An Overview of Autoimmune Diseases

Autoimmune diseases are a case of mistaken identity in which the body's immune system, which ordinarily attacks intruders like viruses and bacteria, attacks itself. There are more than 100 different autoimmune diseases, some of which involve a single organ (e.g. Hashimoto's thyroiditis) and others that attack nearly any organ or tissue (e.g. lupus). Early symptoms, such as fatigue and joint pain, mimic those of other medical conditions, making diagnosis challenging. These conditions can be temporary or, more commonly, lifelong and are sometimes referred to as "invisible disabilities," since people may not appear outwardly ill despite dealing with significant related issues.

Autoimmune diseases affect more than 23.5 million Americans, and more and more diseases are now being attributed to autoimmunity.

The immune system protects us from viruses, bacteria, foreign substances, and even cancer cells, but does so with a delicate balance. Without a good immune response (an underactive immune system), even minor infections could be deadly. That said, an overactive immune response (as with autoimmune diseases) can lead to illness and possibly death.

When, say, a virus enters the body, it mounts an immune response. Lymphocytes and other immune cells rush to the rescue, creating inflammation. T lymphocytes are part of the innate response and function to eliminate any type of intruder. B lymphocytes are part of the learned response and produce antibodies that specifically target the threat.

Ordinarily, the immune system does not attack the body's own cells, and there are several regulatory steps (such as T helper cells) that work to prevent autoimmunity. But it does happen.

There are several different ways in which an autoimmune reaction may be created. These include:

• When a foreign substance or microbe resembles the body: An example of this is rheumatic fever, in which proteins found in group A strep bacteria resemble proteins in the heart muscle; as a result, antibodies attack the heart.
• When normal body cells are altered: An example of this mechanism is a virus altering a body cell so that it is recognized as "non-self" by the immune system.
• If the immune cells that make antibodies (B cells) malfunction and make abnormal antibodies that attack normal cells in the body.
• If a substance in the body that is normally hidden from the immune system (such as the fluid within the eye) enters the bloodstream (such as with trauma).

Autoimmunity does not necessarily mean autoimmune disease. For example, the body may produce antibodies against itself (autoantibodies) that are involved in cleaning up debris after an infection. With autoimmune disease, the reaction causes inflammation and tissue damage.

There is a wide range of autoimmune diseases that together may affect tissues in nearly any region of the body. These conditions fall along a spectrum, but can be broken down into organ-specific diseases (those that affect primarily one organ) and generalized or systemic diseases, which affect many types of tissues or organs. Some of these generalized conditions may affect blood vessels, endocrine glands, the skin, joints, or muscles.

Some of the more common organ-specific autoimmune diseases include:

Autoantibodies may result in the destruction of thyroid tissue and hypothyroidism, as with Hashimoto’s thyroiditis, or in stimulation of thyroid tissue and hyperthyroidism, as with Graves’ disease. With both of these conditions, the symptoms may develop rapidly or occur slowly over time. Autoimmune thyroid disease is very common and thought to be greatly under-diagnosed.

Hypothyroidism may cause symptoms of fatigue, weight gain, constipation, and hair loss, and the condition is treated with lifelong thyroid hormone replacement medication.

Hyperthyroidism, in contrast, often causes nervousness, anxiety, sweating, and heat intolerance, and it may be treated with antithyroid drugs, surgery, or radioactive iodine therapy to destroy the gland.

Type I diabetes, which often arises during childhood or young adulthood, occurs when autoantibodies destroy the beta cells in the pancreas that are responsible for making insulin. Symptoms may include thirst, increased urination, and when severe, diabetic coma. It is treated with lifelong insulin replacement, and careful monitoring is needed to avoid complications such as kidney failure, retinopathy, and heart disease.

