Positive Options for Living with Lupus (11 page)

But if you know the names of your drug and can get on the Internet, you can find out a lot, both good and bad, about your medication.

Here is a list of NSAIDs commonly used to treat lupus:

◗ NSAIDs: salicylates (aspirin—acetylsalicylic acid in fancy dress; Bufferin, Ecotrin, Encaprin), ibuprofen (Advil, Motrin IB, and Nuprin), fenoprofen (Nalfon), ketoprofen (Orudis, Oruvail), piroxicam (Feldene), naproxen (Aleve), diclofenac (Cataflam, Voltaren), nabumetone (Relafen)

◗ COX-2 inhibitors: Celecoxib (Celebrex), valdecoxib (Bextra), etoricoxib (Arcoxia)

Rofecoxib (Vioxx) is the drug that has been withdrawn following the side-effect scare. Lumiracoxib (Prexige) is currently still undergoing clinical trials.

usual with this sort of medical conundrum, “further studies are called for.” Meanwhile, wise old family doctors observe that not only are coxibs now tarnished with the “cardiovascular event”

brush but that in practice some patients taking them still experience the gastric side effects they were supposed to avoid.
And
they cost a great deal more than aspirin or standard NSAIDs. “I foresee them disappearing from the scene,” said one experienced doctor.

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Treating pain is only half of treating lupus—and NSAIDs only a quarter of the drug groups doctors prescribe. For more about additional powerful drugs, turn to Chapter 7.

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Chapter 7

Treating Lupus with Drugs,

Part 2

Doctors are instinctively conservative. If they believe it is safe to

“wait and see”—to avoid intervention and allow the body to correct itself without medical assistance—they probably will do so. If the patient’s symptoms, even temporary ones, are sufficiently severe to make “wait and see” too miserable to endure, they will still first choose the mildest of treatments, the one with the least side effects.

Only if matters become serious do they go in with the big guns. This is why we have discussed NSAIDs first for the treatment of lupus.

Although not side-effect free, they are well known and compara-tively mild. The other drugs in the lupus pharmacy have more serious potential side effects, but balancing this risk, they are generally more effective.

Antimalarial Drugs Are Antilupus

The first group of drugs found to be helpful in lupus was originally designed to attack the malaria parasite, a great example of the serendipity that occasionally blesses the “let’s-see-if-this-will-have-any-effect” approach. The oldest antimalarial drug, quinine, was tried experimentally in lupus as early as the 1890s (see “Lupus in History,” in Chapter 2), and related drugs were used successfully in
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the 1920s to heal the skin lesions associated with discoid lupus.

Several quinine derivatives are still prescribed today, particularly hydroxychloroquine (Plaquenil), chloroquine (Aralen), and quinacrine (Atabrine). Of the three, hydroxychloroquine is most commonly prescribed because it has the lowest side-effect profile.

Treating malaria in its active phase involves reducing fever, so perhaps it is not surprising that antimalarials do this for lupus sufferers too. But they also help with skin lesions, joint inflammation, and fatigue. Characteristically for a serendipitous discovery, there is no clear explanation as to why they should have this effect. They are immunosuppressive. (A study done in Africa showed that antimalarials used conventionally to treat active malaria reduced the response to vaccination, when in fact a protective immune response is the desired effect.) They are also antiviral and anti-inflammatory, though via what mechanism is unclear, possibly by suppressing the production of prostaglandins (as do NSAIDs) or those chemical messengers of inflammation, the cytokines (see Chapter 5). They have two other clearly beneficial actions: They are sun-blocking—

valuable to lupus sufferers who are so often hypersensitive to light—and they lower cholesterol, one of the soluble fats transported in the bloodstream that contribute to cardiovascular disease and the production of blood clots. This is good news for people with lupus, who often have clotting problems, especially during pregnancy, and good news for everyone else too.

. . . and Now the Bad News

There are of course side effects with antimalarials. There is a small risk of the usual upset stomach (about one patient in five), ringing in the ears
(tinnitus),
and occasionally headaches, but the major concern is damage to the retina of the eye.

When hydroxychloroquine is first prescribed it is usually given in quite high doses—up to 400 milligrams (mg) a day—and it can cause temporary visual problems: blurred vision or a “halo effect”

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optimal dose for an antimalarial is quite difficult because the drug does not become effective for at least two weeks, sometimes longer, so this initial side effect can be decisive in determining whether the drug can be used on any given patient. Graham Hughes employs a

“juggling” drug regimen with antimalarials if a patient has severe skin complications. If 400 mg of hydroxychloroquine daily causes vision problems, he reduces the dose by using a different antimalarial (quinacrine) on alternating days. (Quinacrine, also known as mepacrine, is not a first-choice antimalarial because it has its own vision side effects and can also produce slight yellowing of the skin and eye whites.)

The more serious vision side effect of antimalarials was seen more frequently in the past when high doses were used with less caution. It takes the form of pigment deposits in the retina—the area at the back of the eye where images are formed and relayed to the brain. This condition is called
macular retinopathy
and if allowed to continue undetected can lead to blindness. For this reason most hospitals keep a close watch on patients who are taking the drug.

They are advised to protect their eyes from strong light
of all sorts
and
at all times,
and to wear high-quality sunglasses, indoors as well as out, especially if they may be exposed to fluorescent or halogen lighting. In addition the eyes should be examined regularly by a qualified ophthalmologist. The frequency of such examinations can be as little as every few months, but not less than once a year.

