The Lupus Book: A Guide for Patients and Their Families, Third Edition (3 page)

organs after the first 5 years of having the disease.

On the other hand, involvement of the heart, lungs, kidneys, or the presence

of liver or serious blood abnormalities indicates that an
organ-threatening disease
is at work. This may become life-threatening if the patient is not treated with corticosteroids or other interventions. Another 35 percent of all lupus patients fall into this category.

Approximately 10 percent of patients with lupus develop the disease for the

first time from a prescription drug and have what is called
drug-induced lupus
erythematosus
. The drug-induced form is usually less severe than SLE and will disappear after the patient stops taking the particular drug. Occasionally, however, short courses of lupus medication are required for these patients.

Perhaps 5 to 10 percent of the individuals who fulfill the ACR criteria for

SLE may also fulfill the ACR criteria for another autoimmune disorder such as

scleroderma (tight skin with arthritis), dermato-/polymyositis (inflammation of the muscles), or rheumatoid arthritis (a potentially deforming joint inflammation). These patients are said to have
mixed connective tissue disease (MCTD)
if they possess a particular autoantibody (anti-RNP). If they do not, the patients are said to have a
crossover
or
overlap syndrome
. This classification system is summarized in Table 2.2. Finally, a group of patients have lupus-associated

symptoms, signs, or laboratory abnormalities but do not fulfill ACR criteria for any rheumatic disorders. They have an
undifferentiated connective tissue disease
(UCTD)
, which is reviewed in Chapter 23.

WHAT’S IN STORE FOR THE READER

Don’t be overwhelmed by all these facts and figures. This chapter has simply

provided you with an overview of the book, and all the points mentioned will

be discussed again in more detail in later chapters.

We close this first part with a brief historical background and an overview

about who gets lupus (Chapters 3 and 4). In Part II, the heart of the book, we

look at the immune system and how it relates to SLE (Chapters 5 to 9). We

Table 2.2.
Types of Lupus Erythematosus

Cutaneous (discoid) lupus erythematosus (10%)

Systemic lupus erythematosus (70%)

Non-organ-threatening disease (35%)

Organ-threatening disease (35%)

Drug-induced lupus erythematosus (10%)

Crossover or overlap syndrome and/or MCTD (10%)

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Introduction and Definitions

discuss the manifestation of the disease in different areas of the body, such as the joints, the gastrointestinal system, the kidneys, and other organs (Chapters 12 to 20) and talk about the role of blood testing (Chapter 11). I explain the

necessary clinical and diagnostic studies (x-rays, scans, etc.) that are used in assessing lupus (Chapters 12 to 20), as well as problems unique to specific

circumstances, such as pregnancy, infection, and lupus in children and the el-

derly (Chapters 22, 23, 29, and 30). Next, we take up the treatment of lupus—

the physical measures we can take to combat the disease, the various medica-

tions, and the emotional support you will need from your family and physician

(Chapters 24 to 28). Finally, future directions and advances soon to take place are detailed in Chapters 31 and 32.

3

The History of Lupus

‘‘Lupus’’ is the Latin word for ‘‘wolf,’’ and it is common medical lore that the

‘‘butterfly rash’’ seen on the cheeks of many lupus patients is so similar to the facial markings of a wolf that our ancestors chose the name for this reason. The technical name for the disease we know of as lupus—lupus erythematosus—

was first applied to a skin disorder by a Frenchman, Pierre Cazenave, in 1851,

though descriptive articles detailing the condition date back to Hippocrates in ancient Greece.

Accurate treatises on the skin disorders associated with lupus were published

in the mid-1800s by the great Viennese physicians Ferdinand von Hebra and

his son-in-law Moriz Kaposi (for whom Kaposi’s sarcoma is named). The first

suggestions that the disease could be internal (more than skin deep and affecting the organs of the body) appeared in these writings. However, it was Sir William Osler (the founder of our first real medical internship and residency programs

in the 1890s at Johns Hopkins) who wrote the earliest complete treatises on

lupus erythematosus between 1895 and 1903. In addition to describing such

symptoms as fevers and aching, he clearly showed that the central nervous,

musculoskeletal, pulmonary, and cardiac systems could be part of the disease.

