DRESS syndrome pathophysiology: Difference between revisions
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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. | 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=== | ===Genetics=== | ||
*Genetic deficiency of detoxifying enzymes results in accumulation of toxic metabolites and subsequent activation of immunologic reactions.<ref name="pmid11075787">{{cite journal| author=Knowles SR, Uetrecht J, Shear NH| title=Idiosyncratic drug reactions: the reactive metabolite syndromes. | journal=Lancet | year= 2000 | volume= 356 | issue= 9241 | pages= 1587-91 | pmid=11075787 | doi=10.1016/S0140-6736(00)03137-8 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=11075787 }} </ref> | *Genetic deficiency of detoxifying enzymes, such as epoxide hydrolase deficiency, results in accumulation of toxic metabolites and subsequent activation of immunologic reactions.<ref name="pmid11075787">{{cite journal| author=Knowles SR, Uetrecht J, Shear NH| title=Idiosyncratic drug reactions: the reactive metabolite syndromes. | journal=Lancet | year= 2000 | volume= 356 | issue= 9241 | pages= 1587-91 | pmid=11075787 | doi=10.1016/S0140-6736(00)03137-8 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=11075787 }} </ref> DRESS syndrome is more common among slow acetylators.<ref name="pmid1988235">{{cite journal| author=Rieder MJ, Shear NH, Kanee A, Tang BK, Spielberg SP| title=Prominence of slow acetylator phenotype among patients with sulfonamide hypersensitivity reactions. | journal=Clin Pharmacol Ther | year= 1991 | volume= 49 | issue= 1 | pages= 13-7 | pmid=1988235 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=1988235 }} </ref> | ||
*The variation of the incidence of DRESS syndrome across ethnicities may suggest a significant role for genetics in the pathogenesis of DRESS syndrome.<ref name="pmid16415921">{{cite journal| author=Lonjou C, Thomas L, Borot N, Ledger N, de Toma C, LeLouet H et al.| title=A marker for Stevens-Johnson syndrome ...: ethnicity matters. | journal=Pharmacogenomics J | year= 2006 | volume= 6 | issue= 4 | pages= 265-8 | pmid=16415921 | doi=10.1038/sj.tpj.6500356 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=16415921 }} </ref> | *The variation of the incidence of DRESS syndrome across families and ethnicities may suggest a significant role for genetics in the pathogenesis of DRESS syndrome.<ref name="pmid16415921">{{cite journal| author=Lonjou C, Thomas L, Borot N, Ledger N, de Toma C, LeLouet H et al.| title=A marker for Stevens-Johnson syndrome ...: ethnicity matters. | journal=Pharmacogenomics J | year= 2006 | volume= 6 | issue= 4 | pages= 265-8 | pmid=16415921 | doi=10.1038/sj.tpj.6500356 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=16415921 }} </ref> | ||
*DRESS syndrome is associated with certain human leukocyte antigen (HLA), such as:<ref name="pmid15057820">{{cite journal| author=Chung WH, Hung SI, Hong HS, Hsih MS, Yang LC, Ho HC et al.| title=Medical genetics: a marker for Stevens-Johnson syndrome. | journal=Nature | year= 2004 | volume= 428 | issue= 6982 | pages= 486 | pmid=15057820 | doi=10.1038/428486a | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=15057820 }} </ref><ref name="pmid16538176">{{cite journal| author=Hung SI, Chung WH, Jee SH, Chen WC, Chang YT, Lee WR et al.| title=Genetic susceptibility to carbamazepine-induced cutaneous adverse drug reactions. | journal=Pharmacogenet Genomics | year= 2006 | volume= 16 | issue= 4 | pages= 297-306 | pmid=16538176 | doi=10.1097/01.fpc.0000199500.46842.4a | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=16538176 }} </ref> | *DRESS syndrome is associated with certain human leukocyte antigen (HLA), such as:<ref name="pmid15057820">{{cite journal| author=Chung WH, Hung SI, Hong HS, Hsih MS, Yang LC, Ho HC et al.| title=Medical genetics: a marker for Stevens-Johnson syndrome. | journal=Nature | year= 2004 | volume= 428 | issue= 6982 | pages= 486 | pmid=15057820 | doi=10.1038/428486a | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=15057820 }} </ref><ref name="pmid16538176">{{cite journal| author=Hung SI, Chung WH, Jee SH, Chen WC, Chang YT, Lee WR et al.| title=Genetic susceptibility to carbamazepine-induced cutaneous adverse drug reactions. | journal=Pharmacogenet Genomics | year= 2006 | volume= 16 | issue= 4 | pages= 297-306 | pmid=16538176 | doi=10.1097/01.fpc.0000199500.46842.4a | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=16538176 }} </ref> | ||
