Eosinophilic granulomatosis with polyangiitis

Davide Maimone MD PhD (Dr. Maimone of Garibaldi Hospital in Catania, Italy, has no relevant financial relationships to disclose.)
Raymond P Roos MD, editor. (Dr. Roos of the University of Chicago owns stock in Amgen, Express Scripts, Isis, and Merck.)
Originally released November 8, 1996; last updated February 16, 2017; expires February 16, 2020

This article includes discussion of eosinophilic granulomatosis with polyangiitis, Churg-Strauss syndrome, allergic granulomatosis and angiitis, granulomatous eosinophilic angiitis, allergic granulomatosis, allergic angiitis, allergic granulomatosis and angiitis, and granulomatous eosinophilic angiitis. The foregoing terms may include synonyms, similar disorders, variations in usage, and abbreviations.

Overview

Eosinophilic granulomatosis with polyangiitis (formerly known as Churg-Strauss syndrome) is a rare systemic vasculitis almost invariably associated with allergic disorders such as asthma and rhinosinusitis. It involves the small vessels of the lungs, peripheral nerves, skin, and, less frequently, the heart and the gastrointestinal tract. Laboratory abnormalities include marked eosinophilia and the presence of antineutrophil cytoplasmic antibodies. Increased serum levels of cytokines imply that the systemic activation of the immune system and perturbation of the balance of Th1 and Th2 cytokines may contribute to the heterogeneous spectrum of clinical phenotypes. Increased serum levels of IgG4 and the presence of infiltrating IgG4-positive plasma cells in the peripheral nerve of a subgroup of patients may suggest a relationship with IgG4-related disorders. Pathologic hallmarks are necrotizing vasculitis and extravascular granulomas, consisting of infiltrating eosinophils and lymphocytes. If untreated, eosinophilic granulomatosis with polyangiitis may be fatal in 50% of cases within 3 months, with a survival rate of 3% at 5 years. However, progress made in the management of this disorder has dramatically changed the prognosis of these patients, who are now achieving a median survival time longer than 10 years. The judicious use of corticosteroids and immunosuppressants can prevent serious consequences, including death, and lead to a remission in more than 90% of patients. Aggressive forms may require induction protocols, including intravenous high-dose methylprednisolone, cyclophosphamide, or rituximab. Intravenous immunoglobulin, tumor necrosis factor-alpha blockers, anti-IL5 monoclonal antibody (mepolizumab), or autologous hematopoietic stem cell transplantation may be beneficial for refractory forms.

Key points

 

• Eosinophilic granulomatosis with polyangiitis (Churg-Strauss syndrome) is a rare systemic vasculitis associated with eosinophilia and asthma and is characterized by a poor prognosis if left untreated.

 

• Vasculitic infiltrates are responsible for multiple organ involvement, including lung, gut, heart, kidney, nervous system, and skin.

 

• The neurologic picture of eosinophilic granulomatosis with polyangiitis is mainly a mononeuropathy multiplex evolving to a polyneuropathy pattern, but cerebral hemorrhages or infarcts may also occur.

 

• Definitive diagnosis of eosinophilic granulomatosis with polyangiitis relies essentially on tissue biopsy, although eosinophilia and increased levels of antineutrophil cytoplasmic antibodies may contribute to a differential diagnosis with other systemic vasculitides.

 

• Corticosteroids are the mainstay of treatment, but immunosuppressants (eg, cyclophosphamide or methotrexate) and biological drugs (TNF-alpha receptor blockers or monoclonal antibody to CD20 positive B-cells) may be needed to obtain remission in more severe cases.

Historical note and terminology

In 1951, Jacob Churg and Lotte Strauss described 13 patients with asthma, fever, hypereosinophilia, and “symptoms of vascular embarrassment in various organ systems,” particularly the heart, gastrointestinal tract, kidney, skin, and peripheral nerves (Churg and Strauss 1951). At postmortem, they found not only a systemic arteritis, but also generalized, extravascular, granulomatous lesions. The latter distinguished these patients from those with polyarteritis nodosa ("periarteritis nodosa" at the time) and Wegener granulomatosis. Previous examples of arteritis associated with asthma had been considered variants of polyarteritis nodosa (Rackemann and Greene 1939), but Churg and Strauss believed their findings delineated a distinct clinical entity. Although they named the disorder “allergic granulomatosis and angiitis”, it was known until recently as “Churg-Strauss syndrome.”

The 2012 international nomenclature categorizes the systemic vasculitides according to the size of vessels affected and the nature of the pathology. Eosinophilic granulomatosis with polyangiitis (Churg-Strauss syndrome) is defined by “eosinophil-rich and necrotizing granulomatous inflammation often involving the respiratory tract, and necrotizing vasculitis predominantly affecting small to medium vessels, and associated with asthma and eosinophilia” (Jennette et al 2013). Marked eosinophilia in tissue specimens is not diagnostic of eosinophilic granulomatosis with polyangiitis and can be seen in other vasculitides. Eosinophilic granulomatosis with polyangiitis, along with granulomatosis with polyangiitis (Wegener granulomatosis) and microscopic polyangiitis are classified as small vessel vasculitides associated with antineutrophil cytoplasmic antibodies. The addition of a prefix to the name is recommended to indicate antineutrophil cytoplasmic antibody reactivity (ie, ANCA positive or negative). The antineutrophil cytoplasmic antibodies most often found in eosinophilic granulomatosis with polyangiitis are the antimyeloperoxidase type (p-antineutrophil cytoplasmic antibodies) and are more frequent in patients with renal disease of any type and in 100% of those with necrotizing glomerulonephritis.

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