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Necrotizing systemic vasculitis with features of both Wegener's granulomatosis and Churg-Strauss vasculitis.

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We describe a patient who had nasal biopsydemonstrated eosinophilic vasculitis and renal biopsydemonstrated necrotizing glomerulonephritis with tissue
eosinophilia. Despite corticosteroid therapy, the patient's renal function deteriorated, and nodular pulmonary infiltrates developed. Both conditions responded
dramatically when cyclophosphamide was added to the
treatment regimen. The renal disease activity was monitored with the aid of cytodiagnostic urinalysis, a technique of limited, albeit well-established, validity in
monitoring renal allograft patients for signs of tissue
rejection. This technique provided an improved, semiquantitative method for examining urine sediment and,
in this patient, was helpful as a measure of renal disease
Fauci and coworkers have stressed that there is
overlap among the various necrotizing systemic
vasculitides (1). The patient described here had striking tissue eosinophilia, including eosinophilic vasculitis suggestive of Churg-Strauss syndrome, but experiFrom the Departments of Medicine and Pathology, Sections of Nephrology and Rheumatology, Washington Hospital Center, and the Department of Medicine, George Washington University, Washington, DC.
Stuart Henochowicz, MD: Chief Medical Resident, Department of Medicine, Washington Hospital Center; Diane Eggensperger, MD: Department of Pathology, Washington Hospital
Center; Leslie Pierce, MD: Chairman, Section of Nephrology,
Washington Hospital Center, and Associate Professor of Medicine,
George Washington University; Werner F. Barth, MD: Chairman,
Section of Rheumatology, Washington Hospital Center, and Professor of Medicine, George Washington University.
Address reprint requests to Werner F. Barth, MD, Chairman, Section of Rheumatology, Washington Hospital Center, 110
Irving Street NW, #2A-58, Washington, DC 20010.
Submitted for publication April 26, 1985; accepted in revised form December 9, 1985.
Arthritis and Rheumatism, Vol. 29, No. 4 (April 1986)
enced no response to treatment with high doses of
corticosteroids. Her subsequent course and response
to cyclophosphamide therapy were more consistent
with a diagnosis of Wegener's granulomatosis. The
activity of her renal parenchymal disease was monitored by cytodiagnostic urinalysis.
Case report. The patient, a 25-year-old woman,
presented to the Washington Hospital Center on
April 5, 1984, with a 4-month history of migratory
arthralgias, arthritis, and fatigue, and a 2-week history
of hematuria. She complained of arthralgias in both
shoulders and knees. She was noted to have arthritis
of the third left proximal interphalangeal joint, gross
hematuria, proteinuria, and peripheral eosinophilia of
7%. Results of a test for fluorescent antinuclear antibody were negative; her serum creatinine level was 1.1
mg/dl. Her medical history disclosed perennial rhinitis
but no asthma or any known allergies.
Physical examination revealed a pale young
woman who was in no acute distress. Her oral temperature was 98.6"F, and her other vital signs were
normal. Her lungs were clear. Musculoskeletal examination revealed pain on motion of the left shoulder.
Urinalysis revealed red blood cells (RBC) too numerous to count and 1 + proteinuria. A complete blood
count (CBC) revealed 12,500 white blood cells
(WBC)/mm3with 7% eosinophils, a hemoglobin value
of 12.5 gm/dl, a hematocrit level of 39%, and a
moderately elevated zeta erythrocyte sedimentation
rate of 61% (normal 4 4 ) . Ibuprofen was prescribed,
and the patient discharged for further followup as an
Approximately 2 weeks later, the patient was
admitted to the Washington Hospital Center. The
arthralgias and fatigue had continued, and she now had
Figure 1. Eosinophils in granular matrix cast seen on cytodiagnostic urinalysis (hematoxylin and eosin stained, oil immersion,
original magnification x 356).
a diffuse purpuric rash and epistaxis. A CBC performed at the time of admission revealed a WBC count
of 14,000/mm3,with 7% eosinophils; the hemoglobin
value was 10.4 gm/dl, and the platelet count was
500,000/mm3. Her serum creatinine level was 1.2
mg dl.
Skin biopsy revealed a leukocytoclastic
vasculitis. Cytodiagnostic urinalysis, performed according to the method of Schumann et a1 (2), showed a
pattern of glomerulonephritis and tubulo-interstitial
inflammation which was notable for the presence of
eosinophilic casts (Figure 1). A renal biopsy sample
revealed necrotizing glomerulitis and tubulointerstitial
infiltration with lymphocytes, polymorphonuclear
leukocytes, and eosinophils (Figure 2). Otolaryngologic evaluation revealed anterior nasal septal perforation. Nasal biopsy showed acute and chronic
necrotizing inflammation, with lymphoplasmacytes
and eosinophils, as well as perivascular eosinophilic
infiltration. Results of a chest roentgenogram were
A provisional diagnosis of a variant of ChurgSttauss vasculitis was made. One gram of methylprednisolone was given intravenously for 2 days, and prior
to discharge on April 30, oral administration of
prednisone, 80 mg daily, was begun.
