The Lupus Book: A Guide for Patients and Their Families, Third Edition (42 page)

frequently asked how often steroids can be injected into joints, tendons, or ligaments. Studies have suggested that injecting a joint with a steroid more often than every 3 months destroys cartilage and is not advisable. Too many injections into tendons or ligaments can weaken or rupture these structures.

What Types of Steroid Regimens Are Used to Treat Lupus?

Active, organ-threatening lupus should always be treated with steroids. Involvement of lupus in the heart, lung, kidneys, liver, or blood (autoimmune hemolytic anemia or thrombocytopenia) is managed with
high-dose steroids
—one milligram per kilogram (1 kilogram ϭ 2.2 pounds) per day of prednisone for at least

6 weeks. This usually averages out to 40 to 80 milligrams a day. Doses above

40 milligrams a day are considered high. Acute central nervous system vasculitis is treated with high-dose steroids for shorter periods of time, often with additional pulse therapy (see the previous section).

Severe flareups of non-organ-threatening disease warrant
moderate doses
, or 20 to 40 milligrams of prednisone a day. This circumstance arises when a patient complains of severe chest or heart pains that turn out to be pleurisy or pericarditis; manifests active skin disease; or has a severe flare of joint inflammation.

These moderate doses are maintained for a few days to several weeks.

Chronic, mild, non-organ-threatening disease responds to daily doses of 2 to

20 milligrams of prednisone. This is considered
low-dose therapy
. Most patients with non-organ-threatening disease on low- or moderate-dose steroids have other agents added and ultimately are switched over to NSAIDs, antimalarials, or

methotrexate, all of which are safer than using long-term steroids unless the

doses are very low.

What Are Surgical and Stress Doses of Steroids?

The adrenal gland helps compensate the body for stress by releasing extra ad-

renalin (epinephrine and norepinephrine) and steroid. Surgery, for example,

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stresses the body, and we all need extra adrenalin and steroids to handle it.

When lupus patients undergo surgery or face any stressful procedure, doctors

usually give two to three times the usual daily dose of steroids on the day of

the event to ease stress; sometimes it takes a few days before the cortisone doses are back to their original levels.

What Can Steroids Do That’s Bad?

Steroids are a blessing and curse. Without them, many lupus patients would die; but with them, serious complications can arise. Certain reactions to steroids

occur immediately, while other reactions occur in patients who have had higher

doses of the drugs or have taken lower doses for longer periods of time. One

immediate reaction to steroids is a sense of energy. However, they can also

cause palpitations, agitation, and rapid heart rates, and they can make it hard to sleep. Many of my patients tell me that they clean house at 3 A.M. after starting moderate-dose steroids. Heartburn is an early side effect in patients beginning steroids.

As time passes, numerous additional side effects occur that can best be cat-

egorized by organ systems. The
skin
becomes thin and wrinkles easily. Bruises appear, hair loss in the male pattern of baldness from the scalp is noted (in the temples and the upper back of the head), while facial hair increases, along with facial acne. Wound healing is impaired and sores take longer to disappear.

Stretch marks are noted throughout the skin, especially on the abdomen.
Musculoskeletal
problems include muscle weakness and loss of calcium in bones (which can lead to osteoporosis). Clots of fat released by steroids can settle in the blood supply of bones, leading to a condition known as avascular necrosis

or ‘‘dead bone.’’ The skin and muscles become very sensitive to the touch and

fibromyalgia may ensue.

Since steroids are hormones, the
endocrine/metabolic system
is affected.

Among the complications caused by steroids are glucose intolerance, which

eventually becomes diabetes; menstrual irregularity; and central obesity, where one’s body weight is redistributed toward the belly and buttocks and away from

the extremities. Steroids can stunt the growth of children taking these drugs,

and—as discussed earlier—they can suppress the hypothalamic-pituitary-adrenal

axis. The production of fats, especially cholesterol and triglycerides, is increased.

