The immune system is a highly complex system of cells and chemical reactions that fights off infection and protects the body from germs. When germs invade the body, the immune system detects proteins on the surface of the germs and then gears up to remove the foreign invasion. In general the system works very well. However, at times the immune system malfunctions and begins to see normal body proteins as foreign. The immune system then gears up to fight against this “foreign” protein that really is part of normal cells. This is called autoimmunity and causes autoimmune disease, including connective tissue diseases and inflammatory conditions such as arthritis and vasculitis. These are all diseases where the body fights against itself and its normal tissues.
The true reason for the reaction against normal body proteins is not well understood, but some autoimmune diseases are inherited. Some people may have the gene for an autoimmune disease but the gene must be turned on for the disease to occur. The exact triggers are not known and that is why some members of a family may develop disease whereas others do not. The most common belief is that exposure to an infection may be the trigger but the specific infection is unknown. Sometimes the apparent infection is not even noticed or the autoimmune disease develops long after the episode of infection.
Sometimes, an infection can trigger an autoimmune response even after the infection is cleared. This may happen if the protein of the infecting germ is almost identical to the person’s normal cells. This is termed molecular mimicry. Aside from this, infectious particles can alter the immune system directly and alter the cell’s ability to function properly or just interfere with some of the immune system functions. Another way to cause autoimmunity is by a change in the way cells die in the body. Cells in the body die and are cleared through specific pathways. If dying cells are not removed appropriately and linger about, they may start to seem foreign to the body. Another potential cause for autoimmunity may be a change in the way a body normally produces inflammation. Some cells in the body are assigned to police the inflammatory cells and chemicals so they do not get out of hand. The policing mechanism may not work and the system runs out of control. Other theories about autoimmunity exist. It is unlikely that there is a sole culprit, and more likely that small alterations at various levels cause the body to fight against itself.
Autoimmune disease can affect any body part. Because it is a disease that can affect lots of parts of the body at once, many organs can be affected at the start or only a few may be affected initially and then other symptoms occur over time. The diagnosis of an autoimmune disease is not easy and may require repeated history and physical examination sessions along with blood testing. Most of the signs and symptoms of the various autoimmune diseases are categorized into groupings that make up certain disease syndromes. Criteria for each have been established but the criteria are primarily for research purposes to ensure that patients in a study really have the same disease. Patients may be diagnosed with a specific disease without meeting full criteria and their symptoms can and should be treated as they arise. Autoimmune diseases must be diagnosed with extreme care and caution because many other diseases may mimic or appear to be autoimmune when they are not. The danger herein lies with the treatment. Since autoimmunity is a disease of almost a “hyperactive” immune system, the treatment is aimed at suppressing the immune system. Many of the diseases that look like they could be autoimmune disease are infections or cancer, and blocking the immune system in these instances could be fatal. Infections must be ruled out through vigorous testing before treating and diagnosing an autoimmune disease. Even if an autoimmune disease is diagnosed with certainty, the patient must be entirely free of infection before treatment begins.
Although any infection can rev up the immune system and cause changes that look like an autoimmune disease, there are certain classic mimics that will be discussed here. Subacute bacterial endocarditis, which is a bacterial infection of the heart valves, is frequently confused with rheumatoid arthritis and systemic lupus erythematosus (SLE) because all of these cause joint swelling, rashes, and positive laboratory tests. It is important to note that infections themselves cause a surge in inflammatory chemicals and cells and can cause unreliable laboratory tests. The infectious growth on the heart valves may become dislodged and land in the joints, skin, and kidney, causing symptoms that we also see with autoimmune disease. Blood cultures and careful evaluation should always be done to rule out bacterial endocarditis as a cause of the “autoimmune” symptoms.
Another disease that should not be missed is tuberculosis (TB). TB can cause disease all over the body including the lungs, kidneys, and skin. Syphilis and HIV diseases are also commonly misdiagnosed as autoimmune diseases. It is important to realize that the above diseases as well as others may give false-positive laboratory tests that may be confused with autoimmune diseases, but the diagnosis should be based primarily on history and physical examination. In some cases biopsy specimens are critical to confirm the diagnosis.
SLE is the classic autoimmune disease and is discussed in detail elsewhere. In SLE, the primary problem is the production of autoantibodies to several normal proteins found in the core of normal cells. The antibodies form clumps of proteins and cause injury when they deposit on various tissues. In SLE, first-degree relatives of patients with SLE will have a much higher chance of developing the disease: SLE occurs in approximately 25-50% of identical twins versus 5% of fraternal twins. This disease can affect virtually any organ system. The classic symptoms are the butterfly rash on the face, mouth sores, inflammation of the lining of the heart and lungs, and arthritis.
