Behcet’s disease

Behcets DiseaseBehcets Disease Iman GalalIman Galal Pulmonary Medicine DepartmentPulmonary Medicine Department Ain Shams UniversityAin Shams University E-mail: [email protected]: [email protected]

Historical Aspect:Historical Aspect: In 1937,In 1937, Prof. Hulusi Behet,Prof. Hulusi Behet, aa Turkish dermatologistTurkish dermatologist (1889-1948),(1889-1948), described a syndrome characterized bydescribed a syndrome characterized by recurrent oral ulcers, genital ulcers, &recurrent oral ulcers, genital ulcers, & hypopyon uveitis of unknown cause.hypopyon uveitis of unknown cause.

Epidemiology:Epidemiology: Disease prevalence & expression vary geographically & itDisease prevalence & expression vary geographically & it affects people in the Middle Eastern or Far East moreaffects people in the Middle Eastern or Far East more often than those from other regions.often than those from other regions. Turkey has the highest prevalence: 80-370 cases perTurkey has the highest prevalence: 80-370 cases per 100,000 population.100,000 population.

Epidemiology:Epidemiology: People of Mediterranean, Middle Eastern & Asia arePeople of Mediterranean, Middle Eastern & Asia are thought to be at risk of developing Behet's disease.thought to be at risk of developing Behet's disease. In those of Mediterranean & Middle Eastern origin,In those of Mediterranean & Middle Eastern origin, Behet's disease is more common in men than in women.Behet's disease is more common in men than in women. However, in people of Asia, Behet's disease is moreHowever, in people of Asia, Behet's disease is more common in women.common in women. The symptoms of Behet's disease tend to be more severeThe symptoms of Behet's disease tend to be more severe in men.in men.

Epidemiology:Epidemiology: (International gender ( : ratio) distribution) (International gender ( : ratio) distribution)

Pathophysiology:Pathophysiology: The underlying cause of Behet's disease is unknown.The underlying cause of Behet's disease is unknown. As with other autoimmune diseases, the disorder mayAs with other autoimmune diseases, the disorder may represent aberrant immune activity triggered by exposure torepresent aberrant immune activity triggered by exposure to an agent, in patients with a genetic predisposition (HLA B51).an agent, in patients with a genetic predisposition (HLA B51). Some environmental factors that have been suggested asSome environmental factors that have been suggested as possibly being associated with Behet's disease include:possibly being associated with Behet's disease include: Herpes virus,Herpes virus, Hepatitis virus,Hepatitis virus, Bacteria, andBacteria, and Pollutants e.g., industrial waste or chemicals.Pollutants e.g., industrial waste or chemicals.

1.1. Oral lesions:Oral lesions: Oral ulceration is usually an initial symptom & is seen inOral ulceration is usually an initial symptom & is seen in all patients at some time in the clinical course,all patients at some time in the clinical course, sometimes precedes other manifestations by years.sometimes precedes other manifestations by years. Oral aphthae which are grossly & histologically similarOral aphthae which are grossly & histologically similar to common oral ulcers, but tend to be more extensive &to common oral ulcers, but tend to be more extensive & often multiple.often multiple. Lesions heal within about 10 days without scarring.Lesions heal within about 10 days without scarring. Clinical ManifestationsClinical Manifestations

Oral LesionsOral Lesions

2.2. Ocular lesions:Ocular lesions: Ocular disease occurs in 25-75% of patients withOcular disease occurs in 25-75% of patients with Behet's disease & may progress to blindness.Behet's disease & may progress to blindness. Symptoms include blurred vision, eye pain, photophobiaSymptoms include blurred vision, eye pain, photophobia & lacrimation.& lacrimation. Uveitis is often the dominant feature of Behet's disease.Uveitis is often the dominant feature of Behet's disease. It is typically bilateral & episodic.It is typically bilateral & episodic. Clinical ManifestationsClinical Manifestations

2.2. Ocular lesions:Ocular lesions: Hypopyon; a visible layer of pus in the anterior ocularHypopyon; a visible layer of pus in the anterior ocular chamber, is characteristic of Behet's diseasechamber, is characteristic of Behet's disease The most serious ocular problem in patients withThe most serious ocular problem in patients with Behet's disease is retinal disease, as a result of vaso-Behet's disease is retinal disease, as a result of vaso- occlusive lesions.occlusive lesions. Clinical ManifestationsClinical Manifestations

