Benralizumab for severe DRESS in two COVID-19 patients

Schmid‐Grendelmeier, Peter; Steiger, Peter; Naegeli, Mirjam C.; Kolm, Isabel; Lang, Claudia; Maverakis, Emanual; Brüggen, Marie‐Charlotte

doi:10.1016/j.jaip.2020.09.039

Cited by 29 publications

(44 citation statements)

References 9 publications

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“…It has to be considered specially for patients in ICU, who might be under systemic glucocorticoids treatment and eosinophil counts thus dampened. On the other hand, glucocorticoid‐unresponsive massive eosinophilia has been reported in severely affected COVID‐19 patients in association with drug rash with eosinophilia and systemic symptoms, 186 raising the question whether eosinophilia might be resistant to glucocorticoids. Immunophenotyping of whole blood leukocytes in COVID‐19 patients revealed that eosinophil CRTH2 (Chemoattractant receptor‐homologous molecule expressed on T(H)2 cells, CD294) expression was significantly decreased in the severe group compared to the mild group.…”

Section: Laboratory Indicatorsmentioning

confidence: 99%

Risk factors for severe and critically ill COVID‐19 patients: A review

Gao

Ding

Dong

et al. 2020

Allergy

1,161

864

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The pandemic of coronavirus disease 2019 (COVID‐19), caused by the severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2), has caused an unprecedented global social and economic impact, and high numbers of deaths. Many risk factors have been identified in the progression of COVID‐19 into a severe and critical stage, including old age, male gender, underlying comorbidities such as hypertension, diabetes, obesity, chronic lung diseases, heart, liver and kidney diseases, tumors, clinically apparent immunodeficiencies, local immunodeficiencies, such as early type I interferon secretion capacity, and pregnancy. Possible complications include acute kidney injury, coagulation disorders, thoromboembolism. The development of lymphopenia and eosinopenia are laboratory indicators of COVID‐19. Laboratory parameters to monitor disease progression include lactate dehydrogenase, procalcitonin, high‐sensitivity C‐reactive protein, proinflammatory cytokines such as interleukin (IL)‐6, IL‐1β, Krebs von den Lungen‐6 (KL‐6), and ferritin. The development of a cytokine storm and extensive chest computed tomography imaging patterns are indicators of a severe disease. In addition, socioeconomic status, diet, lifestyle, geographical differences, ethnicity, exposed viral load, day of initiation of treatment, and quality of health care have been reported to influence individual outcomes. In this review, we highlight the scientific evidence on the risk factors of severity of COVID‐19.

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Section: Laboratory Indicatorsmentioning

confidence: 99%

Risk factors for severe and critically ill COVID‐19 patients: A review

Gao

Ding

Dong

et al. 2020

Allergy

1,161

864

View full text Add to dashboard Cite

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“…IL-5 is considered the main driver of eosinophil expansion and activation leading to organ damage and dysfunction in DRESS [94]. The efficacy of antibodies targeting the IL-5 / IL-5 receptor axis in severe DRESS are an evidence for the key role of eosinophils in the pathogenesis [95][96][97].…”

Section: Macular and Papular Rashesmentioning

confidence: 99%

Eosinophils in skin diseases

et al. 2021

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Eosinophil infiltration is a common finding in a broad spectrum of skin diseases, despite the fact that the skin is devoid of eosinophils under physiologic conditions. Although cutaneous eosinophilia is reactive, cytokine-mediated in most cases, diseases with an intrinsic mutation-mediated clonal expansion of eosinophils can also manifest on the skin. As eosinophils are involved in host defense, regulate immune responses, generate pruritus, induce remodeling and fibrosis, and can cause tissue damage, they have the capacity to actively contribute to the pathogenesis of diseases. Recent research provided deeper insights in the mechanisms, e.g., bacterial and viral clearance, blister formation, recruitment of cytotoxic T cells, and generation of pruritus, by which eosinophils might come into action. This review aims at providing an overview on the clinical presentations of eosinophil-associated dermatoses and the current understanding of their pathogenic role in these diseases. Further, we discuss the effects of therapies targeting eosinophils.

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“…We and others have reported glucocorticoid‐refractory severe DRESS with massive eosinophilia in COVID‐19 patients. 8 , 9 Besides DDH, other cutaneous eruptions have been associated with SARS‐CoV‐2 infection and have been observed in approximately 1–20% of the patients. 10 , 11 , 12 , 13 , 14 , 15 These various skin manifestations of SARS‐CoV‐2 infection 16 , 17 may be due in part to the SARS‐CoV‐2 spike protein receptor (angiotensin‐converting enzyme 2, ACE2) being expressed by keratinocytes.…”

Section: Introductionmentioning

confidence: 99%

Cutaneous and systemic hyperinflammation drives maculopapular drug exanthema in severely ill COVID‐19 patients

Mitamura¹,

Schulz

Oro

et al. 2021

Allergy

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Background Coronavirus disease‐2019 (COVID‐19) has been associated with cutaneous findings, some being the result of drug hypersensitivity reactions such as maculopapular drug rashes (MDR). The aim of this study was to investigate whether COVID‐19 may impact the development of the MDR. Methods Blood and skin samples from COVID‐19 patients (based on a positive nasopharyngeal PCR) suffering from MDR (COVID‐MDR), healthy controls, non‐COVID‐19—related patients with drug rash with eosinophilia and systemic symptoms (DRESS), and MDR were analyzed. We utilized imaging mass cytometry (IMC) to characterize the cellular infiltrate in skin biopsies. Furthermore, RNA sequencing transcriptome of skin biopsy samples and high‐throughput multiplexed proteomic profiling of serum were performed. Results IMC revealed by clustering analyses a more prominent, phenotypically shifted cytotoxic CD8 + T cell population and highly activated monocyte/macrophage (Mo/Mac) clusters in COVID‐MDR. The RNA sequencing transcriptome demonstrated a more robust cytotoxic response in COVID‐MDR skin. However, severe acute respiratory syndrome coronavirus 2 was not detected in skin biopsies at the time point of MDR diagnosis. Serum proteomic profiling of COVID‐MDR patients revealed upregulation of various inflammatory mediators (IL‐4, IL‐5, IL‐6, TNF, and IFN‐γ), eosinophil and Mo/Mac ‐attracting chemokines (MCP‐2, MCP‐3, MCP‐4 and CCL11). Proteomics analyses demonstrated a massive systemic cytokine storm in COVID‐MDR compared with the relatively milder cytokine storm observed in DRESS, while MDR did not exhibit such features. Conclusion A systemic cytokine storm may promote activation of Mo/Mac and cytotoxic CD8 + T cells in severe COVID‐19 patients, which in turn may impact the development of MDR.

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Benralizumab for severe DRESS in two COVID-19 patients

Cited by 29 publications

References 9 publications

Risk factors for severe and critically ill COVID‐19 patients: A review

Risk factors for severe and critically ill COVID‐19 patients: A review

Eosinophils in skin diseases

Cutaneous and systemic hyperinflammation drives maculopapular drug exanthema in severely ill COVID‐19 patients

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