Damien Picard

Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS): A Multiorgan Antiviral T Cell Response

A dangerous drug reaction may be caused by a severe immune response to reactivated resident herpes viruses. Drug Sensitivity: Don’t Wake Up the Baby (Virus) The benefits of drugs almost always come with a cost. Anticonvulsants and antibiotics are no exception. Some of these commonly used drugs can cause a skin reaction so severe, appearing several weeks after use, that the patient is treated as a burn victim. Called DRESS (drug reaction with eosinophilia and systemic symptoms), this response results in death 10% of the time. A better understanding of DRESS would be a boon to diagnosis and treatment. Data from 40 DRESS patients gathered by Picard and his colleagues now move us a few steps closer to this goal. They find that the symptoms of DRESS are largely a result of activated immune cells directed at herpes virus–related antigens, which home to the skin and visceral organs. The culprit drugs may reactivate quiescent herpes viruses lurking in the patients’ genomes, triggering expansion of these misguided cells. A careful look at the T lymphocytes from 40 patients with DRESS—induced by carbamazepine, allopurinol, or sulfamethoxazole—revealed excess numbers of activated cytotoxic CD8+ T cells, which had surface proteins directing them to skin and other organs. The cells secreted cytokines such as tumor necrosis factor–α (TNF-α) and interferon-γ (IFN-γ) and expressed genes characteristic of inflammation. To get a better handle on the antigen targets of these activated T cells, the authors tested whether the patients showed viral reactivation, which had been noted before in some patients with DRESS. Not only did 76% of the patients show activation of previously quiescent Epstein-Barr virus (EBV) or human herpes viruses 6 or 7 (HHV-6, HHV-7), but a large proportion of the activated CD8 T cells in blood and affected organs carried T cell receptor sequences known to be specific for antigens from EBV. (Specific sequences for HHV-6 or HHV-7 are not available.) Cellular stimulation by antigenic peptides from EBV confirmed this result. The authors propose that DRESS is caused by an EBV (or other similar virus)–driven selection of CD8+ T lymphocytes, which in turn inappropriately attack multiple organs. They think that the culprit drugs may trigger activation of the patients’ dormant EBV by an as yet undefined mechanism, possibly directly. Indeed, they found that the three culprit drugs induce EBV production in EBV-transformed cells from DRESS patients but not from healthy controls, setting the stage for discovering just what it is that makes some people susceptible to DRESS. Drug reaction with eosinophilia and systemic symptoms (DRESS) is a severe, drug-induced reaction that involves both the skin and the viscera. Evidence for reactivation of herpes family viruses has been seen in some DRESS patients. To understand the immunological components of DRESS and their relationship to viral reactivation, we prospectively assessed 40 patients exhibiting DRESS in response to carbamazepine, allopurinol, or sulfamethoxazole. Peripheral blood T lymphocytes from the patients were evaluated for phenotype, cytokine secretion, and repertoire of CD4+ and CD8+ and for viral reactivation. We found Epstein-Barr virus (EBV), human herpes virus 6 (HHV-6), or HHV-7 reactivation in 76% of the patients. In all patients, circulating CD8+ T lymphocytes were activated, exhibited increased cutaneous homing markers, and secreted large amounts of tumor necrosis factor–α and interferon-γ. The production of these cytokines was particularly high in patients with the most severe visceral involvement. In addition, expanded populations of CD8+ T lymphocytes sharing the same T cell receptor repertoire were detected in the blood, skin, liver, and lungs of patients. Nearly half of these expanded blood CD8+ T lymphocytes specifically recognized one of several EBV epitopes. Finally, we found that the culprit drugs triggered the production of EBV in patients’ EBV-transformed B lymphocytes. Thus, cutaneous and visceral symptoms of DRESS are mediated by activated CD8+ T lymphocytes, which are largely directed against herpes viruses such as EBV.

