eMedicine Specialties > Dermatology > Diseases of the Oral Mucosa
Aphthous Stomatitis: Treatment & Medication
Updated: Feb 6, 2009
- Overview
- Differential Diagnoses & Workup
- Treatment & Medication
- Follow-up
Treatment
Medical Care
Recurrent aphthous ulcers are treated using a variety of agents. These are directed at palliation of symptoms, shortening of healing time,28,29 and prophylaxis against future episodes. Many of the treatments are used without research demonstrating therapeutic results specific to aphthous stomatitis. Many episodes can be prevented by avoidance of common triggers such as walnuts and pineapple.
Therapy for recurrent aphthous ulcers must be directed by the extent of the condition, as determined by the patient and the clinician. Patients often report great pain when clinical examination reveals only a minor ulcer of 1-2 mm in diameter. In addition, the frequency and the extent of involvement should direct therapy.
- Topical regimens
- Anti-inflammatory (eg, corticosteroids) and immunomodulatory agents (eg, retinoids, cyclosporin) are used initially.
- Topical gels
- Creams
- Pastes
- Ointments
- Sprays
- Rinses
- Adjuvant rinses reduce bacterial loads, which is thought to reduce inflammation and shorten healing.
- Chlorhexidine gluconate
- Dilute hydrogen peroxide
- Topical lidocaine or benzocaine
- Anti-inflammatory (eg, corticosteroids) and immunomodulatory agents (eg, retinoids, cyclosporin) are used initially.
- Systemic agents
- Colchicine (0.6 mg 3 tid can be used.
- Prednisone (20-80 mg/d) is another possibility.
- Azathioprine use (50 mg/d) has been reported.
- Thalidomide is the only treatment the US Food and Drug Administration (FDA) has approved for the treatment of major aphthae in individuals with HIV infection.
- Miscellaneous
- Bismuth subsalicylate (Kaopectate) may protect raw mucosa and accelerates reepithelialization.
- Multivitamins with iron are recommended but do not have any clear benefit unless the patient has laboratory-confirmed hematinic deficiency.
- Strongly recommend the patient avoid using sodium laurel sulfate. This agent is a detergent found in most dentifrices, and it disrupts the surface of the epithelium. Although it has not been proven causative in recurrent aphthous ulcers, results are equivocal in whether elimination of the agent prevents episodes of ulceration.
Surgical Care
No surgical treatment has been used effectively because of the recurrent nature of recurrent aphthous ulcers.30
Diet
- An elimination diet may help control outbreaks by revealing suspected allergic stimuli that initiate oral lesions. If food exposure is thought to be the culprit, a food diary can be helpful.31,32,33
- A gluten-free diet helps patients with GSE (celiac disease) control outbreaks of aphthae.
- Patients with oral lesions should avoid hard or sharp foods that may gouge existing ulcers or create new ones (koebnerization).
- Advise avoidance of salt and hot spices to prevent pain from unnecessary aphthae irritation. Some patients report aphthae after exposure to nuts, pineapple, cinnamon, or other agents. In such cases, remission may be achieved by avoiding the inciting agent.
Medication
Therapy for this condition is aimed at palliating symptoms, shortening healing time, and reducing the number of episodes (prophylaxis)
Corticosteroids
Topical steroids are the first-line therapy. They are used to suppress immunologic- and inflammatory-mediated attacks resulting in ulceration. They are used to treat idiopathic and acquired autoimmune disorders. The great variety of vehicles includes topical gels, creams, pastes, ointments, sprays, and rinses.
Prednisone (Deltasone)
Systemic corticosteroid for cases of severe aphthae; inactive and must be metabolized to the active metabolite prednisolone. Close follow-up care and monitoring required to monitor for candidiasis and other secondary infections and adverse reactions. Available in 5 mg/5 mL elix.
