- Literally, inflammation of the mouth. Inflammation of the mucous lining of any of the structures in the mouth, which may involve the cheeks, lip, tongue, gingiva, and floor or palate of the mouth. Usually painful and associated with redness, swelling, and sometimes bleeding and ulceration. Affects people of all ages; may be caused by localized injury/irritation or a manifestation of systemic conditions
- System(s) affected: skin/exocrine; ENT; oropharynx; dental
- Primary herpetic infections (age 6 months to 5 years) (most common)
- Hand-foot-mouth disease, herpangina
- Angular stomatitis
- Aphthous stomatitis
- Teenagers and adults
- Primary herpetic infection (college age)
- Aphthous stomatitis (peak onset age 10 to 19 years) (most common)
- Vincent stomatitis (also known as Vincent disease or acute necrotizing ulcerative gingivitis)
- Behçet disease (orogenital lesions)
- Nicotinic stomatitis
- Chronic ulcerative stomatitis (white middle-aged women)
- Very common: herpetic stomatitis, hand-foot-mouth disease, and recurrent aphthous stomatitis (RAS)
- Common: herpangina, nicotinic stomatitis, and denture-related stomatitis
- Remaining causes are uncommon or rare.
Etiology and Pathophysiology
- Allergy: foods, drugs, contact (some erythema multiforme)
- Nutritional deficiencies: vitamin B6 (angular stomatitis), vitamin B12, folate, zinc, magnesium, vitamin C, iron deficiencies
- Malnutrition (gangrenous stomatitis; internationally known as “noma”)
- Viral: herpes simplex I and II (herpetic stomatitis), coxsackie A (herpangina and hand-foot-mouth disease)
- Bacterial (scarlatina)
- Autoimmune disorders (Crohn, Behçet, SLE, celiac, erythema multiforme)
- Neoplastic/hematologic (anemia, leukemia, cyclic neutropenia)
- Smoking (nicotinic stomatitis)
- Hormonal (possibly RAS)
- Uncertain (RAS, Vincent stomatitis, recurrent scarifying stomatitis)
- Traumatic: (mechanical, chemical, or thermal) for example, ill-fitting dentures
- Uremic (uremic/nephritic)
- Medication induced— for example, methotrexate for rheumatoid arthritis
- Chemotherapy or radiation
Immune alterations: Polymorphisms causing high interleukin-1p (IL-1p) and tumor necrosis factor-α (TNF-α) production increase risk for RAS (1). TNF-α is increased 2- to 5-fold in the saliva of patients with RAS.
- Genetic factors
- Food hypersensitivities/allergens; common ones include nuts; shellfish; cinnamon; fruits; metals; dental materials; and ingredients in toothpaste, mouthwash, and gum.
- Local trauma: poor-fitting dentures, tooth brushing, local anesthetic injection, dental work (1)[A]
- Hormonal changes (menstrual cycle, pregnancy, dysmenorrhea) (2)[A]
- Nutritional deficiencies (iron, folate, ferritin, vitamin B6, vitamin B12)
- Tobacco cessation
- Medications, for example, methotrexate, NSAIDS, phenobarbital
- Immunologic: HLA-B12
- Immunologic gastrointestinal diseases: Crohn disease, celiac disease (2)[A]
- Systemic diseases: Behçet syndrome; cyclic neutropenia; HIV infection; periodic fever, aphthous stomatitis, pharyngitis, cervical adenitis (PFAPA); reactive arthritis; Sweet syndrome; mouth and genital ulcers with inflamed cartilage (MAGIC) syndrome (1)[A]
- Cancer therapies
- Avoid causative factors (see “Etiology and Pathophysiology”).
- Herpetic stomatitis; shedding may occur for 2 weeks for primary infection, 60 hours for recurrent infection; avoidance or antivirals with early symptomology
- Good oral hygiene
- Good nutrition: Daily multivitamin does not reduce RAS episodes (2)[A].
- Avoid/discontinue smoking.
