Ferri – Behçet’s Disease

Mar 20, 2020 admin CƠ XƯƠNG KHỚP 0

Behçet’s Disease

  • Monzr M. Al Malki, M.D.

 Basic Information

Definition

Behçet’s disease is a chronic, relapsing, inflammatory disorder characterized by the presence of recurrent oral aphthous ulcers, genital ulcers, uveitis, and skin lesions (Fig. E1).

FIG.E1 

Behçet’s syndrome.
A, Major aphthous ulceration. B, Genital ulceration. C, Superficial thrombophlebitis. D, Dermatographia.
From Kanski JJ, Bowling B: Clinical ophthalmology, a systemic approach, ed 7, Philadelphia, 2010, Saunders.

Synonym

  1. Behçet’s syndrome

ICD-10CM CODE
M35.2 Behçet’s disease

Epidemiology & Demographics

Prevalence

  1. •

    Behçet’s disease is observed in two different geographic locations.

    1. 1.

      One region consists of Eastern Asia, Turkey, and the Mediterranean basin.

      1. 1.

        Prevalence ranges from 18 to 30 cases per 100,000 persons.

      2. 2.

        Turkey has the highest prevalence at 80 to 370 cases per 100,000 persons.

    2. 2.

      The second region consists of North America and Northern Europe.

      1. 1.

        Prevalence ranges from 0.5 to 17 cases per 100,000 persons. Germany has the greatest prevalence.

      2. 2.

        Prevalence of Behçet’s disease in the U.S. is 0.12 to 0.33 cases per 100,000 persons.

  2. •

    In these regions, the prevalence of HLA-B51 is greater in patients with Behçet’s disease.

Predominant Sex

Equal sex distribution

Genetics

No clear pattern of inheritance can be determined. Familial disease was noted in 15% of affected children.

Age

Peak age of onset is between 20 and 40 yr.

Physical Findings & Clinical Presentation

  1. •

    Behçet’s disease typically affects individuals in the third to fourth decade of life and primarily presents with painful aphthous oral ulcers. The ulcers occur in crops measuring 2 to 12 mm and are found on the mucous membrane of the cheek, gingiva, tongue, pharynx, and soft palate.

  2. •

    Genital and perianal ulcers are similar to the oral ulcers. They may result in scarring.

  3. •

    Decreased vision secondary to uveitis, keratitis, and retinal artery occlusion with ischemia may be followed by neovascularization, vitreous hemorrhage and contraction, glaucoma, and retinal detachment. Younger male individuals are at greater risk for ocular involvement.

  4. •

    Skin findings (41%-97%) include nodular lesions, which are histologically divided into erythema nodosum-like lesions, pseudofolliculitis, papulopustular lesions, acneiform nodules, or pyoderma gangrenosum-like lesions (cutaneous aphthosis).

  5. •

    Intermittent, symmetric oligoarthritis (40%-70%) is the most common; ankylosing spondylitis or arthralgias may occur.

  6. •

    Central nervous system (CNS; 30% in U.S. and 5% in Turkey) meningeal findings including headache, fever, and stiff neck can occur. Cerebellar ataxia, pseudobulbar palsy, and dementia occur with involvement of the brainstem. Fig. E2 illustrates the different age distributions at neurologic presentation.

    FIG.E2 

    Distribution of 40 patients with Behçet’s disease over different age groups at neurologic presentation.
    From Al-Fahad SA, Al-Araji AH; Neuro-Behçet’s disease in Iraq: a study of 40 patients, J Neurol Sci 170:105–111, 1999.
  1. •

    Vascular involvement (25%-30%), arterial and venous, of all sizes may cause systemic arterial vasculitis (aneurysms and occlusions), pulmonary artery vasculitis, venous occlusions (including superficial, deep, cerebral, portal, and mesenteric veins), pulmonary embolus, right ventricle thrombosis, and Budd-Chiari syndrome.

  2. •

    GI involvement is more common in Japanese individuals; ulcerative lesions primarily involve distal ileum and cecum, but any region can be affected. GI lesions tend to perforate or bleed and may recur after surgery.

Etiology

The etiology of Behçet’s disease is unknown. An immune-related vasculitis, a perivascular inflammation, or both are thought to lead to many of the manifestations of Behçet’s disease. Multiple triggers for this process have been investigated, including herpes simplex virus infection, streptococcal antigen, and others.

Diagnosis

According to the International Study Group for Behçet’s Disease, the diagnosis of Behçet’s disease is established when oral ulcerations recur at least three times in one 12-mo period plus at least two of the following conditions in the absence of other systemic diseases:

  1. •

    Recurrent genital ulceration

  2. •

    Eye lesions

  3. •

    Skin lesions

  4. •

    Positive pathergy test (erythematous papules or pustules [>2 mm in diameter] at sterile needle injection sites after 24-48 hours)

Differential Diagnosis

  1. •

    Inflammatory bowel disease (ulcerative colitis and Crohn’s disease)

  2. •

    Sprue disease

  3. •

    Herpes simplex infection

  4. •

    Benign aphthous stomatitis

  5. •

    Cyclic neutropenia

  6. •

    Acquired immune deficiency syndrome (AIDS)

  7. •

    Systemic lupus erythematosus

  8. •

    Reiter’s syndrome

  9. •

    Ankylosing spondylitis

  10. •

    Hypereosinophilic syndrome

  11. •

    Sweet’s syndrome

  12. •

    Lichen planus

  13. •

    Pemphigoid

Workup

The diagnosis of Behçet’s disease is a clinical diagnosis. Laboratory tests and x-ray imaging may be helpful in working up the complications of Behçet’s disease or excluding other diseases in the differential.

