Severe Asthma Where Eosinophilic Granulomatosis with Polyangiitis Became Apparent after the Discontinuation of Dupilumab

Ikeda, Miki; Ohshima, Nobuharu; Kawashima, Masahiro; Shiina, Meiko; Kitani, Masashi; Suzukawa, Maho

doi:10.2169/internalmedicine.7990-21

Cited by 16 publications

(11 citation statements)

References 29 publications

(28 reference statements)

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“…Isolated cases of chronic eosinophilic pneumonia [70][71][72], eosinophilic gastritis, [73], and eosinophilic vasculitis [74] have been associated with dupilumab in patients with asthma. Therefore, dupilumab could be considered as being directly related to or unmasking previous vasculitis by discontinuation or reduction of corticosteroids in asthma patients, as reported by Ikeda et al [75] and Murag et al [76]. Importantly, cases reported by Eger et al [77] highlight the importance of considering the blood eosinophil count in asthmatics who switch from an anti-IL-5/5Ra agent to an anti-IL-4/13 agent.…”

Section: Symptomatic Hypereosinophilia Induced By Dupilumab: Case Rep...mentioning

confidence: 97%

See 1 more Smart Citation

Eosinophilia Induced by Blocking the IL-4/IL-13 Pathway: Potential Mechanisms and Clinical Outcomes

Olaguíbel¹,

Sastre²,

Rodríguez³

et al. 2022

J Investig Allergol Clin Immunol

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Currently, five biological drugs for uncontrolled severe asthma treatment are marketed. They all block type 2 inflammatory pathways, either by targeting IgE (omalizumab), the IL-5 pathway (mepolizumab, reslizumab, benralizumab), or the IL-4/13 pathway (dupilumab). Hypereosinophilia has been observed in between 4% and 25% of patients treated with dupilumab, being transient in most cases, but persistent cases of symptomatic hypereosinophilia consistent with eosinophil granulomatosis with polyangiitis (EGPA), eosinophilic pneumonia, eosinophilic vasculitis or sudden worsening of asthma symptoms have been described. Cases of EGPA have been described with all biologics, including anti-IL-5, and with leukotriene receptors antagonists in publications or in the Eudravigilance database. In many cases of EGPA, it appears during systemic steroids tapering or after switching from an anti-IL-5 biologic to Dupilumab, suggesting that systemic steroids or the anti IL-5 were masking the vasculitis. This review aims to substantiate the plausible mechanisms of dupilumab-induced hypereosinophilia and review symptomatic hypereosinophilia cases associated with dupilumab therapy. Blockade of the IL-4/IL-13 pathway cause a reduction of eosinophil migration and blood accumulation by inhibiting eotaxin-3, VCAM-1, and TARC without simultaneously inhibiting eosinophilopoiesis in the bone marrow. When choosing the optimal biologic, it seems necessary to consider the presence of hypereosinophilia (>1,500/mL), where an anti-IL-5/IL-5R is preferable. Also, when changing from an anti-IL-5/5R to an anti-IL-4/13R. Close monitoring of blood eosinophils and clinical evolution seems justified in these situations. Nevertheless, dual therapy with anti-IL-5/5R and anti-IL4/IL-13R may be needed for optimal control since both IL-5, and IL-4/13 pathways can simultaneously contribute to airway inflammation.

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Section: Symptomatic Hypereosinophilia Induced By Dupilumab: Case Rep...mentioning

confidence: 97%

“…Given that EGPA can appear during tapering and discontinuation of systemic corticosteroids, systemic corticosteroids may be masking vasculitis [75,76,83].…”

Section: Egpa In Pivotal Studies On Asthma and Crswnp Treated With Du...mentioning

confidence: 99%

Eosinophilia Induced by Blocking the IL-4/IL-13 Pathway: Potential Mechanisms and Clinical Outcomes

