Behcet Disease

Saad al mohizea

Cont.

Incidance: BD is most prevalent (and more

virulent) in the Mediterranean region, Middle East, and Far East, with an estimated prevalence of 1 case per 10,000 persons

Mortality/Morbidity Sex

symptoms Malaise Weight loss Generalized weakness Headache Perspiration Decreased or elevated temperature Lymphadenopathy Pain of the substernal and temporal regions A history of repeated sore throats, tonsillitis,

myalgias

Major features

Recurrent aphthous ulceration of the oral mucous membrane

Skin lesions - Erythema nodosum, subcutaneous thrombophlebitis, folliculitis (acnelike lesions), cutaneous hypersensitivity

Eye lesions - Iridocyclitis, chorioretinitis, retinouveitis, definite history of chorioretinitis or retinouveitis

Genital ulcers

Minor features

Arthritis without deformity and ankylosis Gastrointestinal lesions characterized

by ileocecal ulcers Epididymitis Vascular lesions Central nervous system symptoms

diagnosis

Complete - Four major features Incomplete - (1) 3 major features, (2) 2

major and 2 minor features, or (3) typical ocular symptom and 1 major or 2 minor features

Possible - (1) 2 major features or (2) 1 major and 2 minor features

Oral ulcers Oral aphthae that occur in patients with BD are

indistinguishable from common aphthae (canker sores).

Aphthae may be more extensive, more painful, more frequent, and evolve quickly from a pinpoint flat ulcer to a large sore.

Lesions can be shallow or deep (2-30 mm in diameter) and usually have a central, yellowish, necrotic base and a punched-out, clean margin.

They can appear singly or in crops, are located anywhere in the oral cavity,

Oral ulcers

persist for 1-2 weeks, and subside without leaving scars.

The most common sites are the tongue, lips, buccal mucosa, and gingiva; the tonsils, palate, and pharynx are less common sites.

The interval between recurrences ranges from weeks to months.

Oral ulcers can be classified into 3 types

Genital manifestations

cause greater scarring. They have been found in 56.7-97% of pt In males, the ulcers usually occur on the scrotum

,penis, and groin. In females, they occur on the vulva, vagina,

groin, and cervix. Ulcers have also been found in the urethral

orifice and perianal area. Epididymitis orchiepididymitis

Cutaneous manifestations

Erythema nodosum–like lesions, which are most common

Papulopustular eruptions Erythema multiforme–like lesions Thrombophlebitis Ulcers Lesions resembling Sweet syndrome Bullous necrotizing vasculitis Pyoderma gangrenosum

Ocular manifestations Ocular involvement is the major cause of morbidity and

the most dreaded complication because it occasionally progresses rapidly to blindness. It is reported in

47-65% of patients with BD. The most diagnostically relevant lesion is posterior

uveitis, Other lesions include anterior uveitis, iridocyclitis, chorioretinitis, scleritis, keratitis, vitreous hemorrhage, optic neuritis, conjunctivitis, retinal vein occlusion, and retinal neovascularization. Hypopyon, which was considered the hallmark of BD, is now uncommon.

.

Eye complications

Eye disease is usually present from the outset but also may develop within the first few years.

Decreased visual acuity is a result of secondary glaucoma, cataracts, or vitreous hemorrhage.

Blindness has been reported to occur within 4-5 years from the onset of ocular symptoms.

Retinal vein thrombosis leading to sudden blindness is not rare

Vascular involvement

This occurs in 7-29% of patients, mostly men. The 4 types of vascular lesions recognized in

persons with BD are arterial occlusions, venous occlusions, aneurysms, and varices.

Affected sites of the venous system are the superior vena cava, inferior vena cava

Arterial complications account for 7% of cases. Aneurysm and occlusion are most common.

Vascular cpmlications

Hypertension originate from renal artery stenosis.

Femoral artery stenosis and intermittent claudication cause avascular necrosis of the femoral head.

Pulmonary vasculitis can produce dyspnea, chest pain, cough, or hemoptysis.

Aneurysm formation accounts for most vascular deaths.

•Gastrointestinal involvement

10% of patients with BD. Anorexia, vomiting, dyspepsia, diarrhea, abdominal distention, abdominal pain

Joint manifestations 50% develope signs or symptoms of synovitis,

arthritis, and/or arthralgia during the course of the disease.