Laboratory Tests

No diagnostic laboratory tests for Behçet’s disease exist. The measurements of T-cell proliferative response to heat shock protein (HSP) and impaired fibrinolytic activity have been proposed for the diagnosis of Behçet’s disease, but the value of testing has not been confirmed.

Imaging Studies

CT scan, MRI, and angiography are useful for detecting CNS and vascular lesions.

Treatment

Treatment is directed at the patient’s clinical presentation and complications (e.g., mucocutaneous lesions, ocular lesions, arthritis, GI, CNS, or vascular lesions).

Nonpharmacologic Therapy

Supportive care and rest during flares, and moderate exercises such as swimming or walking when symptoms improve or disappear

Acute General Rx

  1. •

    Oral and genital ulcers:

    1. 1.

      Topical and intralesional corticosteroids (e.g., triamcinolone acetonide ointment applied tid)

    2. 2.

      Tetracycline tablets 250 mg dissolved in 5 cc water and applied to the ulcer for 2 to 3 min

    3. 3.

      Colchicine 0.5 to 1.5 mg/day PO

    4. 4.

      Thalidomide 100 to 300 mg PO daily

    5. 5.

      Dapsone 100 mg PO daily

    6. 6.

      Pentoxifylline 300 mg/day PO

    7. 7.

      Azathioprine 1 to 2.5 mg/kg/day PO

    8. 8.

      Methotrexate 7.5 to 25 mg/wk PO or intravenously

    9. 9.

      Interferon alfa-2a and interferon alfa-2b (generally given 3 to 19 million units three times weekly)

    10. 10.

      Recent trials have shown that apremilast, an oral phosphodiesterase-4 inhibitor that modulates several inflammatory pathways may be effective in treating oral ulcers (NJEM 372:1510-1518, 2015)

  2. •

    Ocular lesions:

    1. 1.

      Anterior uveitis is treated by an ophthalmologist with topical corticosteroids (e.g., betamethasone drops 1 to 2 drops tid); topical injection with dexamethasone 1 to 1.5 mg has also been tried

    2. 2.

      Infliximab 5 mg/kg single dose

    3. 3.

      Cyclosporine A (5 mg/kg/day) with or without prednisone or azathioprine 1 to 2.5 mg/kg/day PO

  3. •

    CNS disease:

    1. 1.

      Chlorambucil 0.1 mg/kg/day is used in the treatment of posterior uveitis, retinal vasculitis, or CNS disease; patients not responding to chlorambucil can be tried on cyclosporine 5 to 7 mg/kg/day.

    2. 2.

      In CNS vasculitis, cyclophosphamide 2 to 3 mg/kg/day is used. Prednisone can be used as an alternative.

  4. •

    Arthritis:

    1. 1.

      NSAIDs (e.g., ibuprofen 400-800 mg tid PO or indomethacin 50-75 mg/day PO)

    2. 2.

      Sulfasalazine 1 to 3 g/day PO is an alternative treatment.

  5. •

    GI lesions:

    1. 1.

      Sulfasalazine 1 to 3 g/day PO

    2. 2.

      Prednisone 40 to 60 mg/day PO

  6. •

    Vascular lesions:

    1. 1.

      Prednisone 40 to 60 mg/day PO

    2. 2.

      Cytotoxic agents as mentioned previously

    3. 3.

      Heparin 5000 to 20,000 U/day followed by oral warfarin

Chronic Rx

  1. •

    Chronic therapy is usually continued for approximately 1 yr after remission.

  2. •

    Surgery may be indicated in patients with complications of bowel perforation, vascular occlusive disease, and aneurysm formation.

  3. •

    Mortality is associated with early age of onset, arterial involvement, male gender, and frequent disease flares.

Disposition

  1. •

    The aphthous oral ulcers last 1 to 2 wk, recurring more frequently than genital ulcers.

  2. •

    25% of Japanese patients with ocular lesions become blind.

  3. •

    The disease course is unpredictable.

  4. •

    The morbidity of Behçet’s disease comes primarily from ocular and cutaneous involvement; however, mortality relates primarily to large-size vessel involvement and CNS diseases.

Referral

If the diagnosis of Behçet’s disease is suspected, a referral to dermatology, rheumatology, and ophthalmology is indicated because the disease is so rare.

Pearls & Considerations

Comments

  1. •

    The pathergy test refers to the formation of an erythematous papule or pustule of ≥2 mm after oblique insertion of a sterile 20- or 25-gauge needle into the skin after 24 to 48 hours.

  2. •

    Because of the rarity of this disease, data from controlled, prospective, randomized clinical trials are lacking.

Suggested Reading

  • G. Hatemi, et al.: Apremilast for Behcet’s syndrome, a phase 2 placebo-controlled study. N Engl J Med. 372L:1510–1518 2015

Related Content

  1. Behçet’s Syndrome (Patient Information)

 

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