Ocular LesionsOcular Lesions

3.3. Uro-genital lesions:Uro-genital lesions: Genital ulceration occur in 75% of patients with Behet'sGenital ulceration occur in 75% of patients with Behet's disease.disease. The ulcers are similar in appearance to the oral aphthae.The ulcers are similar in appearance to the oral aphthae. Genital ulcers are most commonly found on the scrotumGenital ulcers are most commonly found on the scrotum in men & the vulva in women.in men & the vulva in women. Recurrence is typically less frequent than with oralRecurrence is typically less frequent than with oral ulcerations.ulcerations. Clinical ManifestationsClinical Manifestations

4.4. Cutaneous lesions:Cutaneous lesions: Cutaneous lesions also occur in over 75% of patientsCutaneous lesions also occur in over 75% of patients with Behet's disease.with Behet's disease. They include acneiform lesions, erythema nodosum,They include acneiform lesions, erythema nodosum, pyoderma gangrenosum-type lesions, & palpablepyoderma gangrenosum-type lesions, & palpable purpura.purpura. Clinical ManifestationsClinical Manifestations

Erythema NodosumosumErythema Nodosumosum

Pyoderma GangenosumPyoderma Gangenosum

4.4. Cutaneous lesions:Cutaneous lesions: PathergyPathergy refers to an erythematous papular orrefers to an erythematous papular or pustular response to local skin injury.pustular response to local skin injury. PathergyPathergy is defined as ais defined as a > 5 mm lesion> 5 mm lesion that appearsthat appears 24-48 hours24-48 hours after skin prick by a needle.after skin prick by a needle. Pathergy testPathergy test is a non-specific test.is a non-specific test. Clinical ManifestationsClinical Manifestations

Coetaneous LesionsCoetaneous Lesions

5.5. Arthritis:Arthritis: Non-erosive, asymmetric, usually non-deformingNon-erosive, asymmetric, usually non-deforming arthritis occurs in about one-half of patients witharthritis occurs in about one-half of patients with Behet's disease, particularly during exacerbations.Behet's disease, particularly during exacerbations. Most commonly affects the medium & large joints,Most commonly affects the medium & large joints, including the knee, ankle, & wrist.including the knee, ankle, & wrist. Clinical ManifestationsClinical Manifestations

6.6. Gastrointestinal:Gastrointestinal: Symptoms include abdominal pain, diarrhea, melena, &Symptoms include abdominal pain, diarrhea, melena, & sometimes perforation.sometimes perforation. Gastrointestinal ulcerations occur most often in theGastrointestinal ulcerations occur most often in the terminal ileum, cecum, & ascending colon.terminal ileum, cecum, & ascending colon. Histologically, the intestinal ulcers of Behet's diseaseHistologically, the intestinal ulcers of Behet's disease are indistinguishable from those of ulcerative colitis.are indistinguishable from those of ulcerative colitis. Clinical ManifestationsClinical Manifestations

Clinical ManifestationsClinical Manifestations 7.7. Neurological:Neurological: Occurs in < 20 % of patients being more common in men.Occurs in < 20 % of patients being more common in men. Classically, meningitis or meningoencephalitis, motorClassically, meningitis or meningoencephalitis, motor neurologic deficits, loss of bladder control, headache, &neurologic deficits, loss of bladder control, headache, & psychiatric symptoms including personality changespsychiatric symptoms including personality changes develop more than five years after the diagnosis ofdevelop more than five years after the diagnosis of Behet's disease.Behet's disease. In the terminal stage, dementia becomes evident in aboutIn the terminal stage, dementia becomes evident in about 30% of affected patients.30% of affected patients.

Cerebral Artery AneurismCerebral Artery Aneurism

Clinical ManifestationsClinical Manifestations 8.8. Vascular lesions:Vascular lesions: Vasculitis in BehetVasculitis in Behets disease is Immune-complexs disease is Immune-complex mediated.mediated. Small-vessel vasculitis is common & accounts for much ofSmall-vessel vasculitis is common & accounts for much of the pathologic process in Behet's disease.the pathologic process in Behet's disease. Large vessel vascular involvement occurs inLarge vessel vascular involvement occurs in approximately one-third of patients with Behet'sapproximately one-third of patients with Behet's disease.disease. Superficial & deep venous thrombosis are common.Superficial & deep venous thrombosis are common.

Intracardiac ThrombosisIntracardiac Thrombosis (a)(a) Before treatmentBefore treatment (b)(b) After treatmentAfter treatment

Clinical ManifestationsClinical Manifestations 8.8. Vascular lesions:Vascular lesions: Vascular lesions may lead to stenosis or aneurysmVascular lesions may lead to stenosis or aneurysm formation (may rupture fatal).formation (may rupture fatal). Vascular lesions in the lung, including thrombosis,Vascular lesions in the lung, including thrombosis, aneurysm, & arteriobronchial fistula, causing recurrentaneurysm, & arteriobronchial fistula, causing recurrent episodes of dyspnea, cough, chest pain & hemoptysis.episodes of dyspnea, cough, chest pain & hemoptysis.

