MORPHOLOGYMicroscopicpolyangiitisischaracterizedbysegmentalfibrinoidnecrosisofthemediawithfocaltransmuralnecrotizinglesions;granulomatousinflammationisabsent.Theselesionsresemblethoseofpolyarteritisnodosabutsparemedium-andlarge-sizedarteries,sothatmacroscopicinfarctsareuncommon.Insomeareas(typicallypostcapillaryvenules),onlyinfiltratingneutrophilsundergoingfragmentationareseen,givingrisetothetermleukocytoclastic vasculitis (
Fig.10.26A ).Althoughimmunoglobulinsandcomplementcomponentscanbedemonstratedinearlyskinlesions,mostlesionsare“pauci-immune”(i.e.,showlittleornoantibody).
Previously called Wegener granulomatosis, granulomatosis with polyangiitis (GPA) is a necrotizing vasculitis characterized by a triad of the following:
Necrotizing granulomas of the upper-respiratory tract (ear, nose, sinuses, throat) or the lower-respiratory tract (lung) or both
Necrotizing or granulomatous vasculitis affecting smallto medium-sized vessels (e.g., capillaries, venules, arterioles, and arteries), most prominently the lungs and upper airways but other sites as well
Focal necrotizing, often crescentic, glomerulonephritis “Limited” forms of disease can be restricted to the respiratory tract. Conversely, when widespread the disease may affect the eyes, skin, and other organs, most notably the heart; clinically, widespread GPA resembles PAN with the additional feature of respiratory involvement.
GPA is likely initiated as a cell-mediated hypersensitivity response to inhaled infectious or environmental antigens. PR3-ANCAs are present in almost 95% of cases and probably drive the tissue injury. The ANCA level also is a useful marker of disease activity, as antibody titers fall dramatically with effective immunosuppressive therapy and rise prior to disease relapse.
MORPHOLOGYUpperrespiratorytractlesionsrangefromgranulomatous sinusitis to ulcerative lesions ofthenose,palate,orpharynx;lungfindingsalsovary,rangingfromdiffuseparenchymalinfiltratestogranulomatousnodules.Thereismultifocalnecrotizinggranulomatous vasculitis withasurroundingfibroblasticproliferation(
Fig.10.26B ).Multiplegranulomatacancoalescetoproduceradiographicallyvisiblenoduleswithcentralcavitation(
Fig.10.26BC ).Destructionofvesselscanleadtohemorrhageandhemoptysis.Lesionscanultimatelyundergoprogressivefibrosisandorganization.
Therenal lesions rangefrommild,focalglomerularnecrosisassociatedwiththrombosisofisolatedglomerularcapillaryloops(focal and segmental necrotizing glomerulonephritis) tomoreadvancedglomerularlesionswithdiffusenecrosisandparietalcellproliferationformingepithelialcrescents(crescen-tic glomerulonephritis) (Chapter14).