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Authored by Mounir Bashour, MD, CM, FRCS(C), Director of Ophthalmic Plastic and Reconstructive Surgery, Assistant Professor, Department of Ophthalmology, Sherbrooke University, Canada


Mounir Bashour, MD, CM, FRCS(C), is a member of the following medical societies: American Academy of Ophthalmology, American Association for Pediatric Ophthalmology and Strabismus, American College of International Physicians, American College of Surgeons, American Medical Association, American Society of Cataract and Refractive Surgery, American Society of Mechanical Engineers, American Society of Ophthalmic Plastic and Reconstructive Surgery, Biomedical Engineering Society, Canadian Medical Association, Canadian Ophthalmological Society, Contact Lens Association of Ophthalmologists, International College of Surgeons US Section, Ontario Medical Association, Quebec Medical Association, and Royal College of Physicians and Surgeons of Canada


Edited by John Sheppard, Jr, MD, MMSc, PhD, Program and Laboratory Director, Professor, Departments of Ophthalmology and Pharmacology, Eastern Virginia School of Medicine; Donald S Fong, MD, MPH, Assistant Clinical Professor of Ophthalmology, UCLA School of Medicine; Consulting Physician, Department of Ophthalmology, Southern California Permamente Medical Group; R Christopher Walton, MD, Director of Uveitis and Ocular Inflammatory Diseases Service, Associate Professor, Department of Ophthalmology, University of Tennessee College of Medicine; Lance L Brown, OD, MD, Ophthalmologist, Regional Eye Center, Affiliated With Freeman Hospital and St John's Hospital, Joplin, Missouri; and Hampton Roy, Sr, MD, Clinical Associate Professor, Department of Ophthalmology, University of Arkansas for Medical Sciences

eMedicine Journal, April 19 2002, Volume 3, Number 4

Background: Behçet disease is a systemic disorder characterized by recurrent aphthous ulcers and intraocular inflammation. The clinical triad of uveitis with recurrent oral and genital ulcers bears the name of Hulusi Behçet, a Turkish dermatologist who described 3 patients who had this triad.
The Behçet's Disease Research Committee of the Ministry of Health and Welfare of Japan first proposed formal diagnostic criteria in 1972. This set of criteria, which has been used throughout the world, classifies disease findings into 4 major and 5 minor criteria. When all 4 major criteria are met, the disease is said to be of the complete type, whereas the incomplete type consists of various combinations of major and minor criteria, with added weight given to ocular disease.
In 1990, The International Study Group for Behçet's Disease proposed a separate set of diagnostic criteria for Behçet disease. Based upon these criteria, a diagnosis of Behçet disease requires recurrent oral ulceration and at least 2 additional criteria, including recurrent genital ulcers, ocular lesions, skin lesions, and a positive pathergy test.
Pathophysiology: Cause and pathogenesis of Behçet disease remain unknown.
Frequency:
 In the US: Prevalence of Behçet disease is estimated to be only 1 case per 300,000 per year. In a university hospital setting, Behçet disease was responsible for 12-20% cases of uveitis in Japan compared with only 0.2-0.4% in the US.
 Internationally: Behçet disease occurs worldwide, with predominance among Asians, North Africans, and Europeans who live between the latitudes of 30-45°N. It is one of the main causes of endogenous uveitis in Japan and Turkey, with prevalence rates of 1 case per 10,000 and 8-30 cases per 10,000, respectively.
Race: Behçet disease is most common in Asians, North Africans, and Europeans who live between the latitudes of 30-45°N.
Sex: It is more common in males than in females, with a ratio of 2.3:1.
Age:
 Mean age of onset is in the third decade of life.
 When Behçet disease occurs in young men aged 15-25 years, it takes a more serious form.

