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January 2011: Taking the Mystery out of Autoimmune Diseases

01 Jan 2011

Dr. Laisvyde Smajkic is fellowship-trained in rheumatology and has worked throughout Chicago as a specialist in arthritis and autoimmune diseases. Her focus is on management and education of rheumatic diseases, diagnostic and therapeutic arthrocentesis, glucocorticoid and cytotoxic therapy, and administration of biologic agents. Dr. Smajkic leads the Arthritis Clinic at Weiss. She is fluent in English, Lithuanian and Russian, and is board certified in internal medicine.

Laisvyde Smajkic, M.D.
Rheumatologist and Internist
Weiss Memorial Hospital
(773) 913-2585

Autoimmunity
Our body’s immune system has the ability to distinguish self from non-self. Usually, the immune system cells (called lymphocytes) are tolerant to self, meaning they fight body invaders such as viruses, bacteria and parasites but recognize other cells of the organism as belonging to  “self” and do not react to them. Autoimmunity results when there is a breakdown of the mechanism that regulates immune tolerance. Autoimmunity, however, is not always pathological, meaning it is not always the cause of a problem in a person. Autoimmunity only signifies the presence of autoantibodies (proteins produced against certain molecules in cells of our bodies) or high reactivity of lymphocytes against self-antigens but does not mean it is harmful to the body.

Autoimmunity may be seen in normal individuals (especially the elderly) and may develop during various infectious conditions. Autoimmunity can develop in several different ways:

  • Predisposition by external agents (bacteria, viruses) or internal abnormalities within the immune system cells.
  • A mechanism called “molecular mimicry” or cross-reactivity when structural similarity between the part of a microbe and self-antigen can cause confusion in the immune system and autoreactive lymphocyte development. Intense and prolonged stimulation of B lymphocytes can lead to production of autoantibodies.
  • Unmasking of autoantigens as a result of trauma, inflammation, drug exposure or even as we age, may initiate the autoimmune process.
  • Lastly, immune cells and pathways that regulate the overall function of the immune system can become harmful, causing damage to self.

Autoimmune disease
Autoimmune disease (AID), on the other hand, is the result of some type of tissue or organ injury, which is caused by an abnormal immunologic reaction against its own tissue. Similar pathogenetic mechanisms that result in autoimmunity also are implicated in AID, however, usually many abnormalities need to be present in  addition to other important factors such as age, gender/hormone (AID is much more common in women) and genetic background.

There is no single gene associated with AID. However, we know that many genes are more common in certain autoimmune diseases and so we call them “polygenic” diseases.

Tissue injury and organ dysfunction in autoimmune disease occur by various mechanisms; they are either antibody-mediated or cell-mediated processes. Autoantibodies then cause damage either by blocking or stimulating cell receptors, activating other proteins in the blood (complements), or forming immune complexes which deposit in the vessels of various organs thereby causing their dysfunction.

Types of autoimmune disease
There are two major types of autoimmune diseases: organ-specific and systemic. Organ-specific AID causes dysfunction of a particular organ such as the thyroid (Hashimoto’s thyroiditis, Grave’s disease), pancreas (Type 1 diabetes mellitus), liver (autoimmune hepatitis), skin (Pemphigus vulgaris), blood cells (autoimmune hemolytic anemia, idiopathic thrombocytopenic purpura) or brain (multiple sclerosis).

Patients with these diseases are usually treated by doctors of respective specialties. Conversely, systemic autoimmune diseases affect multiple, diverse organs and tissues, and their autoimmune manifestations are likely to be pathologic in the organ pathology. Systemic lupus erythematosus (SLE) is the prototype of this type of disorder. Systemic AIDs are sometimes called rheumatic AIDs and are cared for by rheumatologists. The most common rheumatic AIDs are SLE, rheumatoid arthritis, systemic sclerosis, Sjogren’s syndrome, antiphospholipid syndrome, idiopathic inflammatory myopathies and vasculitides.

