Dataset Information

Multiple Drug Hypersensitivity.

ABSTRACT: Multiple drug hypersensitivity (MDH) is a syndrome that develops as a consequence of massive T-cell stimulations and is characterized by long-lasting drug hypersensitivity reactions (DHR) to different drugs. The initial symptoms are mostly severe exanthems or drug rash with eosinophilia and systemic symptoms (DRESS). Subsequent symptoms due to another drug often appear in the following weeks, overlapping with the first DHR, or months to years later after resolution of the initial presentation. The second DHR includes exanthema, erythroderma, DRESS, Stevens-Johnson syndrome/toxic epidermal necrolysis (SJS/TEN), hepatitis, and agranulocytosis. The eliciting drugs can be identified by positive skin or in vitro tests. The drugs involved in starting the MDH are the same as for DRESS, and they are usually given in rather high doses. Fixed drug combination therapies like sulfamethoxazole/trimethoprim or piperacillin/tazobactam are frequently involved in MDH, and 30-40% of patients with severe DHR to combination therapy show T-cell reactions to both components. The drug-induced T-cell stimulation appears to be due to the p-i mechanism. Importantly, a permanent T-cell activation characterized by PD-1+/CD38+ expression on CD4+/CD25low T cells can be found in the circulation of patients with MDH for many years. In conclusion, MDH is a drug-elicited syndrome characterized by a long-lasting hyperresponsiveness to multiple, structurally unrelated drugs with clinically diverse symptoms.

SUBMITTER: Pichler WJ

PROVIDER: S-EPMC5472211 | biostudies-literature | 2017

REPOSITORIES: biostudies-literature

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Multiple Drug Hypersensitivity.

Pichler Werner J WJ Srinoulprasert Yuttana Y Yun James J Hausmann Oliver O

International archives of allergy and immunology 20170318 3

Multiple drug hypersensitivity (MDH) is a syndrome that develops as a consequence of massive T-cell stimulations and is characterized by long-lasting drug hypersensitivity reactions (DHR) to different drugs. The initial symptoms are mostly severe exanthems or drug rash with eosinophilia and systemic symptoms (DRESS). Subsequent symptoms due to another drug often appear in the following weeks, overlapping with the first DHR, or months to years later after resolution of the initial presentation. T ...[more]

PMID: 28315874

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Project description:The incidence of hypersensitivity reactions (HSRs) to iodinated contrast media (ICM) has risen over last years, representing an important health problem. HSRs to ICMs are classified into immediate reactions (IRs) and non-immediate reactions (NIRs) according to if they occur within 1 h or longer after ICM administration. The diagnosis of HSRs to ICM is complex as skin test (ST) sensitivity ranges widely, and drug provocation test (DPT) protocols are heterogeneous. In this manuscript, we describe the clinical characteristics of a series of patients confirmed as HSR to ICM and the diagnosis procedure carried out, looking into those cases confirmed as HSRs to multiple ICMs. For this purpose, we prospectively evaluated patients suggestive of HSRs to ICMs and classified them as IRs or NIRs. STs were carried out using a wide panel of ICMs, and in those with a negative ST, a single-blind placebo controlled DPT was performed with the culprit. If ST or DPT were positive, then tolerance was assessed with an alternative negative ST ICM. We included 101 cases (12 IRs and 89 NIRs) confirmed as allergic. Among them, 36 (35.64%) cases were allergic to more than one ICM (8 IRs and 28 NIRs). The most common ICM involved were iomeprol and iodixanol. Although not statistically significant, the percentage of patients reporting anaphylaxis was higher in patients allergic to multiple ICMs compared with patients allergic to a single ICM (50 vs. 25%). Likewise, the percentage of positive results in STs was higher in patients allergic to multiple ICMs compared with those allergic to a single ICM (for IR 62.5 vs. 25%, p > 0.05; and for NIR, 85.71 vs. 24.59%, p < 0.000). In cases allergic to more than one ICM, DPT with negative-ST ICM was positive in more than 60% (24/36) of cases. Therefore, allergy to multiple ICMs is common, associated to severe reactions in IRs, and confirmed frequently by positive STs. The allergological work-up should include DPT not only to establish the diagnosis but also to identify safe alternative ICM, even if ICM is structurally unrelated and ST is negative. More studies are needed to clarify mechanisms underlying cross-reactivity among ICMs.

Project description:BackgroundDrug-induced hypersensitivity syndrome (DIHS)/drug reaction with eosinophilia and systemic symptoms (DRESS) syndrome is an important adverse reaction caused by a few drugs. Reactivation of human herpesvirus 6 (HHV-6) is known to be associated with its pathogenesis. DIHS occasionally manifests as pulmonary lesions with a variety of imaging findings.Case presentationAn 83-year-old woman started taking minodronic acid hydrate 5 years before admission. She noticed a generalized skin rash 44 days before admission and started oral betamethasone-d-chlorpheniramine maleate combination tablets for allergic dermatitis. She developed a fever and cough in addition to the rash, and was referred to our hospital. Laboratory data showed a high level of eosinophils and liver and biliary enzymes. Computed tomography (CT) studies revealed bilateral diffuse ground-glass opacities with ill-defined centrilobular nodules from the central to peripheral regions of the lungs. Transbronchial lung cryobiopsy specimens showed that lymphocyte infiltration was observed in the alveolar walls and fibrinous exudates and floating macrophages in the alveolar lumina. Immunohistochemistry of biopsy specimens showed more CD4+ lymphocytes than CD8+ lymphocytes, while few Foxp3+ lymphocytes were recognized. The serum anti-HHV-6 immunoglobulin G titer increased at 3 weeks after the first test. Based on these findings, we diagnosed her with DIHS. We continued care without using corticosteroids since there was no worsening of breathing or skin condition. Eventually, her clinical symptoms chest CT had improved. Minodronic acid hydrate was identified as the culprit drug based on the positive results of the patch test and drug-induced lymphocyte stimulation test.ConclusionsWe described the first case of DIHS caused by minodronic acid hydrate. Lung lesions in DIHS can present with bilateral diffuse ground-glass opacities and ill-defined centrilobular nodules on a CT scan during the recovery phase. Clinicians should be aware of DIHS, even if patients are not involved with typical DIHS/DRESS-causing drugs.

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Multiple Drug Hypersensitivity.

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Multiple Drug Hypersensitivity.

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