:

• Study responses to antigens and infection in the mucosal lymphoid tissue and peripheral blood.
• Characterize unique immune cell populations present in the mucosal tissue.
• Characterize immunologic and molecular pathways in the tissue cells.

• INCLUSION CRITERIA:

Participants must meet all the following inclusion criteria to be eligible for this study:

• Aged >=1 month. To be seen at the NIH CC, participants must be >=3 years of age.
• Diagnosed with PFAPA or another tonsil disorder, or has symptoms consistent with these conditions, as determined by the investigator.
• Able to provide informed consent (for ages >=18 years) or has a parent or guardian who can provide informed consent on their behalf (for ages <18 years).
• Willing to allow specimens and data to be stored for future research.
• Willing to allow genetic testing on their biospecimens.

Exclusion criteria

An individual who has any condition that, in the judgment of the investigator, may put them at undue risk or make them unsuitable for participation in the study will be excluded.