A case of refractory chronic rhinosinusitis with anti-desmoglein 3 IgG4 autoantibody

Immunoglobulin (Ig) G4-related disease (IgG4-RD) is a systemic, refractory, chronic inflammatory disease characterized by high serum IgG4 levels and histopathological findings of IgG4-positive plasma cell infiltration and fibrosis.1,2 Although recent reports have documented cases of refractory chronic rhinosinusitis (CRS) accompanied by IgG4 infiltration (IgG4-CRS),3e5 the underlying mechanism remains unknown. Desmoglein 3 is an autoantigen of Pemphigus vulgaris (PV), an autoimmune blistering mucocutaneous disease.6 Here, for the first time, we report a case of refractory CRS with treatment-recalcitrant nasal polyposis accompanied by infiltration of IgG4 autoantibody specific for desmoglein 3. This casewas diagnosed asMikulicz's disease because of bilateral submandibular and lacrimal glands swelling. We assessed the relationship between IgG4-CRS and desmoglein 3 autoantibody. A 42-year-old male who visited outpatient clinic of our hospital complained severe nasal obstruction of both sides, and also mass lesion in bilateral submandibular regions in July 2013. Initial medical examination revealed polyps in both nasal cavities and a deviation of the nasal septum toward to the right nasal cavity. Computed tomography (CT) of the paranasal sinuses and neck revealed bilateral sinusitis and bilateral submandibular and lacrimal glands swelling. Serum IgG4 and IgG levels were 383 (normal, 4.8e105 mg/dL) and 1931 mg/dL (normal, 870e1700 mg/dL), respectively. Anti-desmoglein 1 antibody and anti-PB180 antibody were negative (<3; normal, <3); antidesmoglein 3 antibody was very high (4390; normal, <3). Eosinophil proportionwere 7830/mL and 6.3% (normal, <7%). The pharynx, oral mucosa, and skin were normal, showing no lesions by whole body CT. Endoscopic sinus surgery (ESS) and biopsy of the left side of the submandibular gland under general anesthesia were performed in January 2015. The patient was then prescribed an antihistaminic agent and a nasal steroid spray. Although the nasal and paranasal mucosa showed slight swelling after ESS, the nasal condition improved and has remained healthy during follow up. Nasal and paranasal sinus mucosa and submandibular gland tissue obtained during surgery were fixed in neutral-buffered formalin, embedded in paraffin, and sectioned. Immunohistochemical staining was performed with mouse anti-human desmoglein 3 (Hycult Biotech, The Netherlands) and mouse anti-human IgG4