The golden age of pathology in the 1920s and 1930s led to the first detailed

pathologic descriptions of lupus and showed how it affected kidney, heart, and

lung tissues. Early discussions of abnormal blood findings such as anemia (low

red blood cell count or low hemoglobin) and low platelet count (cells that clot blood) appeared during this time. We had to wait until 1941 for the next breakthrough, which took place at Mount Sinai Hospital in New York City. There,

Dr. Paul Klemperer and his colleagues coined the term ‘‘collagen disease’’ on

the basis of their clinical research. Although this term is a misnomer (collagen tissues are not necessarily involved in lupus), the evolution of this line of thinking led to our contemporary classification of lupus as an ‘‘autoimmune disor-

der,’’ based on the presence of ANA and other autoantibodies.

The first arthritis unit with a special interest in lupus was started by Marian Ropes at the Massachusetts General Hospital in Boston in 1932. In those days,

[10]

Introduction and Definitions

no blood test to diagnose lupus was available. In fact, until 1948, there were no effective treatments for lupus except for local skin salves or aspirin. Dr. Ropes observed that half of her patients got better and half of them died during the

first 2 years of treatment. Indirectly, she was classifying her patients into

‘‘organ-threatening’’ and ‘‘non-organ-threatening’’ categories, but in many

cases she had no way short of a tissue biopsy to determine which subset a patient belonged to.

In 1946, a Mayo Clinic pathologist named Malcolm Hargraves performed a

bone marrow examination on a patient and absentmindedly kept a tube from the

procedure in his pocket for several days. In a bone marrow examination, the

physician removes a tissue sample from bone (usually from the sternum or

pelvis, where blood components are made). After finally retrieving the tube,

Hargraves observed a unique cell on his microscope slides, which became

known as the LE cell. Published in 1948, his description of the LE, or lupus

erythematosus, cell was one of the landmark developments in the history of

rheumatology. This cell was representative of the systemic inflammatory pro-

cess; its identification allowed doctors for the first time to diagnose the disease faster and more reliably. Dr. Hargraves and others were quick to show how LE

cells could be looked for in peripheral blood samples and found that 70 to 80

percent of patients with active SLE possessed these cells. At long last, patients with the disease could be readily identified. Researchers were on a roll: in the following year, 1949, another landmark event took place. Dr. Phillip Hench,

another Mayo Clinic physician and the only rheumatologist ever to win the

Nobel Prize in Medicine, demonstrated that a newly discovered hormone known

as cortisone could treat rheumatoid arthritis. This hormone was administered to SLE patients throughout the country, and immediately dramatic lifesaving took

place.

The final chapter of our story evolved during the 1950s, when the concept of

autoimmune disease was formalized and the LE cell was shown to be part of

an antinuclear antibody (or ANA) reaction. This led to the development of other tests for autoantibodies, which enabled researchers to characterize the disease in a more detailed and definitive manner. My mentor, Dr. Edmund Dubois,

amassed an incredible 1000 patients with lupus and was among the first re-

searchers to explore the natural course of the disease and advise how best to

treat it. Also during this time, cancer chemotherapy agents such as nitrogen

mustard were shown to be effective in the management of serious organ-

threatening complications of SLE when used together with corticosteroids.

With this historical context in mind, we now turn our attention to the present

and a discussion of who gets lupus and why.

4

Who Gets Lupus?

Three to five percent of Americans develop an autoimmune disease in their

lifetime if we include thyroiditis and Type I diabetes. How many lupus patients are there in the United States? It is not as easy to answer this question as it might seem. In 1997, the National Arthritis Data Workshop estimated that there

were as few as 239,000 Americans with SLE. These numbers, however, do not

include those patients who have discoid lupus or drug-induced lupus. On the

other hand, the Lupus Foundation of America and the Arthritis Foundation have

suggested that between 500,000 and 1 million Americans have one of the four

forms of lupus (see Table 2.2).

