How do I Manage a Patient with Acute Multiple Ulcers?


Acute multiple ulcers

Acute multiple ulcers are mainly associated with infections or drug intake (erythema multiforme) with an exception of aphthous stomatitis (multiple herpetiform aphthous ulcers), occur in groups, and may or may not be associated with blisters.

Can be categorized as recurrent ulcers with intermittent, lesion-free periods and ulcers preceded by blisters, fever, and malaise.



  • Can occur in any age group or population
  • Infectious ulcers are mainly seen in children and young adults and zoster in elders


  • Red erythematous area
  • Minor aphthous ulcers are up to 10 mm in size. Herpetiform aphthous ulcers are smaller (about 1-3 mm) and occur in groups
  • May be surrounded by an erythematous halo
  • Recurrent herpes simplex infections usually appear at the mucocutaneous junction of the lips
  • Herpangina usually affects soft palate, tonsils, and throat
  • Zoster is associated with hyperesthesia, or paresthesia, and can also affect the eye and ears (Ramsay Hunt syndrome, lesions typically unilateral)
  • Aphthous ulcers appear as white or yellow oval, minute, pinhead-sized, discrete (size is extremely important in the diagnosis) ulcers with an inflamed red border. They can involve any oral site, including the keratinized mucosa, and they increase in size, and coalesce to leave large round ragged ulcers
  • Pain severity: Pain and burning sensation may range from mild to severe depending on the extent of lesions. If there is superadded infection, the pain may be more severe



  • Occasionally associated with a tingling and burning sensation.
  • Infectious ulcers are associated with fever, malaise and sore throat. Ulcers are preceded by a vesicular stage.
  • Lesions due to erythema multiforme present as large blisters or ulcers and often exhibit a rather hemorrhagic base.
  • Zoster is associated with burning pain and itching.


  • Rashes and blistering caused by contact with an allergen and viral infections like zoster and hand, foot and mouth disease.
  • Rashes followed by sores and blisters on hand palms and foot soles, particularly in hand, foot, and mouth disease.
  • In erythema multiforme, skin lesions have a central pink-red ring around a pale center (target lesion). It can also affect the eye and other mucosal surfaces.


Rule Out Local Pathologies

  1. Ask for a detailed illness history:
    • Onset and progression of ulcers
    • Whether ulcers were preceded by vesicles/bulla
    • Lesions or discomfort in the eye or skin
    • Onset and nature of pain (if it is painful)
    • Drug intake or recent restorations
    • Fever (prodrome in herpetic lesions, and because of secondary infection)
    • Medical illnesses or conditions
      Medical history: Pay attention to systemic diseases that may be associated with multiple oral ulcers such as:
    • Hematological diseases (e.g., iron, folic acid, vitamin B12 deficiencies): Inquire about breathlessness and fatigue; check for pallor.
    • Celiac disease (which may lead to presenting a malabsorption syndrome): Inquire about feeling of bloating, flatulence, diarrhea, etc.
    • Inflammatory bowel diseases (e.g., Crohn disease and ulcerative colitis): Inquire about abdominal pain, blood in the stool, diarrhea, etc.
    • Behcet syndrome (includes genital, cutaneous, ocular, or other lesions): Inquire about multisystem involvement, frequent acute episodes and long duration to healing.
    • Immunodeficiencies (e.g.,  HIV infection/AIDS, neutropenia)
      • Ulcers appearing on a regular 3-week cycle may indicate cyclic neutropenia.
      • Advanced HIV infection/AIDS is associated with acute severe herpetic disease, especially if the CD4 count is < 200 cells/mm3. Inquiring about the patient's CD4 count could help diagnose the oral lesions.
    • Autoimmune syndromes (e.g., rheumatoid arthritis, lupus) may be associated with the use of methotrexate (associated with acute oral ulcers). Erythema multiforme is most commonly associated with herpes simplex virus reactivation and medications such as penicillin and NSAIDs.
  2. Perform a complete extraoral and intraoral examination (examine all oral mucosal surfaces):
    • Examine the eyes, lips and facial skin.
    • Examine the nails and hand skin.
    • Perform head and neck lymph node examination.
    • Inspect the ulcers and note their size, shape, number, location, borders, margins, floor, and surrounding areas.
    • Palpate the ulcers with a gloved finger to check for any tenderness and surrounding area.
  3. If the ulcers do not subside after treatment or persist for more than 2 weeks, a biopsy may be advised.