On May 11, the patient was readmitted to the
hospital because of hemoptysis of 3 days duration and
palpable purpura. A CBC done at admission revealed
a hematocrit level of 19% and a WBC count of
25,000/mm3; no eosinophils were noted on the peripheral cell smear. Cytodiagnostic urinalysis again re-
vealed RBC casts. A chest roentgenogram revealed
nodular densities in the left upper lobe. Her serum
creatinine level was 3.6 mg/dl.
The rapid progression of renal disease despite
high doses of prednisone, the palpable purpura, and
the new pulmonary findings were most consistent with
a diagnosis of Wegener’s granulomatosis. She was
given cyclophosphamide, 4 mg/kg/day intravenously,
and she was transfused with 2 units of packed red
blood cells. Bronchoscopy revealed bleeding from the
left and right upper lobes.
The patient’s hospital course was complicated
by massive hemoptysis and the adult respiratory distress syndrome, necessitating endotracheal intubation
and mechanical ventilation for 2 weeks. Her respiratory status improved dramatically with supportive
care and cyclophosphamide and prednisone treatment.
She was extubated 2 weeks after admission and discharged from the hospital on June 1, on a regimen of
cyclophosphamide, 125 mg/day/orally , and prednisone , 60 mg/day/orally.
Six months after discharge, the patient was
symptom-free, doing well, and was able to return to
school. Chest roentgenograms showed clearing of the
nodular densities. Her serum creatinine level had
remained stable at 1.6 mg/dl. The number of casts and
RBCs in her urine had decreased markedly (Table 1).
Methods. Tissue for histologic examination was
placed in formalin and processed routinely. All specimens were thoroughly sectioned, and special stains
were utilized as appropriate.
Urine was prepared for cytodiagnostic urinal-
Figure 2. Renal biopsy specimen showing renal tubules infiltrated
by eosinophils (arrows) in an edematous interstitiurn (hematoxylin
and eosin stained, original magnification x 150).
Table 1. Monitoring of the patient’s renal disease activity, using cytodiagnostic urinalysis*
150, 18% eos
1,550, 13% eos
150, 1% eos
> 1,000
1,040, 1% eos
1,800, rare eos
Type and no. of cellular casts
Hgb 3, RBC 1 , eos 1 , RTC I , granular
10, WBC 1
Hgb 15, RBC 1 , eos 1 , RTC 5, granular 45, WBC 1 , fatty 1
Hgb 1, RBC 1 , RTC 1 , granular 3
Renal biopsy
Cyclophosphamide begun
Hgb 8, RBC 3, RTC 3, granular 10,
Hgb 5, RBC 3, RTC 3, granular 12,
Hgb 1 , RBC 1 , RTC 1 , granular 1
Discharged from hospital,
on a regimen of prednisone
Discharged from hospital,
on a regimen of cyclophosphamide and prednisone
Hgb 0, RBC 0, granular 2
Hgb 1, RBC 1 , RTC 1 , granular 1
Hgb 1 , RBC 0, RTC 1 , granular 1
Leukocyturia due to vaginal contamination
* PNN = polymorphonuclear cells; RBC = red blood cells; eos = eosinophils; Hgb = hemoglobin; RTC = renal tubule cells; WBC = white
blood cells.
ysis according to the method of Schumann et a1 (2).
Ten milliliters of urine was centrifuged, and the supernatant was discarded. The sediment was reconstituted
with normal saline to a volume of 1 ml. Depending on
turbidity, 50-250 p1 of sediment was cytocentrifuged
and stained using a rapid Papanicolaou method. All
fields of 4 slides were examined.
Differential counts of cells per 10 high power
fields (hpf) were made. Counts of blood cells included
erythrocytes, lymphocytes, and polymorphonuclear
cells (PMNs). Eosinophils were tabulated as the percentage of PMNs, counted under oil immersion. Renal
epithelial cells were distinguished as collecting duct
cells, convoluted cells, and necrotic convoluted cells.
Differential counts of casts were also tabulated per 10
hpf. Counts were corrected for the amount of
resuspended sediment pipetted into the cytocentrifuge
chamber. Any background of crystals, organisms, and
cellular debris was also recorded.
Results. The needle biopsy sample from the
kidney contained 10 glomeruli; 2 appeared normal.
The remaining 8 glomeruli showed segmental thrombosis with necrosis and contained 2-3 neutrophils or
eosinophils per glomerular cross-section. Half of the
glomeruli had epithelial crescents. The interstitium
was moderately edematous, with a mild-to-moderate
d8Lrse inflammatory cell infiltrate comprised largely of
active mononuclear cells and approximately 5%
eosinophils. Many tubules contained erythrocytic
casts. No granulomas or giant cells were present, and
cross-sections of several blood vessels revealed no
The biopsy specimen of the nasal septum
showed diffusely necrotizing mononuclear cell inflammation, with sheets of eosinophils in some areas.
