DRESS syndrome pathophysiology
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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Yazan Daaboul, M.D., Serge Korjian M.D.
Overview
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. Genetic deficiency of detoxifying enzymes, such as epoxide hydrolase deficiency, results in accumulation of toxic metabolites and subsequent activation of immunologic reactions. A post-viral reaction (T-cell cross-reacion) has also been postulated due to the high incidence of viral reactivation following DRESS syndrome. On histopathological analysis of skin biopsy, DRESS syndrome is not characterized by a specific finding. Common histopathological findings include non-specific lymphocytic and eosinophilic infiltration with involvement of the papillary dermis and evidence of epidermotropism.
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][6][7]
- HLA-B*1502
- HLA-B*1508
- HLA-B*5701
- HLA-B*5801
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.[8][9][1]
- It is unknown how drug interactions are associated with 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 HHV-7) 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.[10]
Pathology
Microscopic Histopathological Findings
DRESS syndrome is not characterized by a specific finding on histopathological analysis of skin biopsy. The following findings may be present:[11][12][13][14]
- Non-specific lymphocytic infiltration, typically in the perivascular superficial dermis
- Abundance of eosinophils
- Band-like infiltrate of atypical lymphocytes
- Involvement of the papillary dermis
- Dermal edema
- Spongiosis
- Acanthosis
- Vacuolization
- Epidermotropism that resembles mycosis fungoides
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.
- ↑ Mallal S, Phillips E, Carosi G, Molina JM, Workman C, Tomazic J; et al. (2008). "HLA-B*5701 screening for hypersensitivity to abacavir". N Engl J Med. 358 (6): 568–79. doi:10.1056/NEJMoa0706135. PMID 18256392.
- ↑ Hung SI, Chung WH, Liou LB, Chu CC, Lin M, Huang HP; et al. (2005). "HLA-B*5801 allele as a genetic marker for severe cutaneous adverse reactions caused by allopurinol". Proc Natl Acad Sci U S A. 102 (11): 4134–9. doi:10.1073/pnas.0409500102. PMC 554812. PMID 15743917.
- ↑ 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.
- ↑ De Vriese AS, Philippe J, Van Renterghem DM, De Cuyper CA, Hindryckx PH, Matthys EG; et al. (1995). "Carbamazepine hypersensitivity syndrome: report of 4 cases and review of the literature". Medicine (Baltimore). 74 (3): 144–51. PMID 7760721.
- ↑ Tas S, Simonart T (2003). "Management of drug rash with eosinophilia and systemic symptoms (DRESS syndrome): an update". Dermatology. 206 (4): 353–6. doi:69956 Check
|doi=value (help). PMID 12771485. - ↑ Walsh S, Diaz-Cano S, Higgins E, Morris-Jones R, Bashir S, Bernal W; et al. (2013). "Drug reaction with eosinophilia and systemic symptoms: is cutaneous phenotype a prognostic marker for outcome? A review of clinicopathological features of 27 cases". Br J Dermatol. 168 (2): 391–401. doi:10.1111/bjd.12081. PMID 23034060.
- ↑ Chi MH, Hui RC, Yang CH, Lin JY, Lin YT, Ho HC; et al. (2014). "Histopathological analysis and clinical correlation of drug reaction with eosinophilia and systemic symptoms (DRESS)". Br J Dermatol. 170 (4): 866–73. doi:10.1111/bjd.12783. PMID 24329105.