:*HLA-B*1508 | :*HLA-B*1508 | ||
:*HLA-B*1502 | :*HLA-B*1502 | ||
===Pathogenesis=== | ===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.<ref name="pmid9990366">{{cite journal| author=Choquet-Kastylevsky G, Intrator L, Chenal C, Bocquet H, Revuz J, Roujeau JC| title=Increased levels of interleukin 5 are associated with the generation of eosinophilia in drug-induced hypersensitivity syndrome. | journal=Br J Dermatol | year= 1998 | volume= 139 | issue= 6 | pages= 1026-32 | pmid=9990366 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=9990366 }} </ref><ref name="pmid15844647">{{cite journal| author=Kano Y, Shiohara T| title=Sequential reactivation of herpesvirus in drug-induced hypersensitivity syndrome. | journal=Acta Derm Venereol | year= 2004 | volume= 84 | issue= 6 | pages= 484-5 | pmid=15844647 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=15844647 }} </ref><ref name="pmid11075787">{{cite journal| author=Knowles SR, Uetrecht J, Shear NH| title=Idiosyncratic drug reactions: the reactive metabolite syndromes. | journal=Lancet | year= 2000 | volume= 356 | issue= 9241 | pages= 1587-91 | pmid=11075787 | doi=10.1016/S0140-6736(00)03137-8 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=11075787 }} </ref> | *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.<ref name="pmid9990366">{{cite journal| author=Choquet-Kastylevsky G, Intrator L, Chenal C, Bocquet H, Revuz J, Roujeau JC| title=Increased levels of interleukin 5 are associated with the generation of eosinophilia in drug-induced hypersensitivity syndrome. | journal=Br J Dermatol | year= 1998 | volume= 139 | issue= 6 | pages= 1026-32 | pmid=9990366 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=9990366 }} </ref><ref name="pmid15844647">{{cite journal| author=Kano Y, Shiohara T| title=Sequential reactivation of herpesvirus in drug-induced hypersensitivity syndrome. | journal=Acta Derm Venereol | year= 2004 | volume= 84 | issue= 6 | pages= 484-5 | pmid=15844647 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=15844647 }} </ref><ref name="pmid11075787">{{cite journal| author=Knowles SR, Uetrecht J, Shear NH| title=Idiosyncratic drug reactions: the reactive metabolite syndromes. | journal=Lancet | year= 2000 | volume= 356 | issue= 9241 | pages= 1587-91 | pmid=11075787 | doi=10.1016/S0140-6736(00)03137-8 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=11075787 }} </ref> | ||
Revision as of 17:41, 17 September 2015
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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, such as epoxide hydrolase deficiency, results in accumulation of toxic metabolites and subsequent activation of immunologic reactions.[1] DRESS syndrome is more common among slow acetylators.[2]
- The variation of the incidence of DRESS syndrome across families and ethnicities may suggest a significant role for genetics in the pathogenesis of DRESS syndrome.[3]
- DRESS syndrome is associated with certain human leukocyte antigen (HLA), such as:[4][5]
- 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.[6][7][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.[8]
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.
- ↑ Rieder MJ, Shear NH, Kanee A, Tang BK, Spielberg SP (1991). "Prominence of slow acetylator phenotype among patients with sulfonamide hypersensitivity reactions". Clin Pharmacol Ther. 49 (1): 13–7. PMID 1988235.
- ↑ 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.