These closely related systemic illnesses involve multiple individual peripheral nerves, much as in polyarteritis. A characteristic feature is the excess of circulating and tissue eosinophils (more so than in polyarteritis) and a tendency of the vasculitis to involve the lungs and skin, in contrast to the renal and bowel infarctions of polyarteritis nodosa. There is considerable degree of pathologic and clinical overlap between both polyarteritis and Churg-Strauss necrotizing vasculitis with the more benign hypereosinophilic syndrome that is less aggressive and has a greater tendency for eosinophilic infiltration of tissues other than nerve. One medication (zafirlukast, a leukotriene receptor antagonist) that has been used in Europe to treat asthma, has precipitated several cases of Churg-Strauss disease. Rarely, the overall illness has apparently been preceded by treatment with a macrolide antibiotic (e.g., azithromycin), estrogen, or carbamazepine, but these associations are uncertain and most cases are idiopathic.
In Churg-Strauss disease, rhinitis or asthma may be present for years and only later is there marked eosinophilia and organ infiltration, particularly an eosinophilic pneumonitis. The neuropathy that then develops in approximately three-quarters of patients is usually preceded by fever and weight loss and takes the form of an acute, painful mononeuritis multiplex. A granular cytoplasmic pattern of antineutrophil cytoplasmic autoantibodies (c-ANCA) of the same type that occurs in Wegener granulomatosis is found in more than half of cases (see below). The histologic feature in nerve biopsies is similar to polyarteritis nodosa, but the eosinophilic infiltration tends to be more intense. We have seen other types of cutaneous diseases with vasculitic mononeuritis, the most impressive being a massive leukocytoclastic vasculitis of the skin (necrotic polymorphonuclear cells surrounding venules) resulting in large confluent hemorrhagic lesions.
The idiopathic eosinophilic syndrome comprises a heterogeneous group of disorders, the common features of which are a persistent and extreme degree of eosinophilia and eosinophilic infiltration of many organ systems. Neuropathy occurs in fewer than half of the cases, taking the form of a painful diffuse sensorimotor syndrome with axonal damage or of a mononeuritis multiplex (see Moore et al). The pathologic appearance is one of diffuse infiltration of the nerves by eosinophils rather than a vasculitis. The neuropathic effects are attributable to the infiltration itself or to a postulated tissue-damaging effect of the eosinophilic cell.
Treatment Both the Churg-Strauss and the idiopathic hypereosinophilic syndrome are treated initially with high doses of corticosteroids, with which the peripheral eosinophilia, as well as tissue damage, may abate in several weeks or months. Further immunosuppressive treatment in the forms of rituximab as discussed previously, azathioprine, methotrexate, or cyclophosphamide has been used in fulminant or refractory cases, which includes most of the ones that we have seen.