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Lupus
by Dr Asheesh Mehta March 19, 2015
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Lupus is a type of autoimmune disorder in which inflammation occurs all over the body. In the generalised form the condition is known as systemic lupus erythematosus (SLE). There is also a cutaneous form of lupus affecting only the skin. The immune system of our body normally protects against a wide variety of microorganisms capable of causing disease. It also protects us against undesirable cells within our own body such as cancer cells.

Sometimes, however, the immune system attacks tissues of the body itself with varying degrees of damage to them. This sort of undesirable immune response directed against own tissues is called an autoimmune response and causes autoimmune diseases. More than a hundred different diseases have been identified as being due to autoimmune response and their incidence is highest in industrialized and developed countries, these two circumstances usually going hand in hand.

With increasing industrialisation incidence of autoimmune diseases is also rising in developing countries. Reliable statistics for prevalence of all but the commonest diseases are lacking from many developing countries. Diseases may not be reportable or be reported or be misdiagnosed when adequate health care facilities do not penetrate all levels of society. However, general opinion is that SLE is commoner in developed countries and especially so in Europe. It has however been noted that when it does develop in Asians, the disease is more severe with more complications and a higher mortality. SLE affects women much more commonly than men with about 90 per cent of patients being female. Usual age of onset is between about 15 to 45 years of age.

The exact cause of lupus remains unknown. However, a number of factors increasing susceptibility to development of lupus have been identified. Both genetic and environmental factors are implicated. There is an increased incidence in family members of cases.

Some specific genes are also understood to confer increased risk for SLE occurrence. It is possible that infection by a few viruses could lead to later development of lupus in susceptible individuals. The infection could elicit production of antibodies to antigens that share some characteristics with the body’s own cells. These antibodies would then also act against own cells leading to an autoimmune reaction. Smoking is a risk factor for lupus while breastfeeding is considered to be protective. Some reports suggest that vitamin D deficiency may increase risk for lupus developing. Ultraviolet light exposure is also believed to increase risk. The exact cause, as in most autoimmune diseases, remains unclear.

Symptoms of lupus are highly variable and depend on the organs affected by the disease as well as severity of disease. It is a chronic condition with disease activity varying from time to time. Symptoms wax and wane depending on disease activity. They are quite diverse because lupus has the capability of affecting almost all organs of the body. This is the reason lupus regularly finds itself on the list of great mimickers, a reference to diseases with manifestations easily mistaken for a wide variety of other diseases.

The classical presentation is of fever, joint pain and rash in a young woman. Such a combination of symptoms undoubtedly warrants investigation for lupus. However, manifestation is often with other symptoms. Constitutional symptoms include fatigue, fever, muscle and joint pains and weight loss. Confusing matters is the problem that these constitutional symptoms can be due to the disease itself or may also occur as a side effect of medications used to treat it or to concomitant infective illnesses developing more commonly in lupus patients because of compromised immunity.

Lupus arthritis presenting as joint pain and swelling is also quite common. Multiple joints may be involved in the arthritis. Skin rashes are quite common too. The characteristic rash is a butterfly shaped rash on the cheeks and the bridge of the nose. Other types of skin rashes are also quite common. Photosensitivity, an enhanced sensitivity of skin on exposure to the skin is also a prominent feature in many patients. Amongst organ involvement, the kidneys are most often affected in lupus. Involvement varies from mild to severe. In many people renal involvement can only be detected by urine and blood tests while in others the patient suffers acute or chronic kidney failure.

High blood pressure is often present due to renal changes in lupus. The components of the nervous system, lungs, gastrointestinal tract and the cardiovascular system are also often the target of autoimmune damage in lupus. Various types of neurological syndromes including stroke, psychiatric syndromes, peripheral neuropathy, blindness, myasthenic syndrome, etc occur as part of neurological disease while pulmonary involvement causes problems such as pneumonitis, pleural effusion, pulmonary hypertension, pulmonary interstitial fibrosis.

Gastrointestinal manifestations are not so common but can include jaundice, peritonitis, pancreatitis, etc. Cardiac disease due to lupus too does not occur too commonly but includes ischaemic heart disease due to inflammation of coronary arteries, heart failure due to myocarditis and a form of endocarditis. Reduction of all three cellular components of blood, red blood cells, white blood cells and platelets may occur with resultant anaemia, leukpenia and bleeding disorder on account of thrombocytopenia respectively. In effect, SLE can and does affect most organs and systems of the body. Some of the organs such as the kidneys and skin are involved more often and initial presentation can be with acute or chronic symptoms. When symptoms are atypical, lupus can pose a significant diagnostic challenge and be readily overlooked as the cause of disease by the unwary physician.

There is no specific confirmatory test available to diagnose SLE. Rather the condition is suspected from often characteristic symptoms and examination findings and supported by investigations. In the cases with atypical symptoms and signs and where laboratory reports are not strongly corroborative diagnosis can be difficult. This is especially so because of the protean ways of manifestation of this disease.

The American College of Rheumatology has specified criteria for diagnosis of lupus and presence of any 4 of these 11 criteria is considered as adequate for diagnosis. However, in view of possible overlap of symptoms and signs with other conditions, other conditions, especially infective ones for which specific curative treatment may be available need to be ruled out. Laboratory testing for lupus usually involves a battery of tests for in addition to blood counts and urine analysis, inflammatory markers such as ESR and CRP need to be assayed and tests slightly more specific for lupus such as complement levels are also indicated.

Liver and kidney function tests are also more or less mandatory in such cases. Auto-antibodies are ones that act against own tissues and many different types are detectable depending on the type of autoimmune disease. In lupus, testing for various types of such antibodies is required depending on which organs of the body are affected by the disease. Additionally, a range of imaging tests such as x-rays, CT scan, MRI scan, ultrasound scan, etc may be indicated again depending on the organs suspected to be involved.

Biopsies from affected tissues such as skin, kidney, liver, etc are carried out, the indication again depending on the suspected site of disease. Many of these tests are required not only to establish the diagnosis but also to follow up on response to treatment or progress of disease. In people with SLE not supported adequately by health insurance or by state sponsored medical care this is an expensive proposition.

There is no cure for lupus. Rather, the aim is to control the disease. Since it is a chronic illness with often acute exacerbations off and on, treatment has to be continued long-term and doses and types of medications need to be altered or adjusted depending on degree of response, occurrence of side effects to drugs, etc. Drugs used to treat lupus are directed against the undesirable autoimmune response. Since drugs to selectively reduce only the autoimmune response without affecting normal immunity are not available, they all compromise normal immunity to a greater or lesser extent. A variety of agents including hydroxychloroquine, steroids, methotrexate, azathioprine, etc have been used since many years. They may be used alone or in combination depending on response and toxicity.

In general, women with mainly skin and joint manifestations are considered to have milder disease and do not usually require steroids or other more toxic medications. Kidney disease or nervous system disease warrants aggressive treatment usually involving steroids. Toxicity of steroids is often mitigated by using them in short courses rather than continuing them long-term, wherever feasible.

In the last few years monoclonal antibodies have been approved for treatment of SLE. Although these drugs too are not free from toxicity, they do offer excellent response in many women showing resistance to previous treatment. High cost is a significant drawback for the monoclonal antibody drugs such as Belimumab and Rituximab.
 

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