Basics

Description

  • Inflammation of mucous lining of any of the structures in the mouth, cheeks, lip, tongue, gingiva, and floor or roof of the mouth. Usually painful and associated with redness, swelling, and sometimes bleeding. It affects people of all ages. Stomatitis can be result of localized injury/irritation, or the manifestation of systemic conditions.
  • System(s) affected: Skin/Exocrine; ENT; Oropharynx; Dental

Epidemiology

  • Children:
    • Primary herpetic infections (age 6 months–5 years) (most common)
    • Hand-foot-mouth disease
    • Herpangina
    • Angular stomatitis
    • Aphthous stomatitis
  • Teenagers and adults:
    • Aphthous stomatitis (peak onset age 10–19 years) (most common)
    • Vincent stomatitis (also known as Vincent disease or acute necrotizing ulcerative gingivitis)
    • Behçet disease
    • Nicotinic stomatitis
    • Chronic ulcerative stomatitis (white women in late middle age)

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, folic acid, 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)
  • Smoking (nicotinic stomatitis)
  • Hormonal (possibly RAS)
  • Uncertain (RAS, Vincent stomatitis, recurrent scarifying stomatitis, Behçet disease, erythema multiforme)
  • RAS may be associated with vitamin B12, folic acid, vitamin C, and iron deficiencies
  • Bacterial (scarlatina)
  • Traumatic (mechanical, chemical, or thermal)
  • Uremic (uremic/nephritic)
  • Ill-fitting dentures
  • Chemotherapy or radiation

Genetics
Polymorphisms causing high interleukin 1p (IL-1p) and tumor necrosis factor-α (TNF-α) production increase risk for recurrent aphthous stomatitis (1)[B].

Risk Factors

  • Poor oral hygiene
  • Familial connection
  • Dietary deficiencies (iron, folate, B6, B12)
  • Chronic systemic disease; Immune deficiencies
  • Poor fitting dentures
  • Smoking
  • Cancer therapies

General Prevention

  • Avoid causative factors (see “Etiology”).
  • Herpetic stomatitis; shedding may occur for 2 weeks
  • Good oral hygiene
  • Good nutrition: Daily multivitamin does not reduce recurrent aphthous stomatitis episodes (2)[B].
  • Avoid/Discontinue smoking.
  • Properly fitting dentures

Pediatric Considerations
Common causes in the pediatric population (e.g., herpetic [primary], hand-foot-mouth disease, herpangina, traumatic ulcers)

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

Commonly Associated Conditions

  • Pregnancy may bring on recurrent ulcerative stomatitis.
  • AIDS: Associated with severe oral lesions
  • Aphthous ulcers may be associated with Crohn disease or celiac disease.

Diagnosis

History

Patient will complain of burning sensation, intolerance to temperature, and irritation with certain foods.

Physical Exam

The physical exam should include comprehensive oral examination. 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, and headache. Pain will vary. Below is a list of specific characteristics:

  • Allergic stomatitis:
    • Intense shiny erythema
    • Slight swelling
    • Itching
    • Dryness
    • Burning
    • Usual allergens include: Nuts, shellfish, cinnamon, fruits, metals, dental materials, and ingredients in toothpaste, mouthwash, and gum
  • Herpetic stomatitis:
    • Same as allergic stomatitis and low-grade fever; bleeds easily
  • Recurrent aphthous stomatitis
    • Same as allergic stomatitis; often multiple lesions
  • Vincent infection: Necrotic ulceration of interdental papillae and mucous membrane
  • Pseudomembranous stomatitis: Membranelike 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

Differential Diagnosis

  • Hand-foot-mouth disease, herpangina
  • RAS (note can be associated with colitis)
  • Erythema multiforme/Stevens-Johnson syndrome
  • Behçet disease
  • Angular stomatitis
  • Noma (gangrenous stomatitis)
  • Scarlatina (scarlet fever)
  • Cancers of oral mucosa
  • Uremic stomatitis
  • Reactive arthritis
  • Pemphigus/Pemphigoid
  • Squamous cell cancer
  • Cyclic neutropenia
  • Burning mouth syndrome
  • PFAPA (periodic fever, aphthous ulcers, pharyngitis, and adenopathy)

Diagnostic Tests and Interpretation

  • Diagnosis relies on clinical symptoms and history. Testing is not routinely performed.
  • Usually none needed; consider the following for differential diagnosis:
    • Tzanck test of historic interest only; herpes simplex virus (HSV) culture
    • Serologic test for syphilis
    • CBC; cultures to determine secondary infection

Follow-Up Tests & Special Considerations
If not resolving in 7–14 days or getting worse, consider CBC.

Diagnostic Procedures/Other
  • Biopsy if persistent/recurrent/suspicious
  • Immunofluorescence is useful in the differential diagnostic between RAS and bullous skin diseases (3)[C].

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

Treatment

  • No single treatment has been found to have strong evidence to be effective. This is likely reflects the poor methodological rigor of trials and lack of studies rather than the true effect of the intervention. It is also recognized that, in clinical practice, individual drugs appear to work for individual patients (4)[A].
  • Treatment of stomatitis depends on the causative factors. If cause is allergic, identification and removal of the agent are critical. For infectious causes, antibiotic or antifungal regimens. Steroidal anti-inflammatory drugs for systemic conditions with stomatitis manifestation. If the cause of stomatitis is due to medical treatment or cancer therapy, management needs to be more aggressive.

General Measures

  • In most cases, treatment of symptoms only
  • Severe cases may require parenteral fluids, particularly in children.
  • Good oral hygiene
  • Topical anesthesia
  • Analgesics
  • Oral rinses, such as half-strength hydrogen peroxide; avoid oral rinses containing alcohol
  • Smoking cessation
  • Refit dentures; daytime wear only
  • Avoid specific allergens.
  • Replace vitamin deficiencies.
  • Treat malnutrition, if present.

