What we know—and don’t know—about CSS
The exact etiopathogenesis of CSS is unknown.2-4 Although ANCAs are detected in about 40% to 60% of CSS patients, it is not yet known whether ANCAs have a pathogenic role.2-3 Abnormalities in immunologic function also occur, including heightened Th1 and Th2 lymphocyte function, increased recruitment of eosinophils, and decreased eosinophil apoptosis. Genetic factors, including certain interleukin-10 polymorphisms and HLA classes such as HLA-DRB4, may also contribute to CSS pathogenesis.4
Three distinct sequential phases have been described, although these are not always clearly distinguishable.2,5
• The first is the prodromal or allergic phase, which is characterized by the onset of asthma later in life in patients with no family history of atopy. There may or may not be an associated allergic rhinitis.
• In the eosinophilic phase, peripheral blood eosinophilia and eosinophilic infiltration of multiple organs (especially the lungs and gastrointestinal [GI] tract) occur.
• The vasculitis phase is characterized by life-threatening systemic vasculitis of the small and medium vessels that is often associated with vascular and extravascular granulomatosis.
Cutaneous and extracutaneous findings
One-half to two-thirds of patients with CSS have cutaneous manifestations that typically present in the vasculitis phase.2,5 The most common skin finding is palpable purpura on the lower extremities. Macular or papular erythematous eruption, urticaria, subcutaneous skin-colored or erythematous nodules, livedo reticularis, and erythema multiforme–like eruption may also be seen.2,5,6 Skin biopsies will show numerous eosinophils with either leukocytoclastic vasculitis or extravascular necrotizing granuloma.5
Extracutaneous manifestations of CSS include renal, cardiac, GI tract, and nervous system involvement.2,7
To identify patients with a poor prognosis, the 5-factor score (FFS) can be used. This score assigns 1 point each to GI tract involvement, renal insufficiency, proteinuria, central nervous system involvement, and cardiomyopathy.7 CSS patients with an FFS ≥2 have a considerably greater risk of mortality.7