Table 2.

Systemic conditions and syndromes associated with aphthae

Syndromes	Distinguishing characteristics	Work up
Behçet’s disease	Genital ulceration	Eye evaluation for uveitis
	Uveitis/retinitis	Pathergy test
Reactive Arthritis Syndrome	Uveitis	Clinical diagnosis
	Conjunctivitis
	HLA B27 arthritis
Inflammatory bowel disease	Gastrointestinal symptoms, Recurrent bloody or mucous diarrhea	CBC, CMP, FOBT, Colonoscopy
Cyclic neutropenia	Periodic fever	Weekly CBC for 5 consecutive weeks
	Neutropenia
Human immunodeficiency virus (particularly major RAS)	Aphthae tend to be large and slow to heal	HIV antibody testing
Periodic Fever, Aphthous Stomatitis, Pharyngitis, Adenitis (PFAPA) Syndrome	Pharyngitis Cervical lymphadenopathy (painful) Periodic fevers at regular intervals of 2-8 weeks	Clinical diagnosis