Churg–Strauss Syndrome

Update on Pathophysiology and Treatment

Augusto Vaglio; Frank Moosig; Jochen Zwerina

Disclosures

Curr Opin Rheumatol. 2012;24(1):24-30. 

In This Article

Abstract and Introduction

Abstract

Purpose of review: Churg–Strauss syndrome (CSS) has a clear clinical phenotype but its pathogenesis is not fully elucidated. Recent studies have focused on its immunogenetic aspects and cytokine and chemokine-mediated pathogenetic mechanisms, providing the rationale for the use of newer targeted therapies. This study will review recent findings on the pathogenesis of CSS and its therapeutic approaches.
Recent findings: CSS is usually considered a Th2-mediated disease, but Th1 and Th17 responses might also play a role; the reported association between CSS and HLA-DRB4 further underlines the pathogenetic relevance of CD4 + T cells which, thanks to their ability to secrete cytokines such as IL4, IL5, and IL13, promote allergic and eosinophilic reactions. Resident cells such as endothelial and epithelial cells might also amplify the immune response by producing eosinophil-attracting chemokines such as eotaxin-3 and CCL17. Conventional immunosuppressive therapies offer high chances of achieving sustained remission, but steroid exposure remains high. Targeting IL5 with mepolizumab seems promising in sparing steroids, but relapses often follow its withdrawal. B-cell depletion using rituximab has proved effective in refractory CSS cases.
Summary: Current knowledge on CSS pathogenesis is evolving; the identification of key molecular mechanisms will pave the way for newer, more specific treatments.

Introduction

Churg–Strauss syndrome (CSS) is a systemic inflammatory disease characterized by asthma, eosinophilia, and involvement of various organ systems such as the upper and lower respiratory tract, the peripheral nervous system, the skin, the kidney and the gastrointestinal tract. Histology of CSS usually discloses small-vessel vasculitis, eosinophil-rich infiltrates and eosinophilic granulomas. Because of the frequent positivity of antineutrophil cytoplasmic antibodies (ANCAs), which are found in 30–40% of the cases, and the predominant involvement of small vessels, CSS has been grouped with microscopic polyangiitis (MPA) and granulomatosis with polyangiitis (Wegener's) (GPA) under the umbrella term 'ANCA-associated vasculitis' (AAV).[1]

The most common clinical manifestations of CSS include asthma and allergic rhino-sinusitis, with frequent polyp formation; lung involvement is also common, with lung infiltrates and pleural effusions being the most frequent manifestations; skin lesions such as purpura, nodules and urticaria, occur in approximately 50% of the patients; peripheral neuropathy affects about two-thirds of the cases and is often severe.[2] Renal manifestations, occurring in up to 25% of the patients, range from isolated urinary abnormalities to rapidly progressive renal failure, with histological evidence of (usually focal and segmental) pauci-immune crescentic necrotizing glomerulonephritis.[3] Gastrointestinal and cardiac manifestations are found in 30–50% of the patients and may predict an adverse outcome;[4] central nervous system involvement, albeit less frequent, also confers an increased risk of mortality. These clinical features tend to segregate into two different phenotypes, one 'vasculitic', with manifestations due to small-vessel vasculitis (e.g. purpura, mononeuritis multiplex, glomerulonephritis), and one 'eosinophilic', in which organ damage mainly results from tissue eosinophilic infiltration (e.g. pulmonary infiltrates, cardiomyopathy). ANCApositive patients usually show a more vasculitic phenotype.[5,6]

Involvement of the gastrointestinal tract, the heart and the central nervous system, a serum creatinine above 140 mmol/l and proteinuria above 1000 mg/24 h are the five items on which the fivefactor score (FFS) is based. The FFS is the most widely used prognostic score for CSS;[1] its recent re-examination on a large cohort of patients has confirmed the prognostic importance of cardiac and renal insufficiency and gastrointestinal involvement, and identified advanced age as an additional adverse prognostic factor. In this analysis, ear-nose-throat involvement, although not systematically evaluated, was associated with better outcome.[7•] In recent years, major advances have been made in understanding the pathogenesis of CSS, and particularly its immunogenetic aspects, the role of T cells and eosinophils, and that of a complex network of chemokines and cytokines. Some of the pathophysiological principles of the disease have provided the rationale for the use of newer agents such as B-celldepleting and anti-IL5 antibodies, which might become part of the therapeutic armamentarium of CSS. This study will review the most recent findings on the pathophysiology of CSS and its traditional and newer therapeutic approaches.

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