A 60-years-old female came to our Centre for severe chronic rhinosinusitis with nasal polyps (CRSwNP) lasting many years, not controlled by topic steroid therapy, and frequently exacerbated by infectious episodes, especially in the winter months. She required multiple courses of oral corticosteroids (OCS) and antibiotics, with significant impact on quality of life (persistent anosmia, oral breathing, hypoacusis, auricular fullness, sleep disturbance). She had already undergone ENT surgery, but CRSwNP relapsed; the histological examination of the polyps showed marked eosinophilia. She had also moderate persistent asthma, controlled by medium-dose ICS/LABA, with allergic sensitization to house dust mites; myotonic dystrophy type 2, with mutation of ZFN9 gene; autoimmune thyroiditis.

Her physical examination was normal, except for the known muscle weakness. Laboratory tests showed, as important findings: hypogammaglobulinemia (460 mg/dl) with low IgG (511 mg/dl), especially IgG1 (236 mg/dl) and IgG3 (8 mg/dl), with normal IgA and IgM; eosinophilia (741 cells/mmc).

Association of myotonic dystrophy and hypogammaglobulinemia IgG is described in medical literature, configuring an immunodeficiency-like disorder. Despite starting replacement therapy with SCIg (Hizentra®, CSL Behring), no improvement in infectious exacerbations of CRSwNP was observed.

In 2021, once Dupilumab was officially approved for CRSwNP, we started it (300 mg sc every 2 weeks), supposing an underlying T2 inflammation, given also the presence of eosinophilia in polyps and blood and the co-occurrence of asthma.

We observed a dramatic improvement, with complete remission of CRSwNP clinically (complete smell recovery) and endoscopically (polyps’ reabsorption).

CRSwNP in immunedeficiency is not always infectious: T2 inflammation should be considered.