Behcet disease

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Behcet disease is a type of variable vessel vasculitis that most commonly affects young adults (20–40 years of age) from the Mediterranean region to eastern Asia. Patients typically present with recurrent, painful oral and/or genital ulcerations; uveitis and erythema nodosum are also common in patients with Behcet disease. Diagnosis is based on clinical features, but diagnostic studies (e.g., Doppler ultrasound, MRA head) are required to assess for end-organ damage and exclude differential diagnoses (e.g., aphthous stomatitis, reactive arthritis). Management is based on the affected organs and disease severity, but often involves immunosuppressive agents (e.g., glucocorticoids, azathioprine) and colchicine.

• Most commonly affects individuals from the Mediterranean region to eastern Asia, with the highest prevalence observed in Turkey and Japan ^[2]
• Peak incidence: 20–40 years of age
• ♂ > ♀

Epidemiological data refers to the US, unless otherwise specified.

• Possible autoimmune and infectious triggers (e.g., precipitating HSV or parvovirus infection) ^[3]
• Strong HLA-B51 association

• Autoimmune systemic vasculitis that can involve arteries and veins of all sizes
• Characterized by the deposition of immune complexes, proliferation of CD4+ T cells, and increased cytokines

• Recurrent painful oral aphthous ulcers (95–100%)
  • Typically the initial presenting symptom
  • Usually last about 1–4 weeks
• Recurrent genital ulcerations (60–90%)
  • Single or multiple ulcers that resemble oral aphthous ulcers and heal with scarring
  • Most commonly affect the vulva and the scrotum
• Ocular disease (50–80%)
  • Uveitis (iridocyclitis, chorioretinitis), keratitis, and/or retinal vasculitis
  • Typically bilateral
  • More common and severe among men
  • Usually occurs 2–3 years after the onset of oral and/or genital ulcers
• Skin lesions (35–85%)
  • Erythema nodosum, papulopustular lesions, pyoderma gangrenosum, pseudofolliculitis, or acneiform eruptions
  • Dermatographism: formation of urticaria after minor pressure is applied to the skin, likely mediated by local histamine release
  • Positive pathergy skin test: the appearance of an erythematous papule or pustule 48 hours after a 5 mm skin prick with a 20-gauge needle (usually on the forearm) ^[4][5]
• Arthritis (30–70%)
  • Non-erosive, non-deforming, asymmetric monoarthritis or oligoarthritis
  • Usually affects the knees, ankles, hands, and/or wrists
• Gastrointestinal disease: abdominal pain, anorexia, diarrhea, lower GI bleeding, nausea, vomiting
• Vasculopathy
  • Superficial thrombophlebitis
  • Thrombosis of large veins (e.g., deep vein thrombosis, Budd-Chiari syndrome)
  • Arterial thrombosis
  • Aneurysms (e.g., pulmonary artery aneurysms)
• Neuro-Behcet syndrome (5–10%) ^[6]
  • Parenchymal CNS disease: behavioral changes, ataxia, hemiparesis, sudden hearing loss
  • Non-parenchymal CNS disease: cerebral venous thrombosis, intracranial hypertension

PATHERGY: Positive pathergy test, Aphthous oral ulcers, Thrombosis (arterial and venous), Hemoptysis (pulmonary artery aneurysm), Eye lesions (uveitis, retinal vasculitis), Recurrent Genital ulcers, Young at presentation (3^rd decade)

General principles ^[2][5]

• Diagnosis is primarily clinical.
• Diagnostic criteria may be used to establish a diagnosis.
• Diagnostic studies may be required to assess for end-organ damage and to exclude differential diagnoses.

Rule out other conditions before starting potentially unnecessary and harmful immunosuppressive therapy.

Neuro-Behcet syndrome, vascular disease (e.g., pulmonary artery aneurysms), and GI disease are the main causes of mortality in Behcet disease and should be promptly identified and treated. ^[2][5]

Diagnostic criteria

Laboratory studies ^[2][5]

• CBC: leukocytosis
• Inflammatory markers: ↑ ESR, ↑ CRP
• Serology: Autoantibodies (e.g., ANA, ANCA, rheumatoid factor) are usually absent.
• Genetic studies: HLA-B51 testing is not routinely recommended. ^[5][8]

Imaging studies ^[5]

Consider imaging studies based on suspected conditions.

• Doppler ultrasound extremities: VTE and/or arterial aneurysms
• MRI head (with contrast): acute or chronic parenchymal neuro-Behcet
• MRA head: nonparenchymal neuro-Behcet (e.g., cerebral venous thrombosis, cerebral aneurysm)
• CT and CTA chest or abdomen: large-artery aneurysms and/or thrombosis ^[9][10]
• Endoscopic studies: GI involvement and to rule out alternative diagnoses (e.g., Crohn disease, tuberculosis)

Clinical features of Behcet disease may also be present in several other conditions, e.g.: ^[2][5]

• Aphthous stomatitis, e.g., due to vitamin B₁₂, folate, and/or iron deficiency
• GI diseases, e.g., Crohn disease, celiac disease
• Infectious diseases, e.g., tuberculosis, herpes infections, HIV
• Rheumatological diseases, e.g., reactive arthritis, SLE
• Dermatological diseases, e.g., Sweet syndrome, Stevens-Johnson syndrome, pemphigus

The differential diagnoses listed here are not exhaustive.

Approach ^[10][11][12]

• Nonsevere disease
  • Consult a rheumatologist and other specialists as required.
  • Choice of therapy is based on the type of lesions.
• Severe disease : Consult a specialist (e.g., neurology, ophthalmology, surgery) and start treatment early to prevent permanent damage. ^[11]

Up to one-third of patients with GI involvement require emergency surgery as a result of GI perforation, major bleeding, or obstruction. ^[11]

Pharmacotherapy ^[10]

• Ocular disease, CNS disease, and/or vasculopathy
  • Systemic glucocorticoids
  • Glucocorticoid-sparing agents (e.g., azathioprine, infliximab, cyclosporine A, cyclophosphamide, IFN-α, methotrexate)
  • Aggressive treatment is required for severe sight-threatening uveitis.
• Mucocutaneous lesions
  • Topical glucocorticoids; (e.g., triamcinolone ) can accelerate the healing of oral and genital ulcers.
  • Immunomodulatory agents
    • Consider colchicine to prevent lesion recurrence.
    • For colchicine-resistant lesions, consider:
      • Adding apremilast
      • Other immunomodulatory agents (e.g., azathioprine, thalidomide, IFN-α)
• Arthritis
  • First line: colchicine
  • Consider intraarticular glucocorticoids in acute monoarthritis.
  • Consider other immunosuppressive agents (e.g., IFN-α, TNF-α inhibitors, or infliximab) in chronic or recurrent cases.

Patients with severe disease usually require aggressive management with a combination of high-dose glucocorticoids and other immunosuppressive agents.

Supportive care

• Start pain management.
• Prevent complications of glucocorticoid therapy.
• Monitor for adverse effects of immunosuppressants.
• Consider pneumocystis pneumonia prophylaxis.