Systemic lupus erythematosus (SLE) is a chronic inflammatory disease, which can affect the skin, joints, kidneys, lungs, nervous system and other organs of the body. The disease is characterized by the presence of a number of autoaintibodies (Antibodies directed against one’s own body). The clinical course of SLE is characterized by periods of remissions and chronic or acute relapses. Women, especially in their 20s and 30s, are affected more frequently than men. Men though less frequently affected than men tend to have severe disease.
What are the clinical manifestations of the disease?
Patients with SLE may develop multiple symptoms depending on the inflammatory involvement that can affect virtually every organ. Fatigue, fever, and weight loss are typically present some time during the course of the disease, occurring in 50 to 100 percent of patients.
Arthritis (Joint pain & swelling)
Joint symptoms occur in over 90 percent of patients and are often the earliest manifestation. Only a few joints are usually affected, especially the hands, but any join can be affected. The arthritis is moderately painful, and rarely deforming.
Cutaneous (Skin involvement)
Most patients have skin diseases at some time during the course of the illness. The most common lesion is a butterfly shaped red rash, over the cheeks and nose, which appears after sun exposure. It lasts only a few days, but often recurs. Hair loss is common, but baldness is not. Many patients develop oral ulcers, which are usually painless.
Skin rash in SLE
Renal (Kidney involvement)
Renal (kidney) involvement is common in SLE. Inflammation of the filtering device in the kidneys (the glomerulus), can occur (glomerulonephritis). Swelling of the body, high blood pressure and reduced function of the kidneys characterize kidney involvement. Symptoms due to kidney disease range from none to those of severe kidney failure. Damage to the glomerulus allows red blood cells and protein into the urine from the blood. This is usually only detectable through laboratory tests. Kidney involvement is clinically apparent in approximately 50 percent of patients. However, most patients with SLE have subclinical kidney disease that can be demonstrated by renal biopsy. Several forms of glomerulonephritis can occur and renal biopsy is useful to define the type and extent of renal involvement.
Central nervous system (Brain)-Neurologic complications include cognitive defects, anxiety, depression, psychosis, and seizures (epilepsy).
Hematologic (Blood)-Patients with SLE frequent development abnormalities in each of the three blood cell lines.
• Leukopenia (low WBC count) is common. While diagnostically useful, it is usually not symptomatic unless severe.
• Many patients have a mild anemia.
• Thrombocytopenia (Low platelet count) is also frequently seen. However, bleeding usually occurs only with platelet counts below 25,000/mm3.
Heart can get affected in several ways. Inflammation can occur in the outer covering of the heart (pericardium) resulting fluid accumulation around the heart (Pericarditis). Endocarditis (inflammation of the inner lining of the heart) is usually clinically silent but can produce valvular insufficiency. There is also an increasing frequency of coronary artery disease.
What are the precipitating factors?
1. Exposure to the sun, and other sources of ultraviolet light (especially UV-B, and to some extent UV-A) may cause exacerbations or even induce the first sign of lupus. The relapse is usually limited to a rash, although other symptoms can also develop.
2. Infections can initiate lupus or cause a relapse.
3. Stress has been implicated in causing exacerbations, particularly of mild disease.
4. Surgery is another insult that can increase lupus activity. The mechanism is unclear, but may be related to the release of nuclear and other antigens into the bloodstream where they bind to circulating antinuclear antibodies to form immune complexes.
5. Pregnancy can cause an exacerbation or even trigger the first symptoms of lupus; a relapse is more likely to develop in the postpartum period. Therapeutic abortions can also induce a relapse, perhaps via mechanisms related to pregnancy or to the surgery itself.
What is the significance of kidney involvement?
Kidney involvement in SLE is called lupus nephritis. Abnormality may vary from mild (detected only on electron microscopic examination of the kidney tissue) to severe characterized by kidney failure. Identification of the exact nature of kidney involvement is important as the prognosis of SLE is determined by the extent of kidney involvement. Often there is a lack of correlation between the severity of kidney involvement and urine examination findings. The only way to assess the degree of kidney involvement is by doing biopsy of the kidney.
How is the disease diagnosed?
