CHAPTER 170

Autoimmune Disorders

An autoimmune disorder is a malfunction of the body’s immune system that causes the body to attack its own tissues.

Autoimmune disorders can be triggered in many ways.

Symptoms vary depending on which disorder develops and which part of the body is affected.

Several blood tests are usually needed to confirm the presence of an autoimmune disorder.

Autoimmune disorders are treated with drugs that suppress the activity of the immune system.

The immune system defends the body against what it perceives to be foreign or dangerous substances (see page 1096). Such substances include microorganisms, parasites (such as worms), cancer cells, and even transplanted organs and tissues. Substances that can stimulate an immune response are called antigens. Antigens are molecules that may be contained within cells or on the surface of cells (such as bacteria, viruses, or cancer cells). Some antigens, such as pollen or food molecules, exist on their own.

Even cells in a person’s own tissues can have antigens. But, normally, the immune system reacts only to antigens from foreign or dangerous substances, not to antigens from a person’s own tissues. However, the immune system sometimes malfunctions, interpreting the body’s own tissues as foreign and producing antibodies (called autoantibodies) or immune cells that target and attack particular cells or tissues of the body. This response is called an autoimmune reaction. It results in inflammation and tissue damage. Such effects may constitute an autoimmune disorder, but some people produce such small amounts of autoantibodies that an autoimmune disorder does not occur.

Some of the more common autoimmune disorders include rheumatoid arthritis, systemic lupus erythematosus (lupus), and vasculitis, among others. Additional diseases that are believed to be due to autoimmunity include glomerulonephritis, Addison’s disease, mixed connective tissue disease, polymyositis, Sjögren’s syndrome, progressive systemic sclerosis, and some cases of infertility.

Causes

Autoimmune reactions can be triggered in several ways:

A substance in the body that is normally confined to a specific area (and thus is hidden from the immune system) is released into the bloodstream. For example, a blow to the eye can cause the fluid in the eyeball to be released into the bloodstream. The fluid stimulates the immune system to recognize the eye as foreign and attack it.

A normal body substance is altered, for example, by a virus, a drug, sunlight, or radiation. The altered substance may appear foreign to the immune system. For example, a virus can infect and thus alter cells in the body. The virus-infected cells stimulate the immune system to attack.

A foreign substance that resembles a natural body substance may enter the body. The immune system may inadvertently target the similar body substance as well as the foreign substance. For example, the bacteria that cause strep throat have some antigens that are similar to those in human heart cells. Rarely, the immune system may attack a person’s heart after strep throat (this reaction is part of rheumatic fever).

The cells that control antibody production—for example, B lymphocytes (a type of white blood cell)—may malfunction and produce abnormal antibodies that attack some of the body’s cells.

Heredity may be involved in some autoimmune disorders. Susceptibility to the disorder, rather than the disorder itself, may be inherited. In susceptible people, a trigger, such as a viral infection or tissue damage, may cause the disorder to develop. Hormonal factors may also be involved, because many autoimmune disorders are more common among women.

Symptoms and Diagnosis

Autoimmune disorders may cause a fever. However, symptoms vary depending on the disorder and the part of the body affected. Some autoimmune disorders affect certain types of tissue throughout the body—for example, blood vessels, cartilage, or skin. Other autoimmune disorders affect a particular organ. Virtually any organ, including the kidneys, lungs, heart, and brain, can be affected. The resulting inflammation and tissue damage can cause pain, deformed joints, weakness, jaundice, itching, difficulty breathing, accumulation of fluid (edema), delirium, and even death.

Blood tests that indicate the presence of inflammation may suggest an autoimmune disorder. For example, the erythrocyte sedimentation rate (ESR) is often increased, because proteins that are produced in response to inflammation interfere with the ability of red blood cells (erythrocytes) to remain suspended in blood. Frequently, the number of red blood cells is decreased (anemia) because inflammation decreases their production.

However, inflammation has many causes, many of which are not autoimmune. Thus, doctors often obtain blood tests to detect different antibodies that can occur in people who have particular autoimmune disorders. Examples of these antibodies are antinuclear antibodies, which are typically present in systemic lupus erythematosus, and rheumatoid factor or anti-cyclic citrullinated peptide (anti-CCP) antibodies, which are typically present in rheumatoid arthritis. But even these antibodies may sometimes occur in people who do not have an autoimmune disorder, so doctors usually use a combination of test results and the person’s signs and symptoms to decide whether an autoimmune disorder is present.

Treatment

Treatment involves control of the autoimmune reaction by suppressing the immune system. However, many of the drugs used to control the autoimmune reaction also interfere with the body’s ability to fight disease, especially infections.

