The Lupus Book: A Guide for Patients and Their Families, Third Edition (9 page)

sionally
worsen
the disease process in humans.

Until 1989, an amino acid dietary supplement known as
L-tryptophan
was commonly taken to help induce sleep. Amino acids are the building blocks of

proteins. L-tryptophan was removed from the market when it was associated

with the development of a scleroderma-like disorder known as
eosinophilic

myalgic syndrome
, or EMS. The 1989 EMS epidemic was traced to impurities in the manufacture of L-tryptophan, but sporadic cases of a closely related disorder called
eosinophilic fasciitis
had appeared over a 20-year period. It turns out that some cases of EMS or eosinophilic fasciitis may be related to excessive L-tryptophan ingestion in patients who metabolize the drug through an uncommon chemical pathway, which provokes an autoimmune response.

Another amino acid,
L-canavanine
, is present in all legumes but highly concentrated in alfalfa sprouts. Immunologic testing has established that this amino acid is capable of causing or aggravating autoimmune responses (see Chapter

24 for more details). I generally advise my lupus patients to avoid alfalfa sprouts but in general do not limit the intake of legumes.

A polyunsaturated fat, eicosapentaenoic acid, is a major constituent of
fish
oil
. Diets enriched in this chemical ameliorate human rheumatoid arthritis and seem to help animals with lupus. But conflicting results were found when fish

oil capsules were administered to humans with SLE.

[46]

What Causes Lupus?

One group has suggested that an autoantibody called anti-Sm (see Chapter

6), which is found in 20 to 30 percent of patients with SLE, may react with

certain plant proteins in laboratory tests. This interaction theoretically suggests that this autoantibody may be able to make human lupus worse, but it has not

yet been studied.

WHAT ABOUT SUN EXPOSURE OR RADIATION?

Although correlations between diet and lupus remain ambiguous, there is a

strong connection between the disease and the sun’s rays. The sun emits ultra-

violet radiation in three bands known as A, B, and C. The first two, ultraviolet A (UVA) and ultraviolet B (UVB), are important for lupus patients. Some scientists have suggested that when these bands of ultraviolet light hit the skin, they may damage superficial deposits of DNA, which are the body’s building

blocks. This results in the release of by-products that induce the formation of anti-DNA, which is known to damage body tissues.

Other mechanisms, some involving altered apoptosis affected by sunlight in

patients with autoantibodies known as anti-Ro (see Chapter 6), might also be

harmful. The binding of these antibodies to skin cells accelerates or turns on

the disease process. But not all light may be bad. For example, UVA light

treatments, which generally make lupus (e.g., UVA-1) patients worse, are given

to patients with psoriasis. Certain subbands of light seem to reduce inflamma-

tion. The role of sunlight and sun protection in lupus is discussed in detail in Chapter 24.

Cancer patients are frequently given radiation therapy. Despite some concerns

that lupus patients could have their disease flare up when they receive radiation, this occurs very rarely almost entirely in individuals with a scleroderma overlap.

WHY DO LUPUS PATIENTS FEEL WORSE

WHEN THEY HAVE A COLD?

Individuals who carry the lupus ‘‘gene’’ can have the process turned on by a

virus or bacteria. Some of the viruses implicated in SLE causation have fancy

names; they include myxoviruses, reoviruses, measles, rubella, parainfluenza,

mumps, Epstein-Barr, and type C onco- or retroviruses. The evidence for this

stems from the finding of elevated levels of viral antibodies in certain patients, virus particles in lupus tissue, and documentation that microbes can mimic foreign substances or antigens that turn on autoimmunity. Moreover, rats injected

with certain bacterial proteins develop a rheumatoid-like arthritis. Therefore, it is easy to see how patients with autoimmune disease can experience flareups

when they develop infections. Proteins made by the infectious agents may also

Environmental Villains

[47]

be found in the blood or tissue of autoimmune patients and document the pres-

ence of infection.

‘‘LUPUS CLUSTERS’’: HAS THERE EVER BEEN AN

EPIDEMIC OF LUPUS?

