Eosinophilic pleural effusion and stroke with cutaneous vasculitis: Two cases of dupilumab‐induced hypereosinophilia

Lommatzsch, Marek; Stoll, Paul; Winkler, Jörg; Zeise-Wehry, Daniel; Tronnier, Michael; Weber, Marc‐André; Virchow, J. Christian

doi:10.1111/all.14964

Cited by 23 publications

(13 citation statements)

References 9 publications

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“…Unter einer Dupilumab-Therapie kann es zu einem deutlichen (meist transienten) Anstieg der Bluteosinophilen kommen: hier korreliert die Bluteosinophilenzahl nicht mit den Asthma-Symptomen des Patienten (Patienten können trotz hoher Bluteosinophilenzahlen ein gute Asthmakontrolle aufweisen) [127]. Die Bluteosinophilen-Vermehrung bei Biologika-naiven Patienten ist ein wichtiger prognostischer Marker für das Ansprechen auf eine Therapie mit Anti-IL-5-(R)-Biologika: je höher der Bluteosinophilenwert, desto wahrscheinlicher das Ansprechen [128].…”

Section: Leitlinieunclassified

“…* Unterschiedliche Bluteosinophilen-Grenzwerte in den Zulassungsstudien von Mepolizumab, Reslizumab und Benralizumab. ** Eine Dupilumab-Therapie-Einleitung sollte aufgrund der Gefahr schwerer Hypereosinophilien bei Bluteosinophilen-Ausgangswerten > 1500/µl nur in begründeten Fällen erfolgen[127]. & Omalizumab ist für die Behandlung der chronisch spontanen Urtikaria ab einem Alter von 12 Jahren und für die Behandlung der CRSwNP ab 18 Jahren zugelassen.…”

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S2k-Leitlinie zur fachärztlichen Diagnostik und Therapie von Asthma 2023

et al. 2023

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ZusammenfassungDas Management von Asthma hat sich in den letzten Jahrzehnten fundamental gewandelt. Die vorliegende Leitlinie zur Diagnostik und Therapie von Asthma wurde für pneumologisch tätige Fachärztinnen und Fachärzte entwickelt, welche detaillierte und evidenzbasierte Informationen zu den neuen diagnostischen und therapeutischen Optionen von Asthma benötigen. Die Leitlinie zeigt die neue Bedeutung der Biomarker, insbesondere der Bluteosinophilen und des exhalierten NO (FeNO), in den diagnostischen Algorithmen von Asthma. Als erste Asthma-Leitlinie weltweit benennt die vorliegende Leitlinie die nachhaltige Symptomprävention und die Asthma-Remission als Asthma-Therapieziele, welche durch den Einsatz individuell angepasster, krankheitsmodifizierender Medikamente (wie inhalative Steroide, Allergenimmuntherapie oder Biologika) erreicht werden können. Die zentrale Bedeutung der Behandlung von typischen Asthma-Komorbiditäten wird zudem betont. Schließlich wird auch auf besondere Herausforderungen im Asthma-Management eingegangen, wie bspw. die Therapie von Asthma in der Schwangerschaft, die Behandlung von schwerem Asthma oder die Diagnostik und Therapie von arbeitsbedingten Asthma-Formen.

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S2k-Leitlinie zur fachärztlichen Diagnostik und Therapie von Asthma 2023

et al. 2023

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“…However, the ROC curve of CXCR4 was excellent, with an area of 94% under the curve, and a sensitivity of 88%. Although dupilumab‐induced transient eosinophilia seems not clinically relevant in the majority of cases, 22–25 there are case reports with dupilumab‐associated hypereosinophilic syndromes 60–62 . Therefore, CXCR4 on eosinophils might be a valuable predictive marker for stratifying patients who might develop eosinophilia and should be monitored more carefully under the treatment with dupilumab.…”

