Rituximab and dupilumab improve eosinophilic granulomatosis with polyangiitis with multiple pulmonary thrombi

Abstract

Background: Eosinophilic granulomatosis with polyangiitis (EGPA) is characterized by a necrotizing vasculitis with tissue and peripheral blood eosinophilia affecting small and medium-sized arteries, capillaries, and veins. Venous thromboembolic events are uncommon in EGPA. Moreover, there are only a few reported cases of EGPA complicated by pulmonary embolism or infarction.

Case presentation: We report the case of a 43-year-old woman with eosinophilic granulomatosis with polyangiitis and acute respiratory and heart failure due to bilateral pulmonary artery thrombosis and left femoral vein thrombosis 12 years after disease onset. She also had cardiac involvement (myocarditis, pericardial effusion, and diastolic dysfunction), gastrointestinal symptoms, and peripheral neuropathy. The condition was refractory to treatment with systemic corticosteroids, intravenous cyclophosphamide, and mepolizumab, but the thrombosis and associated acute cardiac failure, as well as the cardiac and gastrointestinal symptoms and multiple polyneuropathy, improved after a switch to rituximab. However, the heart failure did not improve sufficiently and the patient continued to need inhaled oxygen at 1 L/min and asthma exacerbations occurred. We then swapped the patient's mepolizumab treatment for dupilumab. Not only did she have no further asthma attacks after switching to dupilumab, but also her vasculitis symptoms improved. Oxygen therapy was discontinued as the heart failure improved 5 months after starting the dupilumab.

Conclusions: This may be the first case report of the successful treatment by rituximab of pulmonary thromboembolism associated with EGPA. In addition, in this patient, treatment with dupilumab was effective not only for the asthma symptoms but also for the symptoms of vasculitis and heart failure.

Keywords: Cyclophosphamide; Dupilumab; Eosinophilic granulomatosis with polyangiitis; Immunoglobulin; Pulmonary thrombosis; Rituximab; Venous thrombus.

Fig. 1

Clinical course of the patient from the time of diagnosis of eosinophilic granulomatosis with polyangiitis to the time of heart failure. AZP azathioprine, CyA cyclosporine A, Eo eosinophil, FFP formoterol fluticasone combination, FP fluticasone propionate, HFA hydrofluoroalkane, ICS inhaled corticosteroid, IVCY intravenous cyclophosphamide, IVIG intravenous immunoglobulin, MPO-ANCA myeloperoxidase-anti-neutrophil cytoplasmic antibody, mPSL methylprednisolone, PSL prednisolone, WBC white blood cell count

Fig. 2

Rituximab-associated changes in the thrombi in both pulmonary arteries and the left common femoral vein thrombus on contrast-enhanced computer tomography (CT). Contrast-enhanced CT images before rituximab initiation (a), immediately after the first course of rituximab (500 mg/week for 4 weeks, repeated 6-monthly) (b), and at 3 months (c), 1 year (d), and 2 years 2 months (e) after the start of rituximab. The thrombi observed before rituximab initiation immediately started to improve with rituximab therapy. Open circles, thrombus present; open squares, thrombus has disappeared

Fig. 3

Lung perfusion scintigraphy before and after rituximab initiation. There were multiple regions of decreased blood flow in both lungs, but predominantly on the right side, before rituximab administration (a). Two years and 2 months after rituximab initiation, blood flow had improved but some areas of decreased flow remained (b)

Fig. 4

Clinical course of the patient from the time of development of thrombi in both pulmonary arteries to the time of last examination. Eo eosinophil, FFP formoterol fluticasone combination, FP fluticasone propionate, HFA hydrofluoroalkane, ICS inhaled corticosteroid, IVIG intravenous immunoglobulin, MPO-ANCA myeloperoxidase-anti-neutrophil cytoplasmic antibody, MTX methotrexate, PSL prednisolone, WBC white blood cell count