The Lupus Book: A Guide for Patients and Their Families, Third Edition (41 page)

must be discontinued. In my opinion, Plaquenil is better tolerated and more

effective than generic hydroxychloroquine. Before giving up on the drug, pa-

tients taking the generic preparation should try brand name Plaquenil. Chloro-

quine has the same side effects as Plaquenil, but they occur more often. In

addition, the drug may sometimes (less than 1 percent of the time) cause hair

to gray, damage muscle cells, and lower blood counts. These reactions are al-

most unheard of with Plaquenil. Long-term use of both drugs can cause black

or blue skin pigment deposits. Quinacrine produces mild abdominal cramps and

diarrhea in up to 30 percent of patients; this is managed by taking Pepto-Bismol.

Also, there may be a reversible yellowing of the skin in 40 percent of patients taking at least 100 milligrams daily (lower doses rarely cause skin changes). As a mild ‘‘upper,’’ quinacrine is capable of inducing a toxic psychosis with manic

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The Management of Lupus Erythematosus

behavior in 1 of 500 patients, but that disappears with its discontinuation. Blood counts should be monitored, although the risk of problems in the absence of an

allergic rash is 1 per 30,000. If an allergic rash breaks out, therapy should cease immediately.

What About the Eyes?

My pet peeve is that too many lupus patients have been frightened away from

antimalarials by doctors who warn them about potential eye toxicity. First of

all, quinacrine, for one, does not affect the eyes in currently used doses. Second, eye toxicity caused by Plaquenil is extremely unusual. Melanin (normal skin

pigment) deposits at the back of the eye, or retina, can be promoted by anti-

malarials, causing blind spots (called scotomas), since we cannot see through

melanin. The risk of this occurring with Plaquenil is 3 percent with 10 years of continuous use, or in 1 patient out of 30. Patients tell me all the time that after a month on the drug, they have blurred vision. They are not making it up;

steroids can not only cause blurred vision but also can lead to cataracts and

glaucoma. Also, many patients started on Plaquenil are also on steroids. If a

lupus patient sees a retina specialist every 6 months, the deposits will be noticed before they cause any symptoms, and if the drug is stopped, the deposits will

disappear in weeks.
The risk of permanent eye damage from Plaquenil with

normal kidney function in any patient who has had eye examinations every 6

months and who has taken the drug in doses of less than 5 mg per kg a day

for less than 10 years is less than 1 in 100,000
.

On the other hand, chloroquine can cause permanent eye damage and must

be used very carefully. The risk of eye toxicity with chloroquine is 10 percent after 10 years, and the changes it causes are not necessarily reversible. All

patients on chloroquine should be examined every 3 months. Additionally,

cloudy vision caused by swelling of the front of the eye (called corneal edema) is common with chloroquine and rare with Plaquenil. It is usually so mild that

most patients continue to take the drug, and it goes away once these agents are stopped. With our increasingly sophisticated technologies, ophthalmologists are coming up with newer methods to evaluate retinal function. Many university

medical centers are trying these technologies out on lupus patients who take

antimalarials. The bottom line is that many subtle abnormalities of no conse-

quence are noted in reports, and this may serve to scare patients, unnecessarily, away from antimalarials. Often, these subtle abnormalities are not found when

the tests are readministered months later. Eye changes from Plaquenil take many years to develop, and any risk of damage disappears when the drug is stopped.

IS CORTISONE REALLY NEEDED?

Steroids are the most effective and most misunderstood treatment for lupus.

They are also the most used and abused therapeutic interventions for the disease.

Big Guns and Magic Bullets: Disease-Modifying Drugs

[219]

Simply stated, if organ-threatening disease is present and steroids are not prescribed, the patient usually loses function in that organ. If mild disease activity is present, other therapeutic alternatives with or without steroids are available, but many physicians have little experience in using these alternatives and tend to overuse steroids. How did things get this way?

