Systemic Diseases Associated with RAU

Main Extraoral Findings

Oral Findings

Diagnostic Criteria

Behçet Syndrome

Recurrent genital aphthae, cutaneous findings (erythema nodosum, pustulosis, folliculitis), ocular (anterior or posterior uveitis, retinal vasculitis), arthritis, CNS signs, cardiovascular, hematologic, pulmonary, and renal findings

Mostly major aphthae of variable shape and size; minor aphthae also common, but herpetiform ulcers are rare

Presence of oral RAU plus two systemic manifestations or positive pathergy test; histology identical to aphthous ulcer

Inflammatory Bowel Disease

Ulcerative colitis, Crohn disease: abdominal pain, diarrhea, hematochezia, fever

Recurrent aphthae of all types as well as granulomatous papules

Endoscopy with biopsies, X-ray barium studies

Gluten-Sensitive Enteropathy/Celiac Disease

Nausea, bloating, crampy abdominal pain, lactose intolerance, malabsorption, anemia, vitamin deficiency, bone loss, dermatitis herpetiformis, gastrointestinal lymphoma

Persistent RAU, glossitis, taste alteration, neuropathies (rare)

Tissue transglutaminase ELISA, anti-endomysial antibody level, endoscopy, duodenal biopsy, CBC, serum iron, ferritin, iron binding capacity, folate, zinc, vitamins B1, B2, B6, and B12, magnesium

HIV Infection

Acute seroconversion syndrome; advanced disease (low CD4 count): low CD4 count, high HIV viral load, fever, night sweats, sore throat, lymphadenopathy, lethargy, rash, dry cough, headache, myalgia, conjunctivitis, nausea, vomiting, diarrhea

Both RAU and aphthous-like ulcers; other oral lesions (candidiasis, Kaposi sarcoma, other infections)

HIV ELISA, CD4 count, HIV viral load assay

Agranulocytosis and Cyclic Neutropenia

Fever, ulcers on other mucosal sites, secondary infection

Aphthous-like ulcers in any location

Granulocyte count, CBC qweek < 5

PFAPA (Marshall Syndrome)

Cyclic or periodic fever, pharyngitis, sinusitis, cervical adenitis

Minor and herpetiform aphthae most common

History and clinical findings

MAGIC Syndrome

Behçet stigmata plus polychondritis

Major and minor aphthae

History and clinical findings

Sweet Syndrome

Fever, neutrophil leukocytosis, erythematous skin papules, plaques, or nodules, pathergy

Rare in classical Sweet’s syndrome; aphthous-like ulcers reported in cases associated with hematologic malignancy

History and clinical findings

Reactive Arthritis (Reiter Syndrome)

Nongonococcal urethritis, HLA HLAB27-positive arthritis, conjunctivitis, uveitis, bacillary dysentery, circinate balanitis, keratoderma blenorrhagicum

Aphthous-like ulcers in any location, geographic tongue (benign migratory glossitis)

History and clinical findings