Behcet Disease

Article Author:
Abdullah Adil
Article Editor:
Jessilin Quint
Updated:
10/27/2018 12:31:25 PM
PubMed Link:
Behcet Disease

Introduction

Behcet’s disease, also known as an oculo-orogenital syndrome, is a chronic remitting and relapsing inflammatory disorder characterized by recurrent oral aphthous ulcers, genital ulcerations, ocular manifestations (e.g., uveitis, conjunctivitis) and other systemic involvement. It is also known as Behcet syndrome and Malignant aphthosis.

Etiology

The exact etiological basis of Behcet’s disease is unknown. It is considered to be an autoimmune disease triggered by infections like herpes simplex virus (HSV), Streptococcus, and Staphylococcus in genetically predisposed individuals. Genetic predisposition to develop this syndrome has been found in HLA-B51 carriers.

Epidemiology

The incidence and prevalence of this disease are high amongst the Far Eastern and Mediterranean ancestries. Turkey has the highest prevalence affecting 420 people per 100,000 population.

It affects patients in their twenties and thirties; however early and late onsets have been reported. Both genders are equally affected by the disease; a male predominance is observed in Arab populations while female predominance is evident in Korea, China, United States, and some northern European countries.

Pathophysiology

Behcet’s disease is characterized by vasculitis of all sized vessels that involves both arterial and venous sides of the circulation. Cell-mediated immunity plays a major role in the pathogenesis of this disease. Helper T- cells type-1 activation leads to increased circulating levels of CD-4 positive and cytotoxic (CD8 positive) lymphocytes in the peripheral blood which target the oral mucosa, skin and other systems of the body. There are number of immunological findings in Behcet's disease;

  • Autoantibodies are circulating in patients' blood against different components like intermediate filaments found in mucous membranes etc.
  • Immune complexes circulating in the blood and their deposition at the involved sites.
  • Decreased complement levels in patients' blood
  • Immunoglobulin and complement deposition in within and around blood vessels.
  • An evidence of the decreased ratio of CD4+ to CD8+ cells has also been observed.

However, the common pathogenic denominator is leukocytoclastic vasculitis which is considered to be pathognomonic for the disease. Due to the involvement of immune complexes, the disease shares a number of common features to other diseases (e.g., SLE)  which have similar pathogenesis. An example of this is erythema nodosum commonly manifested in these diseases.

Histopathology

Histopathological features of the disease are vasculitis and thrombosis. Mucocutaneous lesions biopsies show a neutrophil-predominant reaction with endothelial swelling, extravasation of RBCs and leukocytoclastic vasculitis (suggestive sign of the disease) with fibrinoid necrosis of the blood vessel walls. Some older lesions show lymphocytic perivasculitis. However, a neutrophilic vascular reaction is considered to be the most predominant reaction in Behcet's disease. Involvement of vasa vasorum (vasculitis) may result in the formation of aneurysms in the large arteries.

History and Physical

Typically patients have a history of recurrent painful oral lesions (aphthous ulcers) with odynophagia, foul-smelling breath, photophobia, vision loss, joint pains, and painful genital lesions.

Multiple aphthous ulcers in the oral cavity involving the soft palate, hard palate, buccal mucosa, and tonsils, having a sharp regular border with a grayish base and surrounding bright red halo. Genital lesions may occur on the scrotum in males and vulva and vagina in females.

Ocular manifestations may include conjunctivitis, uveitis, and hypopyon. Retinal vasculitis or posterior uveitis is the most classic ocular sign and an important cause of blindness in these patients. Other secondary ocular complications are cataract, glaucoma and neovascular lesions. Retinal inflammation can lead to vascular occlusion and ultimately results in tractional retinal detachment. Recurrent vasculitic changes can ultimately result in ischemic optic nerve atrophy and can cause blindness.

Non-deforming arthritis of medium and large joints is seen in many patients. The characteristic arthritis is non-erosive, asymmetrical, sterile and seronegative; however symmetrical polyarticular involvement is comm in Behcet's disease. Joint manifestations frequently occur in one knee or ankle and then other as a migratory monoarthritis, then in both joints simultaneously and finally affecting nearly all joints of the body. An important differential to be excluded is an HLA-B27-positive erosive sacroiliitis.

Neurological and gastrointestinal manifestations may also be seen. Neurological manifestations include meningoencephalitis, cerebral venous thrombosis, benign intracranial hypertension, cranial nerve palsies and various pyramidal and extrapyramidal lesions.

Behcet’s disease is characterized by both arterial and venous thrombosis; however arterial involvement is rare. A swollen tender calf (due to deep venous thrombosis) in a patient with orogenital ulcers and eye involvement is highly suggestive of Behcet’s disease.

Evaluation

Diagnosis is mainly clinical, and the diagnostic criteria consist of recurrent oral aphthous stomatitis with two or more of the following clinical findings in the absence of other systemic diseases:

  1. Recurrent painful genital lesions
  2. Ocular lesions; retinal vasculitis or uveitis
  3. Skin lesions (e.g., erythema nodosum, papulopustular lesions)or a positive Pathergy test (a sterile pustule that appears after local trauma to the skin)
  4. Central nervous system (CNS) lesions (e.g., cerebral infarction, meningoencephalitis).

Differential diagnoses include:

  • Sweet syndrome
  • Erythema multiforme
  • Pemphigus

Treatment / Management

Medical Intervention

Treatment is aimed at preventing the recurrence of the disease. Treatment strategy depends on the site and severity of the disease. Following order shows the treatment plan according to involvement sites and severity:

  • Mucocutaneous involvement: Topical antibiotics, topical corticosteroids, sucralfate
  • Ocular disease: topical corticosteroids+mydriatics or cycloplegics
  • Articular involvement (arthritis): Colchicine, NSAIDs, Benzathine penicillins
  • Vascular involvement: Systemic corticosteroids
  • CNS involvement: Systemic corticosteroids
  • GIT involvement: Sulfasalazine, corticosteroids

In pregnancy, prednisolone is the systemic drug of choice without potential side effects related to pregnancy.

For refractory cases, the following drugs are being used as second and third line therapies:

  • Immunomodulators (e.g., azathioprine, cyclosporine)
  • Immunosuppressive drugs (methotrexate, cyclophosphamide)
  • Anti-Tumor Necrosis Factor-alpha (e.g., infliximab)

Surgical Intervention

Surgical interventions are used at the last resort if all the medical interventions failed. It is mostly used in extensive vascular involvement refractory to medical management.

Pearls and Other Issues

Morbidity

 Ophthalmic and neurological complications are the leading causes of morbidity in these patients. Others are severe vascular and extensive gastrointestinal involvement.

Prevention

Severe or progressive recurrent aphthous stomatitis in patients should raise suspicion of the disease, and they should be followed for up to years as potential candidates for Behcet's disease. Especially those with a strong family history.

Patients who are suspected to have this disease should be referred for specialty consultation.

Patients (especially males) who present with systemic involvement as a presenting sign should be treated with systemic drugs.

Patients who have early onset of the disease have a poor prognosis.