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When the Immune System Chooses the Wrong Target

Your symptoms are vague: a feeling of fatigue; some tingling in arms or legs that comes and goes; aching muscles; perhaps a headache.

Are you sick? Or are you just imagining that something's wrong?

Many women who have reported these symptoms to their health care provider have been dismissed as hypochondriacs or suffering from anxiety. But the real diagnosis can be much more subtle, at least at first.

Those symptoms may indicate one of a host of autoimmune diseases such as lupus or multiple sclerosis that develop gradually over time, and strike women many times more frequently than men.

There are about 100 forms of autoimmune disease, and about 75 percent of them occur in women, most often in their childbearing years. Most are rare diseases, yet taken together, they affect about 50 million Americans, or 20 percent of the population. A thyroid disease called Hashimoto's thyroiditis occurs in women 10 times more often than in men. Even more commonly known diseases such as lupus occur up to nine times more often in women. Due to the subtlety and nonspecific symptoms of many autoimmune conditions, several years may elapse before an accurate diagnosis is made, reports the American Autoimmune Related Diseases Association (AARDA). 

What is autoimmune disease?

Our immune system helps protect us against microbic invaders intent on causing us harm. But that well-armed system sometimes turns on itself. Instead of recognizing and destroying viruses, bacteria, and other pathogens, it produces antibodies against healthy cells and tissues.

Health care providers divide autoimmune diseases in two categories—those that attack a specific organ and those that target many organs. In an autoimmune disease such as Hashimoto's thyroiditis, the thyroid is attacked and destroyed. Lupus is a non-organ-specific disease. It plays no favorites, and attacks all organs.

No one is sure why these diseases occur, or why they occur at a higher rate in women. Several theories have been proposed.

The female hormone estrogen may play a role. Estrogen stimulates the immune system, and testosterone suppresses it. A woman's immune system is revved up by estrogen as a survival technique. After all, a mother needs to be able to survive to care for her children. But that hypervigilant immune system then may backfire, sending it on a rampage against the woman's own body.

Autoimmune diseases tend to run in families, which indicates that genes play a role in determining who gets these diseases. But the family ties are odd—one person may have rheumatoid arthritis and another may have lupus, and a third may have diabetes. The diseases are not passed down directly, only the family of diseases.

At least six different genes appear to be involved in autoimmune diseases.

Environmental factors also affect autoimmune diseases. For lupus patients, the sun can trigger an episode of lupus. For other diseases, certain medications act as triggers. Viral infections also can trigger these diseases, or make them worse.

Current research is exploring the activity of the immune system, and the progression of various types of autoimmune diseases.

A difficult diagnosis

Autoimmune diseases are difficult to diagnose because so many symptoms are vague and unrelated. Fatigue, a low-grade fever, vague, or poorly described aches and pains—these could be symptoms of many illnesses.

A thorough medical history and family history can provide the first clues to identify the symptoms.

Nonspecific screening tests are available, but some give too many false positives, which can be traumatic for patients and health care providers.

Another factor in diagnosis is time. The symptoms for these diseases can develop slowly and may be intermittent.

Because of the difficulty in diagnosing these diseases, some patients spend years visiting one expert or another before finding the answer. AARDA says that the typical patient may spend $50,000 before being correctly diagnosed.

But it's important to diagnose autoimmune diseases as early as possible to keep any damage minimal. Misdiagnosis or late diagnosis is the leading cause of death from autoimmune disease, according to AARDA.

Treatment can help patients with these diseases to live normal lives. People with type 1 diabetes can take insulin to control blood sugar levels. Medication can stop progression of lupus and rheumatoid arthritis. With medication, some diseases go into remission for many years.

Hashimoto's thyroiditis

With this disease, the body attacks and destroys the proteins in the thyroid gland. The thyroid gland helps set the rate at which the body uses energy. By damaging the thyroid, Hashimoto's thyroiditis deprives the body of the hormones it produces. It is the most common cause of hypothyroidism, an underactive thyroid.

People with this disease also tend to develop other autoimmune diseases, including pernicious anemia—anemia caused by inability to absorb vitamin B12—and diabetes. Hashimoto's thyroiditis most commonly affects women 30 to 50 years old. Grave's disease is a related autoimmune disease. It is a rare condition in which the immune system overstimulates the thyroid gland, causing hyperthyroidism, an overactive thyroid.

Rheumatoid arthritis (RA)

With this disease, the body targets and destroys cartilage, ligaments, tendons, and bones, particularly those in the hands, causing swelling, pain, and stiffness. It predominantly strikes women from 30 to 60 years old, although it can occur at any age. RA is two to three times more common in women than in men. RA can flare up unpredictably and then quickly go into remission. It also can damage the heart, lungs, and eyes, as well as cause weakness and atrophy of skeletal muscle and nerve damage.

