DISEASE OF THE MONTH

The Churg Strauss Syndrome

JOSEPH A. EUSTACE,* TIBOR NADASDY,† and MICHAEL CHOI*Divisions of *Nephrology and†Pathology, Johns Hopkins University School of Medicine, Baltimore,Maryland.

During the first half of this century, several authors reported avariant of a small vessel vasculitis that appeared similar to thethen recognized polyarteritis nodosa. The condition was dis-tinguished by a significant atopic component, in the form ofallergic rhinitis, bronchial asthma, and hypereosinophilia (1).Such patients frequently had a poor prognosis, with manypatients dying as a result of cardiac complications, often withinmonths of diagnosis. Although it has previously been called byseveral names including allergic angiitis and granulomatosis, itis now most commonly referred to as the Churg Strauss syn-drome (CSS). Renal involvement in this condition is frequentalthough usually mild; however, an increasing number of casereports attest to the potential for severe renal disease to occa-sionally develop.

Several lines of evidence suggest that CSS is not simply thecoincidental development of vasculitis in patients with asthma.The asthma seen in CSS is notable for being of late onset; it isfrequently severe and is associated with a greater degree ofeosinophilia than is typically seen in bronchial asthma. There isoften no personal or family history of atopic disease (2). Inaddition, cases are well described in which the asthma devel-ops shortly before or simultaneously with vasculitis (3,4). Therecognition of CSS as a separate disease entity is important,because its distinctive natural history (2,5), its frequent rapidresponse to treatment, and its good overall prognosis (4) sug-gest pathogenic mechanisms that differ either in nature or indegree compared with other forms of necrotizing vasculitis.

DiagnosisThe accurate diagnosis of CSS remains problematic. None

of the disease features, either clinical or histologic, is on anindividual level pathognomic of the condition. The syndromeis frequently phasic in nature, with the pathologic findingsvarying not only with the anatomical site examined but alsowith the phase of the illness (2). CSS classically develops asnew onset asthma and/or allergic rhinitis, which progresses tohypereosinophilia, often with an associated tissue infiltration,before culminating in frank vasculitis. This sequential devel-

opment of findings is not seen in all cases, and even whenpresent the time course over which progression occurs can behighly variable. Therefore, rather than being dependent on anysingle symptom or pathologic finding at one time point, theaccurate diagnosis of Churg Strauss syndrome requires thepresence of a constellation of findings that may have presentedand evolved over a period of years.

Churg and Strauss in their original 1956 article outlinedthree pathologic features associated with the disease: an eosin-ophilic tissue infiltration, granuloma formation, and a necro-tizing vasculitis involving small and medium-sized vessels (5).Eleven of the 13 patients they described had been studied bypost mortem examination, and all had advanced disease with-out the benefit of effective treatment. Even so, only 10 of their13 patients demonstrated all three pathologic features. Thus, itis not surprising that this triad of pathologic findings shouldyield a low sensitivity for the diagnosis of CSS, especially withthe development of rapidly effective treatment and with histo-logic studies frequently limited to small volume biopsy spec-imens.

To help overcome these limitations, Lanhamet al.proposeda combined clinical and pathologic diagnostic scheme (Table1) (2), and although the validity and accuracy of this schemehas never been assessed objectively, it has nonetheless beenwidely used. More recently, the American Rheumatology As-sociation has proposed alternative diagnostic criteria for CSS(6). The presence of at least four of six findings (Table 1) wasdiagnostic of Churg Strauss, with a sensitivity of 85% and aspecificity of 99.7% within the source population. However,these results have not as yet been validated in an independentsample of patients. The 1994 Chapel Hill consensus conferencefurther defined CSS as an “eosinophil-rich and granulomatousinflammation involving the respiratory tract, and necrotizingvasculitis affecting small to medium sized vessels, and asso-ciated with asthma and eosinophilia” (7).

