Dr. Andrew Churg - History of CSS

Dr. Andrew Churg wrote this vignette about the history of Churg Strauss Syndrome for the American Thoracic Society. They graciously allowed us to post it on our website.

Churg-Strauss Syndrome

Andrew Churg, M.D.

 Churg-Strauss syndrome (CSS) is best understood in the context of the history of vasculitis. The first report of vasculitis is generally credited to Kussmaul and Maier, who in 1866 described periarteritis nodosa, a name later recast as polyarteritis nodosa (PAN). PAN usually affected medium-sized arteries and frequently produced small aneurysms. Although the initial description of PAN was fairly specific, for most of the next 100 years every case of vasculitis tended to be called PAN, even if the sizes and types of vessels involved were completely different and there was no evidence of aneurysm formation.

Starting as early as the 1930s, investigators began to define forms of vasculitis that were clinically and pathologically different from PAN. The original description of Wegener’s granulomatosis (WG) dates to the 1930s (1), and this entity was formally codified by Godman and Churg in 1954 (2). In the late 1940s Davson and colleagues described a microscopic form of PAN, a systemic vasculitis that was accompanied by a necrotizing glomerulonephritis (3). Around the same time Zeek et al. (4) reported cases of what they referred to as hypersensitivity angiitis, a vasculitis that primarily affected small arteries, arterioles, venules and capillaries, and that in some instances was associated with a necrotizing glomerulonephritis. Using current classification schemes, the condition described by Davson and colleagues and some of the cases described by Zeek et al. would now be classified as microscopic polyangiitis (5) MPA, the current preferred term for the microscopic form of polyarteritis.

In 1951 Churg and Strauss (6) reported 13 patients with an unusual form of vasculitis under the title “Allergic Granulomatosis, Allergic Angiitis and Periarteritis Nodosa.” These cases were characterized by (a) history of asthma, (b) serum and tissue eosinophilia, (c) necrotizing vasculitis, (d) a granulomatous response to eosinophilic necrosis. In their 1954 review, Godman and Churg (2) examined the literature and their own experience and suggested that Churg-Strauss syndrome, Wegener’s granulomatosis and microscopic polyangiitis were related types of vasculitis distinct from classic polyarteritis nodosa. In contradistinction to PAN, all three typically affected small vessels, meaning small arteries, arterioles, capillaries, venules and veins, might have glomerulonephritis (in fact, microscopic polyangiitis almost always demonstrates necrotizing glomerulonephritis, and Wegener’s granulomatosis often does); and all three had many clinical similarities. In the last 20 years the idea that CSS, WG and MPA are related has greatly been strengthened by the observation that all three typically do not show deposition of immunoglobulins in tissue (hence are labeled pauci-immune) and that patients with these conditions commonly have circulating anti-neutrophil cytoplasmic antibodies (ANCA) directed against myeloperoxidase or proteinase 3 (7).

The original CSS report was based on autopsies and pre-dated the era of steroids. While the pathologic findings in the original cases appeared quite similar from case to case, subsequent experience has shown that exact definition of CSS is a problem, in part because CSS, like most forms of vasculitis, is very protean in its manifestations, and in part because some early cases do not demonstrate vasculitis (see below). A variety of different criteria have been proposed (8-10): all incorporate asthma and eosinophilia, but there are quite variable requirements for clinical or pathologic vasculitis, and some, such as the ACR criteria (8), incorporate allergic rhinitis. ANCA status, which is extremely helpful diagnostically, needs to be included in a revised formal classification. As a further complication, most asthmatics now are treated with steroids for their asthma, and that treatment in itself may change both the clinical and pathologic appearances of CSS (see below).

Churg-Strauss syndrome (CSS) is still defined, in its broadest sense, as a syndrome comprising asthma, eosinophilia and, when full blown, eosinophil-rich systemic vasculitis. However, the approach to CSS has changed considerably. Starting with the report of Lanham et al. (9), there was a shift toward making a diagnosis based on clinical criteria rather than biopsy material, in part because of the lack of biopsy material, and in part because more modern cases (particularly biopsy material) typically did not show all of the original pathologic manifestations of necrotizing granulomas, necrotizing vasculitis and tissue eosinophilia. In fact, recent data indicate that this combination is quite uncommon (11). While tissue eosinophilia is almost always seen, CSS-type granulomas are relatively infrequent, and vasculitis may or may not be present (see below); when present it is often non-necrotizing.

Further, it has become apparent that CSS has both a clinical and a pathologic evolution. The earliest clinical manifestation is often allergic rhinitis, followed by the development of asthma, and then by vasculitis (9), often with prototypical manifestations such as mononeuritis multiplex (12). Pathologically it is now recognized that early cases may have asthma and tissue eosinophilia without detectable vasculitis; the disease in this setting may manifest as simple eosinophilic infiltration of a lymph node or eosinophilic pneumonia (11). The importance of these early stage cases is that they are very responsive to steroids, whereas cases with full-blown vasculitis may require the addition of cyclophosphamide or a similar immunosuppressive agent. Unfortunately, early-stage cases are often underdiagnosed (11).

