Symptoms generally include fever, an often itchy rash which may be morbilliform or consist mainly of macules or plaques, facial edema (i.e. swelling, which is a hallmark of the disease), enlarged and sometimes painful lymph nodes, and other symptoms due to inflammation-based internal organ involvement, most commonly liver, less commonly kidney, lung, and heart, and rarely pancreas or other organs.
Cardiac involvement usually presents with evidence of left ventricular dysfunction and ECG changes; it occurs more often in individuals taking minocycline, ampicillin, or sulfonamides, and is either a cardiac hypersensitivity reaction classified as an eosinophilic myocarditis which generally resolves or a far more serious acute necrotizing eosinophilic myocarditis which has a mortality rate of more than 50%.
Neurological manifestations of the DRESS syndrome include headache, seizure, coma, and motor dysfunction due to meningitis or encephalitis.
[4][8] The following table gives the percentages for organ involvement and blood abnormalities found in individuals with the DRESS syndrome based on various studies.
[9] Studies have found that certain populations that express particular serotypes (i.e. alleles) of HLA-A, HLA-B, and/or HLA-C have an increased risk of developing the DRESS syndrome in response to specific medications.
Studies indicate that the mechanism by which a drug or its metabolites accomplishes this stimulation involves subverting the antigen presentation pathways of the innate immune system.
Those peptides expressing a drug-related, non-self epitope on their HLA-A, HLA-B, HLA-C, HLA-DM, HLA-DO, HLA-DP, HLA-DQ, or HLA-DR proteins may bind to a T-cell receptor to stimulate the receptor-bearing parent T cell to initiate attacks on self tissues.
[28][22] Thus, only rare individuals are predisposed to develop a SCARs disorder in response to a particular drug on the basis of their expression of specific cell receptor types.
[30] While the evidence supporting these ideas is limited, one study identified the preferential presence of the TCR-V-b and complementarity-determining region 3 in T-cell receptors found on the T cells in the blisters of patients with allopurinol-induced DRESS syndrome.
[31] Variations in ADME, i.e. an individual's efficiency in absorbing, distributing, metabolizing, and excreting a drug has been found to occur in cases of the DRESS syndrome.
Renal impairment is associated with abnormally high blood levels of oxipurinol and an increased risk of developing the DRESS syndrome, particularly the more severe forms of this disorder.
[3][32][33] Currently, it is suspected that the expression of particular HLA proteins and T-cell receptors interact with ADME factors to promote SCARs particularly in their more serious forms.
While these viral reactivations, particularly of human herpes virus 6, have been suggested to be an important factor in the pathogenesis of the DRESS syndrome, studies to date have not clearly determined if they are a cause or merely a consequence of T cell-mediated tissue injury.
[3][4] Currently, screening individuals for the expression of certain HLA alleles before initiating treatment of patients with DRESS-inducing drugs is recommended.
These recommendations include:[3][35] Current trials are underway to evaluate the ability of genetic screening to prevent the DRESS syndrome for dapsone and HLA-B*13:01 in China and Indonesia.
In the past, the mainstay treatment of severe cases of DRESS syndrome was the use, often at high-dosage, of systemic glucocorticoids, relying on the anti-inflammatory actions of these drugs to suppress the eosinophil- and T cell-induced tissue damage caused by the disorder.