Diagnosis>Organ System>

PATHOGENS

• None (idiopathic).
• See DDx below for other conditions causing oral ulcers.

CLINICAL

• Common oral lesions classified by size and duration into minor, major and herpetiform.
• Minor: Small (<5 mm) single or multiple tender ulcerations, persist x7-14 d. Exam: superficial erosions w/ fibrinous covering often surrounded by red halo. Involve mobile mucosa (tongue, floor of mouth, soft palate and buccal/labial mucosa).
• Major: larger painful ulcerations, persist for up to 6 wks, eventually heal w/ scar formation.
• Herpetiform: crops of small ulcers that eventually coalesce; may be mistaken for HSV by appearance.
• In HIV-infected individuals, tend to occur more frequently, last longer and may be more painful. Can significantly effect nutritional health in an already at risk population.
• DDx: viral (HSV, CMV, Coxsackie), fungal (Histoplasma, Cryptococcus, Cryptosporidium, Mucor), bacterial (TB, syphilis), neoplasm (NHL, KS, squamous cell Ca), Behcet's disease, Reiter's syndrome, SLE, bullous pemphigoid, pemphigus vulgaris, dermatitis herpetiformis, Crohn's disease, celiac sprue, pernicious anemia, Sweet syndrome.
• Predisposing factors: Family history, stress (emotional/physical), iron or vitamin deficiencies (folic acid, vitamin B12), allergies, hormonal changes, diet/food hypersensitivity, trauma, immune dysfunction, cyclic neutropenia, sodium lauryl sulfate (toothpaste detergent), celiac sprue, inflammatory bowel disease, pernicious anemia , drugs (NSAIDs, alendronate, nicorandil).

DIAGNOSIS

• Clinical presentation & lesion appearance important. Initial Rx trial w/ topical agents helpful diagnostically. Bx +/- Cx for persistent, atypical appearing ulcerations.
• Oral mucosal Bx required for atypical or non-healing ulcers to exclude possibility of deep fungal infection, viral infection and neoplasms.
• CBC, iron studies, RBC folate, vitamin B12, serum antiendomysial/transglutaminase antibody.
• Consider other etiologies (infectious): HSV: Tzank smear w/ inclusion-bearing giant cells; CMV: multinucleated giant cells; Syphilis: +RPR/FTA; Cryptosporidiosis, mucormycosis, histoplasmosis: +Bx/Cx.
• Consider other etiologies (noninfectious): Behcet's syndrome: genital ulcers, uveitis, retinitis. Reiter's syndrome: uveitis, conjunctivitis, arthritis, HLA B27+. Crohn's: bloody diarrhea, mucus, GI ulcerations. SLE: malar rash, +ANA. Cyclic neutropenia: periodic fever & neutropenia. Squamous cell CA: +Bx, +LN. Bullous pemphigoid/pemphigus vulgaris: diffuse skin involvement.

TREATMENT

• Recommendations represent author's opinion.
• Treatments discussed below apply to idiopathic aphthous ulcers only. Treat underlying condition if present.
• Aphthous ulcers in conjunction w/ Sx of uveitis, conjunctivitis, arthritis, diarrhea, genital ulcerations or other systemic manifestation should prompt search for systemic autoimmune or inflammatory condition.
• Topical corticosteroids are 1st line Rx: reduce ulcer duration and pain compared with controls, but no consistent effect on incidence of ulceration.
• Reserve PO steroids and thalidomide for severe cases refractory to topical Rx.
• Goals of Rx: promote ulcer healing, reduce pain, diminish frequency of recurrence while maintaining nutritional intake.

• Topical corticosteroids: 1st line Rx. Multiple agents can be used: Betamethasone, fluocinonide, fluocinolone, fluticasone, and clobetasol more effective than hydrocortisone & triamcinolone, but higher risk for adrenocortical suppression & predisposition to candidiasis.
• Triamcinolone dental paste (Kenalog in Orabase) or fluocinonide dental paste (Lidex in Orabase): apply to ulcer 2-3 times daily x 5d or clobetasol propionate mouthwash 10 cc x 5 min swish & spit 3 times daily.
• Dexamethasone elixir: 0.5 mg/5 cc swish & spit 3 times daily.
• Amlexanox (Aphthasol 5%) paste: apply 1/4 inch (0.5 cm) topically to ulcer four times a day. Apply following oral hygiene and as soon as possible after noticing symptoms.
• Chlorhexidine 15 cc oral rinse 0.12% swish & spit x 30 sec twice-daily: increases # of ulcer-free days and interval between ulcer development but does not affect incidence/severity of ulceration.
• Tetracycline 250 mg capsule, dissolve in 180 cc water, swish & spit 4 times daily.
• Viscous lidocaine 2%, apply to ulcer w/ cotton swab 4 times daily PRN.
• Triamcinolone injection may be useful for persistent isolated lesions.
• Mile's solution: 60 mg hydrocortisone, 20 cc mycostatin, 2 gm tetracycline, and 120 cc viscous lidocaine (swish & spit). The 2 active ingredients are HC and TCN, but clinical trials have used more potent topical steroids.

• Severe cases only: prednisone 60 mg PO once-daily x 5-7d, then D/C. Rx >7d requires slow taper. Avoid if possible in immunocompromised pts, including HIV.
• Thalidomide 200 mg PO once-daily x 4 wks effective in 2/3 of pts w/ resistant aphthous ulcers. Some pts may require thalidomide maintenance dose (200 mg twice a wk).
• Dapsone, colchicine and pentoxifylline have been reported as potentially effective in refractory cases, although randomized controlled trials are lacking.

• Brush atraumatically (use small-headed, soft toothbrush). Avoid hard/sharp foods/trauma to oral mucosa.
• Correct iron & vitamin deficiencies.
• Exclude potentially offending foods.
• Consider allergy (patch) testing.
• Suppress ovulation if menses/OCP association.
• D/C potentially causal medications.

Drug Comments

Basis for Recommendations

• Jacobson JM, Greenspan JS, Spritzler J, et al.; Thalidomide for the treatment of oral aphthous ulcers in patients with human immunodeficiency virus infection. National Institute of Allergy and Infectious Diseases AIDS Clinical Trials Group.; N Engl J Med; 1997; Vol. 336; pp. 1487-93;
  ISSN: 0028-4793;
  PUBMED: 9154767
  Rating: Basis for recommendation
  Comments:Double-blind, randomized, placebo-controlled study of thalidomide as therapy for oral aphthous ulcers in HIV+ patients. Patients received 4-week course of either 200 mg of thalidomide or placebo PO once-daily. They were evaluated weekly for condition of the ulcers, quality of life, and evidence of toxicity. 55% in thalidomide group had complete healing of aphthous ulcers after 4 weeks vs. only 7% of pts in control group (P<0.001).
  
  

REFERENCES

REFERENCED WITHIN THIS GUIDE

• Initial Evaluation (Zambia specific)