Drug rash with eosinophilia and systemic symptoms

Drug rash with eosinophilia and systemic symptoms or drug reaction with eosinophilia and systemic symptoms (DRESS), also termed drug-induced hypersensitivity syndrome (DIHS), is a rare reaction to certain medications. It involves primarily a widespread skin rash, fever, swollen lymph nodes, and characteristic blood abnormalities such as an abnormally high level of eosinophils, low number of platelets, and increased number of atypical white blood cells (lymphocytes). DRESS usually involves damage to the internal organs via inflammation and the syndrome has about a 1.2-7% mortality rate. Treatment consists of stopping the offending medication and providing supportive care. Systemic corticosteroids are commonly used as well but no controlled clinical trials have assessed the efficacy of this treatment.

DRESS is classified as one form of severe cutaneous adverse reactions (SCARs). In addition to DRESS, SCARs includes four other drug-induced skin reactions: the Stevens–Johnson syndrome (SJS), toxic epidermal necrolysis (TEN), Stevens–Johnson/toxic epidermal necrolysis overlap syndrome (SJS/TEN) and acute generalized exanthematous pustulosis (AGEP). The SCARs disorders have similar disease mechanisms. New strategies are in use or development to screen individuals at risk for DRESS to aid them in avoiding medications that increase the risk of DRESS. Alternative medications are used in all individuals testing positive for these predispositions.

Prior to 1996, there were numerous reports on individuals presenting with a medication-induced disorder now recognized as the DRESS syndrome. For example, anticonvulsants in the 1930s, phenytoin in 1950, and other medications in the ensuing years were reported to do so. The reports often named the disorder based on the medication evoking it, e.g. the anticonvulsant hypersensitivity syndrome, allopurinol hypersensitivity syndrome, and dapsone hypersensitivity syndrome. In 1996, however, the term DRESS syndrome was coined in a report attempting to simplify the terminology and consolidate these various clearly related syndromes into a single underlying disorder.

DRESS syndrome is thought to be a T-cell mediated immunologic reaction. The incidence is estimated to be 1 case per 1,000 people to 1 case per 10,000 people. Worldwide mortality varies between 1.2-7.1%, with the mortality in the United States being approximately 5%.

DRESS syndrome usually begin 2 to 6 weeks but uncommonly up to 8–16 weeks after exposure to an offending drug. DRESS usually begin with a prodrome (early symptoms) of fever, malaise, sore throat with dysphagia, itching, and skin burning. This quickly progresses to a fever and a morbilliform, often itchy rash. The mobilliform rash in DRESS often begins in the trunk and face and spreads to include more than 50% of the body surface area. The rash in DRESS 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 of internal organ involvement, most commonly liver damage (and less commonly kidney, lung, heart, and rarely pancreatic damage). Most cases of DRESS have a generalized lymph node swelling, and this can precede the rash. Facial edema is characteristic of the disease and often presents with creases in the earlobes. Inflammation of the mucous membranes in DRESS usually involves the mouth (oropharynx), but 15% of cases have inflammation of multiple mucosal membranes.

Laboratory findings include increased blood eosinophil and atypical lymphocyte counts, elevated blood markers for systemic inflammation (e.g. erythrocyte sedimentation rate, C-reactive protein), and evidence of internal organ involvement. Liver involvement is detected by measuring blood levels of alanine aminotransferase (ALT), a marker of hepatocyte injury, and alkaline phosphatase (ALP), a marker of bile duct injury. Kidney involvement is more common in older adults and in those with prior kidney or cardiovascular disease. Kidney damage may take the form of severe interstitial nephritis, acute tubular necrosis, or vasculitis and may lead to kidney failure and death. Lung involvement takes the form of interstitial pneumonitis, pleuritis, or the acute respiratory distress syndrome; minocycline and abacavir are the main culprit drugs causing severe lung involvement. However, lung involvement in this disorder typically resolves. 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. Rare manifestations of the disorder include inflammation of the pancreas, gastrointestinal tract, and spleen.

The following table gives the percentages for organ involvement and blood abnormalities found in individuals with the DRESS syndrome based on various studies. There are large variations in the percentages found in different studies and populations.

Tests to determine the causative agent are not available. No gold standard exists for diagnosis, and at least two diagnostic criteria have been proposed, the RegiSCAR criteria and the Japanese consensus group criteria.