Behcet’s Disease

Epidemiology

History: first described in 1937
Geographic Peak: most common in patients with ancestral descent from “Old Silk Route” (China, Japan, Korea, Turkey, Middle East)
- Common in countries bordering the Mediterranean
Prevalence: 80-370 cases per 100k persons in Turkey
Sex: M=F
Peak Age: teens-20’s
Genetics: strongly to HLA-B51 allele (13:1 increased risk on Turkey)
Infectious Agents: increased risk with Herpes Simplex Virus-1 (HSV-1) and Streptococcus

Small Vessel Vasculitis Involving Arterioles, Capillaries, and Venules
- Infiltration with neutrophils and mononuclear cells
- Immune Complexes (with IgG and complement): have been found in serum of patient with active disease, as well as in the lung and other organs
Aneurysms of Bronchial Arteries: may erose into bronchi -> serious or fatal hemoptysis
Pulmonary Arterial Occlusion -> Pulmonary Infarction

Major Criteria (required)
- Recurrent aphthous ulcerations: occurring at least 3x per year
Minor Criteria (2 of 4 criteria)
- Recurrent genital ulceration
- Ocular disease
- Skin lesions: erythema nodosum, skin ulcers
- Positive pathergy test: 2 mm erythematous papule or pustule at prick site 48 hrs after 20-22 gauge needle prick that obliquely penetrated avascular antercubital skin to a 5 mm depth

Pericarditis (see Acute Pericarditis, [[Acute Pericarditis]])
Cardiomyopathy (see Congestive Heart Failure, [[Congestive Heart Failure]])
Endocarditis (see Endocarditis, [[Endocarditis]])
Endomyocardial Fibrosis
Intracavitary Thrombosis
Coronary Artery Disease (see Coronary Artery Disease, [[Coronary Artery Disease]])
Sinus of Valsalva Aneurysm (see Sinus of Valsalva Aneurysm, [[Sinus of Valsalva Aneurysm]])

Genital Ulcers (see Mucocutaneous Ulcers, [[Mucocutaneous Ulcers]])
Erythema Nodosum (see Erythema Nodosum, [[Erythema Nodosum]])
Folliculitis
Acneiform Rash
Cutaneous Vasculitis (see Vasculitis, [[Vasculitis]])
- Splinter Hemorrhages: may be present
- Palpable Purpura (see Purpura, [[Purpura]]): may be present
Positive Pathergy Test: 2 mm erythematous papule or pustule at prick site 48 hrs after 20-22 gauge needle prick that obliquely penetrated avascular antercubital skin to a 5 mm depth

Hypercoagulable State (see Hypercoagulable States, [[Hypercoagulable States]])
- Arterial Thrombosis: involving large arteries
- Venous Thrombosis
  - Inferior Vena Cava Thrombosis
  - Superior Vena Cava Thrombosis
  - Thrombophlebitis/Deep Venous Thrombosis (DVT) (see Deep Venous Thrombosis, [[Deep Venous Thrombosis]])

Aseptic Meningitis/Encephalitis (see Meningitis, [[Meningitis]] and Encephalitis, [[Encephalitis]])
Brainstem White-Matter Lesions: may mimic multiple sclerosis

Recurrent Aphthous Stomatitis or Ulcers (see Mucocutaneous Ulcers, [[Mucocutaneous Ulcers]]): common (almost required for diagnosis)

Incidence: pulmonary manifestations occur in 1-7% of cases
Sex: ulmonary symptoms are more common in males than females
Genetics: pulmonary manifestations affect HLA-B51 positive males <25 y/o more severely

Etiology
- Vasculitis of Small Lung Vessels
- Rupture of Bronchial Veins Due to Thrombosed Superior Vena Cava
- Large Pulmonary Artery Aneurysms
- Pulmonary Arteriovenous Fistulas
Diagnosis
- ABG: elevated A-a gradient hypoxemia
- CXR/Chest CT Patterns
  - Bilateral fleeting infiltrates (common): diffuse or patchy
  - Pleural effusion (70% of cases): may be a chylothorax
  - Hilar vascular prominence (14%):
  - Nodules (10%):
  - Interstitial infiltrates: may appear with chronic or recurrent DAH
- Pulmonary Angiogram: aneurysms of PA tree
- PFT’s: increased DLCO during active alveolar hemorrhage
- FOB: tracheobronchial mucosal ulcerations
  - BAL: RBC’s and hemosiderin-laden macrophages consistent with alveolar hemorrhage
- OLB: may be necessary
  - Tissue Ab staining: immune complexes (IgG + complement) may be found in small pulmonary vessels
Clinical: symptoms usually are present for days-weeks before presentation
- Hemoptysis (77% of cases)
- Cough
- Dyspnea
- Chest Pain
Prognosis: may be fatal in some cases (hemoptysis is the cause of death in 39% of cases)

Anterior or Posterior Uveitis (see Uveitis, [[Uveitis]]): major cause of morbidity
Iridocyclitis
Retinal Vasculitis
- May be asymptomatic
- May lead to blindness

Glomerulonephritis: renal biopsy demonstrates focal segmental necrotizing vasculitis and glomerulonephritis

Corticosteroids + Cyclophosphamide (see Corticosteroids, [[Corticosteroids]] and Cyclophosphamide, [[Cyclophosphamide]])
- Useful for active lung disease and disease in other organs
- May lead to regression of pulmonary artery aneurysms
Cyclosporine A (see Cyclosporine A, [[Cyclosporine A]]): have been effective in some cases
Tacrolimus (see Tacrolimus, [[Tacrolimus]]): have been effective in some cases
Anti-TNF Therapy (see Anti-TNF Therapy, [[Anti-TNF Therapy]]): may produce daramatic results in some cases
Anticoagulation: may be used to treat thrombosis, but immunosuppression is generally preferred (due to risk of hemorrhage)
Pulmonary Artery Embolization: may be effective to control pulmonary hemorrhage
Pulmonary Artery Aneurysm Resection: has been used, but aneurysms may recur at the anastomotic site

Pulmonary hemorrhage is cause of death in 39% of cases: death usually occurs within 6 years of first episode of hemoptysis
2-Year Survival in Presence of Pulmonary Artery Aneurysm: 70%

Cardiac and great vessel involvement in Behcet’s disease. J Card Surg. 2008 Nov-Dec;23(6):765-8
Cardiovascular Complications in Behçet Syndrome. Acute Myocardial Infarction with Late Stent Thrombosis and Coronary, Ventricular, and Femoral Pseudoaneurysms. Tex Heart Inst J. 2009; 36(5): 498–500