A more recent development has been the finding of an association between CSS and leukotriene receptor antagonists (LRA). Soon after the introduction of Zafirlukast and Montelukast, cases of CSS were reported in those taking these LRA (13). There has been considerable debate about whether this was a drug reaction or, because those taking LRA often discontinued or decreased steroid usage, an unmasking phenomenon in which previously undiagnosed but (accidentally) steroid-suppressed CSS became visible (13-18). The appearance of similar cases in individuals never receiving LRA (14-17) but merely changing from systemic to inhaled steroids, or decreasing their steroid dose, has supported the conclusion, now generally accepted, that LRA are not causes of CSS (13,18). This phenomenon is of considerable importance, since new therapies for asthma are also likely to be used to reduce or eliminate steroids, and thus more cases of suppressed (so-called formes frustes) CSS are likely to appear as each new therapy is introduced.

 

1.
Wegener F. Uber eiene eigenartrige rhinogene Granulomatose mit besonderer Beteiligung des Arterienesystems und er Nieren. Beitr Pathol 1939; 102:32-68.
2.
Godman GC, Churg J. Wegener’s granulomatosis. Arch Pathol 1954; 58: 533-553.
3.
Davson J, Ball J, Platt R. The kidney in periarteritis nodosa. Q J Med 1948; 17:175-202.
4.
Zeek PM, Smith CC, Weeter JC. Studies on periarteritis nodosa. III. The differentation between the vascular lesions of periarteritis nodosa and hypersensitivity. Am J Pathol 1948; 24:889-917.
5.
Jennette JC, Thomas DB, Falk RJ. Microscopic polyangiitis (microscopic polyarteritis). Semin Diagn Pathol 2001; 18:3 13.
6.
Churg J, Strauss L. Allergic granulomatosis, allergic angiitis and periarteritis nodosa. Am J Pathol 1951; 27:277-301.
7.
Gross WL, Csernok E, Helmchen U. Antineutrophil cytoplasmic autoantibodies, autoantigens, and systemic vasculitis. APMIS 1995;103:81-97.
8.
Masi AT, Hunder GG, Lie JT, Michel A, Bloch DA, Arend WP, Clabrese LH, Edworthy SM, Fauci AS, Leavitt RY, Lightfoot RW, McShane DJ, Mills JA, Stevens MB, Wallace SL, Zvaifler NJ. The American College of Rheumatology 1990 Criteria for the Classification of Churg-Strauss Syndrome Arthritis and Rheumatism 1990; 33:1094-1100.
9.
Lanham JG, Elkon KB, Pusey CD, Hughes GRV. Systemic vasculitis with asthma and eosinophilia: A clinical approach to the Churg-Strauss syndrome. Medicine (Baltimore) 1984; 63:65-81.
10.
Jennette JC, Falk RJ, Andrassy K, Bacon PA, Churg J, Gross WL, Hagen EC, Hoffman GS, Hunder GG, Kallenberg CG, McCluskey RT, Sinico RA, Ress AJ, van Es LA, Waldherr R, Wiik A. Nomenclature of systemic vasculitides. Proposal of an international consensus conference. Arthritis Rheum 1994; 37:187 192.
11.
Churg A. Recent advances in the diagnosis of Churg-Strauss syndrome. Mod Pathol 2001; 14:1284-1293.
12.
Guillevin L, Cohen P, Gayraud M, Lhote F, Jarrousse B, Casassus P. Churg Strauss syndrome. Clinical study and long term follow up of 96 patients. Medicine (Baltimore) 1999; 78:26 37.
13.
Wechsler ME, Pauwels R, Drazen JM. Leukotriene modifiers and Churg-Strauss syndrome: adverse effect or response to corticosteroid withdrawal? Drug Safety 1999; 21:241-251.
14.
Churg A, Brallas M, Stephen R, Cronin MD and Churg J. Formes Frustes of Churg-Strauss syndrome. Chest 1995; 108: 320-323.
15.
Churg A, Churg J. Steroids and Churg-Strauss syndrome. Lancet 1998; 352:32-33.
16.
Bili A, Condemi JJ, Bottone SM, Ryan CK. Seven cases of complete and incomplete forms of Churg-Strauss syndrome not related to leukotriene receptor antagonists. J Allergy Clin Immunol 1999; 104:1060-1065.
17.
Le Gall C, Pham S, Vignes S, Garcia G, Nunes H, Fichet D, Simonneau G, Duroux P, Humbert M. Inhaled cortocosteroids and Churg-Strauss syndrome: a report of five cases. Eur Respir J 2000; 15:978-981.
18.
Lily CM, Churg A, Lazarovich M, Pauwels R Hendeles L, Rosenwasser LJ, Ledford D, Wechsler ME. Asthma therapies and Churg-Strauss syndrome. J Allergy Clin Immunol 2002; 109:1-19.

 

Dr. Churg is a Professor, Department of Pathology, University of British Columbia.

Copyright © 2004 American Thoracic Society.

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