Since up to one woman in 500 has SLE, one might think that if several people

in a neighborhood had the disease, this would constitute a ‘‘lupus cluster,’’ or perhaps even an epidemic. Indeed, such clusters have been purported to occur

in Moorpark, California; Newtown, Georgia; Boston, and in Nogales and Tuc-

son, Arizona. Environmental pollution has been held to be the inciting source.

However, careful scrutiny has shown that none of the claimed clusters actually

exist. Several factors were responsible for these claims: (1) autoantibodies

among related family members carrying lupus genes, (2) occurrences in com-

munities with large minority populations and greater than usual lupus preva-

lences, (3) media advertising by litigation attorneys trying to suggest that some-body living in a neighborhood who feels unwell may have lupus, (4)

well-meaning family doctors labeling a patient with a positive ANA as having

lupus which was not confirmed by a rheumatologist. Lupus clusters may exist;

however, none has yet been confirmed using accepted field-testing methods.

IS LUPUS CONTAGIOUS?

Beyond the issue of genetic transmission, there is no evidence that lupus can

be spread from one individual to another. No cases of ‘‘contagious’’ lupus have ever been reported. However, several instances have been documented in which

laboratory technicians handling large amounts of lupus blood samples developed

positive ANAs and antibodies to lymphocytes without developing SLE. Similar

claims concerning household contact between lupus patients and nonrelated in-

dividuals or the pets of lupus patients may be valid, but these reports are also not associated with the presence of disease.

Summing Up

Our environment is full of chemicals and microbes that can induce or aggravate

autoimmune diseases. In addition, sun exposure plays a role, as does diet. Only a small percentage of individuals exposed to ‘‘lupogenic’’ materials develop the disease, which suggests that certain genetic signatures greatly augment risk factors. The amount of lupogenic material necessary to bring on the disease is not known, and not everyone at risk becomes symptomatic. It is important to emphasize that if you are genetically at risk, prudent precautions to avoid unnec-

[48]

What Causes Lupus?

essary exposure are advised, but you should try not to become so fearful of the environment that you cannot function socially. While family members may share

certain genetic material with a lupus patient, our research confirms that lupus cannot be spread from one person to another, as in infectious diseases. It is

important to keep in mind that both genetics and the environment play a role

in inducing, easing, aggravating, or accelerating lupus.

9

Drugs That May Cause Lupus

or Produce Flareups

In 1945, Byron Hoffman reported that sulfa-containing antibiotics might pro-

voke a lupus-like syndrome. Since that time, more than seventy agents have

been reported to bring on the disease. In addition, the administration of certain drugs has been found to cause a preexisting lupus to flare up. This chapter

reviews the mechanisms by which this process may occur. It also looks at pub-

lished data on the most problematic drugs and discusses the treatment of drug-

induced lupus.

DRUGS THAT EXACERBATE LUPUS

Most drugs that cause preexisting disease to flare up do so by acting as sun

sensitizing agents or by promoting hypersensitivity or allergy-like reactions.

Antibiotics

Susan was 20 years old when she began complaining of severe burning on

urination. She had been diagnosed with SLE 6 months earlier and had mild

disease, in the form of skin rashes and joint aches. Susan’s lupus was under

excellent control with Naprosyn and Plaquenil. She decided to call her

gynecologist about a bladder problem and was diagnosed as having a uri-

nary tract infection. Her physician placed her on Bactrim DS. Within 2

days, her mild cheek flush had become a bright red rash on her face, fore-

arms, and neck. Her wrist and knees swelled up and she developed a tem-

perature of 102ЊF. When she saw her rheumatologist the next day, he ob-

served not only these physical signs but also that her white blood cell count

and hemoglobin had substantially decreased. He stopped the Bactrim and

put her on 40 milligrams of prednisone daily. She gradually responded to

this regimen and managed to discontinue steroids within 2 weeks. She felt

fine thereafter.

[50]

What Causes Lupus?