- Properly fitting dentures
Common causes in the pediatric population (e.g., primary herpes, hand-foot-mouth disease, herpangina, traumatic ulcers) from oral or fecal transmission
Commonly Associated Conditions
- Pregnancy may bring on recurrent ulcerative stomatitis.
- AIDS: associated with multiple, severe oral lesions
- Aphthous ulcers may be associated with Crohn disease or celiac disease.
- Patient will complain of pain, burning sensation, intolerance to temperature extremes, and irritation with certain foods.
- During review of clinical history, determine the onset, progression, number of ulcers/lesions, size of lesion, duration of each lesion, frequency, site and whether it heals with a scar or not. This information helps diagnose localized versus systemic lesions.
The physical exam should include comprehensive oral examination. Extraoral exam includes inspection and palpation of cervical lymph nodes. Examine and palpate the lips, tongue, cheeks, and hard and soft palate as well as cervical, submandibular, and submental lymph nodes. Erythema and edema are the usual oral manifestations, often with ulcerations. Some will have constitutional symptoms: low-grade fever, malaise, lymphadenopathy, and headache. Pain will vary. Below is a list of specific characteristics:
- Allergic stomatitis
- Intense shiny erythema
- Slight swelling
- Herpetic stomatitis
- Same as allergic stomatitis; may have low-grade fever and easy bleeding
- Same as allergic stomatitis; often multiple lesions
- Vincent infection: necrotic ulceration of interdental papillae and mucous membrane
- Pseudomembranous stomatitis: membrane-like exudate
- Mucous lesions accompanying systemic disease
- Mucous patches (syphilis)
- Strawberry tongue (Kawasaki disease, scarlet fever, staphylococcal toxic shock syndrome)
- Koplik spots (measles)
- Ulcers (erythema multiforme)
- Smooth, fire red, painful (pellagra)
- Hand-foot-mouth disease, herpangina
- Primary herpes simplex virus (HSV)
- Varicella-zoster virus
- Erythema multiforme
- RAS (Note: can be associated with colitis, celiac)
- Lichen planus
- Erythema multiforme/Stevens-Johnson syndrome
- Behçet disease (3)[C]
- Angular stomatitis
- Noma (gangrenous stomatitis)
- Scarlatina (scarlet fever)
- Cancers of oral mucosa, for example, squamous carcinoma (90% of oral cancers) (4)[A]
- Uremic stomatitis
- Reactive arthritis
- Pemphigus vulgaris
- Bullous pemphigoid
- Cyclic neutropenia
- Burning mouth syndrome
- Oral lichen planus
Diagnostic Tests & InterpretationInitial Tests (lab, imaging)
- Diagnosis relies on clinical symptoms and history. Testing is not routinely performed.
- For persistent disease, CBC, erythrocyte sedimentation rate/C-reactive protein, serum vitamin B12, serum/red cell folate, antigliadin, antiendomysial autoantibodies (1)[A]
- Usually none needed; consider the following for differential diagnosis:
- HSV culture (from vesicles)
- Serologic test for syphilis
Follow-Up Tests & Special Considerations
If not resolving in 7 to 14 days or getting worse, consider CBC; cultures to determine secondary infection
- Biopsy if persistent/recurrent/suspicious
- Direct fluorescent antibody testing is useful in the differential diagnosis between RAS and bullous skin diseases (2)[A].
Biopsy suspicious lesion or lesions that fail to heal or chronically recur to rule out oral granulomatosis, tuberculosis, hematologic cancer, or vasculitis.
- To date, no strong evidence for broadly applicable efficacy of a single treatment. This likely reflects the poor methodologic rigor of trials and lack of studies rather than the true effect of the intervention. It is also recognized in clinical practice that certain drugs appear to work for some patients and not for others (2)[A].
- Treatments target the causative factors. If cause is allergic, identification and removal of allergen is critical. For infectious causes, regimens include antibiotics or antifungals. Steroidal anti-inflammatory drugs used for systemic conditions with stomatitis manifestation. If the cause of stomatitis is due to medical treatment or cancer therapy, management needs to be aggressive (4)[A].