All of these classification systems and definitions have ob-vious limitations, especially in patients with mild or limiteddisease or in those who have already been started on therapy(8), especially as the peripheral hypereosinophilia of CSSresponds rapidly to treatment with corticosteroids. Cases havealso been reported that overall are suggestive of CSS but lacka typical feature of the syndrome such as asthma, even in theabsence of prior treatment (9). These diagnostic difficultieshighlight our need to better understand the underlying patho-genesis of the vasculitides to avoid being dependent on super-ficial overlapping clinical features for the purpose of diagnosis.

Correspondence to Dr. Joseph A. Eustace, Division of Nephrology, JohnsHopkins University Hospital, Room 417, 1830 Building, 1830 East MonumentStreet, Baltimore, MD 21205. Phone: 410-614-5376; Fax: 410-955-0485;E-mail: jeustace@welch.jhu.edu

1046-6673/1009-2048Journal of the American Society of NephrologyCopyright © 1999 by the American Society of Nephrology

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EpidemiologyCSS is global in its distribution and has no significant gender

predilection. It occurs in all age groups, although it has beenmost commonly reported in the third through fifth decades oflife. The mean (95% confidence interval) annual incidence ofCSS in northern England between 1988 and 1994 was 2.4 (0.9to 5.3) per million population. This incidence was 30% of thatestimated for Wegener’s granulomatosis and was similar to theincidence of microscopic polyangiitis (10). In a retrospectivestudy from Norway, the estimated prevalence of CSS was 1.3per 100,000 population, compared with 3.3 per 100,000 forpolyarteritis nodosa and 5.3 for Wegener’s granulomatosis(11).

Clinical FeaturesProdromal Phase

Allergic rhinitis is often the first evidence of disease (12)and occurs in up to 70% of cases. It is frequently severe andmay be associated with nasal polyposis, obstruction, and re-current sinusitis, but unlike Wegener’s granulomatosis, thepresence of nasal pain or frank hemorrhage is uncommon.Histologic examination usually reveals diffuse eosinophilia;upper airway granulomata are only rarely found. Asthma usu-ally precedes the development of vasculitis by a period ofweeks to years (3,4); it is often progressively severe andeventually requires oral steroids for adequate control. Eosino-philic tissue infiltration most commonly presents within thelungs as Loffler’s pneumonia or less commonly in a morechronic relapsing form as chronic eosinophilic pneumonia.Gastrointestinal tract infiltration may present as eosinophilicgastroenteritis. Although these conditions are disease entitiesin their own right, they all form part of the spectrum ofeosinophil-mediated disease, which may progress to a moregeneralized multisystem disease process in the form of CSS(12).

Vasculitic PhaseSystemic disease features during the vasculitic phase include

weight loss, anemia, and fever. Rash occurs in up to 70% ofcases and may include an erythematous maculopapular erup-

tion, vasculitic ulcers, and/or subcutaneous nodules (3). Myal-gia and a migratory nonerosive polyarthritis are common butare usually not severe.

Pulmonary involvement represents a vasculitic process witha varying degree of eosinophilic infiltration. It may be associ-ated with progressive dyspnea, alveolar hemorrhage (4), pleu-risy, and the development of eosinophil-rich pleural transu-dates. Radiographic findings are generally nonspecific and,unlike Wegener’s granulomatosis, cavitation rarely develops(3). Transbronchial biopsy revealed evidence of the disease infour of six cases studied by Schnabelet al., even in the absenceof focal radiologic abnormality (13). Bronchial alveolar lavageusually reveals a normal total cell count, but with a dramaticincrease in the percentage of eosinophils (mean 31%; range, 6to 66%).

Cardiac involvement is a common, although often late, man-ifestation of the disease. It was the primary cause of CSS-related death in the pre-corticosteroid era (2), and it still resultsin occasional fatalities despite modern treatment (3,4,9). Acutepericarditis may occur in up to one-third of cases and may beassociated with pericardial effusion. Cardiac tamponade maydevelop and should be considered before initiating aggressivefluid removal with dialysis. Myocarditis may lead to postin-flammatory fibrosis and congestive cardiac failure, while cor-onary vasculitis may result in ischemic heart disease.