Systemic lupus erythematosus
Systemic lupus erythematosus (SLE) classically affects women of childbearing age though men and the elderly also can develop SLE. SLE can involve almost any organ system: from skin, joints, serosal linings of heart and lungs, to kidneys, blood cells and brain. Typically, only a few organs are affected in a particular patient but disease burden increases over time. Patients frequently have systemic symptoms of malaise, weight loss, fever and lymphadenopathy. The hallmark of the disease is positive antinuclear antibodies (ANA) in the blood. SLE as a rule has a fluctuating course with remissions and flares. In some patients, it is mild and stable while in others it can present suddenly with life-threatening manifestations.

Treatment for patients with SLE consists of corticosteroids (prednisone) for acute flares and immunosuppressive/immunomodulating agents, depending on which organ system is involved, for prevention of lupus flares and to keep disease in check. Patients with SLE must remember to avoid sun exposure as mush as possible and wear sunscreen for all outside activities because sun exacerbates SLE.

Rheumatoid arthritis
Rheumatoid arthritis (RA) is also more common in women; the disease usually starts in the 40s-50s but can begin later in life as well. Joints are the main organs affected. Universal symptoms are joint pain (most frequently of the small joints of the hands), swelling, pronounced morning stiffness, and in severe cases – joint deformities. Patients with RA can also have fatigue and weight loss, however, other internal organ manifestations are much rarer when compared to patients with SLE. Infrequently, RA can be associated with vasculitis (inflammation of blood vessels). RA is diagnosed by history and physical exam and supporting laboratory tests (most, but not all, patients have positive antibodies “rheumatoid factor” and/or “anti-cyclic citrullinated peptides” and elevated inflammatory markers in blood) as well as radiologic studies (joint X-rays or sometimes ultrasound or MRI).

Treatment of RA involves reducing joint inflammation with corticosteroids (prednisone) and non-steroidal anti-inflammatory medicines (NSAIDS such as naproxen), disease-modifying anti-rheumatic drugs (DMARDs) such as methotrexate (Trexall), and in some patients – the newest class of RA medications biologic agents (TNF antagonists such as adalimumab, etanercept or infliximab, B cell depleting therapy such as rituximab, or others). Vital treatment for patients with RA is physical therapy with focus on joint range of motion and strengthening exercises.

Systemic sclerosis
Systemic sclerosis (SSc) is a chronic multisystem disorder with the unique feature of thickening of the skin and connective tissue accumulation in the internal organs such as kidneys, lungs, heart and gastrointestinal tract. Apart from excessive fibrosis, SSc also manifests vasculopathy, meaning that vessels gradually become thinner, obliterated and eventually compromise blood flow to the internal organs. Raynaud’s phenomenon, which presents as fingertip or toe pain and/or numbness and color changes to white, red or purple in the cold environment, is a very common symptom of SSc, although it can occur in other autoimmune diseases or even in healthy people. The degree of skin involvement differs in each patient.

There are two major subsets of SSc: limited (only mild skin fibrosis and usually better prognosis) and diffuse (more severe skin involvement and typically worse prognosis). Antinuclear antibody is nearly always positive as is in the case of SLE. Apart from skin changes, patients frequently complain of heartburn, difficulty swallowing, alternating diarrhea and constipation; if their lungs are involved, they develop progressive shortness of breath; if heart or kidneys get affected, these manifestations can be life-threatening and require immediate medical care.
Unfortunately, there is no cure or even very effective therapy for SSc. Some medications such as those used to treat Raynaud’s or heartburn can be very effective for a particular symptom. In patients with lung involvement we occasionally try immunosuppressive medications (such as cyclophosphamide) that can help to stop the disease. In some patients, skin changes regress over time spontaneously, in others they stabilize over time, and in some people the disorder continues to progress gradually.

Sjogren’s syndrome
The main aspect of Sjogren’s syndrome (SjS) is dry mouth and dry eyes caused by lymphocyte attack on salivary and lacrimal glands, respectively. Parotid glands can sometimes get very enlarged and painful. SjS commonly causes fatigue and joint aches. Rarely, SjS can affect lungs, heart or even central nervous system, and these complications can be severe. Fortunately, in most patients symptoms are mild. Sjogren’s syndrome is classified into primary (when it occurs by itself) or secondary (when it is associated with another disease such as RA or SLE). Majority of patients with SjS test positive for autoantibodies (called SSA and SSB antibodies) in their blood.

