Ask the Experts -- Spring 2005
Q: I recently lost a wonderful 3 1/2-year-old golden retriever to undiagnosed lupus. It was not discovered until he was seen by the veterinarian for complications from the disease. I understand that lupus is a somewhat rare disease in canines and often hard to diagnose. Can you tell me more about lupus and which specific breeds are more likely to get the disease?
A: I am sorry about your loss. I lost both my cocker spaniels to lupus a few years ago and I understand how you feel. Lupus is a chronic inflammatory (rheumatic) disease first described in humans in the early 19th century. Lupus was described in dogs (“canine lupus”) in 1965. It also affects reptiles, hamsters, guinea pigs, mice, rats, pigs, mink, rabbits, horses and cats. It is not clear whether there is preference to breed or gender. Some research into canine lupus suggests that it may be more common in cocker spaniels, German shepherds, collies, sheepdogs, beagles and Irish setters.
The cause of lupus in humans and canines remains unknown. However, it’s believed that some factor from the environment (perhaps a germ) triggers the disease. The symptoms of lupus in humans and dogs are similar and may include fever, arthritis (lameness in dogs), skin disease (footpad ulcers in dogs), hair loss, tiredness, and effects from damage to blood cells, lungs, heart, nervous system or the kidneys, if they are involved. These symptoms can be subtle and difficult to recognize. When lupus is suspected, the diagnosis is confirmed by finding the telltale autoantibodies (antibodies against “self”) in the blood.
Lupus can be treated. Indeed, people with lupus lead productive lives for decades with their disease under control. Treatments include anti-inflammatory medications, steroids, and other medical (and sometimes surgical) interventions to try and “reset” the unbalanced immune system. There is no cure for lupus yet but it is often possible for dogs, like people, to live with it successfully. Perhaps the most famous dog with lupus, Millie, former President George H.W. Bush’s Springer spaniel, had her lupus well controlled. -- Richard S. Panush, M.D.
Q: What side effects can I expect from taking steroids?
A: Prednisone is a double-edged sword. It is a very effective anti-inflammatory agent in lupus, and it works fast. But over time, the side effects of higher doses of the medication can be significant. People taking steroids may have side effects that include weight gain (especially in the cheeks and over the back of the neck), acne, hair thinning on the scalp, new facial hair (on the chin or above the lips), mood swings and difficulty concentrating. Your doctor may also discover that your prednisone has caused higher blood pressure, higher glucose levels and higher cholesterol. Prednisone can also weaken bones and damage the blood supply to joints, which usually occurs first in the hips. -- Michelle Petri, M.D., M.P.H.
Q: Should people with lupus who want to eventually become parents bank their eggs or sperm before taking cytotoxic drugs for treatment?
A: As with many things in medicine, this is a matter of risk vs. benefit. For both men and women, the risks of infertility with cyclophosphamide (Cytoxan®) depend on the age of the person, the dose of cyclophosphamide, and whether there have been any additional medications or medical problems related to fertility (for example, polycystic ovarian syndrome, endometriosis, late onset of menses or problems with the veins of the spermatic cord).
Age. In the only clinical trial to prospectively evaluate the effects of cyclophosphamide on fertility in women, after age 30 virtually all women in the study lost their menstrual periods when taking the National Institutes of Health cyclophosphamide regimen. In the single published article that studied cyclophosphamide treatment and fertility in men, the risk of infertility also was shown to rise, at age 24.
Dose. Although this information comes mostly from animal studies, it provides the rationale for stopping the function of the ovaries or testes during treatment with cyclophosphamide. If the ovaries or testes are not functioning, the blood flow is reduced, so the amount of cyclophosphamide exposure should be lower. Studies we have done using lupron (a naturally occurring hormone that influences the release of testosterone and estrogen in the body) to stop ovarian function have shown that menstrual periods can be preserved, even in women over age 30. Estrogen-containing birth control pills also have been used to stop ovarian function, but should not be taken by women with hypertension and antiphospholipid antibodies. The SELENA (Safety of Estrogen in Lupus Erythematosus—National Assessment) study showed that, although birth control pills can be used in women with kidney disease if their high blood pressure is under control, they should not be used when lupus disease is active. In men, testosterone supplementation was shown to be of benefit in one small study.
Other factors. Ovarian or testicular problems that can occur independent of lupus or cyclophosphamide also add to the problem. While it has been reported that fertility is not decreased in women with lupus, we have data showing later start of menstrual periods, fewer pregnancies and earlier menopause—all occurring before diagnosis or treatment of lupus. Whether or not this represents sub-clinical disease, it is directly in opposition to the prevailing belief that excess estrogen is “causing” lupus or is important in initiating lupus.
So, the answer for whether men should bank sperm before taking cyclophosphamide for lupus is a definite “yes” -- provided they can afford it. For example, at our institution, the cost to maintain banked sperm is $250 each year and insurance generally won’t cover the cost.
For women, the question is much harder to answer. To bank eggs requires taking large doses of estrogen to harvest the eggs. Also, unfertilized eggs can be frozen but they don’t preserve well and certainly aren’t as good as fertilized eggs. The cost of the procedure and medical risks are both high. And, unless the woman already has a long-term partner and freezes fertilized eggs, there is less possibility for success with in vitro fertilization down the road. -- Mary Anne Dooley, M.D.
Q: Can you explain the significance of an ANA pattern?
A: ANA, or antinuclear antibodies, is the most common lab test used to confirm a diagnosis of lupus. Two of the most common ANA patterns are called “nuclear homogeneous” and “nuclear speckled.” These occur most frequently in people with lupus, but also occur in other rheumatic diseases, such as rheumatoid arthritis. Another common cause of positive ANA tests with nuclear homogeneous staining are certain drugs such as pronestyl and chlorpromazine. Thus, positive ANA tests of these two patterns by themselves are not very useful in clinical diagnosis.
Certain specific patterns of fluorescence have high diagnostic power. Three patterns are clinically useful: “centromere,” “nucleolar” and “mitochondrial.” The first two patterns are seen primarily in systemic sclerosis. The centromere pattern is rarely seen outside the clinical spectrum of systemic sclerosis and is much more common in the limited form of the disease described as the CREST (calcinosis, Raynaud’s phenomenon, esophageal dysmotility, sclerodactyly and telangiectasia) syndrome.
Antibodies to nucleoli also occur in systemic sclerosis but have a measurable frequency in the other systemic rheumatic diseases. Antibodies to mitochondria, which give a characteristic reticular cytoplasmic pattern and high titers (more than 1/1,000), are seen almost exclusively in primary biliary cirrhosis, a disease with many systemic features and frequent overlap with rheumatic disease, especially systemic sclerosis. -- Morris Reichlin, M.D.
Richard S. Panush, M.D. is Professor and Chair of the Department of Medicine at Saint Barnabas Medical Center in Livingston, NJ.
Michelle Petri, M.D., M.P.H. is in the Department of Rheumatology at Johns Hopkins Hospital in Baltimore. She is a member of the Lupus Now Advisory Board.
Mary Anne Dooley, M.D., M.P.H. is in the Department of Medicine, Rheumatology and Immunology at the University of North Carolina at Chapel Hill. She wrote the Case Study column for the Spring 2004 issue of Lupus Now.
Morris Reichlin, M.D. is at the Arthritis and Immunology Laboratory at the Oklahoma Medical Research Foundation in Oklahoma City. He is the author of the LFA Patient Education brochure, “Laboratory Tests Used in the Diagnosis of Lupus.”