Gastrointestinal involvement is common and often severe,resulting in abdominal pain, ascites, diarrhea, and/or hema-tochezia (2,3,14). It resulted in 8% of the deaths reviewed byLanham in his literature review (2).

Involvement of vasa nervorum results in a mononeuritismultiplex and was found in 72% of cases in Guillevin’s seriesand most commonly involved the common peroneal (84%) andthe ulnar (55%) nerves (4). Cerebral vasculitis may predisposeto hemorrhagic cerebrovascular events, especially in associa-tion with uncontrolled hypertension.

Renal DiseaseTraditionally, renal involvement in CSS has been reported as

being mild. In the pre-corticosteroid literature, early deaths dueto cardiac disease may have limited the potential for wide-spread renal involvement, while the absence up until recentlyof widely accepted diagnostic criteria may also have resulted inmany cases of CSS with a significant azotemic componentbeing labeled as having an alternative diagnosis.

As shown in Table 2, several series have reported a consid-erable degree of renal involvement. In Churg and Strauss’original report, they comment that mild hematuria and albu-minuria were commonly present (5). Three of their 11 patientshad azotemia and one died from uremia. Chumbley reportedthat the incidence of renal involvement was 20% (3). Six of his30 patients had microscopic hematuria, three had slight eleva-tions of serum urea and creatinine, and one died from renalfailure. The incidence of proteinuria is not reported and norenal biopsies were performed. Lanhamet al., in his literaturereview, found 49% of cases to have mild or moderate renalinvolvement and renal failure in 9% (2). Renal failure wassecond only to cardiac disease as a cause of death (occurring in

Table 1. Diagnostic criteria for the Churg Strauss syndromea

Lanham’s criteria (2)asthmapeak peripheral blood eosinophil count.1.5 3 106/ccsystemic vasculitis involving two or more extrapulmonary

organsARA criteria (6) (requires four of the following six findings)

asthmaeosinophilia.10%neuropathynonfixed pulmonary infiltratesparanasal sinus abnormalityextravascular eosinophils

a ARA, American Rheumatology Association.

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18% of recorded fatalities). In the most recent and largestindividual case series by Guillevinet al., 25 of 96 patients(26%) had proteinuria with levels in excess of 1 g/d. Fivepatients are reported as having renal insufficiency, although thedegree of azotemia is not provided, and eight patients werediagnosed as having glomerulonephritis (4).

Clutterbucket al., reviewing the results at HammersmithHospital, reported that renal disease was present in 16 of 19patients with CSS and was frequently severe (15). This highincidence of severe renal involvement may partly reflect refer-ral bias; however, only five of the 16 patients were referredfrom other hospitals. Microscopic hematuria was present in 13patients, granular casts in nine, and red cell casts in three.Twelve patients had proteinuria, with three patients having anestablished nephrotic syndrome. Four cases presented with aserum creatinine.500mmol/L (5.6 mg/dl), two being dialysis-dependent from the time of presentation. A similar potential forsevere renal involvement is also shown by numerous recentcase reports (16–22). The presence or absence of azotemiatherefore does not reliably distinguish CSS from other forms ofrenal necrotizing vasculitis.

Renal histology may on occasion reveal frank vasculitis(Figure 1). Vasculitis involving arteries of varying sizes wasfound in seven of the 13 cases in the Churg autopsy series (5)and in two of the 19 subjects in Clutterbuck’s biopsy series(15). These resembled the changes found in other necrotizingvasculitides but are distinguished, at least before treatment, bya widespread infiltration of activated eosinophils. As in anynecrotizing vasculitis, there may be destruction of the internalelastic membrane and aneurysm formation, as demonstrated inone of eight angiograms in Clutterbuck’s report (15) and innine of 30 in that of Guillevin (4). The more typical histologicfinding by percutaneous renal biopsy is a focal segmental(Figure 2) or a diffuse necrotizing (Figure 3) glomerulonephri-tis. This frequently occurs in the setting of an intense eosino-phil-rich interstitial infiltrate (Figure 2). Churg described theseglomerular changes as usually being mild and affecting only aminority of glomeruli (5). However, in the Hammersmith se-ries of 13 renal biopsy specimens, 11 showed focal glomeru-lonephritis, with necrotizing features present in eight and cres-cents in nine (15).

