Page 30 - The Vasculitides, Volume 1: General Considerations and Systemic Vasculitis

6 Eric L. Matteson

The neuropathologist Friedrich Wohlwill of Hamburg provided the first coherent
description of microscopic necrotizing vasculitis, coining the term microscopic polyarteritis
nodosa in a description of two reported patients in 1923 [22].

Both patients described by Wohlwill [22] had antecedent illnesses characterized by
weight loss, fevers, clinical evidence of nephritis, widespread muscle pain, and paresis
consistent with mononeuritis multiplex. At postmortem examination, there was evidence of
glomerulonephritis, and widespread inflammation of small vessels on microscopic
examination. He also described inflammatory involvement with marked polymorphonuclear
cell infiltration of arterioles, capillaries and venules [22]. Wohlwill [22] conceived of a direct
relationship to the disease described by Kussmaul and Maier, drawing upon his findings of
systemic vascular inflammation and “a well characterized and uniform disease, which
practically demand the assumption of a unified etiology [22].

In 1931, Heinz Klinger described a patient with necrotizing granulomatous vasculitis
with glomerulonephritis that he considered a form of periarteritis nodosa [23]. He also
described a second patient with similar findings and hemoptysis on presentation postulating a
possible infectious etiopathogenesis [23].

Friedrich Wegener reported further patients which were interpreted as forms of
periarteritis nodosa, however, it was clear that he viewed the disease course and related
pathology as unique and anatomically distinctive particularly the invasive granulomatous
process, which he believed to be due to an infectious agent [24, 25], and the granulomatous
vasculitis as a form of rheumatoid or rheumatic disease [26].

In 1949, Churg and Strauss [27] described an eosinophilic form of granulomatous
polyangiitis with the constellation of “allergic granulomatosis, allergic angiitis, and
periarteritis nodosa. This combination of findings was previously reported by Ophüls [28] in
1923 in a patient who with granulomatous nodules, particularly of the pericardium and
peritoneum with eosinophilic infiltration of the bronchi and pulmonary tissue, and
concomitant arteritis, capillaritis, venulitis, and nephritis.

Otani [29] also described a variant of periarteritis nodosa in 1924 in the description of a
35-year-old woman with asthma and eosinophilia. Churg and Strauss [30] provided more
clinical information and systemization to the disease that eventually bore his name in a
subsequent analysis of 13 patients, all of whom had asthma and granulomatous lesions in
small arteries of parenchymal organs including the epicardium. These investigators [30]
considered the disease to be essentially a “malignant expression” of allergic granulomatosis in
contrast to other more benign forms of allergic granulomatosis such as Loeffler syndrome.

In the decades that followed, investigators provided additional clinical observations,
anatomic correlations, and pathophysiologic connections between various forms of
necrotizing vasculitis employing antineutrophil cytoplasmic antibodies (ANCA) that
contrasted with other forms of necrotizing vasculitis. First detected in 1982 in the sera of
patients with Ross River Arbovirus infection and idiopathic segmental necrotizing
glomerulonephritis [31], ANCA have advanced concepts of the immunopathogenesis of
necrotizing vasculitis. Subsequently detected in the sera of patients with GPA and MPA and
to a lesser extent, in eosinophilic GPA (eGPA) [20], further elucidation of the role of these
antibodies led to considerable advances in the understanding of the pathogenesis of systemic
vasculitis [32].

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