Adult
40-80 mg/d PO; short course initially; may be extended; taper if used for longer than 2-3 wk at this dosage
Pediatric
4-5 mg/m2/d PO or 1-2 mg/kg/d PO; short course initially; may be extended; taper if used >5 d
Coadministration with estrogens may decrease clearance; concurrent use with digoxin may cause digitalis toxicity secondary to hypokalemia; phenobarbital, phenytoin, and rifampin may increase metabolism of glucocorticoids (consider increasing maintenance dose); monitor for hypokalemia with coadministration of diuretics
Documented hypersensitivity; viral infection, peptic ulcer disease, hepatic dysfunction, connective-tissue infections, and fungal or tubercular skin infections; GI bleeding or ulceration
Pregnancy
C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus
Precautions
Abrupt discontinuation of glucocorticoids may cause adrenal crisis; hyperglycemia, edema, osteonecrosis, myopathy, peptic ulcer disease, hypokalemia, osteoporosis, euphoria, psychosis, myasthenia gravis, growth suppression, and infections may occur with glucocorticoid use
Dexamethasone (Decadron, Dexasone)
DOC for recurrent aphthous ulcer and various inflammatory diseases. Decreases inflammation by suppressing migration of polymorphonuclear leukocytes and reducing capillary permeability. May use elix 0.5 mg/5 mL (high potency, substituted, fluorinated).
Adult
Swish and expectorate 5 mL qid (pc and hs); NPO for 30 min after each dose; patient may swallow if affected areas cannot be reached by gargling
Pediatric
Not established
None reported
Documented hypersensitivity
Pregnancy
C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus
Precautions
Contact time important for maximizing efficacy; instruct patients to gargle or swish for >5-10 min each time; expectorate each dose to limit systemic adverse effects; systemic absorption may cause Cushing syndrome, reversible suppression of HPA axis, hyperglycemia, and glycosuria
Triamcinolone acetonide (Aristocort)
For inflammatory dermatosis responsive to steroids; decreases inflammation by suppressing migration of polymorphonuclear leukocytes and reversing capillary permeability. Advisable when local disease accessible to patient. Use 0.1% gel.
Adult
Apply a thin film to affected areas; NPO 30-60 min; drying or wiping mucous membranes before application may increase potency.
Pediatric
Not established
None reported
Documented hypersensitivity; viral or fungal oral infections
Pregnancy
C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus
Precautions
Increased risk of secondary candidal infections; systemic absorption may cause Cushing syndrome, reversible HPA-axis suppression, hyperglycemia, and glycosuria
Fluocinonide (Fluonex, Lidex)
High-potency topical corticosteroid that inhibits cell proliferation; immunosuppressive and anti-inflammatory. Advisable when local disease accessible to patient. Use 0.05% gel.
Adult
Apply thin film to affected areas; NPO 30-60 min; drying or wiping mucous membranes before application may increase potency; use of acrylic tray for gingival disease occludes gel and increases potency
Pediatric
Not established
None reported
Documented hypersensitivity; viral or fungal oral infections
Pregnancy
C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus
Precautions
Increased risk of secondary candidal infections; may cause adverse systemic effects if used over large areas, on denuded areas, on occlusive dressings, or during prolonged treatment
Clobetasol propionate (Temovate)
Class I superpotent topical steroid that suppresses mitosis and increases synthesis of proteins that decrease inflammation and cause vasoconstriction. Use 0.05% gel.
Adult
Apply thin film to affected areas; NPO 30-60 min; drying or wiping mucous membranes before application may increase potency; use of acrylic tray for gingival disease occludes gel and increases potency
Pediatric
Not established
None reported
Documented hypersensitivity; viral or fungal oral infections
Pregnancy
C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus
Precautions
May suppress adrenal function in prolonged therapy
Anesthetics
These agents locally relieve pain of recurrent aphthous ulcers.
Lidocaine (Xylocaine)
Amide-type local anesthetic. Decreases permeability to sodium ions in neuronal membranes; inhibits depolarization, blocking transmission of nerve impulses.
Use 2% viscous solution.
Adult
Swish and expectorate 5 mL 5 min ac tid/qid
Pediatric
Administer as in adults
Potential for interactions if systemically absorbed with antiarrhythmics, beta-blockers, or cimetidine
Documented hypersensitivity; avoid in Adams-Stokes syndrome and Wolff-Parkinson-White syndrome
Pregnancy
B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals
Precautions
Must warn patients about risk of aspiration because of loss of sensation (loss of gag reflex) on soft palate and epiglottis
Benzocaine (Americaine, Anbesol)
Para-aminobenzoic acid (PABA) derivative, ester-type local anesthetic, minimally absorbed. Inhibits neuronal membrane depolarization, blocking nerve impulses.
Adult
Apply 10-20% gel to affected areas qid prn
Pediatric
Apply as in adults
Potential for interactions if systemically absorbed with cholinesterase inhibitors or sulfonamides
Documented hypersensitivity; may cause methemoglobinemia in infants
Pregnancy
C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus
Precautions
Not intended for use when infection present
Coating agents
These agents protect and bolster natural mucosal barrier.
