The Lupus Book: A Guide for Patients and Their Families, Third Edition by Daniel J. Wallace Page A

investigators might
    be able to use it as a model for understanding how lupus develops. Unfortu-
    nately, however, DILE may come about through different chemical processes
    unrelated to the evolution of the disease as it unfolds in most cases. Let’s look at some proposed mechanisms by which drugs induce lupus.
    For example, the drug can bind to a part of the cell that alters DNA. This
    altered DNA sets in motion an immunologic reaction, causing the body to make
    anti-DNA. Similarly, drugs can activate T or B lymphocytes and, as part of the
    immunologic response, lead to the formation of antibodies to white blood cells, or antilymphocyte antibodies—a common feature of lupus. Next, a drug can
    induce the hypomethylation of DNA, which results in altered DNA repair and
    autoantibody formation. Also, the drug may make your body so sun-sensitive
    that, if you are genetically predisposed, it can turn on a lupus reaction. Finally, certain drugs are broken down into chemicals, or by-products that promote the
    formation of autoantibodies—the antibodies that attack the body’s own tissue.
    Several genetic factors may also increase the risk of developing DILE. For
    example, the HLA-DR4 genetic marker is associated with hydralazine and D-
    penicillamine-induced lupus. If your liver cannot clear these breakdown products of drugs quickly, this slow clearance system is termed ‘‘slow acetylatation.’’ If you are a slow acetylator and are prescribed procainamide, hydralazine, or isoniazid and if you have a certain genetic makeup, there is an increased chance
    that you will develop DILE. Finally, the absence of certain HLA-derived com-
    plement genes also correlates with DILE.
    Drugs That May Cause Lupus or Produce Flareups
    [53]
    Clinical and Laboratory Features of Drug-Induced Lupus
    Hydralazine is a drug used to lower blood pressure by dilating blood vessels.
    When it was introduced in the early 1950s, much higher doses were used than
    are currently prescribed. Positive ANA tests seem to be related to high doses of hydralazine, as do longer treatment durations. For example, at 5 years, the risk of developing DILE at doses of 50 milligrams daily is zero, but it is 5 percent at 100 milligrams daily and 10 percent at 200 milligrams daily, even though at
    this point more than half of patients will have a positive ANA.
    The average dose of hydralazine is about 50 to 100 milligrams a day. You
    should suspect hydralazine-induced lupus if you begin noticing joint swelling,
    fevers, and weight loss. Rashes or anemia are found 25 percent of the time,
    muscle aches and pain on taking a deep breath are less common, and organ-
    threatening disease is very rare. Nearly everybody with hydralazine-induced lu-
    pus has a positive ANA and specific antibodies called antihistone antibodies.
    Procainamide is an extremely effective, often lifesaving drug that treats irregular heart rhythms. As with hydralazine, the risk of procainamide-induced
    lupus also depends on dose and duration of treatment. Up to 83 percent of all
    individuals given long-term procainamide develop a positive ANA, but only a
    small percentage ever develop full-blown DILE. Its symptoms and laboratory
    results are similar to those of hydralazine-induced lupus, except that pleurisy and pericarditis are more common with procainamide and rashes almost never
    occur. Organ-threatening disease is extremely rare.
    Three other commonly used types of heart medicines are also culprits. Meth-
    yldopa (Aldomet) is an antihypertensive drug that has induced lupus, although rarely. Patients with this syndrome often exhibit a marked anemia and antibodies to red blood cells. Another drug used in treating an irregular heart rhythm,
    quinidine (Quinaglute), occasionally causes positive lupus blood tests and a severe arthritis. A group of blood pressure pills known as beta-blockers infrequently cause a positive ANA test, but only a handful of clinical lupus cases
    have been reported in connection