The exact cause of<unk>  is not known. The current working hypothesis is, in genetically susceptible individuals,<unk>  is caused through alteration to the immune response after exposure to an environmental, occupational, or infectious agent. Some cases may be caused by treatment with tumor necrosis factor (TNF) inhibitors like etanercept. Genetics The heritability of<unk>  varies according to ethnicity. About 20% of African Americans with<unk>  have a family member with the condition, whereas the<unk> me figure for European Americans is about 5%. Additionally, in African Americans, who seem to experience more severe and chronic disease, siblings and parents of<unk>  cases have about a 2.5-fold increased risk for developing the disease. In Swedish individuals heritability was found to be 39%. In this group, if a first-degree family member was affected, a person has a four-fold greater risk of being affected. Investigations of genetic susceptibility yielded many candidate genes, but only few were confirmed by further investigations and no reliable genetic markers are known. Currently, the most interesting candidate gene is BTNL2; several HLA-DR risk alleles are also being investigated. In persistent<unk> , the HLA haplotype HLA-B7-DR15 is either cooperating in disease or another gene between these two loci is associated. In nonpersistent disease, a strong genetic association exists with HLA DR3-DQ2. Cardiac<unk> coid has been connected to tumor necrosis factor alpha (TNFA) variants. Infectious agents Several infectious agents appear to be significantly associated with<unk> , but none of the known associations is specific enough to suggest a direct causative role. The major implicated infectious agents include: mycobacteria, fungi, borrelia, and rickettsia. A meta-analysis investigating the role of mycobacteria in<unk>  found it was present in 26.4% of cases, but they also detected a possible publication bias, so the results need further confirmation. Mycobacterium tuberculosis catalase-peroxidase has been identified as a possible antigen catalyst of<unk> . The disease has also been reported by transmission via organ transplants. A large epidemiological study found little evidence that infectious diseases spanning years before<unk>  diagnosis could confer measurable risks for<unk>  diagnosis in the future. Autoimmune Association of autoimmune disorders has been frequently observed. The exact mechanism of this relation is not known, but some evidence supports the hypothesis that this is a consequence of Th1 lymphokine prevalence. Tests of delayed cutaneous hypersensitivity have been used to measure progression.
Sarcoidosis
Cat-scratch disease
Melioidosis
Tuberculosis
Gamasoidosis
Sporotrichosis
Milk-alkali syndrome
Amyloidosis