Attapulgite (Kaopectate)
Absorbent and protectant.
Adult
Swish and expectorate 5 mL tid/qid
Pediatric
Administer as in adults
If swallowed in sufficient volumes, may impair effective absorption of digoxin, clindamycin, tetracyclines, and penicillamine
Documented hypersensitivity
Pregnancy
B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals
Precautions
May cause constipation at high doses when swallowed
Immunosuppressants
These agents blunt immunologically mediated destruction leading to mucosal ulceration. Systemic immunosuppressants are indicated for severe and recalcitrant cases of aphthous stomatitis.
Azathioprine (Imuran)
Largely converted to active metabolites 6-mercaptopurine and 6-thioinosinic acid; antagonizes purine metabolism and inhibits synthesis of DNA, RNA, and proteins. May decrease proliferation of immune cells, lowering autoimmune activity.
Adult
50-100 mg PO qd
Pediatric
Initial dose: 2-5 mg/kg/d PO/IV
Maintenance dose: 1-2 mg/kg/d PO/IV
Safety and efficacy not established
Allopurinol increases risk of pancytopenia; captopril and ACE inhibitors may increase risk of anemia and leukopenia; may need to increase dose of warfarin; may need to increase dose of pancuronium for adequate paralysis; live virus vaccines; with cotrimoxazole, may increase risk of hematologic toxicity; with rifampicin, may cause transplant rejection; with clozapine, may increase risk of agranulocytosis
Absolute: Allergy to azathioprine; pregnancy or attempting pregnancy; clinically significant active infection
Relative: Concurrent use of allopurinol; previous treatment with alkylating agents (eg, cyclophosphamide, chlorambucil, melphalan, others) because of high risk of neoplasia
Pregnancy
D - Fetal risk shown in humans; use only if benefits outweigh risk to fetus
Precautions
Monitor CBC count weekly to check for blood dyscrasia; increases risk of neoplasia; caution in liver disease and renal impairment; hematologic toxicities may occur; decreases efficacy of immunization vaccines
Check thiopurine methyl transferase (TPMT) level before therapy, and monitor liver, renal, and hematologic function; pancreatitis rare; TPMT testing not entirely reliable; involves testing TPMT activity in RBCs, which is correlated with systemic TPMT activity; functional enzyme test varies among test sites, and kits may contain various amounts of enzyme inhibitor
Alternatively, starting at low doses, monitoring for pancytopenia, then increasing dose; if clinical response not good, patient may be homozygote for high activity and may need increased dose; some recommend checking before treatment in all patients; if TPMT <5 U, no treatment; if 5-13.7 U, 0.5 mg/kg maximum dose; if 13.7-19 U, 1.5 mg/kg maximum dose; and if >19 U, 2.5 mg/kg maximum dose
Thalidomide (Thalomid)
Only FDA-approved therapy for recurrent aphthous ulcer. Immunomodulatory agent that may suppress excessive production of TNF-alpha and may down-regulate selected cell-surface adhesion molecules involved in leukocyte migration.
Adult
100-300 mg PO qd for 4 wk
Pediatric
Not established
May increase sedation effects of alcohol, barbiturates, chlorpromazine, and reserpine; because of teratogenic effects, women must use 2 additional methods of contraception or abstain from intercourse; specific pregnancy prevention program should be started and followed
Documented hypersensitivity; pregnancy
Pregnancy
X - Contraindicated; benefit does not outweigh risk
Precautions
Because of sedation, may need to gradually increase dose to desired level; in addition to teratogenic effects, causes somnolence, dizziness, constipation, and peripheral neuropathy; perform pregnancy test within 24-h of start of therapy (weekly during first month and monthly tests in women with regular menstrual cycles or q2wk with irregular menstrual cycles); bradycardia may occur; use protective measures (eg, sunscreens, protective clothing) against exposure to sunlight or UV light (eg, tanning beds); prescribing physician must enter STEPS program established by manufacturer
Topical immunomodulators
These agents are inhibitors of the formation and/or release of inflammatory mediators.
Amlexanox (Aphthasol)
Mechanism of action unknown. Appears to accelerate healing of aphthous ulcers. Potent inhibitor of formation and release of inflammatory mediators (histamine and leukotrienes) from mast cells, neutrophils, and mononuclear cells in in vitro studies.