Cataracts form and glaucoma develops in the
eyes
.

The
central nervous system
is stimulated, which produces agitation, confusion, difficulty in concentrating, and may even result in psychotic behavior. Patients may become moody and irritable. Some of the
cardiovascular-renal
effects lead to salt and water retention with bloating and puffiness, especially in the face and ankles. Potassium blood levels decrease, often necessitating oral replacement. Salt retention causes blood pressures to rise. The
gastrointestinal system

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The Management of Lupus Erythematosus

is involved, as continued steroid use causes the heartburn to lead to ulcers.

Steroids thin intestinal walls and increase the risk of perforation, especially of diverticula (pouchings) in the colon. The pancreas can also become inflamed by

corticosteroids. Finally, the risk of
infection
is much greater, since steroids prevent antibodies from killing bacteria, viruses, fungi, and parasites.

Not everybody develops all of these complications and many individuals who

are steroid-dependent develop none of them. It is impossible to predict which

complication will occur in whom, except that those who have taken these drugs

in higher doses are more likely to note some of these side effects.

How Does One Get off Steroids?

Unless a person has been on steroids for less than a month, the answer is slowly.

Acute lupus flareups can be treated with short courses of steroids, given as a

Medrol Dosepak, where high doses are dropped to zero within a week. Or

steroids can be injected into the buttocks with Celestone, Aristocort, Depo-

Medrol, or Kenalog, where the drug is out of the system within several weeks.

These short-term treatment courses are rarely if ever associated with serious

problems.

The ideal way for a doctor to taper steroids if a patient has been on the drug

for at least a month is to decrease the dose by 10 percent a week until adrenal replacement levels are reached (7.5 milligrams of prednisone daily). A
steroid
withdrawal syndrome
simulating fibromyalgia frequently mimics disease flareups and must be differentiated from active lupus. This syndrome is self-limited and disappears within 2 to 3 weeks of keeping the steroid doses at the same

level. When adrenal replacement levels are reached, the doctor may wish to

taper more slowly (e.g., 10 percent reductions every few weeks or reduced doses of 5 percent every week or 10 days). On occasion, the doctor may order a

cortrosyn stimulation test
, which evaluates the sluggishness of the adrenal glands and offers guidance as to how fast or slowly the medication can be tapered.

Many of the side effects listed above, especially those of weight gain and bloating, can persist for several months after the drugs have been discontinued.

How Do Doctors Minimize the Side Effects of Steroids?

Since doctors know what can happen when they start patients on cortisone, is

there anything they can do to minimize the reactions that have just been dis-

cussed? The answer is yes, to a certain degree. For example, I sometimes pre-

scribe antacids, H blockers (e.g., Zantac), or proton-pump inhibitors (e.g.,

2

Prilosec), along with steroids. Patients are urged to keep to a low-sodium, low-fat, and low-carbohydrate diet and to limit their calorie intake. Sometimes,

diuretics are prescribed to deal with bloating and fluid retention. Steroid-

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[225]

dependent patients should take in at least 1 gram of calcium daily and a bi-

phosphate (e.g., Fosamax, Actonel) to protect their bones. Mild sedatives allow patients to get some rest at night, and families are counseled to be supportive rather than angry at the appearance or behavior of their loved ones. I also urge my patients to keep active, which minimizes muscle atrophy and osteoporosis,

and counsel them to stay away from friends or colleagues who have colds or

other infections. No environment is ideal for a patient taking steroids, but it can be tailored to some extent to make life more comfortable.

TRADITIONAL IMMUNOSUPPRESSIVE THERAPIES

‘‘Chemotherapy’’ can be a scary-sounding word. Some rheumatologists instead

use the terms ‘‘immunosuppressive,’’ ‘‘cytotoxic,’’ or ‘‘steroid-sparing’’ therapy. Essentially, these therapies are used when serious organ-threatening disease is present and steroids alone are not sufficient to deal with the problem. They are also employed when a patient cannot tolerate high doses of steroids, since

chemotherapies reduce steroid requirements. Chemotherapies are not as scary as

they sound and are very useful agents in the treatment of SLE.

