The Lupus Book: A Guide for Patients and Their Families, Third Edition (32 page)

Summing Up

Lupus in newborns is very rare. Cutaneous neonatal lupus disappears sponta-

neously. Sometimes, the presence of congenital heart block may require per-

manent treatment with a pacemaker or medication that controls the heart’s

rhythm, but this condition usually has a favorable outcome. Recent reports sug-

gest that a minority of neonatal lupus patients may develop lupus during ado-

lescence. Childhood lupus is frequently serious and organ-threatening. Aggres-

sive management increases the chances for a good quality of life during

adulthood. The teen years are fraught with compliance problems and psycho-

social complications that require special attention. For those who develop symptoms of SLE after age 60, drug-induced lupus and other forms of inflammatory

arthritis must be ruled out first as possible culprits. Senior citizens with lupus usually have mild, nonprogressive disease.

23

Is It Really Lupus?

DIFFERENTIAL DIAGNOSIS AND DISEASE ASSOCIATIONS

Ten million Americans have a positive lupus blood test, but probably less than

one million have lupus. Many people fulfill one, two, or three American College of Rheumatology (ACR) criteria for SLE but lack the requisite four criteria

reviewed in Chapter 2. What do they have? Are other autoimmune diseases

present? And while we’re on the subject, are there any other disorders that lupus patients tend to get or are spared from? When your physician considers the

presence of other similar diseases, this decision process is called
differential
diagnosis
. This chapter will put these issues into a practical, logical perspective.

HOW CAN WE TELL IF IT’S LUPUS?

If a person’s rheumatic complaints do not fulfill the criteria for systemic lupus or any other rheumatic disease, what is the problem and how can the doctor tell for sure? First of all, cutaneous (discoid) lupus and drug-induced lupus have

definitions separate from those for SLE, which are reviewed in Chapter 2. A

host of patients with various forms of lupus do not always fulfill the ACR

criteria even when the diagnosis is self-evident. For example, evidence from

biopsies of the kidney will provide clear-cut proof of lupus if the kidney is

affected by the disease.

The average person with symptoms of lupus can take 1 or 2 years to be

diagnosed because the full-blown disease is not present. We call this evolution by its Latin term,
forme fruste lupus
. Similarly, a small percentage of patients with
palindromic rheumatism
develop SLE over a 5- to 10-year period. A pal-indrome is a word or phrase that is the same spelled forward or backward, such

as ‘‘Madam, I’m Adam’’ or ‘‘Dad.’’ Patients with palindromic rheumatism can

be fine one day and have rashes or swollen knees the next. Three days later

they are fine, with no hint of there ever having been a problem. These flareups are cyclical and blood tests are often negative. Half of these patients go on to develop rheumatoid arthritis, but some become patients with lupus.

Is It Really Lupus?

[171]

What if lupus-like symptoms have appeared for years? Many patients have

nonspecific complaints of fatigue or aching along with a positive ANA. Most

immunology laboratories have ANA panels that can be performed. As discussed

in Chapter 11, certain autoantibodies are simply not seen in healthy people. If any patient seeks my consultation and has any of the following abnormal tests

with the above complaints, I know that a real immunologic disorder exists: anti-DNA, anti-Sm, anti-RNP, C3 complement, C4 complement, high Westergren

sedimentation rate, positive rheumatoid factor, high CPK, false-positive syphilis test, anticardiolipin antibody, antineuronal antibody, antihistone antibody, antiribosomal P antibody, anti-Ro (SSA), anti-La (SSB), or a broad gamma globulin

band on serum protein electrophoresis.
In questionable situations, the presence
of these antibodies must be confirmed by a second, independent laboratory
.

Some of the tests are difficult to perform and occasionally false-positive results are obtained.