Adult
Apply 5% paste directly to ulcers with fingertips qid
Pediatric
Not established
None reported
Documented hypersensitivity; contact mucositis
Pregnancy
B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals
Precautions
Discontinue if rash or contact mucositis occurs
Antibacterial agents
These agents treat inflammation of the oral mucosa caused by bacterial or fungal actions.
Chlorhexidine gluconate (PerioGard, Peridex)
Adjunct treatment for gingival disease; binds to negatively charged bacterial cell walls and extramicrobial complex, causing bacteriostatic and bactericidal effects. Effective, safe, and reliable topical wash or PO mouthwash antiseptic.
Adult
Swish 15 mL of 12% oral rinse for 30 seconds bid
Pediatric
Administer as in adults
None reported
Documented hypersensitivity; anterior tooth restorations (potential for staining); periodontitis
Pregnancy
C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus
Precautions
May stain tooth surfaces, restorations, and dorsum of tongue; studies showed increased calculus formation and altered taste perception; avoid contact with eyes and ears
Tetracycline Suspension
Treats gram-positive and gram-negative organisms and mycoplasmal, chlamydial, and rickettsial infections. Inhibits bacterial protein synthesis by binding with 30S and possibly 50S ribosomal subunits. Use oral susp. May have anti-inflammatory in addition to antibacterial mechanism of action.
Adult
15 mL swish and expectorate tid/qid
Pediatric
<8 years: Not recommended
>8 years: Administer as in adults
If swallowed, can increase hypoprothrombinemic effects of anticoagulants
Documented hypersensitivity
Pregnancy
D - Fetal risk shown in humans; use only if benefits outweigh risk to fetus
Precautions
If swallowed, photosensitivity may occur with prolonged exposure to sunlight or tanning equipment; reduce dose in renal impairment; consider drug serum level determinations in prolonged therapy; tetracycline use during tooth development (last half of pregnancy through age 8 y) can cause permanent discoloration of teeth; Fanconilike syndrome may occur with outdated tetracyclines
Topical occlusives
2-Octyl cyanoacrylate
OTC formulations of cyanoacrylate (essentially Super Glue) form a waterproof occlusive barrier over ulcers
Adult
Apply with package applicator tid/qid
Pediatric
Hypersensitivity to active ingredient
Pregnancy
C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus
Precautions
Avoid bonding to unintended surfaces
Hemorheologic agents
May be beneficial in patients who do not respond to other therapies; not first-line treatment.34
Pentoxifylline (Pentoxil, Trental)
Inhibits production of TNF-alpha and reduces migration of neutrophils. Specific action in aphthous stomatitis unclear but has been shown to reduce severity and frequency of episodes.
Adult
400 mg PO tid
Pediatric
Not established
NSAIDS, warfarin, and other medications that can potentially impact hemostasis
Hypertension, pregnancy, myocardial infarction, renal or hepatic failure, porphyria, or hypersensitivity
Pregnancy
C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus
Precautions
Caution in renal impairment
More on Aphthous Stomatitis |
| Overview: Aphthous Stomatitis |
| Differential Diagnoses & Workup: Aphthous Stomatitis |
 Treatment & Medication: Aphthous Stomatitis |
| Follow-up: Aphthous Stomatitis |
| References |
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References
Crivelli MR, Aguas S, Adler I, Quarracino C, Bazerque P. Influence of socioeconomic status on oral mucosa lesion prevalence in schoolchildren. Community Dent Oral Epidemiol. Feb 1988;16(1):58-60. [Medline].
Axéll T, Henricsson V. The occurrence of recurrent aphthous ulcers in an adult Swedish population. Acta Odontol Scand. May 1985;43(2):121-5. [Medline].
MacPhail LA, Greenspan D, Feigal DW, Lennette ET, Greenspan JS. Recurrent aphthous ulcers in association with HIV infection. Description of ulcer types and analysis of T-lymphocyte subsets. Oral Surg Oral Med Oral Pathol. Jun 1991;71(6):678-83. [Medline].
Burton-Kee JE, Mowbray JF, Lehner T. Different cross-reacting circulating immune complexes in Behçet's syndrome and recurrent oral ulcers. J Lab Clin Med. Apr 1981;97(4):559-67. [Medline].
Eglin RP, Lehner T, Subak-Sharpe JH. Detection of RNA complementary to herpes-simplex virus in mononuclear cells from patients with Behcet's syndrome and recurrent oral ulcers. Lancet. Dec 18 1982;2(8312):1356-61. [Medline].