If these precautions are observed there is evidence that antimalarials may be taken for months, or even years, and that in addition they may protect against lupus flare-ups.

Douglas’ Story

Douglas developed lupus in middle age. A t first he attributed the arthritic symptoms to wear and tear; it was only when the distinctive discoid rash appear ed on his scalp that his doct or realized it was lupus. Hydroxychloroquine was prescribed, and after a few weeks the symptoms cleared up. But when the medication was stopped, the symptoms returned. Douglas went back on the antimalarial, this time f or months. It was only when he POL text Q6 good.qxp 8/12/2006 7:39 PM Page 68

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had his routine eye test nearly a y ear later that the ophthalmic optician discovered that there was damage to the retina. Douglas had noticed nothing unusual; as f ar as he was concerned his sight was normal. His doct or changed the medication, v ery apologetic that he had not insisted on Douglas’ having an ophthalmic checkup sooner. Subsequent eye exams showed that the damage was not progressing. Douglas was lucky; sometimes the sight continues to deteriorate even when the drug is stopped.

In the past, antimalarials were always discontinued during pregnancy because of the risk that they might affect the developing fetus. However, an increasing number of studies now suggest that successful pregnancies can be completed by women who are taking hydroxychloroquine, though some obstetricians still prefer to err on the side of caution.

Corticosteroids

Does the hair stand up on the back of your neck at the mention of these drugs? Once highly thought of, they have acquired a bad reputation. When the first drug—
cortisone—
was launched in the 1940s it demonstrated such dramatic reductions in inflammation that it was hailed as a wonder drug, a “cure” for rheumatoid arthritis and lupus, and earned its discoverers, Philip Hench and Edward Kendall, a Nobel Prize.

But in the wake of the rave reviews for the miracle cure came serious side effects (mostly because the drugs were being used in very high doses at the time): weight gain, increased blood pressure, easy bruising and slow healing, cataracts, muscular weakness, elevated blood sugar causing problems with diabetes, less resistance to infection because the immune system was being suppressed, and, with long-term use, thinning of the bones (osteoporosis). Corticosteroids were no longer the flavor of the month.

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help control
metabolism
(how the body generates energy and disposes of waste), the development of sexual characteristics, immune function, the balance of fluids in the body, and its tolerance of stress. There are many steroids with different functions; the sex hormones (testosterone, estrogen, and progesterone), adrenal cortical hormones, bile acids, sterols, anabolic agents, and oral contraceptives are all steroids. Corticosteroids are not the same as anabolic steroids, the ones taken by weight lifters to build muscle. The role of corticosteroids is protective: They maintain the fluid balance in the body and help it cope with stress; along the way they reduce inflammation.

Doses and Delivery Regimen of Steroids in

Lupus Treatment

In the treatment of lupus, the role of steroids is anti-inflammatory.

Nowadays the pros and cons of corticosteroids are better understood, and their use, delivery, and dosage have been refined. They have probably advanced the treatment of lupus more than any other drug, and almost every person with lupus will take them at some time or other, on a short-or a long-term basis. Doctors prescribing them follow strict guidelines.

Getting the dose right—not too much, not too little—is central to the administration of steroids. Inflammation is the healthy response to infection, so if it is suppressed (by drugs) the patient becomes vulnerable to infection; hence it is essential that the dose is kept as low as is effective. In Graham Hughes’ experience, a seriously ill patient may briefly require as much as 60 mg daily, reducing to 30–40 mg after one or two weeks. Milder cases might receive 15–20 mg daily for the first few weeks, reducing to a maintenance dose of 5–10 mg a day. Reducing the daily dose of steroids must always be done gradually and with the cooperation of the patient. It is possible to reduce high doses on a steeper gradient, but a reduction of a dose that is lower than 20 mg must always be extremely gradual—as little as 1 mg a month—in Graham Hughes’ experience.

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(This fine-tuning can be hampered by the difficulty of finding 1 mg tablets, requiring the patient’s cooperation in neatly cutting up pills with a razor blade.)

A number of steroid drug regimens may be employed. They are most commonly taken by mouth; the most widely used drug is prednisolone (or prednisone). ACTH (adrenocorticotrophic hormone) is an injectable form of steroid that is administered twice weekly, and methylprednisolone is given via a drip into a vein. This can obviously only be done in the hospital, but for seriously ill people it can be a useful way of delivering large doses of steroids with surprisingly few side effects. (When steroids are taken by mouth they are available in a coated form to reduce the usual unpleasant gastric side effects.) At the other end of the dose scale is the practice of prescribing steroids to be taken on alternating days, to allow the natural source of steroids—the body’s own adrenal glands—to re-boot. One of the principle side effects of steroid treatment is that the body, recognizing that large amounts of the stuff are washing around, cuts back on home production. This is why coming off steroids must be done gradually—to let the adrenal glands limber up and get back into production.

Taking low-dose steroids, for example 7.5 mg a day, even for a limited period, causes other side effects. Two are quite common: sleep disturbance and increased appetite. As has been explained, steroids control metabolism, which in turn determines when energy and attention levels go up and when they come down, and, accord-ingly, the cycles of attention and sleepiness that constitute your body clock. Some people who take steroids find their body clocks totally reversed; they’re wide awake at three in the morning and sleepy at three in the afternoon, as though they had been working the night shift or had just returned from the other side of the globe with jet lag.