Left Ventricular Pseudo-aneurysmLeft Ventricular Pseudo-aneurysm

Pulmonary Artery AneurismPulmonary Artery Aneurism

Aneurismal DilatationAneurismal Dilatation

Diagnostic Criteria:Diagnostic Criteria:

Complications:Complications: DeathDeath BlindnessBlindness ParalysisParalysis Embolism/thrombosis - pulmonary, vena cava or peripheral.Embolism/thrombosis - pulmonary, vena cava or peripheral. AneurysmsAneurysms AmyloidosisAmyloidosis Thrombotic events (especially with +ve anticardiolipinThrombotic events (especially with +ve anticardiolipin antibodies).antibodies).

Treatment:Treatment: The choice of the treatment depends on the patient'sThe choice of the treatment depends on the patient's clinical manifestations.clinical manifestations. Significant ocular, neurologic, gastrointestinal, vascular,Significant ocular, neurologic, gastrointestinal, vascular, or other serious end organ manifestations typicallyor other serious end organ manifestations typically require treatment with steroids & otherrequire treatment with steroids & other immunosuppressive agents.immunosuppressive agents. Secondary thrombosis may not be preventable bySecondary thrombosis may not be preventable by anticoagulation, instead 80 mg/day of Aspirin is moreanticoagulation, instead 80 mg/day of Aspirin is more favorable.favorable.

Treatment:Treatment: Prednisone alone may not be sufficient to control thePrednisone alone may not be sufficient to control the vasculitis & the addition of other drugs e.g.,vasculitis & the addition of other drugs e.g., immunosuppressive agents is recommended.immunosuppressive agents is recommended. Types of Intravenous ImmunosuppressantsTypes of Intravenous Immunosuppressants:: Traditional immunosuppressantsTraditional immunosuppressants:: Chlorambucil, methotrexate, cyclosporin, or azathioprin.Chlorambucil, methotrexate, cyclosporin, or azathioprin. Monoclonal antibodies:Monoclonal antibodies: Infliximab & interferon-Infliximab & interferon-..

Treatment:Treatment: Low dose aspirin is probably reasonable in patients with Behcet's associated superficial thrombophlebitis. Systemic anticoagulation is often used in patients with deep venous thrombosis.. The presence of pulmonary arteritis rules out the usage ofThe presence of pulmonary arteritis rules out the usage of anticoagulation.anticoagulation. Embolization therapy may be used for both treatment &Embolization therapy may be used for both treatment & prevention of hemorrhage from pulmonary arteryprevention of hemorrhage from pulmonary artery aneurysms,aneurysms,

Treatment:Treatment: ManifestationManifestation MildMild SevereSevere Mouth ulceration Mouth washes Topical steroids Thalidomide , Azathioprine, Infliximab/etanercept Genital ulceration Topical steroids Colchicine in females Thalidomidem Azathioprinem Infliximab Erythema Colchicine, Corticosteroids Arthritis/arthralgia Simple & NSAID Colchicine, corticosteroids, azathioprine, interferon Anterior uveitis Topical steroids Panuveitis, posterior uveitis Azathioprine, Oral cyclosporin, Corticosteroids, Interferon, Infliximab Retinal vasculitis Azathioprine, Oral cyclosporin, Pulsed i.v./oral corticosteroids, Interferon, Infliximab Thrombophlebitis Symptomatic Azathioprine, Low-dose aspirin Arteritis Pulsed i.v./oral corticosteroids, Pulsed i.v./oral cyclophosphamide, Azathioprine Neurological involvement Pulsed i.v. cyclophosphamide or oral azathioprine plus pulsed i.v./oral corticosteroidsInfliximab Gastrointestinal lesions Sulphasalazine, azathioprine, infliximab

Prognosis:Prognosis: Behcet's disease has an undulating course ofBehcet's disease has an undulating course of exacerbations & remissions, and may become less severeexacerbations & remissions, and may become less severe after approximately 20 years.after approximately 20 years. The disease appears to be more severe in young, male, &The disease appears to be more severe in young, male, & Middle Eastern or Far Eastern patients.Middle Eastern or Far Eastern patients. Mucocutaneous, articular and ocular manifestations areMucocutaneous, articular and ocular manifestations are often at their worst in the early years of the disease.often at their worst in the early years of the disease. Half of patients die within three years after the onset ofHalf of patients die within three years after the onset of hemoptysis.hemoptysis.

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Behcet’s disease