There are several reasons for these discrepancies. First of all, some epide-

miologic (epidemiology is the study of relationships among various factors that determine who gets diseases) surveys assumed that all lupus patients were hospitalized over a 7- to 10-year period and thus gathered their data from hospital discharge diagnoses only. But other groups have shown that less than 50 percent of lupus patients are hospitalized over a 10-year follow-up observation period.

Second, data banks from prepaid health plans such as Kaiser-Permanente can

track outpatient diagnoses but generally include only patients who are insurable and working. Moreover, many physicians do not list lupus as a diagnosis on an

insurance form, since it might result in the policy being canceled or the illness being disclosed to fellow employees. Third, surveys conducted by the Mayo

Clinic include a greater than 95 percent Caucasian population, which does not

reflect the true racial makeup of the United States or of the disease. Also, drug-induced lupus lasts only a few weeks in most patients and is infrequently re-

corded. In addition, discoid lupus patients often see only dermatologists and are rarely hospitalized, which makes it difficult for a rheumatology registry to estimate its prevalence. And again, lupus is often not properly diagnosed.

In spite of these misgivings about underestimates, published surveys in the

United States of mostly Caucasian populations find that the prevalence (number

of patients with the disease) of SLE is between 14.6 and 50.8 per 100,000, with an incidence rate per year (number of new cases annually) of 1.8 to 7.6 per

[12]

Introduction and Definitions

100,000. Nearly 80,000 individuals are paid members of the largest lupus sup-

port organization (the majority have lupus), which indicates a considerable

amount of networking on the part of patients with the disease. Based on patients being told that they had lupus by at least one doctor, a Lupus Foundation of

America survey suggested that the prevalence of SLE may be as high as 2

million in the United States.

In Europe, some of the socialized medical systems compile diagnosis-based

data banks. Among overwhelmingly Caucasian populations in Western Europe

and Scandinavia, several surveys show a prevalence ranging from 12.5 to 39

per 100,000.

AGE OF ONSET

Lupus has been recorded in individuals at birth (neonatal lupus) and has been

diagnosed in some people as old as 89. Nevertheless, 80 percent of those af-

flicted with SLE develop it between the ages of 15 and 45. Neonatal lupus is

limited to children of mothers who carry a specific autoantibody (an antibody

that reacts against the body’s own tissues) called the anti-Ro (or SSA) antibody, which will be discussed in Chapter 30. This is one of the autoantibodies that

crosses the placenta. For example, the skin rash of neonatal lupus is a self-

limited process that disappears during the first year of life because the mother’s antibody gets ‘‘used up’’ and the baby cannot make more of it. Children may

develop SLE between the age of 3 and the onset of puberty. This form of lupus

is usually a severe, organ-threatening disease but fortunately accounts for less than 5 percent of all lupus cases. The onset of lupus after age 45 or after

menopause is uncommon, and a diagnosis of lupus past the age of 70 is ex-

tremely unusual. Late-onset lupus is generally mild and does not threaten organ systems, but it can be mistaken for rheumatoid arthritis, Sjo¨gren’s syndrome, or polymyalgia rheumatica (see Chapters 22 and 23 for a discussion of these conditions).

SEX OF SLE PATIENTS

In children and in adults over the age of 50, the incidence of lupus demonstrates only a slight female predominance; however between the ages of 15 and 45,

close to 90 percent of diagnosed patients are women. The reasons for this are

discussed in Chapter 17. Overall, 80 to 92 percent of all Americans with SLE

are women. The percentages are less for discoid lupus, where 70 to 80 percent

are women, and for drug-induced lupus, which occurs equally in males and

females. In light of these statistics, lupus has been called a ‘‘women’s disease.’’

To view the prevalence of lupus in men and women by ages, Table 4.1 sum-