Psoriasis occurs when the immune system erroneously sends signals to skin cells to grow too rapidly. There are several forms of psoriasis, the most common being plaque psoriasis. Plaque psoriasis is characterized by raised (often itchy) red patches called plaques that occur most frequently on the knees, lower back, scalp, and elbows. The treatment options for psoriasis depend on the type and severity. For those who have psoriasis, it is important to screen for a related autoimmune condition, called psoriatic arthritis.

Multiple sclerosis (MS) is a condition in which autoantibodies attack the fatty sheath (myelin) that lines the nerves. The disease can have many different symptoms depending on the particular area of the nervous system that's affected, but may include vision problems, sensory disturbances like numbness and tingling, bladder issues, weakness, loss of coordination, tremors, and more. The condition isn't curable, but newer MS disease-modifying therapies are changing the face of MS by slowing a person's disease progression down.

Guillain-Barré syndrome is a condition in which autoantibodies attack the support cells that line nerves. It often occurs after a viral infection (and rarely, after a flu shot), and it's thought that portions of the infectious organism resemble parts of the nervous system. The syndrome often begins with weakness and changes in sensation in the feet and hands. As the condition ascends up the body, it can become life-threatening without prompt medical care. (Paralysis of the diaphragm requires respiratory support with a ventilator.)

Systemic autoimmune diseases can bring about several different issues, as their effects are felt throughout the body. Examples include:

Systemic lupus erythematosus (lupus) is a prototype of an autoimmune disease that affects multiple organs. The symptoms of lupus may include joint pain, skin rashes, kidney problems, inflammation of the lung and/or heart, anemia, increased clotting (thrombosis), memory problems, and more. Treatment includes lifestyle measures (such as sun protection and smoking cessation) and medications such as corticosteroids, anti-malarial agents, and immunosuppressive drugs.

Rheumatoid arthritis (RA) is characterized by pain, swelling, and without treatment, eventual destruction of joints. Unlike osteoarthritis ("wear and tear" arthritis), the symptoms of RA are more severe. Without early and aggressive treatment, deformity of joints usually occurs. Joints are usually affected symmetrically, with a predilection for the small joints of the hands and feet. In addition to joint inflammation (synovitis), people with RA may develop subcutaneous nodules, pleural effusions, inflammation of the lining of the heart (pericarditis), and more.

Inflammatory bowel disease (IBD), which includes Crohn’s disease and ulcerative colitis, refers to chronic inflammation of the digestive tract. While Crohn's disease may cause inflammation from the mouth to the anus, inflammation in ulcerative colitis only affects the large intestine (called the colon) and the rectum. Symptoms may include diarrhea, abdominal pain, bloody stools, weight loss, and fatigue. Treatment often includes a combination of medications and surgery, as well as careful monitoring as both conditions are associated with an increased risk of developing colon cancer.

In Sjögren's syndrome, autoantibodies attack glands that manufacture tears and saliva. This leads to dry eyes, a dry mouth, and related consequences such as dental decay, loss of the sense of taste, and more. Joint pain and other symptoms may also occur. For roughly half of people, the syndrome occurs alone, while it is associated with another autoimmune condition such as lupus, rheumatoid arthritis, or scleroderma in others.

Antiphospholipid syndrome is a common autoimmune condition that involves autoantibodies against certain proteins in the blood, which results in abnormal clotting. It is often first noted as a cause in women who have frequent miscarriages or preterm births, or when blood clots and/or bruising occur without an obvious cause. Formation of clots can also lead to heart attacks (when they occur in the blood vessels in the heart) or strokes (when clots occur in the brain).

While the symptoms of common autoimmune diseases can vary widely depending on the particular organ or organs affected, there are some symptoms that are common with many of these diseases. Since these symptoms are non-specific, they may be a sign of non-autoimmune conditions as well.

General symptoms may include:

• Fatigue
• Low-grade fever (often a fever that comes and goes)
• Weight changes
• Dizziness
• Muscle and/or joint pain and swelling
• Difficulty concentrating
• Skin rashes
• Digestive issues
• A general feeling of being unwell

Symptoms often follow a relapsing and remitting (waxing and waning) course, with the disease worsening, improving, and then worsening again in an unpredictable manner. Flares may occur, which are defined as the sudden onset of severe symptoms.

