Angioedema with Oral Ulcers: Diagnosis and Management

Initial Evaluation and Diagnosis

The American College of Physicians recommends coagulation studies to exclude biopsy contraindications in patients with oral ulcers, with a strength of evidence level of high 1
Initial blood testing should include full blood count to screen for anemia, leukemia, neutropenia, and other blood disorders, according to the American Academy of Oral Medicine, with a strength of evidence level of moderate 2, 3
Fasting blood glucose should be tested to identify hyperglycemia predisposing to fungal infections, as recommended by the American Diabetes Association, with a strength of evidence level of high 2, 3
HIV antibody and syphilis serology should be tested to exclude infectious causes, according to the Centers for Disease Control and Prevention, with a strength of evidence level of high 2, 3

Biopsy is mandatory for ulcers persisting beyond 2 weeks without clear diagnosis to exclude malignancy and serious systemic diseases, as recommended by the American Cancer Society, with a strength of evidence level of high 2, 3
Multiple biopsies are needed when ulcers have different morphological characteristics, according to the College of American Pathologists, with a strength of evidence level of moderate 2
Direct immunofluorescence (DIF) is required for suspected erosive lichen planus, pemphigoid, and pemphigus, as recommended by the American Academy of Dermatology, with a strength of evidence level of high 2

Tuberculosis should be investigated with history of TB, tuberculin skin test (PPD), interferon gamma release assay (TB-IGRA), and chest CT, according to the World Health Organization, with a strength of evidence level of high 4, 5
Inflammatory bowel disease (Crohn's disease) should be investigated with history of abdominal pain with oral ulcers and colonoscopy, as recommended by the American Gastroenterological Association, with a strength of evidence level of moderate 4, 5
Invasive fungal infection should be investigated with elevated 1-3-β-D-glucan and galactomannan levels, especially in diabetic or immunocompromised patients, according to the Infectious Diseases Society of America, with a strength of evidence level of high 4, 5

Maxillofacial CT should be performed for ulcers near hard tissue to assess bone destruction, as recommended by the American College of Radiology, with a strength of evidence level of moderate 4, 5
Chest CT should be performed to rule out tuberculosis, invasive fungal infection, paraneoplastic syndrome, according to the American Thoracic Society, with a strength of evidence level of high 5
Otolaryngology consultation with nasal CT and nasopharyngoscopy should be considered if indicated, as recommended by the American Academy of Otolaryngology, with a strength of evidence level of moderate 5