Jorizzo JL. Behcet's disease. In: Freedberg IM, Eisen AZ, Wolff K, et al, eds. Dermatology in General Medicine. Vol 2. New York: McGraw-Hill Professional; 1999:2161-5.
Sakane T, Takeno M, Suzuki N, Inaba G. Behcet's disease. N Engl J Med. Oct 21 1999;341(17):1284-91. [Medline].
Studd M, McCance DJ, Lehner T. Detection of HSV-1 DNA in patients with Behçet's syndrome and in patients with recurrent oral ulcers by the polymerase chain reaction. J Med Microbiol. Jan 1991;34(1):39-43. [Medline].
Adisen E, Aral A, Aybay C, Gurer MA. Salivary epidermal growth factor levels in Behçet's disease and recurrent aphthous stomatitis. Dermatology. 2008;217(3):235-40. [Medline].
Ferguson MM, Wray D, Carmichael HA, Russell RI, Lee FD. Coeliac disease associated with recurrent aphthae. Gut. Mar 1980;21(3):223-6. [Medline].
Ferguson R, Basu MK, Asquith P, Cooke WT. Jejunal mucosal abnormalities in patients with recurrent aphthous ulceration. Br Med J. Jan 3 1976;1(6000):11-13. [Medline].
Wray D. Gluten-sensitive recurrent aphthous stomatitis. Dig Dis Sci. Aug 1981;26(8):737-40. [Medline].
Miller MF, Garfunkel AA, Ram C, Ship II. Inheritance patterns in recurrent aphthous ulcers: twin and pedigree data. Oral Surg Oral Med Oral Pathol. Jun 1977;43(6):886-91. [Medline].
Sun A, Chu CT, Wu YC, Yuan JH. Mechanisms of depressed natural killer cell activity in recurrent aphthous ulcers. Clin Immunol Immunopathol. Jul 1991;60(1):83-92. [Medline].
Taylor LJ, Bagg J, Walker DM, Peters TJ. Increased production of tumour necrosis factor by peripheral blood leukocytes in patients with recurrent oral aphthous ulceration. J Oral Pathol Med. Jan 1992;21(1):21-5. [Medline].
Hasan A, Childerstone A, Pervin K, et al. Recognition of a unique peptide epitope of the mycobacterial and human heat shock protein 65-60 antigen by T cells of patients with recurrent oral ulcers. Clin Exp Immunol. Mar 1995;99(3):392-7. [Medline].
Miyamoto NT Jr, Borra RC, Abreu M, Weckx LL, Franco M. Immune-expression of HSP27 and IL-10 in recurrent aphthous ulceration. J Oral Pathol Med. Sep 2008;37(8):462-7. [Medline].
Albanidou-Farmaki E, Poulopoulos AK, Epivatianos A, Farmakis K, Karamouzis M, Antoniades D. Increased anxiety level and high salivary and serum cortisol concentrations in patients with recurrent aphthous stomatitis. Tohoku J Exp Med. Apr 2008;214(4):291-6. [Medline].
Ghodratnama F, Wray D, Bagg J. Detection of serum antibodies against cytomegalovirus, varicella zoster virus and human herpesvirus 6 in patients with recurrent aphthous stomatitis. J Oral Pathol Med. Jan 1999;28(1):12-5. [Medline].
Pedersen A, Hornsleth A. Recurrent aphthous ulceration: a possible clinical manifestation of reactivation of varicella zoster or cytomegalovirus infection. J Oral Pathol Med. Feb 1993;22(2):64-8. [Medline].
Albanidou-Farmaki E, Giannoulis L, Markopoulos A, et al. Outcome following treatment for Helicobacter pylori in patients with recurrent aphthous stomatitis. Oral Dis. Jan 2005;11(1):22-6. [Medline].
Birek C, Grandhi R, McNeill K, Singer D, Ficarra G, Bowden G. Detection of Helicobacter pylori in oral aphthous ulcers. J Oral Pathol Med. May 1999;28(5):197-203. [Medline].
Elsheikh MN, Mahfouz ME. Prevalence of Helicobacter pylori DNA in recurrent aphthous ulcerations in mucosa-associated lymphoid tissues of the pharynx. Arch Otolaryngol Head Neck Surg. Sep 2005;131(9):804-8. [Medline].