What can a doctor do to confirm the disease in a suspected lupus candidate

who has a positive ANA, lupus-like symptoms, and negative tests for other

antibodies? If joint or muscle complaints are prominent, lupus can be distin-

guished from fibromyalgia (discussed below) by a
bone scan
. Lupus can inflame the joints; fibromyalgia does not. In lupus, a bone scan may pick up increased

blood flow to the joints as well as bone and muscle inflammation, whereas

fibromyalgia will produce a normal bone scan. Inflammatory lupus arthritis re-

sponds to a group of medications different from those used in noninflammatory

fibrositic arthralgias. Another useful procedure is the
lupus band test
. Its applications are reviewed in detail in Chapter 12, but in essence the presence of a

specific combination of immune reactants at the junction of the dermis and

epidermis under the skin is seen only in SLE even if there is no rash. Finally, half of all first-degree relatives (parents, siblings, or children) of SLE patients demonstrate a positive ANA on blood testing even though only 25 percent will

ever develop an autoimmune disease and less than 10 percent will become lupus

patients. Nonspecific symptoms in these individuals should be followed closely.

The biggest mistake a doctor can make is to classify a patient as having SLE

when he or she doesn’t have the disease. Occasionally, I come across what I

can only call a ‘‘lupus wanabee.’’ These individuals are convinced they have

the disease on the basis of reading and talking to their friends. It is very difficult to convince them that they don’t. Some want to be diagnosed as having lupus

perhaps for psychological reasons: they want loved ones to pay more attention

to them or feel sorry for them, or they want to prove to family members that

they are not ‘‘crazy.’’ Some may eventually find a doctor who will agree with

their self-diagnosis and treat them. But this is not the sort of illness that can be placated with innocuous and harmless treatments. The therapy for SLE involves

toxic, expensive, and time-consuming treatment. Disease-modifying therapies

(anything other than an NSAID) should never be given unless a firm diagnosis

[172]

Where and How Can the Body Be Affected by Lupus?

has been made or an organ-threatening complication is clinically evident. La-

beling a patient with SLE who does not have the disease can make it difficult

for him or her to obtain gainful employment, health insurance, or life insurance and can mean lifelong stigmatization.

WHAT IS ANA-NEGATIVE LUPUS?

Heidi was sure she had lupus even though six different doctors had obtained

six different negative ANAs in six different labs. She had a butterfly rash

on her cheeks, was tired and achy, and had a checkerboard mottling (called

livedo reticularis) on her legs. Finally, the third rheumatologist she saw

was sympathetic to her predicament. Even though her blood chemistry pro-

files, chest x-ray, electrocardiogram, sedimentation rate, CPK, anti-DNA,

and complement levels were negative or normal, Dr. Schwartz obtained

additional blood for testing. Heidi had a positive anticardiolipin antibody

and a false-positive syphilis serology. These antibodies are seen in 20 per-

cent of discoid lupus patients and are associated with livedo reticularis. Dr.

Schwartz also referred Heidi to a dermatologist, who did a lupus band test

on her cheek rash; it came back positive. A bone scan showed increased

blood flow to her hands and feet, suggesting an inflammatory arthritis. Dr.

Schwartz diagnosed Heidi as having ANA-negative lupus since she fulfilled

the criteria by having arthritis, sun sensitivity, discoid rashes, and a false-

positive syphilis serology. Three years later, Heidi’s ANA blood test be-

came postive.

Until 1985, 10 percent of all lupus patients had a negative ANA test. The

introduction of improved testing material for performing the ANA test has de-

creased this percentage to 3 percent. Between 1980 and 1989, my office treated

464 patients who fulfilled the ACR criteria for lupus; seventeen of them were

ANA-negative. In analyzing this group, we found that patients fell into four

basic categories. One-third had antiphospholipid antibodies and one-third had

biopsy-documented kidney lupus. Of the remaining third, half ultimately became

ANA-positive. The last group had advanced disease; prolonged treatment with

steroids and chemotherapy made their ANA disappear. A variety of rarer causes

of ANA-negative lupus exist, such as the presence of anti-Ro (SSA) antibody

without ANA. Nevertheless, if a patient does not fall into any of these four

categories, some of the lupus-related or lupus-mimicking disorders discussed in this chapter might be the culprit.

WHAT IS AN UNDIFFERENTIATED CONNECTIVE TISSUE

DISEASE (UCTD)?