Like Susan, a disproportionate number of patients with lupus cannot tolerate

arylamine
sulfa
derivatives. Sulfonamide-based antibiotics (e.g., sulfamethoxa-zole) are potent sun sensitizers. Drugs in this class include such commonly used brands as Bactrim, Septra, and Gantrisin, which are frequently prescribed to

young women with urinary tract infections. Some antidiabetic drugs (e.g., Ori-

nase), sulfasalazine (called Azulfidine, used for ulcerative colitis and rheumatoid arthritis), and diuretics also contain sulfa. Even though these non-arylamine

sulfas are generally well tolerated, it is best to be cautious about using these drugs. A greater than expected number of lupus patients are unable to tolerate

penicillin
, and some
tetracyclines
are mildly sun-sensitizing. Patients given min-ocycline for rheumatoid-like arthritis may flare if they really have lupus. I tend to avoid sulfa drugs unless no alternative treatment is available but do not restrict the use of any other antibiotics.

Nonsteroidal Anti-inflammatory Drugs (NSAIDs)

Nonsteroidal anti-inflammatory drugs (NSAIDs) are most frequently used to

treat aches and pains, fevers, or pleurisy (see Chapter 26). NSAIDs run the

gamut in potency from aspirin and ibuprofen to indomethacin. Though not FDA-

approved for use in treating lupus, at least one of these preparations is used by over 90 percent of lupus patients at some point during their disease course.

Rarely, lupus patients taking ibuprofen (Advil, Motrin) complain of high fe-

vers, mental confusion, and a stiff neck. This reversible noninfectious (aseptic) meningitis is practically seen only in SLE patients. Aseptic meningitis has been reported to occur with more than ten NSAIDs, but 90 percent of the published

cases implicate ibuprofen. Despite this, an individual’s risk for aseptic meningitis with ibuprofen is probably less than one in a thousand. To be on the safe side, I tend to use other NSAIDs in treating lupus patients.

Certain NSAIDs sensitize users to sunlight, and toxic reactions have been

reported in some cases. Extra care in prescribing piroxicam (Feldene). Although no longer commercially available in the United States, compounded phenylbutazone has been reported to cause a hypersensitivity reaction in lupus patients, which may lead to severe flareups.

Hormones

Birth control pills in young women and estrogen replacement therapies after

menopause as well as other hormonal preparations are frequently prescribed to

lupus patients. Their use has been controversial, and this complex topic is covered in Chapter 17.

Drugs That May Cause Lupus or Produce Flareups

[51]

DRUG-INDUCED LUPUS ERYTHEMATOSUS (DILE)

Approximately 15,000 to 20,000 new cases of prescription drug-induced lupus

are reported annually in the United States. First identified shortly after the introduction of hydralazine (Apresoline) for hypertension in 1951, DILE is usually a benign, self-limited process. Although more than seventy agents have been

implicated as inciters of drug-induced autoimmunity, most cases are associated

with three products whose use has been decreasing: hydralazine, procainamide

(Pronestyl), and methyldopa (Aldomet). If isoniazid (INH), chlorpromazine

(thorazine), TNF blockers, and D-penicillamine are added to the list, 99 percent of all clinically relevant cases can be accounted for. A more complete list of

these drugs is given in Table 9.1.

Epidemiology of Drug-Induced Lupus

Three principal features distinguish DILE from SLE. First, unlike SLE, DILE

affects the same number of men as it does women. Second, DILE is very rare

among African Americans in the United States. Also, the average age of onset

for DILE is 60, as opposed to the 20-to-40 age group typical for SLE.

Table 9.1.
Drugs Implicated in Provoking Lupus Erythematosus

1. Drugs proven to induce clinical lupus in at least 1 out of 1000 users

Hydralazine (Apresoline)

Methyldopa (Aldomet)

Procainamide (Pronestyl)

D-penicillamine

TNF Blockers (Remicade, Humira,

Enbrel)

2. Drugs proven to induce clinical lupus in at least 1 out of 10,000 users

Isoniazid (INH)

Phenothiazines (including Thorazine)

Sulfasalazine (Azulfidine)

Quinidine

Carbamazepine (Tegretol)

Griseofulvin (Fulvicin)

3. Drugs rarely associated with positive ANAs and very rare clinical lupus