History: Initial ocular involvement may be unilateral, but progresses to bilateral disease in at least two thirds of cases.
 Ocular
 Ocular involvement is seen in about 70% of patients who have Behçet disease.
 In most cases, the ocular symptoms follow the oral and genital ulcers by 3-4 years, although ocular disease is the initial manifestation in about 20% of cases.
 Behçet disease is characterized by severe recurrent attacks of intraocular inflammation.
 Symptoms include periorbital pain, redness, photophobia, and blurred vision.
 Oral aphthous ulcers - Recurrent painful oral aphthous ulcers
 Skin - Cutaneous hypersensitivity is relatively common. Acnelike lesions or folliculitis occur frequently. Migratory thrombophlebitis also can develop.
 Genital ulcers - Recurrent painful genital ulcers
Physical:
 Ocular
 Described in 75% of patients, either anterior segment iridocyclitis or posterior segment involvement.
 The classic finding of this disease, iridocyclitis with hypopyon, is present in about one third of cases.
 Gonioscopy may reveal an occult hypopyon in many cases. One characteristic feature of the hypopyon in Behçet disease is that it may change position with head movement, and it may form and disappear rapidly without sequelae.
 Recurrent attacks may result in posterior synechiae, peripheral anterior synechiae, iris atrophy, and secondary glaucoma.
 Retinal disease is the most serious complication of Behçet disease. The classic fundus finding is retinal vasculitis, which affects both arteries and veins in the posterior pole.
 Ophthalmoscopy shows venous engorgement, retinal hemorrhages, yellow-white exudates deep in the retina, white focal retinal infiltrates, retinal edema, and optic disc edema with hyperemia.
 Severe vasculitis may lead to thrombosis of vessels and secondary ischemic retinal changes. Optic disc edema may be secondary to inflammation and may be seen during the acute phase in at least one fourth of cases.
 Vitreous cellular infiltration almost always is present during the acute phase.
 Retinal neovascularization, secondary to either retinal vein occlusion or chronic inflammation, may result in retinal or vitreous hemorrhage.
 Neovascular glaucoma occurs in as many as 6% of patients and often results in phthisis bulbi.
 Repeated episodes of posterior segment inflammation causes sheathing of retinal vessels, chorioretinal scars, and both retinal and optic nerve atrophy.
 Oral aphthous ulcers
 Recurrent aphthous ulceration of the oral mucosa is the most common nonocular manifestation of Behçet disease.
 They are the first symptoms in 50-70% of patients and develop in as many as 98% of patients.
 The lesions are located on the gingiva, lips, tongue, buccal mucosa, hard palate, uvula, and posterior pharynx.
 A nationwide study in Japan revealed that 97.7% of patients who have Behçet disease have recurrent aphthous ulcers. Ulcers tend to develop in crops, which recur at various frequencies.
 White or yellowish pseudomembrane usually covers the surface of the ulcer.
 They usually heal within 7-10 days with no scarring.
 However, fusion of several small ulcers may produce a large ulcer that leads to scar formation.
 Skin involvement
 Skin involvement appears in 70% of patients. Behçet disease may produce a variety of skin lesions in affected individuals.
 Erythema nodosum, acneiform lesions, thrombophlebitis, and cutaneous hypersensitivity are most common.
 Erythema nodosum lesions, which occur in more than two thirds of patients with Behçet disease, usually are found on the anterior surface of the legs but also may be seen on the face, arms, and buttocks. These lesions appear as slightly raised, red nodules with subcutaneous induration and tenderness. They tend to involute in 10-14 days without ulceration.
 Acneiform lesions occur in almost 60% of patients and may occur in patients who receive corticosteroid treatment; therefore, their presence is of questionable diagnostic usefulness.
 A peculiar feature of Behçet disease is cutaneous hypersensitivity, which results in small pustules that form on skin after it has been scratched, shaved, or pricked with a needle.
 Genital ulcers
 Genital ulcers occur in 80% of patients. They are painful punched-out lesions similar to those that occur in mouth and usually are located in the scrotum or vulva.
 These genital ulcers may be deep and, in many cases, result in scarring. These scars are indicators of old disease and may help in diagnosis.
 Musculoskeletal
 Painful swelling with redness of joints occurs in as many as 50% of patients.
 Transient, recurrent, nondestructive, and nonmigratory arthritis commonly affects large joints such as the knee, ankle, elbow, and wrist. The knee joint is most commonly affected.
 Gastrointestinal
 At least 50% of patients who have Behçet disease develop gastrointestinal symptoms.
 Intestinal erosions and ulcers may cause abdominal pain, melena, and perforation.
 This constellation of intestinal signs and symptoms may simulate Crohn disease and other inflammatory bowel disorders.
 Vascular
 Thrombophlebitis is found in 15% of these patients.
 Obliterating thrombophlebitis, arterial occlusion, and aneurysm may occur in vessels of all sizes.
 Neurologic: Multiple neurological disorders that involve pyramidal and extrapyramidal tracts, cerebellum, and the cranial nerves occur in 8-25% of patients who have Behçet disease.
Causes:
 Since the disease is characterized by a vasculitis, the underlying mechanism is believed to be an autoimmune process.
 Although familial occurrences have been reported, no consistent inheritance pattern has been established; however, human leukocyte antigen B5 (HLA-B5) is associated with Behçet disease and poor visual prognosis.
 Considerable evidence now points toward a more specific association with human leukocyte antigen B51 (HLA-B51), a split antigen of HLA-B5.
 The frequency of HLA-B51 is 57% in Japanese patients who have Behçet disease compared to only 14% in the control group, which equates to a relative risk of 7.9 for this marker.
 Restriction fragment link polymorphism studies showed linkage disequilibrium between HLA-B51 locus and tumor necrosis factor-b gene. This finding may imply that lower levels of tumor necrosis factor-b may contribute to activation of inflammatory cascade in Behçet disease.
 In Japan, an association has been found between human leukocyte antigen A26 (HLA-A26) and Behçet disease.
 The disease occurs more frequently in temperate northern parts of Japan than in subtropical southern parts, a distribution that suggests that environmental factor influences the prevalence of disease.
 Other diagnostic considerations
 It is important to consider other forms of uveitis in the differential diagnosis, especially in those patients who have a mild or atypical presentation of Behçet disease.
 Human leukocyte antigen B27 (HLA-B27)-related anterior uveitis also may give recurrent iridocyclitis with hypopyon, but it is typically unilateral.
 Since Behçet disease is a bilateral panuveitis, other inflammatory processes that affect both eyes must be considered. Syphilis causes a retinitis with vitreitis rather than a strict vasculitis. The diagnosis for syphilis is confirmed by serology.
 Sarcoidosis, another bilateral inflammatory process, may have posterior pole findings similar to those in Behçet disease but is generally more indolent, in contrast to the explosive recurrent attacks of Behçet disease. Furthermore, the vasculitis seen in sarcoidosis usually is not occlusive in nature and typically involves only veins compared with the involvement of both arteries and veins in Behçet disease.
 Other conditions that may mimic the ocular changes of Behçet disease include collagen vascular diseases and viral retinitis.