Treatment of patients with SjS consists of measures and medications to restore eye and mouth lubrication. Frequent visits to the eye doctor and the dentist are very important. For many patients hydroxychloroquine (Plaquenil) is beneficial for fatigue and arthritis. Only rarely do patients need aggressive immunosuppressive therapy.

Antiphospholipid syndrome
Antiphospholipid syndrome signifies the presence of autoantibodies which interfere with regulation of blood clotting. Patients with this syndrome are prone to develop blood clots in their veins, arteries or smallest vessels, capillaries. Women can suffer pregnancy loss (usually in the second trimester) if blood clots develop in the blood vessels which supply nutrients to the placenta. Antiphospholipid syndrome (APS) is categorized into primary (when it occurs alone) and secondary (when it is associated with another disease, most commonly SLE).

Management of APS involves life-long anticoagulation (“blood-thinning” medications) and avoidance of factors that could precipitate blood clot formation. Women taking birth control pills should avoid medication containing estrogen because it can precipitate blood clotting.

Idiopathic inflammatory myopathies (dermatomyositis and polymyositis)
Polymyositis and dermatomyositis share the common feature of muscle inflammation. Dermatomyositis has very specific skin changes that make it easier to diagnose. Dermatomyositis generally affects children and younger adults, whereas polymyositis is more common in elderly. Both of these autoimmune disorders have a higher risk (compared to the general population) of associated malignancy, therefore doctors ensure that patients with these diseases are up to date with their cancer screening tests. The main feature of myositis is muscle weakness that can occur in the arms and/or legs. Proximal parts of the arms and legs (thighs) are classically affected so the patients complain of difficulty reaching things overhead, brushing their hair or trouble getting out of a chair or bathtub without assistance. Both diseases can cause interstitial lung disease. When inflammation occurs in throat muscles it can cause difficulty swallowing. To confirm inflammatory myopathy, diagnostics studies such as laboratory tests for muscle enzyme levels and autoantibodies, electromyography, thigh MRI and sometimes muscle biopsy are performed.

Dermatomyositis and polymyositis are treated with high-dose steroids which are later replaced by other immunosuppressive medications. It can take months to years to effectively control the disease; regular visits to the rheumatologist are imperative. Physical therapy with the focus on regaining muscle strength is an essential part of treating myositis.

Vasculitides
While there are many different types of vasculitis they all share one common feature: inflammation and damage of blood vessels. Blood supply dysfunction from vasculitis can eventually injure internal organs. These manifestations can vary greatly from patient to patient, even with the same type of vasculitis.

Vasculitis syndromes are classified by several characteristics, including the size of the vessels involved, the mechanism of how inflammation occurs and if autoantibodies are produced. Overall, it is one of the most challenging areas in medicine. Controlling disease in a patient with vasculitis requires a very close relationship between the patient and the rheumatologist because most of the time powerful immunosuppressive medications (such as cyclophosphamide) are required. Alternatively, for more common and less aggressive vasculitis conditions (such as temporal arteritis) which occur almost exclusively in elderly, corticosteroid therapy with the slow taper over a year or two is usually a very effective therapy.

Rheumatic conditions that mimic systemic autoimmune diseases
A number of rheumatic diseases, while not autoimmune in origin, sometimes present similarly to systemic autoimmune diseases because in addition to causing arthritis they also manifest multiple systemic symptoms. These inflammatory disorders include seronegative spondyloarthropathies (psoriatic arthritis, ankylosing spondylitis, reactive arthritis), crystal arthropathies (gout and pseudogout), and infectious arthritis (such as Lyme disease). Other conditions that rheumatologists regularly treat but do not involve inflammatory processes are osteoarthritis, osteoporosis and fibromyalgia syndrome.

For more information
If you would like more information about autoimmune diseases, or would like an appointment, please call Dr. Smajic’s office at (773) 913-2585.