Page 47 - The Vasculitides, Volume 1: General Considerations and Systemic Vasculitis

Overview of Primary and Secondary Vasculitides 23

heart, stomach, and kidney. Decades later, Churg and Strauss [42] described the clinical and
postmortem findings of thirteen patients with asthma, fever, and hypereosinophilia,
accompanied by eosinophilic exudation, fibrinoid change, and granulomatous proliferation or
the so called allergic granuloma. The latter was found within vessels walls and in
extravascular connective tissue of major organ systems, leading to cardiac, pulmonary,
gastrointestinal, skin, PNS and CNS manifestations. In 1990, the American College of
Rheumatology (ACR) [43] developed criteria for the classification of EGPA that included
ascertainment of four or more of the following: asthma, eosinophilia of >10%,
mononeuropathy or polyneuropathy, non-fixed pulmonary infiltrates on chest radiograph,
paranasal sinus abnormality, and extravascular eosinophils on tissue biopsy that included an
artery, arteriole or venule. These criteria were inadequate since a patient with asthma and
paranasal sinusitis could also fit the designation of EGPA. The 1994 CHCC [1] characterized
EGPA as an eosinophil-rich and granulomatous inflammatory process that involved the
respiratory tract, with necrotizing vasculitis that affected small to medium-sized vessels such
as capillaries, venules, arterioles and arteries, with associated asthma and eosinophilia.
Among 383 patients enrolled in the FVSG Cohort [44] who satisfied the ACR criteria [43] or
in 1994 CHCC definition for EGPA [45], the mean age at presentation was 50 years without
sex predominance. Clinical manifestations at presentation included asthma (91%), peripheral
neuropathy (51%), weight loss (49%), ear, nose and throat signs (48%), non-erosive sinusitis
and polyposis (41%), skin lesions (39%), purpuric rash (22%), lung infiltrates (38%),
gastrointestinal involvement (23%), renal manifestations (22%), cardiomyopathy (16%), CNS
(5%), and cranial nerve involvement (3%). A total of 108 (31%) patients tested positive for
ANCA with significantly more frequent ear, nose and throat, peripheral nerve and renal
involvement, but less frequent cardiac manifestations. Small numbers of children have been
included in large studies of EGPA sufficient to allow comparisons to adults. Among 133
vasculitic patients in the ARChiVe registry, only two were reported to be of the EGPA type
[46].

Granulomatosis with Polyangiitis
Godman and Churg [47] described the syndrome of GPA that included granuloma in the

nasopharynx, sinuses and lower respiratory tract with focal segmental glomerulonephritis and
disseminated small vessel vasculitis. In a landmark article, Godman and Churg [47]
concluded that MPA, EGRA and GPA were related to one another yet distinct from PAN.
This astute conclusion was based mainly on pathological features was later substantiated by
their common association with ANCA, but not so for PAN [48]. Fauci and colleagues [49]
and Hoffman and colleagues [50] at the National Institutes of Health (NIH), respectively
reported a prospective series of eighty-five patients with GPA, and a retrospective assessment
of 180 patients followed for 6 months to 24 years. The presenting signs included pulmonary
infiltrates (71%), sinusitis (67%), arthritis and arthralgia (44%), fever (34%), cough (34%),
otitis (25%), and hemoptysis (22%), with an overall predominance of organ system
involvement in the lung (94%), paranasal sinuses (91%), kidney (85%), joints (67%), and
nasopharynx and nose (64%). Fauci and colleagues [49] established the efficacy of
cyclophosphamide and prednisone in achieving complete remissions in 93% of patients, as
well as, the tendency of patients to relapse and accrue additive mortality from both disease
and treatment. The characteristic histopathology is a necrotizing granulomatous vasculitis
which may be found in lung and renal biopsy tissue although the latter is less common.

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