Interstitial changes usually consist of edema and a diffuseeosinophilic infiltrate with associated lymphocytes, neutro-phils, and plasma cells, and on occasion may be associatedwith only minimal glomerular pathology (15,23). Interstitialgranulomata, usually with a core of degenerating eosinophilsand situated adjacent to a venule, as described in Churg andStrauss’ original autopsy series (5), have since only rarely beendescribed in renal biopsy specimens (2). Tubular changes are

Table 2. Renal involvement in the Churg Strauss syndromea

Author Total RenalInvolvement Mild/Moderate Advanced

Churg and Strauss (5) 13 8 (62%) 7 1Chumbleyet al. (3) 30 6 (20%) 5 1Lanhamet al. (2) 16 14 (88%) 13 1Shimamotoet al. (14) 64 52 (81%) 52 0Clutterbucket al. (15) 19 14 (74%) 10 4Reid et al. (9) 23 13 (57%) 13 0Guillevin et al. (4) 96 25 (26%) NA NATotal 261 (100%) 132/261 (51%) 100/107 (94%)b 7/107 (6%)b

a NA, not available.b Expressed as percentage of those with renal involvement of known severity.

Figure 1.Polyarteritis-like segmental necrosis and inflammation of amedium-sized artery from the mesentery. This case had no renalinvolvement. Hematoxylin and eosin stain,3100.

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usually mild and nonspecific. Immunofluorescence micros-copy has revealed only nonspecific staining in areas of seg-mental necrosis, while electron microscopy typically revealsthe absence of dense deposits.

In addition to intrinsic renal disease, renal dysfunction mayalso result from an obstructive uropathy due to vasculiticinvolvement of the ureters and the lower genito-urinary tract.Chumbleyet al. described granulomatoid involvement of theprostate in three patients (3), with one of the three patientspresenting with obstructive uropathy. In Churg and Strauss’original series, one patient had thickened nodular dilated ure-ters (5), and several case reports have confirmed the potentialfor ureteric vasculitis with an associated stenosis and obstruc-tion (4,24–26).

Laboratory FindingsTypical laboratory findings in CSS include a normochromic

normocytic anemia, leukocytosis, and an acute-phase responsewith elevated erythrocyte sedimentation rate and C-reactiveprotein levels. In the series by Lanhamet al., the peak eosin-ophil count varied from 1,500 to 29,0003 106/L. In the samestudy, six of eight patients in whom levels were measured had

elevated Ig E levels (2). Low levels of circulating IgE immunecomplexes, rheumatoid factor (2,3), and antinuclear antibodies(4) have also occasionally been described, but in most casesappear to be nonspecific. Measurements of complement, cryo-globulin, and infectious hepatitis serology are usually unre-markable.

Anti-Cytoplasmic Neutrophil AntibodiesAn analysis of the association between CSS and anti-cyto-

plasmic neutrophil antibodies (ANCA) is difficult, becausevarious studies have used different diagnostic criteria for CSS,as well as varied methods in the performance and interpretationof ANCA assays. Approximately one-half to two-thirds ofreported patients with CSS are ANCA-positive. Individualstudies have found ANCA in seven of 17 (41%) (27), 20 of 42(47%) (4), 10 of 17 (58%) (9), six of nine (60%) (28), six ofnine (60%) (29), nine of 14 (64%) (30), and 11 of 13 patients(85%) (31).

