We have reviewed the medical records of 301/327 consecutive patients i
n whom anti-neutrophil cytoplasmic antibodies (ANCA) were detected by
the Regional Immunology Laboratory in Northern Ireland between January
1988 and October 1991 (45 months). We have collected data for each pa
tient regarding age, sex, smoking habit, area of residence, and detail
s of any other autoantibody activity. Clinical diagnosis was establish
ed, with the number of organ systems involved and the evidence for tha
t involvement (symptomatic, biochemical, radiological, and histologica
l). Diagnoses were divided into four groups according to their recogni
sed vasculitic features and these were related to the pattern of immun
ofluorescence and maximum ANCA titre detected. The most frequent diagn
osis was rheumatoid arthritis (18.2% of patients) and the connective t
issue disorders as a whole accounted for 27.9% of patients. ANCA were
also detected in a wide range of clinical conditions which are not ass
ociated with vasculitis and these patients were an important source of
'false-positives'. The positive predictive value (PPV) of ANCA of all
patterns and titres for vasculitic conditions was 27%, however, the d
etection of a classical ANCA pattern at high titre (greater than or eq
ual to 1:640) was associated with an increased PPV of 75%. The coexist
ence of an antinuclear antibody (ANA) reduces the PPV of both classica
l and perinuclear ANCA, although perinuclear ANCA with antimyeloperoxi
dase specificity had an improved PPV. We conclude that ANCA testing sh
ould not be used as the only screening investigation for vasculitis bu
t should be in a rational investigative scheme. The interpretation of
a positive ANCA result must take into account the presence of other au
toantibodies and the full range of non-vasculitic conditions when the
clinical situation is not typical of vasculitis.