SNOWMASS, COLO. — Rheumatology would be well served if the term “ANCA-associated vasculitis” was banished from the medical lexicon, Dr. Gary S. Hoffman asserted at a symposium sponsored by the American College of Rheumatology.
“Practitioners who accept this nomenclature may be misled and apply the concept of [antineutrophil cytoplasmic antibody-associated] vasculitis or—the greatest disservice of all, but one well embedded in the literature now—'ANCA disease,' in a fashion that's detrimental to patient care. They mistakenly assume [antineutrophil cytoplasmic antibodies] are required for disease, correlate with disease activity, and can be used as a guide to treatment,” said Dr. Hoffman, professor of medicine at the Cleveland Clinic Foundation/Lerner College of Medicine.
In fact, the rheumatologist continued, none of that's true.
“This is not an academic argument,” he added. “I see ANCA being misused on almost a weekly basis in patients sent to me.”
The resultant patient harm can take the form of delayed diagnosis and treatment of small-vessel vasculitis because of excessive reliance upon a negative ANCA test, or, conversely, inappropriate use of powerful immunosuppressive agents in ANCA-positive patients with sinusitis but no small-vessel sinusitis, Dr. Hoffman continued.
Dr. Hoffman readily conceded his position is controversial. ANCA's proponents use the term ANCA-associated vasculitis to refer to four diseases in which ANCA is present to a variable extent.
These include Wegener's granulomatosis, microscopic polyangiitis, Churg-Strauss syndrome, and immune complex-negative rapidly progressing glomerular nephritis.
He argued that these conditions are actually strikingly different both clinically and pathologically.
And ANCA can't serve as a true unifying principle, since it's not universally present in these diseases.
Indeed, in the two best studies to date in Churg-Strauss syndrome, one from France and the other Italy, only 38% of patients with the disorder were ANCA positive at diagnosis, indicating the disease is not driven by ANCA.
“My concern is that the terms ANCA-associated vasculitis and ANCA-disease dumb down the complexity of these diseases to the clinician,” Dr. Hoffman explained.
ANCA testing is unequivocally of value in the diagnosis of small-vessel vasculitides in patients with a moderate to high pretest probability.
Under those circumstances, a positive result may eliminate the need for biopsy.
When the pretest probability is low, however, ANCA testing will have substantial false-positive and -negative rates, according to Dr. Hoffman.
He cited a landmark study of the diagnostic value of ANCA in idiopathic systemic vasculitis which concluded the test is negative in 15%-20% of affected patients (Kidney Int. 1998;53:743-53).
Serial ANCA testing should definitely not be used to guide immunosuppressive therapy or try to predict relapse, in Dr. Hoffman's view.
“Don't ever base your treatment decision making primarily on the ANCA test,” he stressed. “That is a surefire formula for getting your patient in trouble.”
He cited a recent rigorously conducted study by the Wegener's Granulomatosis Etanercept Group involving 156 patients followed with serial ANCA testing over nearly 3 years.
The investigators concluded ANCA titers bore little relationship to disease activity. Increases in pro-proteinase 3-ANCA or mature PR3-ANCA weren't significantly associated with relapse, and decreases weren't associated with remission (Ann. Intern. Med. 2007;147:611-9).
Audience member Dr. Ulrich Specks of the Mayo Clinic, Rochester, Minn., observed that ANCA testing “has many pitfalls and can be misleading.” But he is firmly convinced ANCA influences disease phenotype.
Dr. Hoffman concurred.
“People who are high-titer ANCA positive tend to have more severe disease. ANCA may enhance the pathogenic process that is already established. I think it may well be much like anti-double-stranded DNA in lupus and rheumatoid factor in rheumatoid arthritis,” Dr. Hoffman commented.