Scleroderma

This disease causes a thickening of the skin, blood vessels, and connective tissues. The body's immune system makes scar tissue in the skin, internal organs, and small blood vessels. It can affect the esophagus, intestines, lungs, heart, and kidneys. It predominantly affects women in their 30s and 40s. Symptoms vary, but can include dry eyes and dry mouth, pain in the fingers and toes, and muscle soreness. One symptom of scleroderma is Raynaud's phenomenon, in which the blood vessels in the fingers and toes spasm in reaction to cold. Thickening of skin and blood vessels can result in loss of movement and shortness of breath or, more rarely, in kidney, heart, or lung failure.

Multiple sclerosis (MS)

MS affects the central nervous system, attacking the covering of the nerves and keeping the nerves from communicating with the body to do things like walk, talk, or write. The destruction causes a variety of neurological symptoms. Symptoms can occur intermittently, allowing a person to lead a fairly normal life. At the other extreme, the symptoms may become constant, resulting in a progressive disease with possible blindness, paralysis, and premature death. The disease typically affects women between 20 and 40 years old, although men also develop this condition at approximately half the rate of women. In young adults, it is the most common disabling disease of the nervous system. White women were more likely to have MS, compared with women of other races.

Lupus

With lupus, the body's immune system attacks the joints, skin, kidneys, heart, lungs, blood vessels, and brain. Some of the signs and symptoms include a bright rash of the face, pain and swelling in the joints, unexplained fever, chest pain when you breathe, extreme fatigue, and unusual loss of hair. According to the Lupus Foundation of America, most lupus patients between the ages of 15 and 45 are women. However, after the onset of menopause, the percentage of women with lupus falls to 75 percent, and the percentage of men with lupus who are over the age of 50 increases to 25 percent.

Crohn's disease and ulcerative colitis

With Crohn's disease, the body's immune system attacks the intestine and may cause bleeding and inflammation in any part of the intestinal tract. Other symptoms are diarrhea, nausea, vomiting, abdominal cramps, and pain that is difficult to control. The symptoms of ulcerative colitis are often similar to Crohn's disease, but only the colon and rectum are affected.

Psoriasis

Psoriasis affects the skin and sometimes the eyes, nails, and joints of both men and women, usually those ages 15 to 35. Severe cases can cover the entire body. This condition is also associated with psoriatic arthritis.

Guillain-Barré syndrome

Guillain-Barré syndrome (GB) attacks the nerves of men or women of any age. GB is subdivided into acute inflammatory demyelinating polyneuropathy, acute motor axonal neuropathy, acute motor sensory axonal neuropathy, and Fisher syndrome. GB is marked by paralysis that starts in the feet and legs and moves upward through the body. Weakness or tingling in the legs is an early symptom. GB can result in total paralysis, including the muscles of breathing, requiring a mechanical ventilator to be able to breathe. Most patients recover, some remain weak, and recurrences are not uncommon. GB may be related to viral and bacterial infections. Some cases of GB have occurred after a bout of influenza, and a few were brought on by an influenza vaccine produced in 1976 against the A/New Jersey influenza strain. GB has also followed Campylobacter jejuni infection, which is a common foodborne bacterium.

Myasthenia gravis

Myasthenia gravis affects skeletal (voluntary) muscles, causing weakness. It often affects eye movement, facial expression, chewing, talking, and swallowing. It's more likely to occur in women under age 40, and men over age 60.

Wegener's granulomatosis

Wegener's granulomatosis targets the respiratory tract, including lungs and sinuses, and kidneys. Common signs: persistent runny or stuffy nose, chronic cough, recurrent nosebleeds, or ear congestion. It hits men and women equally, usually in middle age.

Graves' disease

Graves' disease causes an overactive thyroid, the gland that helps regulate your metabolism. Signs can include bulging eyes, weight loss, tremors, increased sweating, increased appetite, congestive heart failure, irritability, and muscle weakness. Most patients are women, usually ages 20 to 30.

Women vs. men: The autoimmune disease ratio

Hashimoto's thyroiditis 10:1

Systemic lupus erythematosus 9:1

Sjogren's disease 9:1

Mixed connective tissue disease 10:1

Chronic autoimmune hepatitis 8:1

Graves' disease 7:1

Rheumatoid arthritis 2.5:1

Scleroderma 3:1

Type 1 diabetes 1:1

Multiple sclerosis 2:1