HLA-B27 Syndromes
Retinitis, CMV
Sarcoidosis
Syphilis, Ocular Manifestations of
Uveitis, Classification
Uveitis, Evaluation and Treatment

Other Problems to be Considered:
Collagen vascular diseases
Viral retinitis

Lab Studies:
 Diagnosis of Behçet disease is based on clinical findings rather than on specific laboratory test results. Some tests are useful adjuncts in the evaluation of patients who have Behçet disease.
 The pathergy test (or Behçetine test) may be useful in patient evaluation; the test result is a nonspecific inflammatory reaction to a needle prick or an intradermal injection of saline. The reaction, which varies from an indurated erythema to pustule formation, occurs in 40-60% of patients who have Behçet disease.
 Several other laboratory tests may help in the evaluation of a patient who has Behçet disease. During episodes of acute inflammation, patients may have high erythrocyte sedimentation rates, high C-reactive protein levels, or increased number of peripheral leukocytes.
Imaging Studies:
 Fundus fluorescein angiography shows diffuse retinal vascular leakage and occlusion of retinal vessels.
 Fluorescein leakage from retinal vessels may be seen before any clinical signs of vasculitis.
 During acute inflammation, retinal vascular leakage is prominent, especially in the radial peripapillary area.
 Affected retinal and optic nerve vessels leak fluorescein profusely during early transit and their walls stain in late transit.
 Fluorescein angiography also may reveal macular ischemia and cystoid macular edema.
Histologic Findings: Histopathologic changes include necrotizing, leukocytoclastic, and obliterative vasculitis, which affect arteries and veins of all sizes and is probably immune-complex mediated. Only a few eyes that have had active disease have been examined histologically. Vasculitis is the key feature of Behçet disease. Underlying changes seen in the eye are similar to those that occur in other organs of the body.
During acute inflammation, the iris, ciliary body, and choroid show diffuse infiltration with neutrophils. In late stages, there is proliferation of collagen fibers, thickening of the choroid, formation of cyclitic membrane, and sometimes hypotonia and phthisis bulbi. Lymphocytic and plasma cell infiltration occurs during remission. Of all ocular tissues, the retina suffers the most damage. In the phase of acute inflammation, there is severe vasculitis with marked infiltration of leukocytes in and around blood vessels. Recent and old hemorrhages are present. Retinal vessels have thickened basement membranes with swollen endothelial cells, which can lead to thrombus formation and vascular obliteration.