Specific symptoms will vary depending on the underlying disorder and may include:

• Joint symptoms, such as redness, pain, and joint swelling that is more severe than would be expected with osteoarthritis
• Skin rashes, such as a "butterfly rash" on the face with lupus
• Vasculitis, inflammation of blood vessels that can lead to damage wherever blood vessels are affected (e.g. aneurysms)

Many autoimmune conditions are suspected based on a particular combination of symptoms, although two people can have the same diagnosis and very different symptoms.

For example, scleroderma (systemic sclerosis) is characterized by something called CREST syndrome, which stands for the combination of calcinosis (build-up of calcium), Raynaud's syndrome (a condition in which the hands become cold and often blue or white upon exposure to cold temperatures), esophageal dysfunction, sclerodactyly (a condition in which the fingers resemble sausages), and telangiectasias (abnormally dilated capillaries that cause the appearance of "spider veins").

It's not uncommon for people who have one autoimmune disease to develop another. This can be related to a genetic predisposition or a common trigger.

An example is a combination of rheumatoid arthritis with autoimmune thyroiditis, or the combination of celiac disease with type I diabetes, autoimmune liver disease, or rheumatoid arthritis.

The term multiple autoimmune syndrome is used to describe people who have three or more autoimmune diseases. There are different types of this syndrome, but frequently one of the three conditions is skin related (such as alopecia areata or vitiligo).

There are a number of factors that are thought to underlie the development of autoimmune diseases as well as factors that are associated with an elevated risk.

Possible causes of autoimmune disease and/or flare-ups include:

• Infectious diseases: It's thought that autoimmunity may occur when a component of a virus or bacteria resembles proteins in the body, or instead, by the infection upregulating the immune system. Some specific microorganisms linked with autoimmune disease include: the Epstein-Barr virus, cytomegalovirus (CMV), and group A Streptococcus.
• Environmental factors: Lack of sunlight, vitamin D deficiency, chemical exposure, and other environmental factors have been linked to different types of autoimmune diseases. A number of studies have also linked a more sterile environment (fewer pets, cleaner homes, etc.) with the development of some autoimmune conditions. The theory behind the "hygiene hypothesis" is that as people are exposed to fewer antigens (such as dust mites, animal hair, etc.), an overactive immune system attacks itself.
• Lifestyle: Smoking appears to triple the risk of developing rheumatoid arthritis and has also been linked with other autoimmune conditions such as Grave's disease and MS. Obesity is considered a "pro-inflammatory" state that may account for its role as a risk factor. The Western diet (high fat, high sugar, high protein, high salt), in general, is thought to possibly promote the development of autoimmune diseases.
• Gut bacteria: More and more, research is pointing to a connection between the bacteria that live in a person's digestive tract (gut flora) and a number of health conditions, including autoimmune diseases.
• Genetics: Several autoimmune diseases appear to run in families to varying degrees, with research in progress looking at specific genes.

Risk factors vary depending on the particular condition, but include:

• Sex: Many autoimmune conditions are more common in women. In addition, hormonal factors can play a role in flare-ups of many of these conditions.
• Age: Many autoimmune conditions first appear during the childbearing years.
• Weight: Some autoimmune conditions are more common in people who are overweight, while others are more common in people who have a history of eating disorders.
• Ethnicity: Different conditions vary, with type I diabetes being more common in white people, and severe autoimmune conditions being more prevalent in African-American, Hispanic, and Native-American women.
• Geography: Some autoimmune diseases such as multiple sclerosis, inflammatory bowel disease, and type I diabetes are more common in northern latitudes, especially the pacific northwest (geographical differences could, in turn, be linked with vitamin D exposure (there is an inverse relationship between UV exposure and MS) or ethnicity (such as Scandinavian heritage).
• Smoking: Tobacco use is associated with an increased risk of many of these conditions.
• Medications: Some medications may increase risk of certain conditions, such as is the case with procainamide and lupus.