Section: Discussionmentioning

confidence: 99%

Dupilumab‐induced eosinophilia in patients with diffuse type 2 chronic rhinosinusitis

Ryser,

Yalamanoglu,

Valaperti

et al. 2023

Allergy

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BackgroundDupilumab, a monoclonal anti‐IL‐4Rα antibody, is approved for several type 2 mediated inflammatory diseases like asthma, atopic dermatitis, and diffuse type 2 chronic rhinosinusitis (CRS). Clinical studies had reported a transient increase in blood eosinophils during dupilumab therapy.This study aimed to assess the impact of elevated blood eosinophils on clinical outcome and to investigate the cause of high blood eosinophil levels under dupilumab therapy.MethodsPatients suffering from diffuse type 2 CRS treated with dupilumab were examined on days 0, 28, 90, and 180 after therapy start. Sino‐Nasal‐Outcome‐Test Score (SNOT‐22), Total Nasal Polyp Score (TNPS), and blood samples were collected. Cytokine measurements and proteomics analysis were conducted. Flow cytometry analysis measured receptor expression on eosinophils.ResultsSixty‐eighty patients were included. Baseline eosinophilia ≥0.3G/L was observed in 63.2% of patients, and in 30.9% of patients, eosinophils increased by ≥0.5G/L under dupilumab. Subjects with eosinophilia ≥0.3G/L at baseline had the best SNOT‐22 mean change compared to no eosinophilia. Eosinophil elevation during dupilumab therapy had no impact on clinical scores. The eosinophil adhesion molecule VCAM‐1 decreased significantly during therapy in all patients. The chemokine receptor CXCR4 was significantly down‐ and IL‐4 upregulated in subjects with eosinophil increase.ConclusionOur findings suggest that increased eosinophils in type 2 CRS are associated with a good clinical response to dupilumab. Patients with elevated IL‐4 at baseline developed dupilumab‐induced transient eosinophilia. We identified the downregulation of VCAM‐1 and surface markers CD49d and CXCR4 on eosinophils as possible explanations of dupilumab‐induced eosinophilia.

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“…In our patient, we observed leukocytosis and eosinophilia. Lommatzsch et al presented a case that involved dupilumab-induced hypereosinophilia, which led to eosinophilic pleural effusion within the first six weeks after treatment initiation [ 9 ]. Another study showed that blood eosinophils transiently increased after dupilumab in patients with asthma or chronic sinusitis, but not in atopic dermatitis or eosinophilic esophagitis.…”

Section: Discussionmentioning

confidence: 99%

Dupilumab-Associated Eosinophilic Granulomatosis With Polyangiitis

Persaud¹,

Karmali²,

Sankar³

et al. 2022

Cureus

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A 58-year-old Caucasian male developed generalized weakness, bilateral upper and lower extremity arthralgias, left pedal edema, and a new rash over two weeks after receiving one dose of dupilumab for chronic sinusitis. He was found to be positive for perinuclear anti-neutrophil cytoplasmic antibodies and myeloperoxidase, with evidence of interstitial lung disease on CT imaging. A skin biopsy showed eosinophilic vasculitis and a kidney biopsy showed pauci-immune glomerulonephritis. He was diagnosed with eosinophilic granulomatosis with polyangiitis due to dupilumab exposure.

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Eosinophilic pleural effusion and stroke with cutaneous vasculitis: Two cases of dupilumab‐induced hypereosinophilia

Abstract: https://www.cdc. gov/vacci nes/covid -19/info-by-produ ct/clini cal-consi derat ions.

Cited by 23 publications

References 9 publications

S2k-Leitlinie zur fachärztlichen Diagnostik und Therapie von Asthma 2023

S2k-Leitlinie zur fachärztlichen Diagnostik und Therapie von Asthma 2023

Dupilumab‐induced eosinophilia in patients with diffuse type 2 chronic rhinosinusitis

Dupilumab-Associated Eosinophilic Granulomatosis With Polyangiitis

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