SOME AUTOIMMUNE DISORDERS

DISORDER	MAIN TISSUES AFFECTED	CONSEQUENCES
Autoimmune hemolytic anemia	Red blood cells	Anemia (decreased number of red blood cells) develops, causing fatigue, weakness, and light-headedness. The spleen may enlarge. The anemia can be severe and even fatal.
Bullous pemphigoid	Skin	Large blisters, surrounded by red, swollen areas, form on the skin. Itching is common. With treatment, the prognosis is good.
Goodpasture’s syndrome	Lungs and kidneys	Symptoms, such as shortness of breath, coughing up blood, fatigue, swelling, and itching, may develop. The prognosis is good if treatment begins before severe lung or kidney damage occurs.
Graves’ disease	Thyroid gland	The thyroid gland is stimulated and enlarged, resulting in high levels of thyroid hormones (hyperthyroidism). Symptoms may include a rapid heart rate, intolerance of heat, tremor, weight loss, and nervousness. With treatment, the prognosis is good.
Hashimoto’s thyroiditis	Thyroid gland	The thyroid gland is inflamed and damaged, resulting in low levels of thyroid hormones (hypothyroidism). Symptoms may include weight gain, coarse skin, intolerance to cold, and drowsiness. Lifelong treatment with thyroid hormone is necessary and usually relieves the symptoms completely.
Multiple sclerosis	Brain and spinal cord	The covering of affected nerve cells is damaged. As a result, the cells cannot conduct nerve signals normally. Symptoms may include weakness, abnormal sensations, vertigo, problems with vision, muscle spasms, and incontinence. Symptoms vary over time and may come and go. The prognosis varies.
Myasthenia gravis	The connection between nerves and muscles (neuromuscular junction)	Muscles, particularly those of the eyes, weaken and tire easily, but the weakness varies in intensity. The pattern of progression varies widely. Drugs can usually control the symptoms.
Pemphigus	Skin	Large blisters form on the skin. The disorder can be life threatening.
Pernicious anemia	Certain cells in the stomach’s lining	Damage to cells in the stomach’s lining makes absorbing vitamin B12 difficult. (Vitamin B12 is necessary for the production of mature blood cells and the maintenance of nerve cells.) Anemia results, often causing fatigue, weakness, and light-headedness. Nerves can be damaged, resulting in weakness and loss of sensation. Without treatment, the spinal cord may be damaged, eventually contributing to loss of sensation, weakness, and incontinence. The risk of stomach cancer is increased. Otherwise, with treatment, the prognosis is good.
Rheumatoid arthritis	Joints or other tissues, such as lung, nerve, skin, and heart tissue	Many symptoms are possible. They include fever, fatigue, joint pain, joint stiffness, deformed joints, shortness of breath, loss of sensation, weakness, rashes, chest pain, and swellings under the skin. The prognosis varies.
Systemic lupus erythematosus (lupus)	Joints, kidneys, skin, lungs, heart, brain, and blood cells	The joints, although inflamed, do not become deformed. Symptoms of anemia, such as fatigue, weakness, and light-headedness, and those of kidney, lung, or heart disorders, such as fatigue, shortness of breath, itching, and chest pain, may occur. A rash may develop. The prognosis varies widely, but most people can lead an active life despite occasional flare-ups of the disorder.
Type 1 diabetes mellitus	Beta cells of the pancreas (which produce insulin)	Symptoms may include excessive thirst, urination, and appetite, as well as various long-term complications. Lifelong treatment with insulin is needed, even if the destruction of pancreatic cells stops, because not enough pancreatic cells remain to produce enough insulin. The prognosis varies greatly and tends to be worse when the disease is severe and lasts a long time.
Vasculitis	Blood vessels	Vasculitis can affect blood vessels in one part of the body (such as the nerves, head, skin, kidneys, lungs, or intestine) or several parts. There are several types. Symptoms (such as rashes, abdominal pain, weight loss, difficulty breathing, cough, chest pain, headache, loss of vision, and symptoms of nerve damage or kidney failure) depend on which part of the body is affected. The prognosis depends on the cause and how much tissue is damaged. Usually, the prognosis is much better with treatment.

Did You Know…

Antigens, substances that can trigger an immune response, can even exist on a person’s own cells.

Autoimmune disorders or susceptibility to autoimmune disorders may be inherited.

Virtually any organ can be affected by an autoimmune disorder.

Drugs that suppress the immune system (immunosuppressants), such as azathioprine, chlorambucil, cyclophosphamide, cyclosporine, mycophenolate, and methotrexate, are often given, usually by mouth and often for a long time (see table on page 1130). However, these drugs suppress not only the autoimmune reaction but also the body’s ability to defend itself against foreign substances, including microorganisms that cause infection and cancer cells. Consequently, the risk of certain infections and cancers increases.

Often, corticosteroids, such as prednisone, are given, usually by mouth. These drugs relieve inflammation as well as suppress the immune system. Corticosteroids given for a long time have many side effects (see box on page 568). When possible, corticosteroids are used for a short time—when the disorder begins or when symptoms worsen. However, cortico-steroids must sometimes be used indefinitely.

Certain autoimmune disorders (for example, multiple sclerosis and thyroid disorders) are also treated with drugs other than immunosuppressants and corticosteroids. Treatment to relieve symptoms may also be needed.

Etanercept, infliximab, and adalimumab block the action of tumor necrosis factor (TNF), a substance that can cause inflammation in the body. These drugs are very effective in treating rheumatoid arthritis, but they may be harmful if used to treat certain other autoimmune disorders, such as multiple sclerosis. These drugs can also increase the risk of infection and certain cancers.

Certain new drugs specifically target white blood cells. White blood cells help defend the body against infection but also participate in autoimmune reactions. Abatacept blocks the activation of one kind of white blood cell (T cell) and is used in rheumatoid arthritis. Rituximab, first used against certain white blood cell cancers, works by depleting certain white blood cells (B lymphocytes) from the body. It is effective in rheumatoid arthritis and is under evaluation in a variety of autoimmune disorders. Other agents directed against white blood cells are being developed.

Plasmapheresis is used to treat a few autoimmune disorders. Blood is withdrawn and filtered to remove the abnormal antibodies. Then the filtered blood is returned to the person.

Some autoimmune disorders resolve as inexplicably as they began. However, most autoimmune disorders are chronic. Drugs are often required throughout life to control symptoms. The prognosis varies depending on the disorder.