Medical Care:
 The goals of therapy in Behçet disease are to suppress inflammation, to reduce the frequency and severity of recurrences, and to minimize involvement of the retina.
 To be effective, treatment must be started early. Extent of involvement and severity of disease determine the choice of medication. Treatment options include corticosteroids, cytotoxic agents, cyclosporine, and colchicine.
 Corticosteroids
 Systemic corticosteroids effectively suppress all phases of ocular involvement in Behçet disease.
 Although these drugs do not prevent visual deterioration, systemic corticosteroid therapy may still be helpful, especially when used in concurrence with other immunosuppressive agents.
 Prednisone may be used in a pulse mode to treat Behçet disease, with a 1g bolus given intravenously over 1 hour and repeated once a day for 3 days. The pulse treatment is repeated as needed.
 In Japan, systemic corticosteroids are not used for ocular disease. This decision is based upon the findings of several retrospective studies that show long-term visual outcomes to be worse in patients who receive systemic corticosteroids compared to those who did not.
 Cytotoxic agents
 Chlorambucil, cyclophosphamide, and azathioprine are the cytotoxic agents used most commonly for treatment of Behçet disease.
 Chlorambucil was the first cytotoxic drug to be used in the treatment of ocular Behçet disease. This slow-acting alkylating agent may be administered on an outpatient basis.
 Cyclophosphamide is an alkylating agent that is superior to corticosteroids in the control of inflammation in Behçet disease, but profound bone marrow toxicity limits its usage. Since cyclophosphamide acts faster and is more toxic than chlorambucil, its use is reserved for very refractory cases.
 Azathioprine is a mercaptopurine derivative that is effective in the treatment of Behçet disease.
 All of these cytotoxic agents may produce variable degrees of bone marrow suppression and may affect reproductive organs resulting in azoospermia and amenorrhea.
 Cyclosporine
 Cyclosporine inhibits T-lymphocyte activation and consequently is safer than cytotoxic agents; however, renal complications may occur.
 Usual starting dose is 5 mg/kg per day. Cyclosporine does not appear to induce permanent immunosuppression; therefore, patients need continuous treatment for many years.
 A rebound phenomenon has been noted after withdrawal of cyclosporine therapy.
 These factors have limited the use of cyclosporine for the treatment of Behçet disease, but a study conducted in Japan found that a starting dose of 5 mg/kg per day effectively limited the frequency of ocular inflammatory attacks in 70% of patients with Behçet disease who previously had refractory disease.
 Colchicine
 Colchicine is a plant alkaloid that interferes with microtubule function, which results in dysfunction of neutrophils.
 Colchicine may be used with other drugs and may enable the disease to be controlled using lower doses of immunosuppressants. The optimum dosage of colchicine is 0.5-1.0 mg/d.
 In Japan, colchicine is considered the drug of choice because of its few side effects and because of the presumed poor long-term prognosis of systemic corticosteroids.
 When colchicine fails to limit recurrences, treatment is switched to or combined with cyclosporine.
 It appears that the best results may be obtained using a combination of drugs, such as corticosteroids with either cytotoxic agents or cyclosporine.
 Overall, no safe and conclusive treatment exists for patients with Behçet disease. The treatment regimen needs to be tailored to the severity and extent of disease in each individual case.
 The goal of therapy is to suppress inflammation, to prevent sequelae, and to minimize the systemic side effects of treatment.
Consultations:
 Uveitis service if available
 Gastroenterology
 Rheumatology