A relatively small number of research groups have publishedwidely on various aspects of ANCA testing both in CSS and inother vasculitides. Due to the relative rarity of CSS, manydifferent reports that refer to CSS in different contexts, fromeach individual center, are based on the same small number ofpatients. As a result, therefore, there is a considerable degree of

Figure 2.A small area of segmental glomerular necrosis from a renalbiopsy with the pattern of focal necrotizing glomerulonephritis and10% glomerular involvement. Also note the intense interstitial inflam-matory cell infiltrate, which in this case contains numerous eosino-phils. Hematoxylin and eosin stain,3200.

Figure 3.Extensive glomerular necrosis from a renal biopsy showingthe pattern of diffuse necrotizing and crescentic glomerulonephritiswith 80% glomerular involvement. Hematoxylin and eosin stain,3200.

J Am Soc Nephrol 10: 2048–2055, 1999 The Churg Strauss Syndrome 2051

overlap in the published literature. To help overcome this bias,we have summarized the single most informative report fromeach group that refers to ANCA type in three or more patientswith CSS (Tables 3 and 4). Most reviews of CSS refer to apredominance of perinuclear staining by direct immunofluo-rescence; however, as shown in Table 3, the presence of acytoplasmic staining pattern is not uncommon. Whether thisvariation in the ratio of perinuclear to cytoplasmic staining indifferent studies reflects random variation, differences in diag-nostic criteria, or other potential factors such as genetic orgeographical variability is not established. Studies examiningantigen specificity by enzyme-linked immunosorbent assayhave shown a strong predominance of anti-myeloperoxidaseantibodies in subjects with CSS. Several patients have beendescribed who showed a cytoplasmic staining pattern by indi-rect immunofluorescence, but who failed to demonstrate theusually associated anti-proteinase 3 (PR3) antibody with theenzyme-linked immunosorbent assay (30). Whether these pa-tients have an alternative ANCA target other than the PR3antigen, or whether these discrepant results reflect the difficul-ties in standardizing anti-PR3 assays (29) is unknown.

EtiologyThe etiology of CSS is difficult to investigate because evi-

dence of the initiating event may no longer be present by thetime the disease reaches clinical attention. Several authors haveimplicated inhaled allergens in both this condition and inWegener’s granulomatosis. Support for this theory comes fromcase reports of CSS developing and recurring following expo-sure to inhaled antigens (4), as well as a proposed seasonalpredominance of cases of CSS. Guillevinet al. reported 14patients as having undergone desensitization with a variety ofagents and four as having been vaccinated in the immediateperiod before CSS being diagnosed (4). CSS has also beendescribed in association with macrolide antibiotics and theleukotriene receptor antagonist Zafirlukast (32). However,whether the above associations are causative or the result ofconfounding by indication, with early disease-related symp-toms leading patients to receive the treatment, is unclear.Zafirlukast blocks the leukotriene LT-B4 and LT-D4 receptors,thereby inhibiting smooth muscle contraction and interstitialedema formation, but it does not show the wider spectrum ofanti-eosinophilic effects of corticosteroids. If treatment withsteroids had been commenced for asthma, associated with

early, undiagnosed CSS, then the subsequent replacement ofsteroids by Zafirlukast might well be expected to be temporallyassociated with an increase in the underlying disease activityand with it, the diagnosis of clinically evident CSS.

The pathogenic role, if any, of ANCA antibodies in thedevelopment of CSS is unknown. Their absence in approxi-mately one-third of patients suggests that at least in theircurrently described form, they are not a necessary requirementfor the presence of the syndrome. In addition, neither thepresence nor type of ANCA has been shown to be associatedwith a particular disease feature or outcome in CSS.

PathophysiologyThe central feature of CSS is an eosinophil-associated small

vessel vasculopathy. The degree of eosinophil infiltration isgreatly in excess of that seen in ordinary inflammatory states.Using monoclonal antibodies, Taiet al. were able to demon-strate that activated eosinophils and eosinophil degranulationproducts were present within both vessel walls and granulo-mata (33). Several authors have been able to show a correlationbetween the eosinophil level (and eosinophil degranulationproducts) and CSS disease activity.