Let us begin our story in 1855, when Thomas Addison noticed that the adrenal

gland above the kidney had physiologic functions. Even though it was soon

shown that the hypothalamus and pituitary controlled some of these functions,

the adrenal gland’s ability to act independently on occasion excited interest in this area. Tissue from adrenal cortex extracts was broken down and analyzed.

By 1942, the structures of 28 steroids from the adrenal cortex had been eluci-

dated. Ultimately, five of them were shown to be biologically active: in other

words, they did something. Enter Phillip Hench, the only rheumatologist ever

to win the Nobel Prize in Medicine. As early as 1929, he had observed that

patients with rheumatoid arthritis went into remission during pregnancy, and he speculated that a metabolite was responsible. As soon as Hench became aware

of the ongoing research on the adrenal cortex, he speculated that these steroids might be the ‘‘metabolite’’ he was looking for. In 1949, Dr. Hench and his

colleagues at the Mayo Clinic gave cortisone to a patient with rheumatoid ar-

thritis, who had a dramatic response. Numerous steroid preparations became

available during the 1950s, and rheumatologists eventually determined—largely

as a result of trial and error—which preparations should be used and in what

amounts for inflammation. Lupus patients first received cortisone in 1950, and

they have been using its derivatives ever since.

How Do Steroids Work?

Steroids are hormones that play an important role in the body regulating
physiologic
functions. Doses above and beyond what the body makes have different actions, termed
pharmacologic
functions. The pharmacologic activities of steroids include stabilizing cells so that they are less likely to become involved in inflammatory processes. Steroids block numerous chemical pathways. They also

decrease the number of circulating lymphocytes—the white blood cells respon-

sible for immunologic memory.

Within the brain lies the hypothalamus, an organ that makes a chemical called

corticotropin-releasing hormone (CRH)
. This hormone travels downstream a short distance to the pituitary gland and induces the pituitary to make
adrenocorticotropic hormone (ACTH)
. The ACTH then stimulates the adrenal cortex to make steroids. This network, known as the
hypothalamic-pituitary-adrenal
axis
, governs how much steroid our body makes. An average adrenal gland makes the equivalent of 7.5 milligrams of prednisone a day. Through a negative

feedback loop, patients taking more than 7.5 milligrams of prednisone daily

prevent the release of CRH and ACTH, which stops the adrenal gland from

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The Management of Lupus Erythematosus

making steroids. This is why steroids cannot be discontinued suddenly; it takes months for the hypothalamic-pituitary-adrenal axis to return to normal after steroid doses drop below 7.5 milligrams of prednisone a day. Adrenal insufficiency, also called Addison’s disease (named after the discoverer of the adrenal cortex), is a potentially serious condition characterized by a critical shortage of steroids in the body. Dosages of prednisone in the 10- to 15-milligram range usually do

not completely shut down the adrenal gland but make it sluggish; on this dosage, the adrenal cortex may make only 2 to 5 milligrams instead of 7.5 milligrams

a day. Taking more than 15 milligrams of prednisone for a month usually shuts

off the hypothalamic-pituitary-adrenal axis and no steroid is made by the body.

Figure 9 (in Chapter 17) illustrates these concepts.

Why Are There So Many Different Kinds of Steroids?

In addition to the numerous natural steroid derivatives, specially engineered

synthetic steroids have become available. The most important preparations are

listed in Table 27.1. Prednisone is the most commonly used oral preparation,

followed by prednisolone and dexamethasone. Prednisolone is almost the same

as prednisone, but some patients tolerate it better and it can be the steroid of choice for patients with liver disease. These agents are usually given once a

day, but in the presence of acute inflammation they are metabolized (or used

up) more quickly and must be given 2 to 4 times a day. Dexamethasone enters

the central nervous system better than prednisone or prednisolone and is the

steroid of choice for neurosurgeons treating postoperative swelling. It has a

longer duration of action: dexamethasone is prescribed no more often than once

a day and sometimes just several times a week. A newer steroid preparation,

deflazacort, is available in Europe and Mexico (as Calcort) and may have fewer

side effects than the compounds listed above, but its absorption is variable.