- In most cases, treatment of symptoms only; analgesics
- Severe cases may require parenteral fluids; particularly in children
- Good oral hygiene
- Topical anesthesia
- Oral rinses such as half-strength hydrogen peroxide, nonalcohol chlorhexidine gluconate. Avoid oral rinses containing alcohol.
- Smoking cessation
- Refit/remake dentures; daytime wear only (5)[B]
- Avoid specific allergens.
- Replace vitamin deficiencies.
- Treat malnutrition, if present.
- Acetaminophen or ibuprofen for analgesia
- Topical corticosteroids, colchicine, and cytotoxic drugs for Behçet disease (3)[A]
- 2% viscous lidocaine (Xylocaine) swish and spit for local discomfort; max of 8 doses/day. Precautions: Toxic dose of topical lidocaine is uncertain, but likely only 25–33% of dose may have significant absorption from open ulcers or mucous membrane.
- Liquid diphenhydramine (Benadryl) by mouth or swish and spit, for allergic reactions
- “Miracle mouth rinses”: various combinations of the following in equal parts; use swish and spit QID:
- Maalox or Mylanta, diphenhydramine, lidocaine
- Maalox or Mylanta, diphenhydramine, Carafate
- Duke’s: nystatin, diphenhydramine, hydrocortisone
- Steroid oral rinses or topical preparations for aphthous ulcers (Kenalog in Orabase) or steroids injected into lesions for severe cases
- Antibiotics for gangrenous stomatitis (penicillin and metronidazole are reasonable first-line agents; often start with IV)
- Sucralfate (Carafate) suspension 1 tsp swish in mouth or place on ulcers QID (helpful)
- Acyclovir 200 to 800 mg 2 to 5 times per day for 2 to 10 days for herpetic stomatitis depending on first episode versus recurrence
- Topical 0.2% hyaluronic acid gel for recurrent aphthous ulcers
- Chemical cauterization with silver nitrate for aphthous stomatitis (treatment can cause burning sensation)
- Thalidomide 200 mg 1 to 2 times per day for 3 to 8 weeks in HIV-positive patients with nonhealing aphthous ulcers (extreme caution for birth defects)
- For candidiasis: nystatin PO suspension 400,000 U (4 mL) QID for 10 days; swish and swallow (1 mL QID for infants).
- Antifungal ointment (e.g., nystatin [Mycostatin]) for candidiasis-complicating angular stomatitis
- For prevention or reducing severity of mucositis with cancer treatments, these agents have some evidence of benefit: allopurinol, aloe vera, amifostine, cryotherapy, glutamine (IV), honey, keratinocyte growth factor, laser, and polymyxin/tobramycin/amphotericin (PTA) antibiotic pastille/paste (2)[B].
- Contraindications: allergy to specific medication
Complementary and Alternative Medicine
- IV fluids in severe cases involving dehydration owing to oral ulcerations
- For infants with painful stomatitis, feeding can be particularly challenging. Topical or PO analgesic agents should be used prior to bottlefeeding; nasogastric feeds or parenteral, as needed
Lesions need to be followed until resolved; biopsy if they fail to resolve, continuously recur, or appear suspicious
Avoid spicy, acidic, and sharp foods. Keep hydrated.
- Aphthous ulcers: http://www.aaomp.org/public/aphthous-ulcerations.php
- Mouth sores (English and Spanish): http://www.nlm.nih.gov/medlineplus/mouthdisorders.html
- Herpetic/hand-foot-mouth disease/erythema multiforme: self-limited—1 to 3 weeks
- RAS: 7- to 14-day course per episode
- Vincent: may progress to fascial space infection with airway compromise or sepsis
- Nicotinic: resolves with smoking cessation
- Denture: resolves with proper fitting, careful oral hygiene, and daytime-only denture wear
- Stevens-Johnson: resolution in ~6 weeks with adequate supportive care
- Recurrent ulcerative: recurs over time, but overall prognosis is good
- Recurrent scarifying: Occasional patients suffer continuous ulcers; others have recurrence with eventual scarring. Prognosis is otherwise good.