The pathophysiology of eosinophil-mediated disease hasrecently been reviewed elsewhere (34). From the viewpoint ofCSS, it is noteworthy that activated eosinophils are able toinduce vascular endothelial cell activation (35). As in otherinflammatory states, this depends on the interaction of a com-plex network of chemical mediators. The novel, relativelyeosinophil-specific chemokine eotaxin (35) may play an im-portant role in this process. Eotaxin upregulates the expressionof the adhesion molecules ICAM-1 and VCAM-1 and selec-tively increases eosinophil binding to activated endothelialcells. Moreover, its actions may be specific for certain vascularbeds (36). Recently, Wadaet al. isolated eotaxin in the urine ofa patient with a severe renal eosinophilic interstitial infiltratebut not from patients with the hypereosinophilia syndrome butno renal disease (37). The eotaxin level in addition correlatedwith the original patient’s disease activity.

The eosinophil may also be directly responsible for some ofthe classical disease features of CSS, by virtue of the release ofits stored cationic proteins, such as eosinophilic cationic pro-tein, which is implicated in the cardiotoxicity that is seen inboth CSS and in the hypereosinophilia syndrome, and eosino-

Table 3. Direct immunofluorescence anti-neutrophil cytoplasmic antibody assay results in the Churg Strauss syndromea

Center/Research Group Total p-ANCA c-ANCA Negative

Hammersmith Hospital, London (30) 14 3 3 8University of Lubeck, Bad Bramstedt, Germany (27) 17 2 5 10Project for ANCA Assay Standardization (29) 9 3 3 3French Vasculitis Study Group (4) 42b 15 1 22Total 82 (100%) 23 (30%) 12 (15%) 43 (52%)

a ANCA, anti-neutrophil cytoplasmic antibodies; p, perinuclear; c, cytoplasmic.b Pattern not specified in four subjects.

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phil-derived neurotoxin, which may contribute to the develop-ment of peripheral neuropathy.

TreatmentCSS frequently responds rapidly to corticosteroids (4). Cor-

ticosteroids suppress gene transcription of various cytokines,and inhibit the prolongation of eosinophil survival in extravas-cular tissues (38). In the Hammersmith experience, severalpatients with azotemia but with serum creatinine levels,200mmol/L (2.3 mg/dl) on presentation were treated with pred-nisolone alone. The creatinine level returned to normal in allpatients, despite four having crescentic disease associated withnecrotizing features on biopsy (39).

Some authors recommend the routine use of cyclophospha-mide either by the oral or intravenous route in all patients withCSS, using a protocol devised for other necrotizing vasculiti-des (12). One justification for this approach is the concern thatby the time it is evident that steroids are inadequately control-ling the disease, significant irreversible tissue damage mayalready have occurred (12), although the frequency with whichthis occurs is unclear. Eosinophilia in some patients is knownto be relatively resistant to steroid suppression, possibly due toalterations in steroid receptor density or to variations in tran-scription factors (40). This variability may partly explain theinadequate response of some patients to steroids alone andsuggests that it is this subgroup that might benefit most fromadjuvant immunosuppressive therapy.

Although the routine use of cyclophosphamide has provenbeneficial in other forms of necrotizing vasculitis, these bene-fits may not be identical in patients with CSS. In particular, insteroid-sensitive patients, the potential long-term complica-tions of cyclophosphamide may negate any additional benefitsof its use. Interferon-a is also a potent inhibitor of eosinophileffector functions (41). It has recently been reported to achievecontrol in four patients with aggressive disease, two of whomhad achieved an incomplete remission after treatment withsteroids and cyclophosphamide (42). Azathioprine (3,9), cy-closporin (43), and immunoglobulin infusions (44,45) havealso been used in an adjuvant setting in CSS, although theirrole in disease treatment remains uncertain. A future potentialavenue of treatment is the development of monoclonal anti-bodies against targets such as interleukin-5. The eotaxin recep-

tor offers a potentially potent target for such an intervention, asa result of its relative selectivity for eosinophils (34).

