Description

• 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

Epidemiology

Age considerations:

• Children
  • 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)

Prevalence

• 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

Genetics
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.

Risk Factors

• 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]
• Stress/anxiety
• 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

General Prevention

• 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

Pediatric Considerations
Common causes in the pediatric population (e.g., primary herpes, hand-foot-mouth disease, herpangina, traumatic ulcers) from oral or fecal transmission

Geriatric Considerations
Certain etiologies are more likely in the geriatric population (e.g., ill-fitting dentures, nutritional deficiencies) (2)[A].

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.

History

• 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.

Physical Exam

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
  • Itching
  • Dryness
• Herpetic stomatitis
  • Same as allergic stomatitis; may have low-grade fever and easy bleeding
• RAS
  • 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)
  • Varicella-zoster virus

Differential Diagnosis

• 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
• PFAPA
• Oral lichen planus

Diagnostic Tests & Interpretation

Initial 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

Diagnostic Procedures/Other

• Biopsy if persistent/recurrent/suspicious
• Direct fluorescent antibody testing is useful in the differential diagnosis between RAS and bullous skin diseases (2)[A].

Test Interpretation
Biopsy suspicious lesion or lesions that fail to heal or chronically recur to rule out oral granulomatosis, tuberculosis, hematologic cancer, or vasculitis.

General Measures

• 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.

Medication

• 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 (aluminum hydroxide and magnesiumhydroxide) or Mylanta (aluminum hydroxide and magnesium hydroxide), diphenhydramine, lidocaine
  • Maalox or Mylanta, diphenhydramine, sucralfate (Carafate)
  • Duke’s: nystatin, diphenhydramine, hydrocortisone
• Steroid oral rinses or topical preparations for aphthous ulcers (triamcinolone [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

• Laser treatments—Nd:YAG can be used to shorten course (2)[A].
• Replenish vitamin deficiencies; homeopathic substances (mercurius solubilis, Natrum muriaticum, phosphorus, sulfuric acid, nitric acid)

Admission, Inpatient, and Nursing Considerations

• 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

Follow-up Recommendations

Patient Monitoring
Lesions need to be followed until resolved; biopsy if they fail to resolve, continuously recur, or appear suspicious

Diet

Avoid spicy, acidic, and sharp foods. Keep hydrated.

Patient Education

Patient handouts

• Aphthous ulcers: http://www.aaomp.org/public/aphthous-ulcerations.php
• Mouth sores (English and Spanish): http://www.nlm.nih.gov/medlineplus/mouthdisorders.html

Prognosis

• 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

Complications

• 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.

ICD-10

• 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

ICD-9

• 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

SNOMED

• 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)