Several blood vessels showed fibrinoid necrosis and
mural infiltration by both eosinophils and neutrophils.
Scattered giant cells were found, but there were no
granulomas. Stains for fungi and bacteria revealed
superficial clusters of gram-positive cocci.
A punch biopsy of the skin showed leukocytoclastic vasculitis, but eosinophils were not present.
Stains for fungi and bacteria were negative.
Discussion. Our patient initially presented with
arthralgias, rhinitis, nonthrombocytopenic purpura,
hematuria, and mild renal insufficiency. Eosinophilia
was noted on the peripheral blood smear and in biopsy
material obtained from the kidney and nasal mucosa.
Our initial impression was that she had a variant of the
Churg-Strauss syndrome, a systemic vasculitis characterized by asthma and tissue eosinophilia (3). Nasal
disease in this entity is usually manifested as rhinitis or
polyposis, although necrotizing lesions, such as the
nasal perforation noted in our patient, have been
described (4). Renal disease is characteristically mild
and responsive to steroid therapy (5).
Despite high doses of corticosteroids over a
2-week period, our patient developed nodular pulmonary lesions, new crops of purpuric lesions on her
skin, and rapidly worsening renal function. The more
appropriate clinical diagnosis, despite the tissue
eosinophilia, became Wegener’s granulomatosis. Consistent with this diagnosis were the nasal perforation,
nodular pulmonary lesions, and severe necrotizing
Peripheral eosinophilia is generally not seen in
patients with Wegener’s granulomatosis (3,6,7). Renal
disease, once present, can assume a fulminant course,
with rapid progression to renal failure (63). Steroid
therapy is usually of no benefit in preventing pulmonary or renal disease, whereas cyclophosphamide has
been noted to induce remission in more than 90% of
patients (9). Prompt institution of cyclophosphamide
therapy in our patient resulted in stabilization and
eventual remission of the disease activity.
The remarkable feature of the case presented
here is the pronounced eosinophilia in the nose and
kidney tissues. This finding has not been described
before in patients with Wegener’s granulomatosis.
Both Wegener’s granulomatosis and ChurgStrauss syndrome usually present as readily delineable, distinctive diseases. Overlap between these 2
entities has not been well described. Overlap was
postulated in 1954 by Godman and Churg (6), who
described a patient with Wegener’s granulomatosis
and eosinophilic pulmonary infiltrates.
Cytodiagnostic urinalysis was of value in following the course of our patient’s renal disease and in
demonstrating tissue eosinophilia. This method of
evaluating urine sediment is much more sensitive,
specific, and reproducible than routine urinalysis. Traditional criteria for assessing the sediment are utilized,
with glomerular injury reflected by the numbers and
types of casts and cells exfoliated. Renal tubular injury
is reflected in the degree and origin of epithelial cells
last in the urine. Renal parenchymal inflammation can
be assessed by the degree of tubular injury in addition
to the presence and numbers of white cell casts,
bacterial or fungal casts, or viral inclusions. By following serial counts of cells and casts, and the values
on dipstick determinations, the activity of renal disease and its response to therapy can be monitored
The use of cytodiagnostic urinalysis in the
detection of renal allograft rejection has been well
described (13-15). To date, there have been no reports
of clinical studies utilizing cytodiagnostic urinalysis in
evaluating renal disease in the non-transplant patient.
In this patient, the initial cytodiagnostic
urinalysis revealed severe exfoliation of renal tubule
cells, marked eosinophiluria, and leukocyturia with
casts composed of WBCs, eosinophils, RBCs, and
hemoglobin. These findings reflected severe renal tubular injury, renal parenchymal eosinophilic inflammation, and glomerulonephritis. Renal biopsy was
consistent with the urinary cytodiagnostic findings.
Eosinophiluria was alleviated by prednisone therapy.
However, the numbers of tubule cells, polymorphonuclear leukocytes, and casts remained markedly elevated, reflecting continued activity of the renal disease. Two weeks after initiation of cyclophosphamide
treatment, the tubule cell and polymorphonuclear
leukocyte counts dropped dramatically. RBC and hemoglobin casts were absent. These findings, along
with the stabilization of the serum creatinine level,
reflect the successful suppression of renal disease by
administration of cytotoxic drugs. We have found this
technique to be a useful adjunct in the management of
other patients with collagen diseases.
Although most patients with systemic vasculitis
can be readily categorized, there are some who manifest an overlap syndrome. The patient described here
probably had an overlap of the Churg-Strauss syndrome and Wegener’s granulomatosis. This concept of
an overlap syndrome has important clinical and therapeutic implications.
Acknowledgments. We thank Sheryl Warshel for her
help in typing the manuscript and Susan Schweitzer, MS,
MT (ASCP) for performing the cytodiagnostic urinalyses.
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features, churg, granulomatosis, systemic, necrotizing, vasculitis, wegener, straus
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