VASCULIDITES WITH PROMINENT RESPIRATORY MANIFESTATIONS

Abstract

The spectrum of vasculitis is extremely diverse and frequently confusing. Several of the vasculitis variants can present with respiratory symptoms that may masquerade as common allergic disorders. The clinician who is faced with seemingly new and isolated respiratory tract symptoms may be lulled into a diagnosis of either an infectious or allergic disorder. Persistence of the condition despite what appears to be appropriate therapy should prompt the allergist/immunologist to consider alternative diagnoses with similar presentations. Among the more likely possibilities are the granulomatous vasculidites known for their prominent respiratory tract manifestations. The immunopathogenesis of these diverse conditions has been elucidated in the past several years, facilitating a description of how cross-regulating mechanisms allow a shift from Type 1 to Type 2 cytokine production, or vice versa. This helps to explain why there are so many apparent similarities in these seemingly divergent disease processes. 19 It is now established that the CD4 Th-2 type cell is associated with mast cell and eosinophil growth and differentiation as well as IgE production by B cells in the induction of allergic inflammation. The associated CD4 Th-2 cytokine profile comprises IL-4, -5, -10 and -13, and the responsible stimulus is either an allergen or a helminth. On the other hand, disorders with a Th-1 profile appear to act in concert with activated macrophages to provide a cytokine cascade composed of IL-1 and IL-2, interferon gamma, and tumor necrosis factor. The stimulating antigen includes bacteria, viruses and mycobacteria. This article focuses on those vasculitic disorders that appear to have a Th-1 cytokine profile in which the final inflammatory result is frequently an epithelial cell granuloma such as that seen in sarcoidosis, Wegener's granulomatosis, Churg-Strauss syndrome, and several collagen vascular disorders with prominent vasculitic manifestations. These disorders have been generically referred to as the respiratory vasculidites . It is possible that future research will permit an even better understanding of the regulating mechanisms that shift the immune response along one cytokine path or another. It is also possible that some of these disorders have elements of both cytokine profiles, explaining some of their confusing similarities.