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
Physiology
- 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
Diagnosis
- ANA/RF: variable
- Anti-DNA: negative
- C3/C4/CH50: normal
- ANCA: positive
- Anti-GBM: negative
Clinical Diagnostic Criteria
- 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
Clinical Manifestations
Cardiovascular Manifestations (rare)
Dermatologic Manifestations
- 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
Hematologic Manifestations
- 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]])
Neurologic Manifestations
- Aseptic Meningitis/Encephalitis (see Meningitis, [[Meningitis]] and Encephalitis, [[Encephalitis]])
- Brainstem White-Matter Lesions: may mimic multiple sclerosis
Oral/Gastrointestinal Manifestations
- Recurrent Aphthous Stomatitis or Ulcers (see Mucocutaneous Ulcers, [[Mucocutaneous Ulcers]]): common (almost required for diagnosis)
Pulmonary Manifestations
General Comments
- 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
Recurrent Pneumonia (see Pneumonia, [[Pneumonia]])
- Epidemiology: occurs in 60% of cases
- Clinical
- Cough
- Dyspnea
- Pleuritic Chest Pain
Cryptogenic Organizing Pneumonia (COP) (see Cryptogenic Organizing Pneumonia, [[Cryptogenic Organizing Pneumonia]])
Diffuse Alveolar Hemorrhage (DAH) (see Diffuse Alveolar Hemorrhage, [[Diffuse Alveolar Hemorrhage]])
- 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)
Pulmonary Arterial Occlusion with Pulmonary Infarction (see Pulmonary Infarction, [[Pulmonary Infarction]])
Pleurisy/Pleural Effusion (see Pleural Effusion-Exudate, [[Pleural Effusion-Exudate]])
Ophthalmologic Manifestations
- Anterior or Posterior Uveitis (see Uveitis, [[Uveitis]]): major cause of morbidity
- Iridocyclitis
- Retinal Vasculitis
- May be asymptomatic
- May lead to blindness
Renal Manifestations
- Glomerulonephritis: renal biopsy demonstrates focal segmental necrotizing vasculitis and glomerulonephritis
Rheumatologic Manifestations
Other Manifestations
- Arterial Aneurysms
- Fever (see Fever, [[Fever]]): occurs in 55% of cases
Treatment
- 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
Prognosis
- 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%
References
- 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