Differential response to biologics in a patient with severe asthma and ABPA: a role for dupilumab?
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llergy, Asthma & Clinical Immunology Open Access
CASE REPORT
Differential response to biologics in a patient with severe asthma and ABPA: a role for dupilumab? Carlo Mümmler1,2, Bernd Kemmerich3, Jürgen Behr1,2, Nikolaus Kneidinger1,2 and Katrin Milger1,2*
Abstract Background: Allergic bronchopulmonary aspergillosis (ABPA) is a severe hypersensitivity reaction to aspergillus species colonizing the airways of patients with asthma or cystic fibrosis. Biologics including anti-IgE and anti-IL5 antibodies have strongly changed the treatment of severe asthmatics and have partly been reported to be effective in the treatment of ABPA. Recently, dupilumab, an anti-IL4-Rα antibody which inhibits signaling by the Th2-cytokines IL4 and IL13, has been approved for the treatment of severe asthma. Case presentation: Here, we report the case of a 49-year-old woman with severe asthma and ABPA, who was uncontrolled despite maximum inhalative therapy, anti-IL5-Rα antibody and continuous oral steroid therapy. Moreover, trials of itraconazole as well as omalizumab showed insufficient efficacy. Lung function revealed peripheral obstruction. FeNO and IgE were increased, eosinophils were suppressed under treatment while marked increases had been documented previously. Switching to dupilumab led to a complete resolution of pulmonary symptoms, resolution of exacerbations and complete withdrawal of oral steroids. A drastic improvement in lung function was noted, with an increase in FEV1 of almost 1 l. FeNO was normalized and IgE strongly reduced. Conclusion: Our case highlights that a patient may exhibit differential treatment responses to the currently available asthma biologics and suggests switching treatment if outcome is insufficient. A potential role for dupilumab in the treatment of ABPA warrants future studies. Keywords: ABPA, Aspergillosis, Asthma, Dupilumab, IL13, IL4 Background Allergic bronchopulmonary aspergillosis (ABPA) is a hypersensitivity reaction to aspergillus species that predominantly affects cystic fibrosis and asthma patients [1]. Aspergillus colonization of the bronchial mucus leads to an activation of the innate immune system with a Th2predominant T cell response [2–5]. Clinical features of ABPA comprise frequent asthma exacerbations, productive cough, airway obstruction, fever, and finally *Correspondence: [email protected]‑muenchen.de 1 Department of Internal Medicine V, Ludwig-Maximilians-University of Munich (LMU), Marchioninistr.15, 81377 Munich, Germany Full list of author information is available at the end of the article
leads to end-stage lung disease. Diagnostic criteria are a predisposing condition, high total serum IgE levels, aspergillus-specific IgE or positive aspergillus skin test, aspergillus-specific IgG, peripheral blood eosinophilia and imaging findings consistent with ABPA [1, 6]. Clinical management involves oral corticosteroids and systemic therapy with azoles. In recent years, several studies and case reports showed efficacy for anti-IgE antibody and IL5/IL5-Rα antibodies in the t
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