1. Behcet's disease is a systemic autoimmune vasculitis characterized by recurrent oral and genital ulcers. It can affect multiple organ systems including eyes, skin, joints, gastrointestinal tract, and nervous system. 2. The disease is named after Turkish dermatologist Hulusi Behcet who first described the triple symptom complex in 1937. It is more common in countries along the Silk Road. Genetic factors like HLA-B51 are associated with increased risk. 3. Pathogenesis involves inflammation of blood vessels due to immune dysregulation. Diagnosis is based on clinical criteria including oral/genital ulcers, skin lesions, eye inflammation, and positive pathergy test. Treatment focuses on

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Behcet Disease Topology
Prepared by
Mostafa Askar Askar
Molecular Biology Department
Introduction:
Behcet Disease: One of the largest types of autoimmune diseases.
Behçet's disease (beh-CHETS), sometimes called Behçet's syndrome, Morbus
Behçet, Adamantiades syndrome, or Silk Road disease. Behçet's disease (BD) was
named in 1937 after the Turkish dermatologist Hulusi Behçet, who first described the
triple-symptom complex of recurrent oral aphthous ulcers, genital ulcers, and uveitis.
As a systemic disease, it can also involve visceral organs such as the gastrointestinal
tract, pulmonary, musculoskeletal, cardiovascular and neurological systems. This
syndrome can be fatal due to ruptured vascular aneurysms or severe neurological
complications.

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History
Behçet disease is named after Hulusi Behçet (1889–1948), the Turkish
dermatologist and scientist who first recognized the syndrome in one of his patients
in 1924 and reported his research on the disease in Journal of Skin and Venereal
Diseases in 1936. The name (Morbus Behçet) was formally adopted at the
International Congress of Dermatology in Geneva in September 1947. Symptoms of
this disease may have been described by Hippocrates in the 5th century BC, in his 3rd
Epidemion-book. Its first modern formal description was published in 1922.
Epidemiology
The syndrome is rare in the United States, but is common in the Middle East and
Asia. It is not associated with cancer. One study has revealed a possible connection to
food allergies, particularly to dairy products. An estimated 15,000 to 20,000
Americans have been diagnosed with this disease. In the UK, it is estimated to have
about 1 case for every 100,000 people. Globally, males are affected more frequently
than females. In the United States, more females are affected than males. In an
epidemiologic study, 56% of patients with Behçet's disease developed ocular
involvement at a mean age of 30.

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Signs and symptoms
Oral Lesions
 Oralulceration is usually an initial symptom
 Oralaphthae which are grossly
 Lesions heal within about10 days withoutscarring.
Uro-genital Lesions
 Genital ulceration occurs in 75 percent or more of patients with Behcet's
disease.
 The ulcers are similar in appearanceto the oral aphthae.
 Genital ulcers are most commonly found on the scrotum in men and the vulva
in women
 Recurrence is typically less frequent than with oral ulcerations.

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Cutaneous Lesions
 Cutaneous lesions also occur in over 75 percent of patients with Behcet's
disease.
 May include acneiformlesions, erythema nodosum, pyoderma gangrenosum-
type lesions, and palpable purpura.
Arthritis
 Nonerosive, asymmetric, usually nondeforming arthritis occurs in about one-
half of patients with Behcet's disease, particularly during exacerbations.
 Most commonly affects the medium and large joints, including the knee,
ankle, and wrist.
Ocular
 Ocular diseaseoccurs in 25 to 75 percent of patients with Behcet's disease,
and may progress to blindness.
 Symptoms, including blurred vision, eye pain, photophobia, lacrimation,
floaters
 Uveitis is often the dominant feature of Behcet's disease. Itis typically
bilateral and episodic.
 Hypopyon, a visible layer of pus in the anterior ocular chamber, is
characteristic of Behçet's disease
 The most serious ocular problem in patients with Behçet's diseaseis retinal
disease, as a resultof vaso-occlusivelesions.

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Gastrointestinal
 Symptoms include abdominal pain, diarrhea, melena, and sometimes
perforation.
 Gastrointestinalulcerations occur most often in the terminal ileum, cecum,
and ascending colon.
 Histologically, the intestinal ulcers of Behçet's disease are indistinguishable
fromthose of ulcerative colitis.
 Itis often difficult to distinguish between Behçet's disease and inflammatory
bowel diseases, becauseof the similarity in extraintestinal symptoms
Neurologic
 Neurologic diseaseoccurs in less than one-fifth of patients with Behcet's
disease, more frequently in men than women.
 Classically, meningitis or meningoencephalitis, neurologic deficits such as
motor disturbances and brain-stemsymptoms, and psychiatric symptoms
including personality changes develop more than five years after Behçet's
diseaseis diagnosed.