In 1947, a patient with severe discoid lupus had
nitrogen mustard
ointment applied to the skin and the rashes healed. Shortly thereafter—and in the days

before dialysis—this agent was given to patients with severe kidney disease and proved to be lifesaving. However, nitrogen mustard is messy and inconvenient;

the doctor has to wear a Darth Vader-like space suit to apply the ointment, while intravenous mustard must be given in the hospital and patients become quite ill from it. Efforts were made to improve upon this useful compound, and this led

to the introduction of
cyclophosphamide
in the early 1960s. Also known as Cytoxan, it is chemically similar to nitrogen mustard but much better tolerated.

Until the early 1980s, Cytoxan was given as a daily pill. Even though it proved to be effective in managing severe lupus and was steroid-sparing, several problems arose. First of all, patients had to drink gallons of water daily to prevent a condition known as hemorrhagic cystitis. This was manifested by bloody urine

and sometimes evolved into bladder cancer. Also, most patients lost their hair

and had to wear wigs. Further, many young women stopped menstruating and

became sterile. Cytoxan also upset the stomach and lowered blood counts, which

made patients more susceptible to infection. Finally, Cytoxan use for several

years was associated with a 5 to 10 percent risk of developing a malignancy in

10 to 20 years. Cytoxan and nitrogen mustard are alkylating agents; their effects simulate total-body irradiation. In the early 1980s, a kinder, gentler way of

administering Cytoxan was found. This involved once-a-month intravenous ad-

ministration. When Cytoxan was used in a cyclical fashion, the incidence of

hemorrhagic cystitis dropped to less than 5 percent; patients did not lose their hair if they wore an ice cap or head tourniquet while getting the drug; newer

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The Management of Lupus Erythematosus

medicines that minimized nausea became available (e.g., ondansetron, also

known as Zofran); the malignancy risk decreased to less than 1 percent; and

fewer patients became sterile. However, most female patients over the age of

30 who take at least nine monthly doses of cyclophosphamide in a 1-year period

stop menstruating.

Recent studies have suggested that patients with organ-threatening disease

who do not quickly respond to steroids benefit from the addition of intravenous, intermittent Cytoxan. For severe kidney disease (Chapter 19), doctors usually

give Cytoxan once a month for 6 months and then every 2 to 3 months until 2

years have elapsed. Cytoxan does not always work; up to 30 percent of patients

who take the drug benefit from the addition of a second agent or therapy such

as Imuran.

When I prescribe chlorambucil, I make every effort to limit its use to less

than 2 years.

In the early 1960s, an agent became available that prevented patients with

kidney transplants from rejecting them. Not a chemotherapy, since it does not

treat cancer,
azathioprine (Imuran)
has turned out to be a solid addition to the rheumatologist’s therapeutic arsenal. A slight modification of
6-mercaptopurine
, which is used for inflammatory bowel disease, Imuran blocks inflammation pathways and is FDA-approved for rheumatoid arthritis. Numerous studies exam-

ining the role of Imuran in SLE have shown that it has modest effects on serious lupus but has the advantage of reducing steroid requirements. Some investigators are studying its use in combination with Cytoxan for kidney disease. I occasionally come across patients who refuse Cytoxan because it is more important

for them not to compromise their chances of having children than it is to dras-

tically reduce their risk of dialysis. Other patients choose Imuran because they are concerned about the carcinogenicity of alkylating agents.

Imuran ends up being used frequently as a compromise between potent che-

motherapies and an ongoing requirement for high doses of oral steroids. Imuran

is generally well tolerated; about 15 to 20 percent of patients have some stomach upset, which can be managed by dividing the doses or lowering them. Imuran

does not alter fertility, and although it is not without risk, thousands of kidney transplant patients have had normal children while taking the drug (Chapter 30).