The disease is suspected on the basis of clinical features and confirmed by investigations. American Rheumatologic Association (ARA) has laid down 11 criteria, 4 of which will have to be present to make diagnosis of SLE. However, it is important to recognize that patients may present with symptoms confined to one organ system. Further, many of the common manifestations are nonspecific. Most physicians rely on the ARA revised Criteria for the Classification of SLE. It should be noted that these criteria were developed for the classification of SLE patients. A patient can be diagnosed to have SLE without satisfying the ARA criteria.
The antinuclear antibody (ANA) test is the best diagnostic test for SLE and should be performed whenever SLE is suspected. The ANA is positive in significant titer in the vast majority of patients with SLE. If ANA is negative the probability of having SLE is very small.
There are two autoantibodies that are highly specific for SLE: anti-double-stranded DNA (dsDNA) antibodies ; and anti-Sm antibodies. Complement levels in the blood are reliable markers of disease activity. Active SLE is characterized by low complement levels.
What is the treatment of SLE?
There is no permanent “cure” for SLE. The purpose of the treatment is to reduce symptoms, limit damage to vital organs, and to reduce the risk of recurrence are available. Diet and nutrition, exercise, and preventive measures including immunizations, avoiding certain medications, and issues related to pregnancy are among the most important general issues for patients with SLE.
A number of medications are commonly used in the treatment of SLE.Nonsteroidal antiinflammatatory drugs (NSAID) (ibuprofen ,Diclofenac and Valdecoxib) are generally effective for joint pain due to arthritis.Systemic corticosteroids are the mainstay of treatment in SLE. Prednisolone is initiated at a dose of 1 mg /Kg daily in divided doses. In severe cases methylprednisolone 20 mg /Kg daily may be administrated intravenously for three days followed by 0.5 mg/Kg of prednisolone daily. Immunosuppressive agents are used for patients with significant organ involvement of kidneys, blood, lungs, or central nervous system. These drugs include azathioprine, cycloposphamide and mycophenolate mofetil.
Azathioprine may be given 2 mg/ Kg daily orally. Blood counts need to be checked frequently. This drug in combination with prednisolone has been found to be quite effective when there is significant kidney involvement. The other combination is monthly intravenous injections of cyclophosphamide along with prednisolone. This has been found to be effective in the treatment of severe type of kidney involvement due to SLE. However, data from CMC Vellore has shown that azathioprine is as effective as cyclophosphamide in the treatment of lupus nephritis. Furthermore, severe infections were more common in patients who received cyclophosphamide. Mycophenolate mofetil is a relatively new drug used in the treatment of lupus nephritis. Studies have shown this drug to be useful when the disease is refractory to other drugs.
In refractory cases modalities like intravenous immune globulin, cyclosporine and stem cell transplantation may be attempted.
Women with SLE should not become pregnant until the disease has been controlled completely for at least six months. Active SLE may cause may result in miscarriage and foetal abnormalities. Furthermore, flaring up of SLE can occur during pregnancy.
Women with SLE who have experienced repeated miscarriages or have had problems with blood clots should be screened for antibodies in the blood (antiphospholipid antibodies). If such antibodies are present, some type of blood thinning treatment (anticoagulation) may be necessary.
SLE can run a varied clinical course, ranging from a relatively benign illness to a rapidly progressive disease with severe organ failure and death. Most patients experience periods of relapse and remissions, which may be associated with the use of high dose steroids during the treatment of severe flares.
Poor prognostic factors-Poorer survival in patients with SLE is also associated with the presence of the following patient specific characteristics:
• Male sex
• Young age
• Older age
• Poor socioeconomic status
• Presence of antiphospholipid antibodies
Side-effects of treatment
Despite the reduction in long-term mortality, patients with SLE are still at risk for significant illness due both to active disease and the side effects of drugs such as corticosteroids and cytotoxic agents. As examples, use of steroids can lead to generalized thinning of the bones (osteoporosis) or localized damage to the bones of the hip and knee (avascular necrosis). Steroids can also cause tiredness, memory difficulties, and difficulty in concentrating. Side-effects become particularly important problems as patients live longer with their illness. Cytotoxic drugs like cyclophosphamide can reduce the resistance power of the body resulting in infections.