DRESS syndrome pathophysiology
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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief:
Overview
Pathophysiology
The exact pathogenesis of DRESS syndrome is poorly understood. It is thought that an interaction between genetic and environmental factors is responsible for the development of DRESS syndrome.
Genetics
- Genetic deficiency of detoxifying enzymes results in accumulation of toxic metabolites and subsequent activation of immunologic reactions.[1]
- The variation of the incidence of DRESS syndrome across ethnicities may suggest a significant role for genetics in the pathogenesis of DRESS syndrome.[2]
- DRESS syndrome is associated with certain human leukocyte antigen (HLA), such as:[3][4]
- HLA-B*1508
- HLA-B*1502
Pathogenesis
- It is thought that toxic accumulation of metabolites results in the activation of interleukin-5 (IL-5), which results in the activation of eosinophils and the downstream inflammatory cascade.[5][6][1]
- It is unknown how drug interactions are associated viral activation and clinical manifestations of DRESS syndrome, but expansion of both virus-specific and non-specific T-cells is often observed with DRESS syndrome and herpes virus reactivation (e.g. CMV, EBV, HHV6, and HHV7) is common among patients with DRESS syndrome. Accordingly, it has been postulated that in addition to the clonal expansion of drug-specific T-cells, antiviral T-cells may cross-react with drugs and result in concomitant expansion of viral-specific T-cells.[7]
References
- ↑ 1.0 1.1 Knowles SR, Uetrecht J, Shear NH (2000). "Idiosyncratic drug reactions: the reactive metabolite syndromes". Lancet. 356 (9241): 1587–91. doi:10.1016/S0140-6736(00)03137-8. PMID 11075787.
- ↑ Lonjou C, Thomas L, Borot N, Ledger N, de Toma C, LeLouet H; et al. (2006). "A marker for Stevens-Johnson syndrome ...: ethnicity matters". Pharmacogenomics J. 6 (4): 265–8. doi:10.1038/sj.tpj.6500356. PMID 16415921.
- ↑ Chung WH, Hung SI, Hong HS, Hsih MS, Yang LC, Ho HC; et al. (2004). "Medical genetics: a marker for Stevens-Johnson syndrome". Nature. 428 (6982): 486. doi:10.1038/428486a. PMID 15057820.
- ↑ Hung SI, Chung WH, Jee SH, Chen WC, Chang YT, Lee WR; et al. (2006). "Genetic susceptibility to carbamazepine-induced cutaneous adverse drug reactions". Pharmacogenet Genomics. 16 (4): 297–306. doi:10.1097/01.fpc.0000199500.46842.4a. PMID 16538176.
- ↑ Choquet-Kastylevsky G, Intrator L, Chenal C, Bocquet H, Revuz J, Roujeau JC (1998). "Increased levels of interleukin 5 are associated with the generation of eosinophilia in drug-induced hypersensitivity syndrome". Br J Dermatol. 139 (6): 1026–32. PMID 9990366.
- ↑ Kano Y, Shiohara T (2004). "Sequential reactivation of herpesvirus in drug-induced hypersensitivity syndrome". Acta Derm Venereol. 84 (6): 484–5. PMID 15844647.
- ↑ Shiohara T, Kano Y (2007). "A complex interaction between drug allergy and viral infection". Clin Rev Allergy Immunol. 33 (1–2): 124–33. doi:10.1007/s12016-007-8010-9. PMID 18094951.