- Behçet disease may recur for several years. Overall prognosis is related to other aspects of the disease.
- Angular cheilitis: After correction of mechanical problems, allergic disorders, and nutritional deficiencies, the prognosis is good.
- Gangrenous stomatitis: most serious stomatitis, requiring aggressive treatment with IV antibiotics and débridement to avoid death
- Scarlatina: Prognosis is related to other manifestations of the disease.
- Uremic: depends on the underlying renal disease
- Recurrent scarifying stomatitis may result in intraoral scarring with restriction of oral mobility.
- Behçet disease may result in visual loss, pneumonia, colitis, vasculitis, large-artery aneurysms, thrombophlebitis, or encephalitis.
- Gangrenous stomatitis may lead to facial disfigurement and even death.
- Scarlet fever may result in cardiac disease.
- Herpetic stomatitis may be complicated by ocular or CNS involvement.
Slebioda Z, Szponar E, Kowalska A. Recurrent aphthous stomatitis: genetic aspects of etiology. Postepy Dermatol Alergol. 2013;30(2):96–102. [PMID:24278055]
- A69.1 Other Vincent’s infections
- B00.2 Herpesviral gingivostomatitis and pharyngotonsillitis
- B08.4 Enteroviral vesicular stomatitis with exanthem
- B08.5 Enteroviral vesicular pharyngitis
- K05.10 Chronic gingivitis, plaque induced
- K12.0 Recurrent oral aphthae
- K12.1 Other forms of stomatitis
- 054.2 Herpetic gingivostomatitis
- 074.0 Herpangina
- 074.3 Hand, foot, and mouth disease
- 101 Vincent’s angina
- 523.10 Chronic gingivitis, plaque induced
- 528.00 Stomatitis and mucositis, unspecified
- 528.2 Oral aphthae
- 186659004 Herpangina
- 186963008 Vincent’s angina
- 266108008 hand foot and mouth disease (disorder)
- 426965005 aphthous ulcer of mouth (disorder)
- 57920007 herpetic gingivostomatitis (disorder)
- 61170000 stomatitis (disorder)
- Stomatitis is often self-limiting and requires only pain relief treatment and supportive care.
- Consider broad differential diagnosis.
- Treat all underlying conditions.
- Depending on geographic location, age of patient, and comorbidities, be prepared to treat worsening or severe causes aggressively.
Sheila O. Stille, DMD
Hugh Silk, MD, MPH, FAAFP
Aphthous stomatitis. A small punched-out erosion has erythema surrounding a yellow-white center.
Aphthous stomatitis. Larger, more extensive aphthae are seen in this woman, who has Behçet's syndrome.
- Tarakji B, Gazal G, Al-Maweri SA, et al. Guideline for the diagnosis and treatment of recurrent aphthous stomatitis for dental practitioners. J Int Oral Health. 2015;7(5):74–80. [PMID:23772946]
- Belenguer-Guallar I, Jiménez-Soriano Y, Claramunt-Lozano A. Treatment of recurrent aphthous stomatitis. A literature review. J Clin Exp Dent. 2014;6(2):e168–e174. [PMID:24790718]
- Taylor J, Glenny AM, Walsh T, et al. Interventions for the management of oral ulcers in Behçet’s disease. Cochrane Database Syst Rev. 2014;(9):CD011018. [PMID:25254615]
- Riley P, Glenny AM, Worthington HV, et al. Interventions for preventing oral mucositis in patients with cancer receiving treatment: oral cryotherapy. Cochrane Database Syst Rev. 2015;(12):CD011552. [PMID:26695736]
- Loster JE, Wieczorek A, Loster BW. Correlation between age and gender in Candida species infections of complete denture wearers: a retrospective analysis. Clin Interv Aging. 2016;11:1707–1714. [PMID:27920509]
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