The novel approaches to the treatment of eosinophilic granulomatosis with polyangitis

Abstract

Eosinophilic granulomatosis with polyangitis (EGPA; formerly Churg–Strauss syndrome) is a systemic granulomatous vasculitis with eosinophilia in patients with a history of allergic airway diseases such as bronchial asthma [1]. Necrotizing vasculitis predominantly affects small-to-medium vessels in EGPA. EGPA is a rare disease affecting no more than 0.5 in 10,000 people globally. Pathogenesis of EGPA is unknown and presumed to be multifactorial and the disease can be triggered by exposure to allergens or drugs. EGPA is a longstanding, life-threatening disease. Severe organ manifestations can occur in the heart, kidney and lungs. Peripheral neuropathy due to mononeuritis multiplex is also a troublesome disease condition. Five-factor score, that is, reduced renal function, proteinuria, gastrointestinal involvements (hemorrhage, infarction or pancreatitis), involvement of CNS and cardiomyopathy, can predict the prognosis of the disease [2]. Anti-neutrophilic cytoplasmic antibodies (ANCA), mainly against myeloperoxidase, are detected in approximately 40–50% of the patients; thus, EGPA is presently classified as an ANCA-associated vasculitis (AAV) [3]. Biomarkers to monitor disease activity of EGPA include blood eosinophil count and CRP. In addition, eosinophilic cationic protein and titers of myeloperoxidaseANCA may also reflect disease activity. C-C chemokine-ligand 17 (CCL17), eotaxin-1, eotaxin-3, IL-5 and IL-25 are speculated to be involved in its pathogenesis [1]; however, their diagnostic specificity will require further study. Glucocorticoids (GCs) remain the conventional therapy for EGPA for remission induction, however, adverse effects of GCs are frequently encountered due to their longterm use [4]. For those patients with a fivefactor score of 1 or higher, cyclophosphamide (CY)-pulse therapy in association with GC is recommended since the combination therapy produces sustained remission for longer months [5]. Remission can be maintained with azathioprine or methotrexate. The target-oriented, interdisciplinary treatment can improve therapeutic outcome in EGPA [6]. However, some of the cases are resistant to conventional treatments and relapses are commonly observed. In this regard, a relapse rate of 41%, from an average of 26 months after initial treatment, has been reported [5]. Several new approaches are being taken to treat EGPA for the last several years. Among them, the most potentially effective drug is rituximab (RTX), a chimeric anti-CD20 monoclonal antibody that has been used to treat malignant lymphoma, rheumatoid arthritis and, more recently, microscopic polyangitis as well as granulomatosis with polyangitis. RTX has been proven to be efficacious for AAV in two separate studies [7,8]. It has also been shown to induce remission in AAV and to maintain it better than other agents [9]. However, until recently, its efficacy in EGPA has remained unclear. In this aspect, we successfully treated an EGPA patient with RTX who were refractory to GC, CY and intravenous gammaThe novel approaches to the treatment of eosinophilic granulomatosis with polyangitis