BOSTON — Despite the availability of “pretty good therapies” for Wegener's granulomatosis and microscopic polyangiitis, “these forms of small-vessel vasculitis still regularly kill people, so do not underestimate the misery associated with them,” said Dr. Peter Merkel at a meeting on rheumatology sponsored by Harvard Medical School.
“These are bad diseases that cause major, permanent damage to multiple organ systems,” said Dr. Merkel of Boston University. “While the available treatments can effectively induce remission in some patients, many other patients die. Some die early from hemorrhage or other problems; some die later from concurrent disease or treatment toxicity. The important thing to remember is that these diseases kill.”
The first line of defense against such an outcome is the accurate diagnosis of acute disease, and early, aggressive therapy. Unfortunately, a number of obstacles can get in the way of both, Dr. Merkel said.
Because these conditions are relatively rare, “many rheumatologists don't see a lot of these patients and thus do not have a good sense of the spectrum of the disease and its presentations,” he noted.
When a patient presents with symptoms suggestive of acute vasculitis, “the first thing to do is look for trouble,” said Dr. Merkel. “There's always more to acute vasculitis than you think. If you look for trouble, you will almost certainly find it, and this is important because you want to find and treat the worst part of the disease first.” A good evaluation for potential small-vessel vasculitis should include a full medical history and physical. “This is not a 20-minute visit. It requires a long, comprehensive examination with a full set of labs,” Dr. Merkel stressed. “Certainly, one of the first things is to get a urine specimen to assess possible kidney involvement, and, for dipstick positive specimens, you have to be willing and able to do a microscopic examination of the urinary sediment right then and there,” he said. “Early changes in urine are critical to evaluating these patients, and in order to identify such changes, the specimen for microscopic examination has to be as fresh as possible. If you send the specimen to the lab, the red cells and formed solids will have disintegrated.”
Unfortunately, microscopic examination of urine sediment is a “lost art,” said Dr. Merkel. “It requires a degree of skill acquired through practice. It's hard to get used to doing if you're not seeing hundreds of patients with these diseases, and most rheumatologists are not seeing hundreds of these patients,” he said.
“However, if you're not comfortable doing this, you cannot take care of these patients on your own.”
Testing for antineutrophil cytoplasmic antibodies (ANCA) is also necessary. “Although there is a subset of patients who test negative for ANCA, a positive test is a useful diagnostic and prognostic marker for Wegener's granulomatosis and microscopic polyangiitis,” Dr. Merkel stressed.
Chest x-rays are also considered an essential diagnostic tool, “but they often miss things,” said Dr. Merkel. “Anyone being evaluated for possible Wegener's should have a CT scan of the chest—and often even the head and neck—to look for subparotid disease or tracheal narrowing.” Because upper-airway and lung involvement are devastating, “it's important to have a low threshold when looking for neck disease, so you can get it early,” he said.
Pulmonary function testing and an ophthalmological examination to identify inflammatory eye disease should be conducted, as should audiograms, said Dr. Merkel. “Hearing loss, in particular, is an underappreciated problem in small-vessel vasculitis. Audiograms are noninvasive and cheap, and should be standard practice in these patients.”
Although electromyography and nerve conduction studies may be useful for identifying and localizing neurologic involvement in these diseases, “they are painful, annoying, and expensive tests and generally unnecessary if you do a proper examination,” said Dr. Merkel.
Before making a diagnosis, “rule everything else out, particularly infections,” Dr. Merkel stressed. “Infections are the great mimicker and cotraveler of vasculitis, so be sure to look for them.”
As the diagnostic criteria for these conditions are fulfilled, get a good team together to address the multiple organ system assaults, said Dr. Merkel. And, in the case of acute disease, “jump right in with glucocorticoids, especially if you suspect acute glomerulonephritis or pulmonary hemorrhage. These are among the few true rheumatoid emergencies, and nothing works faster for acute ANCA-associated vasculitis than steroids.” Immunosuppressive therapy, which is the mainstay of treatment for these conditions, “can usually wait until the patient is more stable or the diagnosis has been confirmed, but you don't want to miss treating acute renal or pulmonary disease, or even bad eye disease, because the consequences can be devastating,” he said.