Treatment is aimed toward individual symptoms as they occur. Medication is given to reduce the inflammatory response.
Drug Category: Anti-inflammatory agents -- Systemically interfere with events leading to inflammation.
Drug Name
Colchicine -- Decreases leukocyte motility and phagocytosis in inflammatory responses. Used to prevent recurrent attacks.
Adult Dose 0.5-1 mg/d PO
Pediatric Dose Not established
Contraindications Documented hypersensitivity; severe renal, hepatic, GI, or cardiac disorders; blood dyscrasias
Interactions Sympathomimetic agent toxicity and effect of CNS depressants are increased significantly with colchicine
Pregnancy C - Safety for use during pregnancy has not been established.
Precautions Risk of renal failure, hepatic failure, permanent hair loss, bone marrow suppression, numbness or tingling in hands and feet, disseminated intravascular coagulopathy, and decreased sperm count; dose-dependent GI upset is common
Drug Category: Corticosteroids -- Systemic corticosteroids are not useful in the long-term management of Behçet disease. Some authors use corticosteroids as initial therapy especially in mild cases. However, other authorities state that there is no role for corticosteroids in the treatment of this disease. Systemic corticosteroids should be used only for short periods of time and probably in combination with immunosuppressive therapy. Topical or sub-Tenon corticosteroids have proven effective.
Drug Name
Prednisone (Deltasone, Orasone, Meticorten) -- May decrease inflammation by reversing increased capillary permeability and suppressing PMN activity. Use smallest dose for shortest duration to achieve therapeutic effect. Use in combination with immunosuppressive therapy. Also may use pulse IV therapy over a 3-day period.
Adult Dose 1-1.5 mg/kg/d initially; taper after therapeutic effect achieved
Pediatric Dose Not established
Contraindications Documented hypersensitivity; viral infection, peptic ulcer disease, hepatic dysfunction, connective tissue infections, and fungal or tubercular skin infections; GI disease
Interactions Coadministration with estrogens may decrease prednisone 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
Pregnancy B - Usually safe but benefits must outweigh the risks.
Precautions Risk/benefit decision must be made in each individual case as to dose and duration of treatment and as to whether daily or intermittent therapy should be used; use lowest effective dose; psychic derangements may appear when corticosteroids are used, ranging from euphoria, insomnia, mood swings, personality changes, and severe depression, to frank psychotic manifestations; existing emotional instability or psychotic tendencies may be aggravated by corticosteroids
Avascular or aseptic necrosis of femoral head has been associated with long-term corticosteroid treatment and also has occurred in patients receiving high-dose short-term therapy (more likely to occur in patients with predisposing illness such as rheumatoid arthritis or systemic lupus erythematosus)
Enhanced effect of corticosteroids exists in patients with hypothyroidism and with cirrhosis; use aspirin and nonsteroidal anti-inflammatory agents cautiously in conjunction with corticosteroids in patients with hypoprothrombinemia; patients on corticosteroid therapy subjected to unusual stress, increased dosage of rapidly acting corticosteroids before, during, and after stressful situation indicated; may mask signs of infection, and new infections may appear during their use; there may be decreased resistance and inability to localize infection when corticosteroids used; if corticosteroids have to be used in the presence of bacterial infections, institute appropriate anti-infective therapy

Drug Name
Prednisolone acetate 1% (Pred Forte) -- Treats acute inflammations following eye surgery or other types of insults to eye. Decreases inflammation and corneal neovascularization. Suppresses migration of polymorphonuclear leukocytes and reverses increased capillary permeability. In cases of bacterial infections, concomitant use of anti-infective agents is mandatory; if signs and symptoms do not improve after 2 days, reevaluate patient. Dosing may be reduced, but advise patients not to discontinue therapy prematurely.
Useful for acute iritis. Frequent dosing (q1-2h) useful initially, followed by gradual taper.
Adult Dose 1 gtt qid or greater depending on severity of uveitis
Pediatric Dose Not established
Contraindications Documented hypersensitivity; viral, fungal, or tubercular infections
Interactions None reported
Pregnancy C - Safety for use during pregnancy has not been established.
Precautions Prolonged ophthalmic use may result in increased intraocular pressure in some individuals; if these products are used for 10 d or longer, monitor intraocular pressure; in diseases causing thinning of the cornea or sclera, perforation has been known to occur with use of topical preparations containing corticosteroids; protracted use of topical corticosteroids in the eye may result in the development of posterior subcapsular cataracts; in patients with a history of herpetic infection of the cornea, reactivation of the disease may occur with use of topical ophthalmic corticosteroids; shake eye suspensions well before use
Drug Category: Immunosuppressive agents -- Used to treat acute attacks and reduce frequency of recurrences.
Drug Name
Cyclophosphamide (Cytoxan, Neosar) -- Chemically related to nitrogen mustards. As an alkylating agent, the mechanism of action of the active metabolites may involve cross-linking of DNA, which may interfere with growth of cells. DOC for severe Behçet disease. Must be administered by an experienced clinician.
Adult Dose 50-150 mg PO qd
Pediatric Dose Not established
Contraindications Documented hypersensitivity; severely depressed bone marrow function
Interactions Allopurinol may increase risk of bleeding or infection and enhance myelosuppressive effects; may potentiate doxorubicin-induced cardiotoxicity; may reduce digoxin serum levels and antimicrobial effects of quinolones; chloramphenicol may increase half-life while decreasing metabolite concentrations; may increase effect of anticoagulants; coadministration with high doses of phenobarbital may increase rate of metabolism and leukopenic activity; thiazide diuretics may prolong cyclophosphamide-induced leukopenia and neuromuscular blockade by inhibiting cholinesterase activity
Pregnancy D - Unsafe in pregnancy
Precautions Administer cautiously to patients with leukopenia, thrombocytopenia, tumor cell infiltration of bone marrow, previous x-ray therapy, previous therapy with other cytotoxic agents, impaired hepatic or renal function; because cyclophosphamide may exert a suppressive action in immune mechanisms, consider interruption or modification of dosage for patients who develop bacterial, fungal, or viral infections; this is especially true for patients receiving concomitant steroid therapy and perhaps those with a recent history of steroid therapy, since infections in some of these patients have been fatal; varicella-zoster infections appear to be particularly dangerous under these circumstances; it is recommended that patients being considered as candidates for long-term therapy have their renal function monitored prior to treatment; regularly examine urine for red cells that may precede hemorrhagic cystitis

