The typical patient is a middle aged man, although women and individuals of other ages can be affected. Classic presentations include bilateral pneumonitis with nodules and cavitary lesions (95%), chronic sinusitis (90%), mucosal ulcerations of the nasopharynx (75%), and renal disease (80%). Patients with mild renal involvement may demonstrate only hematuria and proteinuria, whereas more severe disease may portend rapidly progressive renal failure. Rash, myalgias, articular involvement, neuritis, and fever also may occur. If untreated, the mortality rate at 1 year is 80%. Treatment with steroids, cyclophosphamide, TNF inhibitors, and anti–B-cell antibodies (rituximab) has improved this picture considerably. Most patients with GPA now survive, but remain at high risk for relapses that may ultimately lead to renal failure.
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Churg-Strauss syndrome (also called allergic granulomatosis and angiitis) is a small-vessel necrotizing vasculitis classically associated with asthma, allergic rhinitis, lung infiltrates, peripheral eosinophilia, extravascular necrotizing granulomas, and a striking infiltration of vessels and perivascular tissues by eosinophils. It is a rare disorder, affecting 1 in 1 million individuals. Cutaneous involvement (with palpable purpura), gastrointestinal bleeding, and renal disease (primarily as focal and segmental glomerulosclerosis) are the major associations. Cytotoxicity produced by the myocardial eosinophilic infiltrates often leads to cardiomyopathy. Cardiac involvement is seen in 60% of patients and is a major cause of morbidity and death.
Churg-Strauss syndrome may stem from “hyperresponsiveness” to some normally innocuous allergic stimulus. MPO-ANCAs are present in a minority of cases, suggesting that the disorder is pathogenically heterogeneous. The vascular lesions differ from those of PAN or microscopic polyangiitis by virtue of the presence of granulomas and eosinophils.
Thromboangiitis obliterans (Buerger disease) is characterized by segmental, thrombosing, acute and chronic inflammation of mediumand small-sized arteries, principally the tibial and radial arteries, with occasional secondary extension into the veins and nerves of the extremities. Buerger disease occurs almost exclusively in heavy tobacco smokers and usually develops before 35 years of age. Direct EC toxicity caused by some component of tobacco is suspected; alternatively, a reactive compound in tobacco may modify vessel wall components and induce an immune response. Indeed, most patients with Buerger disease are hypersensitive to tobacco extracts. A genetic predilection is suggested by an increased prevalence in certain ethnic groups (Israeli, Indian subcontinent, Japanese) and an association with certain HLA haplotypes.
MORPHOLOGYInthromboangiitisobliterans,thereisasharply segmental acute and chronic transmural vasculitis of mediumand small-sized arteries, predominantlythoseoftheextremities.Intheearlystages,mixedinflammatoryinfiltratesareaccompaniedbyluminalthrombosis;smallmicroabscesses,occasionallyrimmedbygranulomatousinflammation,alsomaybepresent(
Fig.
10.27 ).Theinflammationoftenextendsintocontiguousveinsandnerves(afeaturethatisrareinotherformsofvasculitis).Withtime,thrombicanorganizeandrecanalize,andeventuallythearteryandadjacentstructuresbecomeencasedinfibroustissue.
Fig. 10.27 Thromboangiitisobliterans(Buergerdisease).Thelumenisoccludedbythrombuscontainingasterileabscess(arrow), andthevesselwallisinfiltratedwithleukocytes.