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

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]])

  • xxx

Chylothorax (see Pleural Effusion-Chylothorax, [[Pleural Effusion-Chylothorax]])

  • Epidemiology: uncommon

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]])

  • Clinical
    • Chest Pain

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