Drug Name
Chlorambucil (Leukeran) -- Aromatic nitrogen mustard derivative, which acts as a bifunctional alkylating agent. Alkylation takes place through the formation of a highly reactive ethylenimonium radical. Probable mode of action involves cross-linkage of the ethylenimonium derivative between 2 strands of helical DNA and subsequent interference with replication.
Adult Dose 0.1 mg/kg/d PO for 3-6 wk; adjust dose depending on blood counts
Pediatric Dose Not established
Contraindications Documented hypersensitivity; previous resistance to medication
Interactions None reported
Pregnancy D - Unsafe in pregnancy
Precautions Caution in history of seizure disorders or diagnosed with bone marrow suppression

Drug Name
Cyclosporine (Sandimmune) -- Potent immunosuppressive agent with narrow therapeutic range, shown to decrease number and severity of attacks of Behçet disease.
Adult Dose 2.5-5 mg/kg/d PO qd or divided bid
Pediatric Dose Not established
Contraindications Documented hypersensitivity; uncontrolled hypertension or malignancies; do not administer concomitantly with PUVA or UVB radiation in psoriasis since it may increase risk of cancer
Interactions Carbamazepine, phenytoin, isoniazid, rifampin, and phenobarbital may decrease cyclosporine concentrations; azithromycin, itraconazole, nicardipine, ketoconazole, fluconazole, erythromycin, verapamil, grapefruit juice, diltiazem, aminoglycosides, acyclovir, amphotericin B, and clarithromycin may increase cyclosporine toxicity; acute renal failure, rhabdomyolysis, myositis, and myalgias increase when taken concurrently with lovastatin
Pregnancy C - Safety for use during pregnancy has not been established.
Precautions May cause increases in serum creatinine and urea levels, even at recommended doses as a result of reduced glomerular filtration rate (ie, nephrotoxicity); functional changes are dose dependent and reversible, and usually respond to dose reduction; although less frequent, some patients may develop structural changes in the kidney during long-term treatment; close monitoring of renal function is required; abnormal values may necessitate dose reduction; risk of renal structural changes is greater if serum creatinine level increases >30% from patient's baseline value; thus, regular measurements of serum creatinine levels are essential

Further Outpatient Care:
 Patients should receive follow-up care as needed.
Prognosis:
 Spontaneous remissions and relapses characterize the natural history of ocular Behçet disease.
 Visual prognosis in countries that have the highest prevalence of disease (Japan and Turkey) is poor.
 In these 2 countries, more than 50% of cases result in legal blindness within 4 years of onset.
 The prevalence of blindness in North America is 25%.
 Possible explanation for this discrepancy includes genetic heterogeneity, with the occurrence of more severe disease in the Middle and Far East.

Medical/Legal Pitfalls:
 Early diagnosis leads to a more prompt treatment and fewer sequelae.
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