Behcet's Disease

What Is Behcet's Disease?

Behcet's disease, Behcet syndrome, or Silk Road disease, is rare but of worldwide prevalence, especially along the Silk Road countries. It mainly affects the younger and middle-aged population between 20 to 40 years old and is more prevalent in men than in women. It is a chronic syndrome and an inflammatory disorder involving the ocular, oral, and genital regions of the body. The other name for this syndrome is malignant apthosis. This mucocutaneous inflammatory disorder with uveitis (inflammation inside the eye) and systemic vasculitis affects arteries and veins, leading to a multisystemic manifestation of a broadened disease spectrum.

The increased prevalence of this disease across the Silk Route gave it the name Silk Road disease (in people originating from the ancient trading routes between China and the Mediterranean basin). Though attributable genetic elements have been identified like HLA-B1 or B5 carriers who are at an increased predisposition to develop this disease, other factors like tumor necrosis factor, or TNF, histocompatibility class 1 chain genes, and heat shock proteins have also been found to be carriers that may be inherited over a familial route. This autoimmune inflammatory condition is due to the pathogenesis of the body's natural immune cells, which mistake the healthy tissue cells for foreign cells and attack the blood vessels, leading to systemic vasculitis.

What Is the Pathophysiology of Behcet’s Disease?

Cell-mediated immunity in which Type 1 helper T cell activation leads to increased T-lymphocyte circulating levels accounts for the multisystemic presentation of Behcet disease. Pro-inflammatory cytokines (IL-1, IL-8, IL-12, IL-17, IL-37, and TNF) are the pathophysiology behind the increased inflammatory response.

Mucocutaneous lesions, including oral aphthous ulcers and erythema nodosum, are attributed to or researched due to this increased neutrophil activation (leading to a neutrophilic vascular reaction that causes tissue injury to the body's healthy tissue cells). Circulating immune complexes play a role in causing neutrophil-stimulated vasculitis. A biopsy of the mucocutaneous lesions shows a predominance of neutrophil cells apart from endothelial swelling seen histopathologically.

Erythrocytes or red blood cell extravasation is also a pathologic finding, along with the blood vessels' fibrinoid necrosis. The neutrophilic vascular reaction is the diagnostic criterion histopathologically in Behcet disease. The formation of aneurysms in the large arteries or vasculitis is a well-observed clinical feature. Exposure to certain infectious microorganisms like Streptococcus bacterium, Staphylococcus aureus, and Prevotella sp has remained elusive in linkage to Behcet's disease. However, research suggests they may have an environmental role in causing systemic infection.

What Are the Signs and Symptoms of Behcet’s Disease?

The main clinical symptoms that should prompt the patient to consult the physician in this condition are usually the occurrence of these features:

• Reddening of the eyes

• Eye pain.

• Blurred vision.

• Mouth ulcerations.

• Genital ulcers.

• Skin acne.

• Headache.

• Joint pains.

• Joint stiffness or joint swellings.

What Are the Investigations Required for Diagnosis of Behcet’s Disease?

Diagnosis of Behcet's disease can be made by

• A complete blood count and routine blood examination are done to rule out any underlying medical conditions.

• X-rays to check for lung infections.

• To further investigate the symptoms, CT (computed tomography) or MRI (magnetic resonance imaging) scans are advised.

• Skin Biopsy.

• Pathergy test (in which the skin tissue is needle pricked to observe and check if red spots begin to appear within 24 to 48 hours of the test time).

What Are the Systemic Manifestations of Behcet’s Disease?

Ocular Manifestations:

• Bilateral uveitis of the anterior and posterior uveal tracts.

• Erythema - skin redness due to inflammation or an injury.

• Photophobia - Discomfort caused to the eyes due to bright light.

• Vision loss may be observed in progressive disease cases (untreated).

• Retinal vasculitis - leading to vision loss or blindness.

• Conjunctivitis (inflammation of the eye’s conjunctive - maybe rare but observed as well).

• Severe retinal disease. ·

Musculoskeletal Manifestations:

• Oligoarthritis (involves two to four joints) or polyarthritis (involves five or more joints) or monoarthritis (involves one joint).

• Peripheral joint and spine involvement (arthritis).