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Vascular
 Small-vesselvasculitis is common and accounts for much of the pathologic
process in Behçet's disease.
 Large vesselvascular involvementoccurs in approximately one-third of
patients with Behcet's disease.
 Superficial and deep venous thrombosis is common.
Cause
The cause is not well-defined, but it is primarily characterized by auto-inflammation
of the blood vessels.
In fact, no one knows yet why the immune system starts to behave this way in
Behçet's disease.
An association with the GIMAP family of genes on the long arm of chromosome
7 (7q36.1) has been reported. The genes implicated
were GIMAP1, GIMAP2 and GIMAP4.
(GIMAP) This gene encodes a protein belonging to the GTP-binding superfamily and
to the immuno-associated nucleotide (IAN) subfamily of nucleotide-binding proteins.
The encoded protein of this gene may be negatively regulated by T-cell acute
lymphocytic leukemia 1 (TAL1). In humans, the IAN subfamily genes are located in
a cluster at 7q36.1.
Pathophysiology
A large number of serological studies show a linkage between the disease and human
leucocytes antigen HLA-B51. HLA-B51 is more frequently found from the Middle
East to South Eastern Siberia, but the incidence of B51 in some studies was 3 fold
higher than the normal population. However, B51 tends not to be found in disease

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when a certain SUMO4 gene variant is involved, and symptoms appear to be milder
when HLA-B27 is present. (Small ubiquitin-related modifier 4 is a protein that in
humans is encoded by the SUMO4 gene.
(This gene is a member of the SUMO gene family. This family of genes encodes
small ubiquitin-related modifiers that are attached to proteins and control the
target proteins' subcellular localization, stability, or activity. The protein described
in this record is located in the cytoplasm and specifically modifies IKBA, leading to
negative regulation of NF-kappa-B-dependent transcription of the IL12B gene. A
specific polymorphism in this SUMO gene, which leads to the M55V substitution,
has beenassociated with type I diabetes)
At the current time, a similar infectious origin has not yet been confirmed that leads
to Behçet's disease, but certain strains of Streptococcus sanguinis has been found to
have a homologous antigenicity.

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Finally
Both innate and adaptive immune systems are activated in BD, with a
proinflammatory and Th1-type of cytokine profile. BD may be linked to a specific,
primary immune abnormality with a genetic mutation aVecting an adhesion molecule
or a proinflammatory cytokine, which predisposes to early or more intense neutrophil
and T cell responses. Alternatively, a broad intracellular signaling abnormality of a
transcription factor, which lowers the threshold of inflammatory responses to external
stimuli, as proposed for familial Mediterranean fever with decreased pyrine
expression of neutrophils, may be present (hyperreactivity model). However, an
adaptive immune system is also crucial in BD, with possibly both external
(streptococcal, superantigens) and internal (heat shock or organ-specific proteins)
antigens driving the pathogenic tissue T cell infiltrations. Better characterisation of
pathogenic immune cell subsets, systemic and local antigens, and abnormal cell-
activation mechanisms may help in the future to develop more specific and less toxic
immunotherapeutic approaches to the still unsatisfactorily treated BD.
Diagnosis
4 "hallmark" symptoms:
 genital ulcers (including anal ulcers and spots in the genital region and
swollen testicles or epididymitis in men)
 skin lesions (papulo-pustules, folliculitis, erythema nodosum, acne in post-
adolescents not on corticosteroids)
 eye inflammation (iritis, uveitis, retinal vasculitis, cells in the vitreous)
 pathergy reaction (papule >2 mm dia. 24-48 hrs or more after needle-prick). Positive
pathergy test. In a pathergy test, your doctor inserts a sterile needle into your skin and then examines the
area one to two days later. If the pathergy test is positive, a small red bump forms under your skin where the
needle was inserted. This indicates your immune system is overreacting to a minor injury.

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Another clinical manifestations
 mouth ulcers
 arthritis/arthralgia
 nervous system symptoms
 stomach and/or bowel inflammation
 deep vein thrombosis
 superficial thrombophlebitis
 epididymitis
 cardio-vascular problems of an inflammatory origin
 inflammatory problems in chest and lungs
 problems with hearing and/or balance
 extreme exhaustion
 changes of personality, psychoses
 any other members of the family with a diagnosis of Behçet disease.
Treatment
Current treatment is aimed at easing the symptoms, reducing inflammation, and
controlling the immune system. High doseCorticosteroid therapy (1 mg/kg/d oral
prednisone) is indicated for severe disease manifestations.
Anti-TNF therapy such as infliximab has shown promise in treating

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References
http://ard.bmj.com/content/60/11/996.full.html#related-urls
Article citedin:
http://ard.bmj.com/content/60/11/996.full.html#ref-list-1