Many patients feel ill, have a positive ANA, and a couple of swollen joints, but do not fulfill the American College of Rheumatology (ACR) criteria for SLE.

Is It Really Lupus?

[173]

Their doctor says, ‘‘You don’t have lupus, but have a collagen disorder of some kind.’’ Over the last few years, rheumatologists have examined this group of

patients and followed them over a period of years. The insights garnered from

these observations allow us to finally clarify what to call patients who have an

‘‘almost lupus’’ condition. Several years ago, the University of Utah enlisted

the cooperation of 10 academic centers to identify patients who had autoimmune

features, early disease, and did not fulfill criteria for lupus, rheumatoid arthritis, scleroderma, or any other disorder. 410 patients labeled as having ‘‘UCTD’’

were enrolled. The outcomes after 5 years among the group were no disease

(18 percent), lupus (14 percent), scleroderma (5 percent), rheumatoid arthritis (4 percent), primary Raynaud’s (18 percent), polymyositis (1 percent), mixed

connective tissue disease (4 percent), still UCTD (36 percent).

In other words, although many patients evolve another rheumatic disease,

there are probably a million Americans with UCTD. Its features include rashes,

swollen joints, fatigue, fevers, swollen glands, Raynaud’s, pleurisy, high sedimentation rates, and a positive ANA. Rarely organ threatening and less serious

than SLE, most UCTD patients are managed with nonsteroidal anti-

inflammatory drugs (e.g., ibuprofen), hydroxychloroquine (Plaquenil), and oc-

casionally low doses of steroids or methotrexate. It’s important to remember

that these classifications are used by doctors and insurance companies for cat-

egorization purposes, estimates of disease prevalences, and as criteria for en-

rollment in research studies. Your doctor needs to treat you as a unique indi-

vidual with a specific set of symptoms, signs, and laboratory findings whose

management is tailored to best improve the way you feel and decrease potential

risks.

WHAT NONRHEUMATIC DISORDERS MIMIC LUPUS?

Many diseases mimic SLE; they fall into several broad general categories. For

example, almost every disorder of
hormonal imbalance
—from thyroid abnormalities or pregnancy to evolving menopause to diabetes—can appear with

symptoms such as fatigue, aching, and feeling feverish that may lead the doctor to order lupus blood tests.
Blood or tissue malignancies
ranging from lymphoma to breast cancer can give positive ANAs and induce constitutional complaints.

Infectious processes
, especially from viruses, are associated with positive ANAs as well as lupus-like symptoms. All these possibilities should be ruled out before a diagnosis of lupus is made. Neurologic disorders, such as multiple sclerosis

or myasthenia gravis, can coexist with or be difficult to differentiate from SLE.

Finally, the presence of
substance abuse
,
malnutrition
,
primary psychiatric disorders
, or
allergies
need to be considered.

[174]

Where and How Can the Body Be Affected by Lupus?

HOW CAN WE DIFFERENTIATE LUPUS

FROM OTHER RHEUMATIC DISEASES?

Especially during the first year of symptoms, rheumatoid arthritis, scleroderma, mixed connective tissue disease, inflammatory myositis, and other forms of systemic vasculitis can be very difficult to differentiate from each other. It is not usually critical to make the diagnosis at first, since steroids and immune-suppressive therapy can be used to treat critical complications of any of these disorders.

Rheumatoid arthritis
(RA), which afflicts 4 million Americans, is the only autoimmune rheumatic disease that is more common than lupus. In its initial

presentation, RA can be difficult to tell from lupus; but within several months, the diagnosis usually becomes obvious. One-quarter, or 25 percent, of patients

with lupus have a positive rheumatoid factor and 25 percent with rheumatoid

arthritis have a positive ANA. Antibodies to cyclic citrullinated peptide is another antibody which, if present, is quite specific for RA. The hallmark of RA

is an autoimmune reaction in the synovium, the tissue lining the joint. It is

uncommonly complicated by systemic organ involvement, and deforming rheu-

matoid joint disease causes erosions (actual bone destruction) that resemble a