Vascular and Cardiac Manifestations:

• Superficial or deep thrombophlebitis - blood clot causing inflamed and swollen veins.

• Myocarditis - inflammation of the heart muscles.

• Endocarditis - inflammation inside heart valves and chambers.

• Coronary artery vasculitis - blood vessel inflammation.

• Coronal aneurysms (weakened and bulging area in an artery).

• Budd-Chiari syndrome or vena cava obstruction.

• Vasculitis of carotid, femoral and popliteal arteries.

• Pulmonary aneurysms.

• Thromboembolism - blood clot obstructing the blood vessel.

• Aortitis - inflammation of the aorta.

Neurologic Manifestations:

• Elevated protein in the cerebrospinal fluid.

• Cerebellar and pyramidal tract involvement.

• Cranial or peripheral nerve involvement.

• Headaches and papilledema.

• Sinus thrombi.

Gastrointestinal Manifestations:

• Mucosal ulcerations of ileum, cecum, colon, and esophagus.

• Ileocecal ulcerations or lesions.

Renal Manifestations:

• Amyloidosis - abnormal buildup of amyloid.

• Glomerulonephritis. ·

Other Systemic Manifestations:

• Epididymitis.

• Anemia - lack of enough healthy red blood cells in the blood.

• Leukocytosis.

• Inflammatory marker elevation.

• Meningitis - inflammation of the spinal cord and brain’s membranes.

Orogenital Manifestations:

• These are the most commonly reported and observed clinical features in a patient presenting with Behcet syndrome. Oral lesions are painful and may occur anywhere in the soft palate, hard palate, buccal mucosa, lips, gingival tissue, or tonsils. These lesions are both painful and recurrent, and routine dental examination can also prompt the dental surgeon to suspect severe systemic illnesses associated with an inflammatory immune response presenting in the oral cavity. Oral ulcerations are indicative or confirmative in almost all patients presenting with Behcet disease and are the first clinical features to present in the patient.

• Genital ulcerations are recurrent in up to 80 percent of affected patients. However, in sharp contrast to the nature of oral lesions or ulcers, genital ulcers are usually self-healing with a bit of scarring. These ulcers occur in the scrotum region of the males and the females upon the vulva or the vaginal parts.

What Are the Risk Factors for Behcet’s Disease?

• Age: The disease affects males and females between 20 to 30 years of age. It can also affect children and elderly people.

• Sex: The disease severely affects men but can occur in both males and females.

• Gender: A certain type of gene present in the body is responsible for causing this disease.

• Place of Living: The disease commonly occurs in people from East and Middle East Asia, like Japan, Turkey, Iran, and China.

What Is the Differential Diagnosis of Behcet’s Disease?

• Systemic lupus erythematosus ( SLE).

• Seronegative arthritis.

• Reactive arthritis.

• Multiple sclerosis.

• Inflammatory bowel disease (IBD).

• Sarcoidosis.

• Polychondritis.

• Herpetic infections.

• Sacroiliitis.

• Axial inflammatory arthritis.

• Systemic vasculitides.

How to Manage Behcet's Disease?

Behcet's disease is always associated with a significant physical and psychological impairment for life. Hence, multisystemic management should be provided, which depends on medical intervention by the physician, gastroenterologist, dentist, maxillofacial surgeon, nephrologist, cardiologist, and neurologist as per the extent of organ damage and clinical symptoms exhibited by the individual. Younger individuals, especially the male population affected, need immediate treatment after the detection of Behcet's disease. Otherwise, the long-term prognosis will be affected due to the high mortality rates. Hence, early intervention is required. The treatment varies widely depending on the organ affected, ranging from corticosteroids to immunosuppressive agents. Surgery mainly treats pulmonary or neural aneurysms (localized swelling of arteries is called aneurysms) and prevents their recurrence.

Conclusion:

To conclude, Behcet's disease is a lifelong systemic disease that needs multi-specialty intervention, psychological support, and, most importantly, diagnosis at the earliest to prevent the high rates of mortality risk that arise due to the complications developed by these individuals. Complications of the condition are mainly associated with clinical manifestations that, if left untreated, such as uveitis, which can further cause blindness or vision problems. Therefore, one must consult the doctor immediately to avoid such complications.