The most frequent minor feature in childhood-onset BD is reported to be arthritis

Multiple-joint involvement is common. Clinical features have been reported as pain (57

cases), tenderness (52 cases), swelling (48 cases), limitation of joint movement (26 cases), warmth (11 cases), and morning stiffness (10 cases).

Neurologic manifestations

varies from 3.2-49%. Neurologic involvement may present (in various

combinations) as meningoencephalitis, a multiple sclerosis–like illness, acute myelitis, stroke,

Neurologic involvement is one of the most serious complications, leading to severe disability and a high fatality rate.

Neurologic manifestations usually occur within 5 years of disease onset

Severe headache is the most frequent initial neurological symptom.

other Pregnant women may experience more

severe symptoms, more in the first trimester. Myocarditis Major hemoptysis may result from pulmonary

vascular thrombosis, aneurysms, or vasculitis.

Cases with renal involvement, such as mild asymptomatic glomerulonephritis,may occur

The pathergy phenomenon is considered an outstanding feature of BD

Causes

HLA-B51 MICA allele is a polymorphic MHC class

I–related gene A (MICA) family. significantly associated with BD (74%), compared with controls (45.6%)

Acquired hypersensitivity to streptococcal antigens

HSV DNA was found with PCR

 DDX

Acute Febrile Neutrophilic Dermatosis Aphthous Stomatitis Erythema Multiforme Erythema Nodosum Herpes Simplex Lupus Erythematosus, Acute Pyoderma Gangrenosum Stevens-Johnson Syndrome and Toxic Epidermal Necrolysis Inflammatory bowel disease (Crohn disease

LAB Mild anemia and leukocytosis are observed in some

patients with chronic disease. The ESR, C-reactive protein value, and other acute

phase reactants may be elevated during the active stage of BD, but they do not correlate well with the clinical activity.

An increase in alpha-2 globulins is often observed. Serum immunoglobulin levels, especially immunoglobulin A, may be elevated.

Circulating immune complexes are often present. Rheumatoid factor and antinuclear antibodies are

absent.

HISTOLOGY

Histologic Findings: The etiology and pathogenesis of BD remain obscure, although many reviews describe a lymphocytic vasculitis. Vasculitis is thought to affect vessels of all sizes; the various skin lesions are thought to be secondary to small vessel vasculitis.

T-cell subsets with a preponderance of helper-inducer cells over T suppressor-cytotoxic cells have been observed in lesions

TREATMENTLocal therapy Tetracycline doc for aphthous stomatitis The patient dissolves the contents of a 250-mg

tetracycline capsule in 5 mL of water or flavored syrup and holds the solution in the mouth for approximately 2 minutes before swallowing. This is repeated 4 times daily.

Topical corticosteroids are effective for oral or genital ulcerations if they are applied during the prodromal stage of ulceration.

Other useful drugs include lidocaine gel (2%), sucralfate suspension, and 5% amlexanox

SYSTEMIC RX.Corticosteroids are the mainstay of treatment for all

the various clinical manifestations. Although they have a beneficial effect on acute manifestations, no definite evidence indicates they are effective for controlling progression.

Mucocutaneous lesions and arthritis have been treated with nonsteroidal anti-inflammatory drugs, zinc sulfate, levamisole, colchicine, dapsone, or sulfapyridine and thalidomide. Immunosuppressive therapy with azathioprine, chlorambucil, or cyclophosphamide has been used.

TREATMENT

Uveitis and central nervous system involvement is treated with systemic corticosteroids, azathioprine, or cyclosporine

Anticoagulants are given to patients with thromboses.

FK506 has been particularly noteworthy. The Japanese FK506 study group reported that FK506 was effective in treating refractory uveitis in a dosage-dependent manner

SURGICAL Gastrointestinal perforation Enterocutaneous fistula formation Spontaneous arterial aneurysm formation Thrombotic obstruction in large-caliber vessels Cardiac involvement Proper timing for surgical treatment is

important. Delayed wound healing or inflammation at

operative sites may be related to pathergy.

EM

Electron microscopic observations Examination of erythema nodosum–like

lesions shows microvascular changes and lymphocyte-mediated fat cell lysis. Additionally, small dermal blood vessels embolized by thrombi are observed at the sites of the needle prick reaction and at the erythema nodosum–like lesions