Rao JK, Allen NB, Feussner JR, Weinberger M
A prospective study of antineutrophil cytoplasmic antibody (c-
ANCA) and clinical criteria in diagnosing Wegener's
granulomatosis
Lancet
(Oct) 346:926-931 1995
Rao et al. performed a prospective study to determine how c-ANCA may be
useful in patients with suspected vasculutis and in whom Wegener's
granulomatosis is in the differential diagnosis. They also looked at the
effect of baseline corticosteroid use or disease activity on c-ANCA values
in these patients. The patient population included inpatients and
outpatients
evaluated by a
rheumatologist for possible vasculitis at Duke University Medical Center
between January and December 1993. They excluded patients with known
Wegener's and patients who had received immunosuppressive or disease
modifying antirheumatic therapy at the time of evaluation. A second group
of
patients was obtained by review of records from patients who had an ANCA
test in the clinical immunology laboratory. ANCA was performed by indirect
immunofluorescence. Diagnosis of Wegener's granulomatosis was based on the
1990 American College of Rheumatology (ARC) criteria for Wegener's
granulomatosis.
Of the 346 patients eligible for study, 252 were retained, 174 of whom had
not received steroids. 191 patients were entered in the study by direct
referral, this group having more symptoms and symptomatic leukocytoclastic
vasculitis compared with those obtained by reviewing laboratory records for
positive ANCA (n=78). Follow-up information was obtained in 84% (212)
patients at a mean of 5.1 months.
By ACR criteria, the diagnosis of Wegener's was established in 25 patients,
and the c-ANCA was
positive in 7 of these, for a sensitivity of 7/25 or 28%. During the follow
up period, six of these
25 patients were diagnosed with Wegener's granulomatosis by typical clinical
and
histopathologic findings, and five of the six were c-ANCA positive. Nine of
the 25 were ultimately
diagnosed with other vasculitides, and the remaining 10 were diagnosed with
other diseases. None of
the patients initially negative by ACR criteria were
diagnosed with Wegener's during follow up. Fourteen of the 212
patients overall had a positive c-ANCA. The overall specificity was
therefore 96%.
The positive predictive value of the test was 0.5.
The specificity of the c-ANCA test was not effected by baseline steroid use;
however,
the sensitivities were poor in all patients, whether on or off steroids. In
patients with inactive disease, the sensitivity of c-ANCA was half that of
patients
with active disease.
The authors conclude that the c-ANCA test is extremely specific independent
of steroid use or disease activity. A negative c-ANCA is therefore likely
to be a "true negative" in patients with suspected vasculitis.
Sensitivity, however, was much less than in previous studies, being only
28%, in patients with ACR-defined Wegener's granulomatosis and only
33% in patients with active disease. It is acknowledged, however, that
sensitivity would have been
much higher based on the biopsy criteria for a Wegener's diagnosis (5/6 such
patients being c-ANCA
positive). In any case, nearly 50% of the
patients with a positive c-ANCA did not have Wegener's granulomatosis. The
authors state that basing therapeutic decisions on a positive c-ANCA test
and clinical symptoms of Wegener's granulomatosis alone may be seriously
flawed.
The authors also point out that their study differs from others by its
prospective nature, using patients with suspected vasculitis and
application of a single reference standard, the 1990 ACR criteria. They
also pointed out the limitations of their study including the referral bias
associated with using university-based rheumatologists and the small number
of patients with biopsy proven Wegener's granulomatosis. They also note
that of the 16 patients lost to follow-up, some may have eventually
developed Wegener's granulomatosis and also, because not every patient had
a biopsy, those with occult disease might not have been diagnosed.
Comment: This study helps the clinician put c-ANCA testing in
perspective. The c-ANCA must be interpreted within the context of the
patient's
clinical picture, diagnostic studies, and likelihood of the disease.
(Krane)
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ARF etiology :
Acute glomerulonephritis/RPGN
Proteinuria/Hematuria :
Vasculitis (Wegener's PAN, etc.)