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. 2024 Jan 1;160(1):37-44.
doi: 10.1001/jamadermatol.2023.4450.

Management of Adult Patients With Drug Reaction With Eosinophilia and Systemic Symptoms: A Delphi-Based International Consensus

Marie-Charlotte Brüggen  1   2   3   4 , Sarah Walsh  4   5 , M Milad Ameri  1   2   3 , Natalie Anasiewicz  1 , Emanual Maverakis  6 , Lars E French  4   7   8 , Saskia Ingen-Housz-Oro  4   9   10   11 ; DRESS Delphi consensus group; Richiiro Abe  12 , Michael Ardern-Jones  13 , Haudrey Assier  9 , Annick Barbaud  14 , Benoit Bensaid  15 , William Bernal  16 , Claire Bernier  17 , Alain Brassard  6 , Eva Brezinová  4   18 , Rosario Cabañas  19   20   21 , Adela Cardones  22 , Chia-Yu Chu  23 , Ser-Ling Chua  4   24 , Vincent Descamps  25 , Biagio Didona  4   26 , Sherrie Jill Divito  27 , Roni Dodiuk-Gad  28   29   30 , Scott Elman  31 , Krisztian Gaspar  32 , Charlotte G Mortz  33 , Natsumi Hama  12 , Haur Yueh Lee  34 , Barbara Horváth  35 , Lukas Jörg  36 , Benjamin H Kaffenberger  37 , Vesta Kucinskiene  4   38 , Bénédicte Lebrun-Vignes  39 , Rannakoe J Lehloenya  40 , Damian Meyersburg  4   41 , Robert Micheletti  42   43 , Brigitte Milpied  4   10   44 , Fumi Miyagawa  45 , Arash Mostaghimi  27 , Mirjam Nägeli  1 , Luigi Naldi  46 , Eva Oppel  7 , Elizabeth J Phillips  47 , Tasneem Pirani  16 , Annamari Ranki  4   48 , Tarja Mälkönen  48 , Misha Rosenbach  42 , Carmen Salavastru  4   40 , Delphine Staumont-Salle  49 , Heidi Sandberg  48 , Jane Setterfield  50 , Kanade Shinkai  24   51 , Tetsuo Shiohara  52 , Angele Soria  53 , Danielle Tartar  6 , George-Sorin Tiplica  4   54 , Stephan Traidl  1   55 , Artem Vorobyev  56 , Camilla von Wachter  2 , Scott Worswick  57 , Yung-Tsu Cho  23
Affiliations

Management of Adult Patients With Drug Reaction With Eosinophilia and Systemic Symptoms: A Delphi-Based International Consensus

Marie-Charlotte Brüggen et al. JAMA Dermatol. .

Abstract

Importance: Drug 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.

Objective: To reach an international, Delphi-based multinational expert consensus on the diagnostic workup, severity assessment, and treatment of patients with DRESS.

Design, setting, and participants: The 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/measures: The 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.

Results: In 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 relevance: This 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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Conflict of interest statement

Conflict of Interest Disclosures: Prof Brüggen reported grants and research funding from the Swiss National Science Foundation, the Christine Kühne-Center for Allergy Research and Education, the FreeNovation Foundation, the LEO Foundation, the Olga Mayenfisch Foundation, the University of Zurich, LEO Pharma, and the Eczema Foundation of Pierre Fabre; speaking and/or consultation fees from Eli Lilly, LEO Pharma, AbbVie, GSK, and AstraZeneca; and honoraria from speaking/presentation and educational events for the Christine Kühne-Center for Allergy Research and Education, FOMF, and ADR-AC. Dr Bernal reported personal fees from Versantis and Flagship Pioneering outside the submitted work. Dr Chua reported nonfinancial support from Novartis, Almirall, and UCB, as well as personal fees from Boehringer Ingelheim, Novartis, and UCB outside the submitted work. Dr Divito reported grants from the National Institutes of Health during the conduct of the study, personal fees from Adaptimmune outside the submitted work, and a provisional patent issued. Prof Dodiuk-Gad reported serving as a consultant/investigator for Sanofi, AbbVie, Pfizer, Janssen, Novartis, La Roche-Posay, Dexcel, and Eli Lilly. Prof Horváth reported personal fees paid to their institution from Janssen-Cilag, UCB, and Argenx, as well as grants paid to their institution from AbbVie and Novartis outside the submitted work. Dr Kaffenberger reported grants from the Dermatology Foundation outside the submitted work. Prof Lehloenya reported grants from the National Research Foundation during the conduct of the study. Dr Micheletti reported personal fees from Vertex and grants from Acelyrin, Pfizer, Amgen, and Cabaletta Bio outside the submitted work. Dr Mostaghimi reported personal fees from hims and hers, AbbVie, Sun Pharma, Pfizer, Digital Diagnostics, Lilly, Equillium, ASLAN, Boehringer Ingelheim, and Acom outside the submitted work. Dr Phillips reported personal fees from Verve, Novavax, Janssen, AstraZeneca, Biocryst, Regeneron, and UpToDate outside the submitted work. Dr Rosenbach reported personal fees from Merck, Janssen, and Novartis during the conduct of the study. Dr Salavastru reported royalties from Springer Nature. Dr Staumont-Salle reported grants from AstraZeneca and personal fees from GSK outside the submitted work. Dr Tiplica reported personal fees from LEO Pharma, Antibiotice SA, and Genesis Pharma outside the submitted work. Dr Traidl reported grants from Sanofi and personal fees from LEO Pharma, Janssen, Lilly, and La Roche-Posay outside the submitted work. Dr Cho reported personal fees from Novartis, AbbVie, Sanofi, and Viatris outside the submitted work. No other disclosures were reported.

Figures

Figure 1.
Figure 1.. Flowchart of the 2-Round DELPHI Process
In the first round, 100 statements were scored, of which 82 were appropriate and 7 were discarded. In the second round, the 11 statements from the first round that exhibited uncertain levels of agreement and disagreement were revised. Two additional statements were introduced. As a result, 93 statements achieved consensus.
Figure 2.
Figure 2.. Baseline and Complementary Diagnostic Workup Based on the Delphi Consensus
A, Investigations that should be performed in all patients with suspected drug reaction with eosinophilia and systemic symptoms (DRESS) and complementary examinations that are recommended in patients with specific suspected organ damage and/or severe disease. B, Workup investigating human herpes virus (HHV) reactivations, including serological investigations of HHV reactivations associated with DRESS in the basic workup and serological investigations of viral reactivations associated with DRESS in selected patients only. HHV-7 reactivation can be suspected in patients with DRESS with another confirmed HHV reactivation. CMV indicates cytomegalovirus; CNS, central nervous system; CT, computed tomography; EBV, Epstein-Barr virus; eGFR, estimated glomerular filtration rate; MRI, magnetic resonance imaging; PCR, polymerase chain reaction; PNS, peripheral nervous system; ProBNP, Pro–B-type natriuretic peptide. aInvolve specialists of the respective disciplines.
Figure 3.
Figure 3.. Proposed DRESS Severity Grading Based on the Delphi Consensus Statements
AP indicates alkaline phosphatase; DRESS, drug reaction with eosinophilia and systemic symptoms; N ↑, fold increase of the normal upper limit value. aInvolvement of other organ(s) of any severity.
See this image and copyright information in PMC

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