Mansour-Ghanaei F, Asmar M, Bagherzadeh AH, Ekbataninezhad S. Helicobacter pylori infection in oral lesions of patients with recurrent aphthous stomatitis. Med Sci Monit. Dec 2005;11(12):CR576-9. [Medline].
Porter SR, Barker GR, Scully C, Macfarlane G, Bain L. Serum IgG antibodies to Helicobacter pylori in patients with recurrent aphthous stomatitis and other oral disorders. Oral Surg Oral Med Oral Pathol Oral Radiol Endod. Mar 1997;83(3):325-8. [Medline].
Padeh S, Stoffman N, Berkun Y. Periodic fever accompanied by aphthous stomatitis, pharyngitis and cervical adenitis syndrome (PFAPA syndrome) in adults. Isr Med Assoc J. May 2008;10(5):358-60. [Medline].
Rogers RS 3rd, Hutton KP. Screening for haematinic deficiencies in patients with recurrent aphthous stomatitis. Australas J Dermatol. Dec 1986;27(3):98-103. [Medline].
Alidaee MR, Taheri A, Mansoori P, Ghodsi SZ. Silver nitrate cautery in aphthous stomatitis: a randomized controlled trial. Br J Dermatol. Sep 2005;153(3):521-5. [Medline].
Brice SL. Clinical evaluation of the use of low-intensity ultrasound in the treatment of recurrent aphthous stomatitis. Oral Surg Oral Med Oral Pathol Oral Radiol Endod. Jan 1997;83(1):14-20. [Medline].
Arikan OK, Birol A, Tuncez F, Erkek E, Koc C. A prospective randomized controlled trial to determine if cryotherapy can reduce the pain of patients with minor form of recurrent aphthous stomatitis. Oral Surg Oral Med Oral Pathol Oral Radiol Endod. Jan 2006;101(1):e1-5. [Medline].
Eversole LR, Shopper TP, Chambers DW. Effects of suspected foodstuff challenging agents in the etiology of recurrent aphthous stomatitis. Oral Surg Oral Med Oral Pathol. Jul 1982;54(1):33-8. [Medline].
Hay KD, Reade PC. The use of an elimination diet in the treatment of recurrent aphthous ulceration of the oral cavity. Oral Surg Oral Med Oral Pathol. May 1984;57(5):504-7. [Medline].
Wright A, Ryan FP, Willingham SE, et al. Food allergy or intolerance in severe recurrent aphthous ulceration of the mouth. Br Med J (Clin Res Ed). May 10 1986;292(6530):1237-8. [Medline].
Thornhill MH, Baccaglini L, Theaker E, Pemberton MN. A randomized, double-blind, placebo-controlled trial of pentoxifylline for the treatment of recurrent aphthous stomatitis. Arch Dermatol. Apr 2007;143(4):463-70. [Medline].
Axell T, Henricsson V. Association between recurrent aphthous ulcers and tobacco habits. Scand J Dent Res. Jun 1985;93(3):239-42. [Medline].
Bittoun R. Recurrent aphthous ulcers and nicotine. Med J Aust. Apr 1 1991;154(7):471-2. [Medline].
Akintoye SO, Greenberg MS. Recurrent aphthous stomatitis. Dent Clin North Am. Jan 2005;49(1):31-47, vii-viii. [Medline].
Brice SL, Jester JD, Huff JC. Recurrent aphthous stomatitis. Curr Prob Dermatol. 1991;4(3):113-27.
Chakrabarty AK, Mraz S, Geisse JK, Anderson NJ. Aphthous ulcers associated with imiquimod and the treatment of actinic cheilitis. J Am Acad Dermatol. Feb 2005;52(2 Suppl 1):35-7. [Medline].
Challacombe SJ, Barkhan P, Lehner T. Haematological features and differentiation of recurrent oral ulceration. Br J Oral Surg. Jul 1977;15(1):37-48. [Medline].
Embil JA, Stephens RG, Manuel FR. Prevalence of recurrent herpes labialis and aphthous ulcers among young adults on six continents. Can Med Assoc J. Oct 4 1975;113(7):627-30. [Medline].
Field EA, Brookes V, Tyldesley WR. Recurrent aphthous ulceration in children--a review. Int J Paediatr Dent. Apr 1992;2(1):1-10. [Medline].
Field EA, Rotter E, Speechley JA, Tyldesley WR. Clinical and haematological assessment of children with recurrent aphthous ulceration. Br Dent J. Jul 11 1987;163(1):19-22. [Medline].