Based on the clinical examination and biopsy (if available), a diagnosis is determined.

Differential diagnosis

  • Herpetiform ulcers: usually in clusters at nonkeratinized mucosa, but may involve any site in the oral cavity.
  • Erythema multiforme: if sudden onset of ulcers along with fever, target skin lesions and crusting of lips (especially palm of the hands, neck, and face are frequently involved).
  • In young patients:
    • Acute multiple ulcers with rashes on hands and feet are suggestive of hand, foot and mouth disease.
    • Herpangina: acute multiple ulcers on soft palate and throat.
    • Primary herpes simplex infections (primary herpetic gingivostomatitis): acute multiple ulcers on keratinized mucosa along with gingivitis, fever and lymphadenopathy.
  • Zoster: unilateral lesions which abruptly stop at midline and associated with pain and paresthesia.
  • Recurrent herpes simplex infection: recurrent episodes of vesicles and ulcerations at the mucocutanous junction of lips.


Common Initial Treatments

Lesions are usually self-limiting and heal without scarring.

To alleviate pain and discomfort:

  • Advise patients to use topical anesthetics (20% benzocaine gel [e.g., Orabase® B]) or anesthetic mouthwashes containing benzydamine hydrochloride (e.g., Tantum).
    • These should be used judiciously, as the anesthetized oropharyngeal mucosa may affect the gag reflex and could theoretically lead to choking.
    • If possible, use after meals or wait 30 mins after eating before rinsing with local anesthetics.
  • If the ulcers are clustered in a particular area, the patient could use a medication stent to localize the anesthetic agent instead of anesthetizing the whole mouth.

If the ulcers are caused by viral infections:

  • Use 5% topical acyclovir. If easily washed away with saliva, can make a medication stent that covers the affected area, in which the patient puts the cream.
    • Acyclovir is more efficacious if used at the onset of the prodrome (burning or tingling prior to the appearance of the lesions).
  • Prescribe antibacterial mouthwashes (e.g., Listerine® or chlorhexidine) to avoid secondary infection and facilitate healing.
    • Listerine® has a high alcohol content, which will cause significant pain and may dry the mouth and thereby favour superinfection. You may ask the patient's pharmacist to make a chlorhexidine 0.12% alcohol-free mouth rinse.
  • Topical corticosteroids can be prescribed if there is a severe clinical presentation of nonviral lesions.
  • An elixir of dexamethasone can be prescribed: a potent anti-inflammatory agent (0.5 mg/5 mL).
    • Rinse with 1 teaspoon for 2 mins q.i.d., do not swallow.
  • High-potency topical steroids (e.g., 0.05% clobetaso) can be prescribed.    
    • Apply locally q. 4-6 h.
  • If the patient has a fever that is significantly uncomfortable, recommend using acetaminophen 500 mg q. 4-6 h. (not to exceed 4 g/24 h. in patients with normal liver function) or ibuprofen 400 mg q. 4-6 h. (avoid in patients with renal disease or peptic ulcer disease).

For the nonviral ulcers (refractory cases):

  • Use triamcinolone (e.g., Kenalog®) in Orabase®: apply 5 min, b.i.d. or t.i.d.


  • Patients should rinse with over-the-counter mouthwashes, maintain proper oral hygiene, and use over-the-counter local anesthetics.
  • Make sure the discomfort associated with the ulcers does not prevent the patient from getting proper nutrition. Following a soft diet is recommended, as well as avoiding spicy foods and citrus fruits.
  • A minority of ulcers may have one of the following etiologies, which could be addressed in your recommendations:
    • Use of toothpastes containing sodium lauryl sulfate (SLS): suggest the patient to try a SLS free toothpaste
    • Trauma
    • Stress
    • Cessation of smoking
    • Menstrual cycle association
    • Food allergy




Dr. Auluck is a clinician research fellow with the British Columbia Oral Cancer Prevention Program, Vancouver, BC.


Acknowledgement: I am grateful to Dr. Michele Williams for her help in creating and revising this article. Michele was an oral medicine specialist and clinical professor in dentistry at the University of British Columbia and an oral medicine leader at the BC Oral Cancer Prevention Program. She passed away in January 2015.

Suggested Resources

  1. Silverman S, Eversole LR, Truelove E. Essentials of Oral Medicine. BC Decker publication; 2002.