The diagnosis of an autoimmune disease can take time and sometimes several opinions. In fact, and unfortunately, the average person spends four and a half years (seeing at least four doctors) before a diagnosis is made.

The diagnostic process begins with a careful history, though this can be frustrating since many people have seemingly unrelated symptoms. A physical exam can sometimes suggest an autoimmune condition based on joint swelling, characteristic rashes, and more, but further testing is most often needed. There isn't one single test that can diagnose autoimmune diseases conclusively (with rare exceptions such as with type I diabetes), and evaluation usually includes a number of tests including:

• Erythrocyte sedimentation rate (ESR or sed rate) test
• C-reactive protein (CSR) test
• A complete blood count (CBC)
• A comprehensive metabolic panel
• Antinuclear antibody (ANA) test: Antinuclear antibodies are autoantibodies that attack structures in the nucleus of cells. Different patterns on the ANA are correlated with different diseases.
• Rheumatoid factor (RF) test
• Thyroid peroxidase antibodies test

There are many other tests that may be recommended depending on the condition that is suspected.

Imaging tests may be used when evaluating specific symptoms related to autoimmune conditions, such as X-rays of joints that are swollen or an echocardiogram (ultrasound of the heart) if a pericardial effusion is suspected.

The treatments for autoimmune disease vary with the particular disease.

For many of these conditions, the course is unpredictable, and treatments may change over time.

In general, treatment can be thought of as consisting of:

• Managing symptoms: For example, non-steroidal anti-inflammatory medications to control joint pain.
• Replacement: For conditions such as type I diabetes or autoimmune hypothyroidism, insulin or thyroid hormone are given.
• Controlling inflammation: Medications such as corticosteroids and tumor necrosis factor inhibitors (biologic drugs) are needed to control inflammation related to many autoimmune conditions
• Preventing complications: Careful blood sugar control is needed in people with type I diabetes to reduce complications, whereas early and aggressive treatment is needed with rheumatoid arthritis to prevent joint deformity.

Clinical trials are also in progress looking for newer, better ways to manage these conditions.

Most autoimmune conditions are relapsing-remitting disorders. It can be hard to predict when you will feel well and when you won't. In addition, many people with these disorders appear outwardly healthy, sometimes leading to less understanding and support from friends and loved ones. That said, there are many things that people with autoimmune disease can do themselves to better cope with the day to day frustration and symptoms:

• Eat a healthy diet: For those who have celiac disease or diabetes, monitoring diet is critical. Yet for others with autoimmune disease it's important to learn about how to have healthy gut bacteria.
• Practice good sleep hygiene: Get an adequate amount of rest every night, and try to wake up and go to sleep at the same time each day.
• Exercise: Mild to moderate exercise is important for most people, but not pushing it and knowing when to stop is equally important.
• Practice stress management: Stress management is helpful when coping with any medical condition, and especially important with a stressful condition such as autoimmune disease.
• Know your triggers: With some conditions, there are triggers that are associated with flares of the disease. It's helpful to identify them and then look at ways to reduce your exposure.

Anyone coping with a serious medical condition needs support, but this is even more true for those living with "invisible diseases." In-person support groups and online support communities can be helpful, as they provide an opportunity to connect with others who are similarly coping with an unpredictable and often misunderstood condition. Some groups are based on specific conditions, whereas others are symptom-based. The National Coalition of Autoimmune Patient Groups is a good place to begin when looking for these communities.

If you or a loved one are coping with an autoimmune disease, it's important to be your own advocate. The journey to a diagnosis, and later to an effective treatment, can be frustrating and even lonely. Fortunately, there is a great deal of research looking into both the causes and treatments of these conditions.