Behсet's disease: Description, Causes and Risk Factors:
Alternative Names: Triple symptom complex, Behçet syndrome, recurrent hypopyon, iridocyclitis septica, cutaneomucouveal syndrome, oculobuccogenital syndrome, uveoencephalitic syndrome.
Behсet's disease is a chronic, relapsing-remitting, occlusive vasculitis affecting multiple organ systems in the body. It is a multifaceted syndrome, characterized by mouth and genital ulcerations (sores) and uveitis. The disease occurs worldwide, however it has a much higher incidence in the latitudes between 30? and 45? N, around the Mediterranean basin extending through Middle East and Orient. The striking similarity of the distribution of Behçet's disease to the ancient Silk Road suggests that an inherited tendency to develop Behçet's Disease was spread by merchants who traveled these trading routes.
The exact cause of Behсet's disease is unknown, but it may be an autoimmune disorder, which means the body's immune system mistakenly attacks some of its own healthy cells. Both genetic and environmental factors may be responsible for Behcet's disease. Behets disease is not contagious and does not spread from one person to another.
The genetic locus most widely studied in Behсet's disease is the human leukocyte antigen (HLA) complex on chromosome 6p21. Disease susceptibility has consistently been associated with polymorphisms in the HLA-B gene, particularly HLA-B*51. This has been con?rmed in all ethnic groups, although the association is stronger in Turkish and Japanese patients than in Caucasians. HLA-B*51 has at least 34 allelic variants: the association has been re?ned to the most common molecular subtypes, HLA-B*5101 and HLA-B*5108.15 HLA-B*57 has recently also been associated with disease susceptibility in Caucasians, in whom it carried a relative risk of disease equivalent to that of HLA-B*51.
The biological mechanism whereby speci?c HLA-B alleles confer disease susceptibility remains unknown. It is not clear whether these are primary associations or whether risk alleles are in linkage disequilibrium with other, causative polymorphisms. Candidates include MICA*00917 or TNF-1031C16, both of which are also present on the HLA-B*5101 haplotype. Furthermore, these associations are not invariable: the relative risk of disease associated with HLA-B*51 varies widely in different ethnic populations, and the disease-associated alleles are present at high frequency in some populations in whom the disease is virtually unknown.
This indicates that other factors must also be involved in disease susceptibility, and a recent genome-wide scan has identi?ed a second susceptibility locus on chromosome 6p. Polymorphisms in other candidate genes outside the HLA have also been studied, including coagulation factor V, endothelial nitric oxide synthase, and intercellular adhesion molecule-1. Many of these studies were, however, conducted on a limited number of patients, and positive ?ndings have not been replicated. Thus, the contribution of other genetic variants to disease susceptibility remains unknown.
There is, however, no doubt that an in?ammatory response to several autoantigens is found in Behets disease. Anti-endothelial antibodies, for example, are a frequent but nonspeci?c ?nding. The retinal S antigen is an interesting candidate autoantigen found mainly in the retina. Other putative autoantigens include heat shock proteins, killer immunoglobulin-like receptors, tropomyosin, co-stimulatory molecules, oxidized low-density lipoprotein and the retinal S antigen. However, whether any of these autoantigens are truly pathogenic or whether the immune response directed towards them results from the profound in?ammatory reaction associated with disease activation remains unknown.
There is also strong evidence for generalized aberrant T-cell responses in Behсet's disease. When compared with healthy controls, patients with Behcet's disease have an increased number of circulating gamma-delta T-cells. These cells exhibit early activation markers and produce in?ammatory cytokines, although their target antigen is unclear. An increased production of interferon gamma (IFN-?) by alpha-beta T-cells has also been demonstrated in active Behcet's disease, and circulating T-cells are predominantly of the T-helper 1 (Th1) phenotype. The mechanism by which these abnormalities contribute to disease pathogenesis is, however, uncertain: some authors have suggested that the primary abnormality is a defect in T-cell signal transduction, which results in a lowered threshold for activation to multiple antigens. Alternatively, an increased production of interleukin-12 (IL-12) by antigen-presenting cells may bias the T-cell response towards a Th1 phenotype and result in enhanced nonspeci?c in?ammation.
The most plausible environmental trigger is an infectious agent, and evidence of ongoing or previous infection with a variety of viral agents has been sought. These include herpes simplex virus 1, the hepatitis viruses, and parvovirus B19. Potential bacterial triggers including mycobacteria, Borrelia burgdorferi, Helicobacter pylori and a variety of streptococcal antigens. Most recently, antibodies to Saccharomyces cerevisiae have been proposed as a serological marker of disease, but the clinical relevance of this ?nding is uncertain.
Adult males are most commonly affected. The mean age at onset ranges from the mid 20s to the 50s. Behсet's disease is relatively rare in children and the elderly. Although a definitive pattern of inheritance has not been proven, cases that appear to run in families have been reported. While Behсet's disease classically has periods of active and inactive disease, it can become chronic in a given organ system.
Symptoms may include:
Mouth sores and canker sores.
- Acne likes sores on the body especially on the lower legs.
- Sores in the genitals.
- Joint swelling and pain.
- Abdominal pain.
There is no single diagnostic test for Behсet's disease. Several laboratory tests have been studied,but none have been found to be specific for disease activity. In patients with Behçet's diseaseaffecting the brain, increased cerebrospinal fluid protein and cell count may be detected. Agenetic predisposition with a strong association with the HLA-B51 gene appears to play animportant role in the cause of Behçet's.
The diagnosis of Behсet's disease is therefore based on findings present during history-takingand careful examination. Five different sets of criteria for the diagnosis of Behсet's disease havebeen used, with the differences in these criteria hindering interpretation of different studies. Aninternational study group was formed in 1990 to develop new internationally agreed upondiagnostic criteria for Behсet's disease. These criteria require the presence of oral ulceration(sores) plus any two of the following: genital ulceration; typical eye lesions; typical skin lesions;or a positive skin test for pathergy.
Although there is no cure for Behcet's disease, people can usually control their symptoms with proper medication, rest, and exercise. Treatment goals are to reduce discomfort and prevent serious complications such as disability from arthritis or blindness. The type of medicine and the length of treatment depend on the person's symptoms and their severity.
Colchicine, nonsteroidal antiinflammatory drugs, corticosteroids and immunosuppressants may be used in the treatment of Behсet's disease. Therapy is tailored to the individual patient. Acute anterior uveitis generally responds to corticosteroid eye drops. Inflammation involving the back of the eye requires treatment that is more aggressive with corticosteroids given by injection and/or pill (systemic therapy). Systemic corticosteroids are helpful in treating acute manifestations. Corticosteroids alone are neither sufficient nor safe for long-term management and prevention of blindness. Immunosuppressive drugs, such as cyclosporine, azathioprine, and chlorambucil may be considered. Cyclosporine, either alone or in combination with corticosteroids, is effective for the ocular lesions, but its nephrotoxicity, occurring in 20-30% of patients, restricts usage. Chlorambucil—also often in combination with corticosteroids—has been shown to be effective. Similar to other ocular inflammatory diseases, surgery may be required to deal with the complications of Behçet's disease. The heightened inflammatory response of patients with Behçet's disease to trauma, including surgery, should be considered but should not be regarded as an absolute contraindication to surgery.
NOTE: The above information is educational purpose. The information provided herein should not be used during any medical emergency or for the diagnosis or treatment of any medical condition.
DISCLAIMER: This information should not substitute for seeking responsible, professional medical care.