Rheumatoid arthritis is also a classic autoimmune disease and can affect organs other than joints. The nonjoint manifestations can involve the heart, lungs, skin, and eyes. The trigger for rheumatoid disease is not known.
The inflammatory muscle diseases are another group of diseases that have an autoimmune basis. These diseases cause breakdown of muscle and weakness. The hallmark of these diseases is muscle weakness of the shoulder and hip areas, with or without associated muscle pain. Patients have difficulty raising their arms to or above their heads, and difficulty getting out a chair or walking up stairs or inclines. In severe cases, the disease may affect the neck muscles and the head may feel heavy. Respiratory muscle weakness and breathing problems can also occur, as well as swallowing difficulties. As implied by the name, these diseases affect mainly the muscles, but the lungs themselves may also be affected, causing an inflammatory lung disease and resulting in heart failure. The skin may also display a classic rash. In children, the rash is called a heliotrope rash and it is a purple or violaceous discoloration of the upper and lower eyelids. In adults, the rash may appear as shiny plaque-like lesions over the knuckles of the hands. There may also be joint pain without joint swelling.
Laboratory tests in the inflammatory muscle diseases show breakdown of muscles but also signs of autoimmunity on special testing. Specific tests can predict lung involvement or worse prognosis. Muscle testing via electrical analysis of the muscles and nerves, and also muscle biopsy are critical since other muscle diseases that are not autoimmune related can only be diagnosed with a biopsy. In one of these diseases, adults with both skin and muscle disease (dermatomyositis) have a 25% increased chance of having cancer before, during, or after the disease develops.
Scleroderma is another interesting manifestation of autoimmune disease. Again, the exact cause is not clear, but cases have been noted to cluster within families that have other autoimmune diseases. Scleroderma causes skin tightening and hardening. Certain cells that are responsible for scarring and scar tissue formation appear hyperactive in this disease. The more scar tissue they deposit, the less able the tissues are to breathe and this loss of breathability or oxygenation causes even more scar tissue to be deposited. Autoantibodies are associated with scleroderma but it is not clear if they are a cause or a result of the process.
Patients with scleroderma may develop a wide variety of symptoms, ranging from Reynaud’s phenomenon (sensitivity and skin color changes in response to cold) or calcium deposits, and some small amount of skin tightening, to kidney failure, lung damage, and severe thickening of the skin that encases the whole body. The gastrointestinal tract and heart may also be involved. Treatment of scleroderma is very difficult and can only slow the disease. However, it is important to be aware of the diagnosis and work toward treatment.
Another family of classic autoimmune diseases is a group of diseases causing inflammation of the blood vessels (vasculitis). Inflammation of the blood vessels in these diseases may be due to an allergic response, or cell changes within the vessel wall, or dying off of vessels. Each of these diseases tends to involve only the small, medium, or large arteries. Vasculitis is associated with fever, general illness, and can involve multiple organs. In situations where a diagnosis of vasculitis is considered, infection must be ruled out or treated, and the degree of organ involvement must be determined. Examination of the skin, hands, oral or vaginal lining, urine, stool, and complete blood work must be done to look for any abnormality. Often a biopsy will allow the disease to be categorized.
Small vessel vasculitis usually involves the skin, joints, and gastrointestinal tract. An example is hypersensitivity vasculitis, which is a response to something outside the body. Behcet’s syndrome causes eye ulcerations and gastrointestinal problems in people of Mediterranean or Far East background. Small vessel diseases may also involve the brain, causing very subtle behavioral changes or obvious neurological symptoms. Medium vessel vasculitis commonly involves the lungs and kidneys. Some classic syndromes are polyarteritis nodosa, allergic granulomatosis and angiitis, Churg-Strauss vasculitis, and Wegener’s vasculitis. The large vessel diseases include Takayasu’s arteritis, temporal arteritis, and polyarteritis nodosa. A good and detailed history usually reveals classic symptoms of these disorders.
Autoimmunity does not only cause rheumatologic disorders. Diabetes, thyroid diseases, and other endocrine diseases may also be autoimmune, as well as some neurologic diseases and blood diseases. Many gastrointestinal illnesses are associated with abnormalities of the immune system. More than one autoimmune disease may be found in the same patient, or members of a patient’s family may have different autoimmune diseases. It is important to look for those patterns to help diagnose some of these conditions, because diagnosis is often difficult. These diseases can get better or worse in cycles and more symptoms can occur over time. Often, the symptoms are treated while the entire process of disease is unfolding. Patience, thoroughness, and keeping an open mind will help to diagnose patients who have these relatively rare diseases.