Treatment with IL5-/IL-5 receptor antagonists in drug reaction with eosinophilia and systemic symptoms (DRESS)

Gschwend, Anna; Helbling, Arthur; Feldmeyer, Laurence; Mani-Weber, Ulrich; Meincke, Cordula; Heidemeyer, Kristine; Bossart, Simon; Jörg, Lukas

doi:10.1007/s40629-022-00224-7

Cited by 11 publications

(21 citation statements)

References 30 publications

(86 reference statements)

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“…Anti‐IL‐5/anti IL‐5R therapy has proven effective in severe allergic diseases, 87 and improvement has also been observed in most DRESS patients with eosinophilia. This suggests a significant role of IL‐5 in this form of DRESS 84 Severity of DH : If, as proposed, the eosinophilia/IL‐5 TCR signalosome results from a more affine TCR‐drug/peptide/HLA interaction, the presence of eosinophilia may indicate that a longer‐lasting T‐cell stimulation takes place leading to more severe clinical symptoms.…”

Section: Discussionmentioning

confidence: 81%

Section: Discussionmentioning

confidence: 89%

“…Screening for eosinophilia is part of the diagnostic work up for patients with DHR 1 . Demonstrating eosinophilia may not only support the diagnosis of a DHR but may also suggest that the DH involves a (particular) p‐i stimulation.Conversely, there are several p‐i stimulations in which eosinophilia is absent: p‐i stimulations are more frequent than eosinophilia in DH. Targeting the beginning of a cascade of events (T cells and IL5) could potentially block all sequential effects: Corticoid‐resistance: Eosinophilia in some DH‐related conditions is not (or not sufficiently) responsive to corticosteroid therapy 84,85 . Based on the IL‐5‐TCR signalosome hypothesis, it would be reasonable to evaluate therapies that more precisely interfere with the TCR signalosome, such as, for example, JAK inhibitors 86 …”

Section: Discussionmentioning

confidence: 99%

“…Targeting the beginning of a cascade of events (T cells and IL5) could potentially block all sequential effects: Corticoid‐resistance: Eosinophilia in some DH‐related conditions is not (or not sufficiently) responsive to corticosteroid therapy 84,85 . Based on the IL‐5‐TCR signalosome hypothesis, it would be reasonable to evaluate therapies that more precisely interfere with the TCR signalosome, such as, for example, JAK inhibitors 86 …”

Section: Discussionmentioning

confidence: 99%

“…• Corticoid-resistance: Eosinophilia in some DH-related conditions is not (or not sufficiently) responsive to corticosteroid therapy. 84,85 Based on the IL-5-TCR signalosome hypothesis, it would be reasonable to evaluate therapies that more precisely interfere with the TCR signalosome, such as, for example, JAK inhibitors. 86 • Anti-IL-5/anti IL-5R therapy has proven effective in severe allergic diseases, 87 symptoms.…”

Section: Summary and Con Clus Ionmentioning

confidence: 99%

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Drug hypersensitivity and eosinophilia: The decisive role of p‐i stimulation

Pichler

Thoo

Yerly

2023

Allergy

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Eosinophilia is a common finding in drug hypersensitivity reactions (DHR). Its cause is unclear, as neither antigen/allergen‐driven inflammation nor clonal expansion is involved. Most delayed‐DHRs are due to p‐i (pharmacologic interaction of drugs with immune receptors). These are off‐target activities of drugs with immune receptors that result in various types of T‐cell stimulation, some of which involve excessive IL‐5 production. Functional and phenotypic studies of T‐cell clones and their TCR‐transfected hybridoma cell lines revealed that some p‐i‐induced drug stimulations occur without CD4/ CD8 co‐receptor engagement. The CD4/CD8 co‐receptors link Lck (lymphocyte‐specific protein tyrosine kinase) and LAT (linker for activation of T cells) to the TCR. Alteration of Lck or LAT can result in a TCR signalosome with enhanced IL‐5 production. Thus, if a more affine TCR‐[drug/peptide/HLA] interaction allows bypassing the CD4 co‐receptor, a modified Lck/LAT activation may lead to a TCR signalosome with elevated IL‐5 production. This “IL‐5‐TCR‐signalosome” hypothesis could also explain eosinophilia in superantigen or allo‐stimulation (graft‐versus‐host disease), in which evasion of CD4/CD8 co‐receptors has also been described. It may open new therapeutic possibilities in certain eosinophilic diseases by directly targeting the IL‐5‐TCR signalosome.

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Section: Discussionmentioning

confidence: 81%

Section: Discussionmentioning

confidence: 89%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Summary and Con Clus Ionmentioning

confidence: 99%

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Drug hypersensitivity and eosinophilia: The decisive role of p‐i stimulation

Pichler

Thoo

Yerly

2023

Allergy

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Management of Adult Patients With Drug Reaction With Eosinophilia and Systemic Symptoms

Brüggen,

Walsh,

Ameri

et al. 2024

JAMA Dermatol

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ImportanceDrug reaction with eosinophilia and systemic symptoms (DRESS) is a rare but potentially fatal drug hypersensitivity reaction. To our knowledge, there is no international consensus on its severity assessment and treatment.ObjectiveTo reach an international, Delphi-based multinational expert consensus on the diagnostic workup, severity assessment, and treatment of patients with DRESS.Design, Setting, and ParticipantsThe Delphi method was used to assess 100 statements related to baseline workup, evaluation of severity, acute phase, and postacute management of DRESS. Fifty-seven international experts in DRESS were invited, and 54 participated in the survey, which took place from July to September 2022.Main Outcomes/MeasuresThe degree of agreement was calculated with the RAND-UCLA Appropriateness Method. Consensus was defined as a statement with a median appropriateness value of 7 or higher (appropriate) and a disagreement index of lower than 1.ResultsIn the first Delphi round, consensus was reached on 82 statements. Thirteen statements were revised and assessed in a second round. A consensus was reached for 93 statements overall. The experts agreed on a set of basic diagnostic workup procedures as well as severity- and organ-specific further investigations. They reached a consensus on severity assessment (mild, moderate, and severe) based on the extent of liver, kidney, and blood involvement and the damage of other organs. The panel agreed on the main lines of DRESS management according to these severity grades. General recommendations were generated on the postacute phase follow-up of patients with DRESS and the allergological workup.Conclusions and RelevanceThis Delphi exercise represents, to our knowledge, the first international expert consensus on diagnostic workup, severity assessment, and management of DRESS. This should support clinicians in the diagnosis and management of DRESS and constitute the basis for development of future guidelines.

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