Behçet's Disease (Behçet, 1937) and Recurrent Aphthous Stomatitis

© Dr. Maged N. Kamel Boulos - MediCAD Multimedia, 1995-98. All rights reserved.


Behçet's disease (BD) is a chronic multisystem disorder characterized mainly by a triad of (1) recurrent aphthous stomatitis (RAS), (2) genital ulcers, and (3) ocular lesions.

BD more commonly affects individuals of Mediterranean origin, from the Middle East, China, Korea and Japan. There is an association with HLA-B5 and HLA-B51.


Clinical Manifestations:

I. Major criteria:

  1. Recurrent aphthous stomatitis (RAS): in 90%-100% of cases.

  2. Recurrent painful genital ulcers that tend to heal with scars: in 64%-88% of cases.

  3. Ocular lesions: Uveitis with conjunctivitis (early) and hypopyon (late), retinal vasculitis (posterior uveitis) that may result in blindness, iridocyclitis and optic atrophy.

  4. CNS lesions: meningoencephalitis, cerebral infarction, psychosis, cranial nerve palsies, cerebellar and spinal cord lesions, hemi- and quadriparesis.

  5. Skin lesions: erythema nodosum, papulopustular lesions and acneform nodules. Pathergy test: at the site of a needle puncture a pustule surrounded by erythema may appear in some, but not all, patients.

II. Minor criteria:

  1. Arthralgia: large joint arthropathies that are subacute, non-migratory, self-limiting and non-deforming

  2. Superficial or deep migratory thrombophlebitis, especially of lower limbs.

  3. Intestinal lesions: inflammatory bowel disease with discrete ulcerations.

  4. Lung affection: pneumonitis.

  5. Haematuria and proteinuria.



The common denominator in all systems is vasculitis, usually leucocytoclastic vasculitis.



Viral, immunological, genetic, and ecological causes have been postulated, but the evidence is still inconclusive for any of these.

There are many immunological findings in BD:

  1. The presence of circulating autoantibodies against mucous membranes.

  2. Increased levels of circulating immune complexes, the highest levels being in patients with systemic manifestations.

  3. Demonstration, by DIF, of immunoglobulins and complement deposition within and around blood vessel walls or in the subepithelial zone.

  4. Decreased T-helper (T4) : T-suppressor (T8) ratio.



  1. Topical tetracycline mouthwash is the drug of choice for oral ulcers in BD. Topical steroids and anaesthetics may be used for oral lesions.

  2. Systemic treatment includes corticosteroids, azathioprine, cyclophosphamide, colchicine, dapsone, thalidomide, cyclosporine, levamisole, or chlorambucil.


Differential diagnosis of BD:

I. Other oculomucocutaneous syndromes:


Main lesions



Oral and genital



1. Behçet's disease



Erythema nodosum

2. Sweet's syndrome


Conjunctivitis, episcleritis

Inflamed tender papule or nodule

3. Erythema multiforme



Target (iris) lesions

4. Cicatricial pemphigoid

Bullae, erosions

Erosions with scarring

Occasional dome-shaped bullae

5. Pemphigus



Multiple flaccid bullae

6. Reiter's syndrome



Keratoderma blenorrhagica


Other oculomucocutaneous syndromes: ulcerative colitis, herpes simplex, syphilis, lupus erythematosus and mixed connective tissue disease.


II. Other causes of recurrent aphthous stomatitis (RAS):

RAS is a common disease which probably afflicts at least 20% of the population. It is characterized by recurring episodes of ulcers, each lasting from 1 to about 4 weeks before healing. Aphthae typically are small, round or ovoid ulcers with a circumscribed margin, erythematous halo and a yellow grey floor.


Aetiology of RAS:

  1. Behçet's disease.

  2. Haematinic deficiency: in 10%-20% of cases; deficiencies of iron, folic acid or vitamin B12.

  3. Gastrointestinal disease: pernicious anaemia, coeliac disease and dermatitis herpetiformis (rare in DH), Crohn's disease and ulcerative colitis.

  4. Endocrine factors: In some women, RAS are clearly related to a fall in progestogens in the luteal phase of the menstrual cycle.

  5. Immunological factors: There is no evidence that RAS is an autoimmune disease. However, CMI mechanisms may be involved in the pathogenesis of RAS. There may be cross-reacting antigens between the oral mucosa and microorganisms such as streptococcus sanguis or its L form. Immunodeficiency: A few RAS patients have an immune defect such as AIDS.

  6. Genetic factors: There is a positive family history in 1/3 of RAS patients. There is increased frequency of HLA-A2, A11, B12 and DR2 in RAS patients.

  7. Trauma: orthodontic appliances and thermal injury ('pizza burn'), certain foods.

  8. Stress and cessation of smoking may play a role.

  9. Acrodynia (Pink disease): Oral and perioral ulceration, hypersalivation, gingivitis and early tooth loss are features of acrodynia caused by mercury poisoning, now rarely seen.

  10. Oculomucocutaneous syndromes: (see table above)

  11. Other causes: (see table below)

Other causes of oral ulcers

Viral infections: Herpes simplex stomatitis, chickenpox and herpes zoster, hand, foot and mouth disease, herpangina (Coxsackie viruses), infectious mononucleosis (EBV) and CMV

Bacterial infections: Tuberculosis, syphilis, oropharyngeal gonorrhoea and acute necrotizing gingivitis (mixed, mainly anaerobic, flora)

Fungal infections: Blastomycosis, coccidioidomycosis, cryptococcosis and histoplasmosis

Skin diseases: Erosive lichen planus, epidermolysis bullosa acquisita

Oral squamous cell carcinoma and other oral malignant primary or metastatic neoplasms

Leukaemia and neutropenia

Vasculitis, e.g. Wegener's granulomatosis

Cytotoxic agents as methotrexate

Irradiation of oral mucosa


There are three main clinical types of RAS:


Minor aphthous ulcers

Major aphthous ulcers

Herpetiform ulceration

Age of onset

Childhood or adolescence

Childhood or adolescence

Young adults

The lesions

Up to about 6 ulcers, 2-4 mm each, on the lips, cheecks, ventrum of tongue and floor of mouth; uncommon on gingiva, palate or dorsum of tongue

Up to about 6 ulcers, 10 mm each, found on any area of oral mucosa, including dorsum of tongue or palate

10-100 ulcers, initially tiny: 1-2 mm but ulcers coalesce, on any site but often on ventrum of tongue


Minimal symptoms

More painful

Extremely painful

Duration of each ulcer

Up to 10 days

Up to 1 month

Up to 1 month

Other comments

The most common type of aphthae, little or no evidence of scarring

May heal with scarring

Affect females predominantly. Similarity to herpetic stomatitis gave herpetiform ulceration its name, but there is no evidence that HSV is involved.


Treatment of RAS:

  1. Exclude systemic diseases and treat predisposing factors.

  2. Topical tetracycline mouthwash, 0.2% aqueous chlorhexidine gluconate mouthwash.

  3. Topical steroids in Orabase four times daily.

  4. Thalidomide in doses of up to 300 mg daily (especially in major aphthae), dapsone, colchicine.


© Dr. Maged N. Kamel Boulos - MediCAD Multimedia, 1995-98. All rights reserved.