Drug-related relapses in drug reaction with eosinophilia and systemic symptoms (DRESS)

Abstract

Background A drug reaction with eosinophilia and systemic symptoms (DRESS) is a severe T cell mediated hypersensitivity reaction. Relapses of symptoms in the recovery phase are frequent and linked to the reduction of the corticosteroid treatment, to viral reactivations or to the exposure to new drugs. Here, we analyzed, how often the exposure to new drugs leads to new sensitization or drug-related relapses without detectable sensitization. Methods 46 patients with DRESS treated in the allergy division of the Inselspital, Bern University Hospital, were retrospectively assessed. Drug-related relapses were analyzed in terms of frequency and whether a possible sensitization evaluated by skin tests and/or lymphocyte transformation tests (LTT) to the new drugs was detectable. Furthermore, drug tolerance was evaluated in a subset of patients. Results 56 relapses were observed in 27 of 46 patients with DRESS (58.7%). 33 (58.9%) of these relapses were associated with the use of new drugs, 30 drug-related relapses were evaluated by patch test and/or lymphocyte transformation test. In 8/30 (26.7%) drug-related relapses, a sensitization to the new drug was demonstrated, suggesting the emergence of a multiple drug hypersensitivity syndrome (MDH). 14 patients experienced 22 drug-related relapses without any detectable sensitization and only 1/6 patients developed new symptoms upon reexposure. Conclusion Patients with DRESS frequently suffered from drug related relapses. Half of the patients with drug-related relapses developed a MDH with proven sensitizations not only to the DRESS inducing drugs, but also to newly applied drugs. When not sensitized, drugs involved in drug related relapses could be reintroduced, if needed. Here, we propose a procedure for drug testing and future management of drug-related relapses in DRESS.

Advances and highlights in T and B cell responses to drug antigens

“…A recently published work showed that if there is an exposure to antibiotics during the active phase of DRESS, it can trigger a sensitization to the administered drug; which is explained by the massive activation of reactive immune cells 91 . A later manuscript has shown that other drugs such as radiocontrast media, proton pumps inhibitors or analgesics could be also involved in DRESS relapses 46 …”

“…45 The immune system requires at least 7 days in order to prime a new T cell-mediated reaction (usually 2-8 weeks). 46 During the effector response, the time will depend on the clinical entity, with symptoms in MPE taking between 7 and 12 days to appear, and a longer period of time in severe allergic reactions such as Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN) or DRESS. These differences could be explained by the drug interaction with the immune system, hapten hypothesis or p-i concept.…”

“…91 A later manuscript has shown that other drugs such as radiocontrast media, proton pumps inhibitors or analgesics could be also involved in DRESS relapses. 46 These relapses may be associated with unknown mechanisms, and, in most cases, patients tolerate the drug after the complete recovery. On the contrary, relapses with proven sensitization to secondary drugs may trigger a multiple drug hypersensitivity syndrome and therefore, culprit drugs cannot be readministered.…”

Pustular psoriasis flare‐up in a patient with COVID‐19

“…However, other viruses such as Epstein-Barr Virus (EBV) have been precipitating factors for other skin disorders such as pustular DRESS Syndrome. 26 Therefore, the…”

“…The last important issue is that some infectious agents are documented to be responsible for psoriasis exacerbations, such as HCV, rhinovirus, and coronavirus. However, other viruses such as Epstein‐Barr Virus (EBV) have been precipitating factors for other skin disorders such as pustular DRESS Syndrome 26 . Therefore, the potential of any infection to induce psoriasis, particularly the significant role of COVID‐19 in giving rise to the pustular form, should not be neglected.…”