G Oumlker E, Rodenhuis S. Early onset of oral aphthous ulcers with weekly docetaxel. Neth J Med. Oct 2005;63(9):364-6. [Medline].
Greenspan JS, Gadol N, Olson JA, et al. Lymphocyte function in recurrent aphthous ulceration. J Oral Pathol. Sep 1985;14(8):592-602. [Medline].
Hutton KP, Rogers RS 3rd. Recurrent aphthous stomatitis. Dermatol Clin. Oct 1987;5(4):761-8. [Medline].
Kleinman DV, Swango PA, Pindborg JJ. Epidemiology of oral mucosal lesions in United States schoolchildren: 1986-87. Community Dent Oral Epidemiol. Aug 1994;22(4):243-53. [Medline].
Letsinger JA, McCarty MA, Jorizzo JL. Complex aphthosis: a large case series with evaluation algorithm and therapeutic ladder from topicals to thalidomide. J Am Acad Dermatol. Mar 2005;52(3 Pt 1):500-8. [Medline].
Lewkowicz N, Lewkowicz P, Dzitko K, et al. Dysfunction of CD4+CD25high T regulatory cells in patients with recurrent aphthous stomatitis. J Oral Pathol Med. Sep 2008;37(8):454-61. [Medline].
Murray B, McGuinness N, Biagioni P, Hyland P, Lamey PJ. A comparative study of the efficacy of Aphtheal in the management of recurrent minor aphthous ulceration. J Oral Pathol Med. Aug 2005;34(7):413-9. [Medline].
Natah SS, Hayrinen-Immonen R, Hietanen J, Malmstrom M, Konttinen YT. Quantitative assessment of mast cells in recurrent aphthous ulcers (RAU). J Oral Pathol Med. Mar 1998;27(3):124-9. [Medline].
O'Sullivan EM. Nicorandil-induced severe oral ulceration. J Ir Dent Assoc. Winter 2004;50(4):157-9. [Medline].
Porter SR, Scully C, Flint S. Hematologic status in recurrent aphthous stomatitis compared with other oral disease. Oral Surg Oral Med Oral Pathol. Jul 1988;66(1):41-4. [Medline].
Porter SR, Scully C, Pedersen A. Recurrent aphthous stomatitis. Crit Rev Oral Biol Med. 1998;9(3):306-21. [Medline].
Savage NW, Seymour GJ, Kruger BJ. T-lymphocyte subset changes in recurrent aphthous stomatitis. Oral Surg Oral Med Oral Pathol. Aug 1985;60(2):175-81. [Medline].
Ship II, Morris AL, Durocher RT, et al. Recurrent aphthous ulcerationsand recurrent herpes labialis in a professional school student population. Oral Surg Oral Med Oral Pathol. 1960;13:1191-202.
Spouge JD, Diamond HF. Hypersensitivity reactions in mucous membranes. I. The statistical relationship between hypersensivity diseases and recurrent oral ulcerations. Oral Surg Oral Med Oral Pathol. Apr 1963;16:412-21. [Medline].
Ueta E, Umazume M, Yamamoto T, Osaki T. Leukocyte dysfunction in oral mucous membrane diseases. J Oral Pathol Med. Mar 1993;22(3):120-5. [Medline].
Veloso FT, Saleiro JV. Small-bowel changes in recurrent ulceration of the mouth. Hepatogastroenterology. Feb 1987;34(1):36-7. [Medline].
Vujevich J, Zirwas M. Treatment of severe, recalcitrant, major aphthous stomatitis with adalimumab. Cutis. Aug 2005;76(2):129-32. [Medline].
Wolverton SE. Comprehensive Dermatologic Drug Therapy. Philadelphia: WB Saunders; 2001: 167-8.
Woo SB, Sonis ST. Recurrent aphthous ulcers: a review of diagnosis and treatment. J Am Dent Assoc. Aug 1996;127(8):1202-13. [Medline].
Wray D, Charon J. Polymorphonuclear neutrophil function in recurrent aphthous stomatitis. J Oral Pathol Med. Sep 1991;20(8):392-4. [Medline].
Further Reading
Keywords
recurrent aphthous ulcers, aphthous stomatitis, canker sores, recurrent aphthous stomatitis, RAS, recurrent aphthous ulcers, RAU, periadenitis mucosa necrotica recurrens, RAU minor, RAU major, herpetiform RAU, Sutton's disease