Budesonide (Entocort), a steroid absorbed by mucosal surface has recently been

approved for use in inflammatory bowel disease, but has not been studied in

lupus.

Oral steroids can be taken daily or on an alternate-day schedule. Taking twice

the dose every other day has the theoretical advantage of decreasing the risk of infection and should only be considered once a patient’s clinical condition is

stabilized.

Local steroids
are used for skin involvement of lupus. They are of two types, fluorinated and nonfluorinated, and they are available in several forms: creams, gels, solutions, ointments, and occlusive dressings. Fluorinated steroids are very potent; if used too often, they cause skin thinning and atrophy. They should

never be applied to the face continuously for more than 2 weeks at a time.

Nonfluorinated steroids are very safe but much weaker, can be purchased with-

out a prescription (e.g., Cortaid), and are used for facial rashes. The most ef-Big Guns and Magic Bullets: Disease-Modifying Drugs

[221]

Table 27.1.
Some Oral, Injectable, and Intravenous Steroid Preparations
Equivalent

Hormone Preparation

in Milligrams

Comment

Cortisone acetate (Cortone)

25

Very short-acting; must be given

every 6 hours

Hydrocortisone (Hydrocortone;

20

Short-acting; works within minutes

Solu-Cortef)

Deflazacort

6

May be safer for bones and stom-

ach lining; not available in the

United States

Prednisone (Orasone; Deltra)

5

Takes 2 to 4 hours to work and

lasts 18 hours; most popular

preparation

Prednisolone (Hydeltra)

4

Almost the same as prednisone;

preferred if liver disease is pres-

ent

Methylprednisolone (Medrol)

4

Similar to prednisone and predni-

solone; used intravenously as

Solumedrol

Triamcinolone (Aristocort;

4

Popular as an injection and as a

Kenalog)

dermatologic preparation for

rashes

Dexamethasone (Decadron)

0.75

Lasts 24 to 36 hours; good pene-

tration in the central nervous

system

Betamethasone (Celestone)

0.6

Popular as an injection and for

rashes; matures fetal lungs in

pregnant patients with lupus at

risk for delivering prematurely

Budesonide (Entocort) EC

1.8

Used for asthma and allergies as

inhalers; new oral preparation

fective topical salves are ointments. Though oily and gloppy, they are 80 percent absorbed. Creams are the best tolerated. They dry the skin but are only 20

percent absorbed and are therefore less effective than ointments. A dermatologist can also deliver steroids into the skin by injection, or into lesions. This highly effective technique means using thin needles and injecting discoid lesions and

areas of hair loss with steroid solutions.

Pulse steroids
are administered in high doses intravenously. Examples include methylprednisolone (Solumedrol) and dexamethasone (Decadron). These are

given in dosages equivalent to 1000 milligrams of prednisone per day to achieve high anti-inflammatory levels in critically ill patients. The effect of pulse steroids often lasts for weeks. Patients who cannot tolerate oral steroids may occasionally be given monthly pulse steroids. Hospitalized patients who cannot take any

medications by mouth (e.g., after surgery) are given intravenous steroids in

lower doses that simulate a corresponding oral dosage.

Steroids can also be given
intraarticularly
or
intramuscularly
—in other

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The Management of Lupus Erythematosus

words, into a joint or muscle. Steroids injected into joints consist of preparations that have more of a water or oil base. Water-based preparations do not stay in

the joint and quickly enter the bloodstream. These include hydrocortisone, dex-

amethasone, and methylprednisolone (e.g., Hydeltra-TBA and Depo-Medrol).

Thicker preparations stay in joints for weeks (betamethasone or triamcinolone;

Celestone, Kenalog, Aristocort), and one triamcinolone preparation, Aristospan, never really enters the bloodstream and stays in a joint for months. The choice of steroid depends on the patient’s clinical picture: If the problem is limited to one joint, Aristospan is advised; but if a patient complains especially of knee pain but also hurts all over, Kenalog is used. Aristospan is not widely prescribed because of its expense—it costs five times more than some other brands. I am