The only prospective randomized clinical trial of treatmentof CSS has been conducted by the French “Polyarteritis No-dosa Study Group;” however, interpretation of their findings islimited because their studies include patients with CSS, clas-sical polyarteritis nodosa, and microscopic polyangiitis. Theirresults are not stratified by the underlying diagnosis. Theyfound that for this heterogeneous group, the use of cyclophos-phamide in addition to steroids did not improve 10-yr survivalrates, but did appear to result in fewer episodes of diseaserelapse and better quality of life (46). The addition of plasma-pheresis with either steroids alone or combined treatment withsteroids and cyclophosphamide did not appear to offer anyadditional benefit.

PrognosisOverall, the prognosis for treated CSS appears to be good

(3,4,47). Guillevinet al. reported a 6.5-yr actuarial survivalrate of 72%, with an initial clinical remission being achieved in91% of patients (4). With follow-up, 22 of 96 patients sufferedfrom a total of 28 relapses, which were preceded in most casesby an elevation in serum eosinophil levels. Only three patientssuffered from multiple relapses. Seventeen of the 22 patientswho relapsed responded to an increase in immunosuppression.However, four patients failed to respond and died (4). In theHammersmith experience, six of 16 patients relapsed, four ofthese episodes were preceded by a decrease in steroid dose, andonly one patient suffered from multiple relapse (2). The renalprognosis is also favorable. In the Hammersmith series, threeof four patients who presented with advanced azotemia re-gained independent function; the exception had evidence ofchronic scarring on biopsy and failed to respond to therapy(39). In the Guillevin series, no patient was recorded as suf-fering from a renal relapse after remission (4). Multivariateanalysis of the presenting features of the 96 patients reportedby Guillevin showed that cardiac and gastrointestinal, but notrenal, involvement were significantly associated with a pooroutcome.

Long-term morbidity after the remission of active diseaseusually relates either to the sequelae of damage sustainedduring the vasculitic phase or to complications of the immu-

Table 4. Antigen-specific anti-neutrophil cytoplasmic antibody in the Churg Strauss syndromea

Center/Research Group Total Anti-MPO Anti-PR3 Negative

University Hospital, Gro¨ningen, The Netherlands (31) 13 10 1 2Hammersmith Hospital, London (30) 14 9 NA NAUniversity of Lubeck, Bad Bramstedt, Germany (27) 17 2 5 10Project for ANCA Assay Standardization (29) 6 3 2 1French Vasculitis Study Group (4) 11b 10 0 0Total 61 (100%) 34 (56%) 8 (13%) 13 (21%)

a MPO, myeloperoxidase; PR3, proteinase 3; NA, not available.b ANCA pattern reported as nonspecific in one case.

J Am Soc Nephrol 10: 2048–2055, 1999 The Churg Strauss Syndrome 2053

nosuppressive therapy. Asthma may persist and require ongo-ing steroid therapy, while slowly progressive congested heartfailure may also occur. Peripheral neuropathy is often a fre-quent and troublesome long-term complication.

SummaryThe Churg Strauss Syndrome is an eosinophil-associated

small vessel vasculitis. Although its pathogenesis may be dis-tinctive and the association with severe late-onset asthma typ-ical, the clinical features during the vasculitic phase widelyoverlap with those of the other forms of necrotizing vasculitis,and no single clinical or histologic feature is pathognomic ofthe condition. Renal involvement is common, although usuallymild, and even when severe it tends to respond well to treat-ment. The prognosis for both patient and renal survival withadequate treatment is in general good. The optimal treatmentstrategy, however, is uncertain, and may differ from that for theother vasculitides. In particular, in contrast to Wegener’s gran-ulomatosis, the need for routine cyclophosphamide treatment isunconfirmed and requires further study.

AcknowledgmentsDr. Eustace was supported by National Institutes of Health Renal

Disease Epidemiology Training Grant 5-32-DK07732. The authorsthank Dr. W. A. Briggs for his review of this manuscript.

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