Medication (Drugs)

  • Acetaminophen or ibuprofen for analgesia
  • Steroids, colchicine, and cytotoxic drugs for Behçet disease
  • 2% viscous lidocaine (Xylocaine) swish and spit for local discomfort
  • Liquid diphenhydramine (Benadryl) by mouth or swish and spit, for allergic reactions
  • “Miracle mouth rinses”: Various combinations of the preceding in equal parts; use swish and spit q.i.d.:
    • Maalox or Mylanta, diphenhydramine, lidocaine
    • Maalox or Mylanta, diphenhydramine, Carafate
    • Duke’s: Nystatin, diphenhydramine, hydrocortisone
  • Steroid oral rinses (see “General”) or topical preparations for aphthous ulcers (Kenalog in Orabase) or oral steroids injected into lesions for severe cases
  • Antibiotics for gangrenous stomatitis (penicillin and metronidazole are reasonable 1st-line agents; often start with IV)
  • Acyclovir 200–800 mg 5×/d × 7–14 days for herpetic stomatitis
  • Sucralfate (Carafate) suspension 1 tsp swish in mouth or place on ulcers q.i.d. (helpful)
  • Topical 0.2% hyaluronic acid for recurrent aphthous ulcers
  • Chemical cauterization with silver nitrate for aphthous stomatitis (treatment can cause burning sensation)
  • Topical minocycline for aphthous stomatitis (5)[C]
  • Thalidomide 20 mg 1–2×/d × 3–8 weeks in HIV-positive patients with nonhealing aphthous ulcers (extreme caution for birth defects)
  • For candidiasis: Nystatin PO suspension 400,000 U (4 mL) q.i.d. × 10 days; swish and swallow (1 mL q.i.d. 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 (6)[A]
  • Contraindications: Allergy to specific medication
  • 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.

Complementary and Alternative Medicine

  • Avoiding toothpaste with sodium lauryl sulfate reduces duration of recurrent aphthous stomatitis (7)[B].
  • Replenish vitamin deficiencies.

In-Patient Considerations

IV Fluids
In severe cases involving dehydration owing to oral ulcerations

Nursing
For infants with painful stomatitis, feeding can be particularly challenging. Topical analgesic agents should be used prior to bottle-feeding. Nasogastric feeds or parenteral, as needed.

Ongoing Care

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, sharp, hard, and dry foods.

Patient Education

Patient handouts:

Prognosis

  • Herpetic/Hand-foot-mouth disease/Erythema multiforme: Self-limited: 1–3 weeks
  • RAS: 7–14-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: After correction of mechanical problems, allergic disorders, and nutritional deficiencies, the prognosis is good.
  • Gangrenous: 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.

Codes

ICD-9

  • 054.2 Herpetic gingivostomatitis
  • 074.0 Herpangina
  • 074.3 Hand, foot, and mouth disease
  • 101 Vincent's angina
  • 528.00 Stomatitis and mucositis, unspecified
  • 528.2 Oral aphthae

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
  • K12.0 Recurrent oral aphthae
  • K12.1 Other forms of stomatitis
  • K13.0 Diseases of lips

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)

Clinical Pearls

  • Stomatitis is often self-limiting and requires only pain relief treatment.
  • Consider broad differential diagnosis to determine etiology.
  • Treat all underlying conditions.
  • Depending on geographic location, age of patient, and comorbidities, be prepared to treat worsening or severe causes aggressively.

Authors


Hugh J. Silk, MD, MPH
Sheila O’Grady Stille, DMD, MAGD

Figures

Figure 12-1

Aphthous stomatitis. A small punched-out erosion has erythema surrounding a yellow-white center.
Figure 12-2

Aphthous stomatitis. Larger, more extensive aphthae are seen in this woman, who has Behçet's syndrome.

Bibliography

  1. Guimaraes AL, Correia-Silva Jde F, Sá AR, et al. Investigation of functional gene polymorphisms IL-1 beta, IL-6, IL-10 and TNF-alpha in individuals with recurrent aphthous stomatitis. Arch Oral Bio. 2007;52(3):268–272.
  2. Lalla RV, Choquette LE, Feinn RS, et al. Multivitamin therapy for recurrent aphthous stomatitis: A randomized, double-masked, placebo-controlled trial. J Am Dent Assoc. 2012;143:370–376.  [PMID:22467697]
  3. Wilhelmsen NS, Weber R, Miziara ID. The role of immunofluorescence in the physiopathology and differential diagnosis of recurrent aphthous stomatitis. Revista Brasileira de Otorrinolarin- gologia. 2008;74(3):331–336.
  4. Brocklehurst P, Tickle M, Glenny A-M, et al. Systemic interventions for recurrent aphthous stomatitis (mouth ulcers). Cochrane Database Syst Rev. 2012;9:CD005411. doi: 10.1002/14651858.CD005411.pub2  [PMID:22972085]
  5. Gorsky M, Epstein J, Raviv A, et al. Topical minocycline for managing symptoms of recurrent aphthous stomatitis. Spec Care Dentist. 2008;28:27–31.  [PMID:18271771]
  6. Worthington HV, Clarkson JE, Bryan G, et al. Interventions for preventing oral mucositis for patients with cancer receiving treatment. Cochrane Database Syst Rev. 2010:CD000978.  [PMID:21154347]
  7. Shim YJ, Choi JH, Ahn HJ, et al. Effect of sodium lauryl sulfate on recurrent aphthous stomatitis: A randomized controlled clinical trial. Oral Dis. 2012;18(7):655–660. Epub 2012 Mar 21.  [PMID:22435470]


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