Olaguíbel¹,

Sastre²,

Rodríguez³

et al. 2022

J Investig Allergol Clin Immunol

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“…On the contrary, a case by Adachi et al showed that treatment with dupilumab reduced symptoms caused by EGPA such as leg edema, abdominal pain, and dyspnea [7]. Another case by Ikeda et al included a patient who presented with EGPA only after discontinuing dupilumab [8].…”

Section: Discussionmentioning

confidence: 99%

“…Another case by Ikeda et al. included a patient who presented with EGPA only after discontinuing dupilumab [ 8 ].…”

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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“…It was reported that patients who developed eosinophilic disorders after dupilumab initiation had a clinical history suggestive of systemic eosinophilic disease or received several cycles of SCS tapering prior to an adverse event 8 . Some patients developed EGPA after dupilumab discontinuation or after switching biologics from anti-IL-5 or anti-IL-5 receptor alpha antibodies to dupilumab 9,10 . In our case, the development of EGPA-related symptoms and the re-elevation of ANCA were observed without a history of SCS tapering after dupilumab initiation.…”

Section: Discussionmentioning

confidence: 99%

A case of eosinophilic granulomatosis with polyangiitis developed after dupilumab administration in patients with eosinophilic chronic rhinosinusitis and asthma

Suzaki

Tanaka

Yanai

et al. 2022

Preprint

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Background:Eosinophilic granulomatosis with polyangiitis (EGPA) is a form of anti-neutrophil cytoplasmic antibody (ANCA) associated vasculitis characterized by eosinophil-rich granulomatous inflammation and small-to-medium vessel vasculitis associated with asthma, rhinosinusitis and eosinophilia. EGPA is often difficult to distinguish from severe asthma and eosinophilic chronic rhinosinusitis in cases when there are no findings that clearly suggest vasculitis. Dupilumab, an anti-IL-4Rα monoclonal antibody, is expected to be effective in eosinophilic airway inflammatory diseases, such as severe asthma and refractory chronic rhinosinusitis. Although transient eosinophilia and eosinophilic pneumoniae have been reported in patients with severe asthma and chronic rhinosinusitis with nasal polyps after the administration of dupilumab, few studies have examined the development of EGPA.Case presentation:We report a case of 61-year-old woman treated with dupilumab for refractory eosinophilic chronic rhinosinusitis and eosinophilic otitis media complicated by severe asthma. Although she had a previous history of eosinophilic pneumoniae and myeloperoxidase (MPO) ANCA positivity, there were no apparent findings of vasculitis suggesting EGPA before the initiation of dupilumab therapy. After the second administration of dupilumab, several adverse events developed, including worsening of ECRS, EOM and asthma, and neuropathy. Blood test showed an increase in the levels of eosinophils and re-elevation of MPO-ANCA levels after the administration of dupilumab therapy. Therefore, dupilumab therapy was discontinued owing to the development of EGPA, and prednisolone and azathioprine administration was initiated for a remission induction therapy. Conclusion:To the best of our knowledge, this is the first case report that suggests that dupilumab may directly trigger the manifestation of vasculitis in patients who were previously MPO-ANCA-positive. Although the precise mechanism of how dupilumab could trigger the development of EGPA requires further elucidation, to measure MPO-ANCA in patients with multiple eosinophilic disorders prior to the initiation of dupilumab might be helpful when considering the possibility of a latent EGPA. When administering dupilumab to patients with previous history of MPO-ANCA positivity, clinicians must carefully monitor and collaborate with other specialists in the pertinent fields of study for appropriate usage.

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Severe Asthma Where Eosinophilic Granulomatosis with Polyangiitis Became Apparent after the Discontinuation of Dupilumab

Cited by 16 publications

References 29 publications

Eosinophilia Induced by Blocking the IL-4/IL-13 Pathway: Potential Mechanisms and Clinical Outcomes

Eosinophilia Induced by Blocking the IL-4/IL-13 Pathway: Potential Mechanisms and Clinical Outcomes

Dupilumab-Associated Eosinophilic Granulomatosis With Polyangiitis

A case of eosinophilic granulomatosis with polyangiitis developed after dupilumab administration in patients with eosinophilic chronic rhinosinusitis and asthma

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