Poor Benefit/Risk Balance of Intravenous Immunoglobulins in DRESS

D rug reaction with eosinophilia and systemic symptoms (DRESS), sometimes called hypersensitivity syndrome, is a severe druginduced reaction with visceral involvement and blood abnormalities associated with reactivations of viruses of the herpes family: human herpesvirus (HHV)-6 HHV-7, Epstein-Barr virus (EBV), and cytomegalovirus (CMV). Our research group recently reported that the immune response in DRESS, previously thought to be directed against drug components, is in fact mediated by tumor necrosis factor (TNF)– and interferon(INF)–secreting CD8 T lymphocytes, which are directed against previously quiescent HHVs reactivated by the drug and home to the skin and visceral organs. Oral corticosteroid treatment is often proposed for severe DRESS, but oral corticosteroids might favor a relapsing course of the syndrome. Some researchers, based on the presence of antiviral IgGs in intravenous immunoglobulins (IVIGs) and their numerous immunologic effects, have suggested that IVIGs might be effective in a few patients with DRESS, although these patients were concomitantly treated with systemic corticosteroids. The aim of the present study was to evaluate the safety and efficacy of IVIGs in patients with DRESS and to assess the evolution of immunologic and virologic parameters after treatment.

Outbreak of Mycobacterium chelonae in France

Tattooing is common worldwide.1 Various infections have been reported, including local infections mainly due to pyogenic bacteria and systemic infections such as hepatitis B and C and HIV.2 3 We report a large outbreak of Mycobacterium chelonae skin infection occurring in France over eight months that was related to contaminated ink. Forty eight patients presented with skin lesions, mainly pustules, occurring from 3 to 35 …

Prolonged evolution of drug reaction with eosinophilia and systemic symptoms: clinical, virologic, and biological features.

Prolonged Evolution of Drug Reaction With Eosinophilia and Systemic Symptoms: Clinical, Virologic, and Biological Features Drug reaction with eosinophilia and systemic symptoms (DRESS) is a rare and severe drug-induced reaction characterized by systemic involvement and an unusually long latency of onset after exposure to medication. Because this syndrome is not easily identified, it remains underdiagnosed. Its physiopathological characteristics are still incompletely understood, involving reactivation of dormant herpesviruses triggered by the culprit drug.1 Moreover, herpesvirus reactivations might even have an impact on the severity and duration of DRESS.2 Usually, DRESS resolves within 1 month; however, some patients have prolonged evolution, sometimes associated with flare-ups. In addition, some patients with DRESS can develop persistent renal insufficiency or autoimmune symptoms following acute hypersensitivity events.3 Factors associated with prolonged evolution have not been identified to date. Our study aimed to assess clinical and biological features associated with prolonged evolution in a prospective cohort of 40 patients with DRESS. Methods | Patients with DRESS were included according to the criteria described in our previous investigation.1 The study was approved by our local ethics committee (ClinicalTrials.gov, NCT 00213447). Written consent was obtained from patients. On the basis of a study in which median duration of disease was estimated at 30 days,2 prolonged evolution was defined by the persistence, at least up to day 90, of at least 1 clinical and/or 1 laboratory abnormality. Viral DNA from Epstein-Barr virus (EBV), cytomegalovirus, and human herpesvirus (HHV) types 6 and 7 was quantified by means of real-time polymerase chain reaction (RT-PCR) in serum and peripheral blood mononuclear cells of patients. Statistical analysis used nonparametric tests, the Wilcoxon test, and the Fisher exact test.

Atypical nodular panniculitis.

Suppurative panniculitis usually occurs among immunocompromised patients and can be caused by opportunistic pathogens or by secondary infectious lesions in the context of septicemia. Herein we report the case of an 82-year-old woman with multiple red nodules on the leg caused by Pseudomonas aeruginosa, not related to a blood disseminated infection. The present case represents an unusual presentation of indolent suppurative panniculitis caused by P. aeruginosa.