Systemic Lupus Erythematosis (SLE) is an autoimmune disorder of connective tissue with multi-system involvement and usually proceeds by remissions and relapses. It may begin insidiously or acutely and subacutely. Many cases present with arthralgia for months before characteristic rashes appear and suspicion about the disease is entertained.
Systemic Lupus Erythematosis (SLE) is widely prevalent all over the-world. It occurs in women 3-5 times as often as in men and usually begins around the age of 20. Women in reproductive age group are commonly involved but the disease is also common in paediatric age group and elderly.
Between 15-17% of lupus patients first develop their disease after the age of 60 years. The presentation and course of disease in elderly is different from that of young patients.
The exact aetiology of the disease is unknown. A number of factors ranging from genetic, environmental, sex hormones to drugs have been incriminated. Genetic predisposition is indicated by higher incidence of the disease in identical twins.
First degree relatives of patients of Systemic Lupus Erythematosis (SLE) have 5-10% chances of inheriting the disease. HLA type DR2, DR3 and inherited deficiency of Cl, C2 and C3 complements increase susceptibility to the disease.
Environmental factors like ultraviolet light, viruses, bacterial infections, female hormones all contribute to the pathogenesis. Drugs like hydralazine and procainamide are associated in the production of disease.
Systemic Lupus Erythematosis (SLE) is a multi system disease with features suggestive of autoimmune mechanism. A number of antibodies are produced against several nuclear antigens and these include antinuclear antibodies (ANA) against DNA, Histones, Nucleolar antigens and non-histone proteins bound to RNA.
There is suppression of T-lymphocyte function with activation of polyclonal B cells. Interaction of auto antibodies with their antigens results in the formation of immune complexes which are deposited in various organs.
Immune complex mediated tissue damage occurs. Pathology of the disease is characterized by wide spread damage affecting capillaries, arterioles and venules. There is inflammation with fibrinoid change.
Collagen scleroisis and degeneration of the wall of small blood vessels. Predominant cells include plasma cells and lymphocytes. Haematoxylin bodies along with immune complex deposition arc seen in inflammatory infiltrates.
Systemic Lupus Erythematosis is variable in its presentation. It varies from mild to persistent forms interspersed with periods of remissions and exacerbation. Systemic symptoms includes fever, general malaise, tiredness, fatigue and weight loss. Joint involvement along with skin lesions form the common mode of presentation. Later in the disease various organs are involved.
More than 80% of all cases of Systemic Lupus Erythematosis (SLE) experience arthralgia which in some take up the form of arthritis which involves small joints of the hand along with large joins like wrists hip and knees. Joint involvement closely resembles that of Rheumatoid arthritis.
In some joint involvement is transient while others have features of puffiness of hands and feet, myositis, tenosynovitis and fascitis. Subcutaneous nodules could be present during the course of the disease. Bony erosions and joint deformities are uncommon.
These are the most prominent and specific of the disease seen in more than 50% of the patients. Classically there is ertythematous, flat or raised maculopapular eruption present over the cheeks, and bridge of the nose forming a Butterfly type of rash. There is increased photo-sensitivity and ultraviolet light exacerbates it.
Chronic cutaneous form of lupus (CCLE) has well defined discoid lesions involving principally the face. There is wide spread cutaneous involvement of hands, limbs and trunk. Erythematous lesions either oval or round with follicular plugging and telengactesia may be seen. There is atrophy and scarring and when this involves the scalp. Hair loss (Alopecia) may occur.
Mucous lesions in SLE are not common. They may be in the form of small painless ulcers in the mouth.
Heart is involved in more than 40% of cases. Cardiac involvement includes Pericarditis, pericardial effusion and myocarditis. An important lesion is endocarditis which involves the mitral valve leaflets, the non-bacterial vegetations forming on either side of leaflets (Libman-Sacks endocarditis).
Aortic valve lesions, congestive heart failure and cardiac tamponade are uncommon. Conduction defects are seen in come cases of Systemic Lupus Erythematosis (SLE). Cutaneous vaseulitis in the form of Raynaud’s phenomenon, purpuric lesions, necrotic ulcers of the fingers and livedo reticularis is seen in 10-20% of patients.
Pleurisy and pleural effusion are the commonest manifestation of Systemic Lupus Erythematosis present in more than 50% of patients. Most patients do not manifest them early. It is usually inter-current infections which bring them to attention. Interstitial pneumonitis leading to fibrosing alveolitis develops in few. Pulmonary hypertension and ARDS (Adult Respiratory distress syndrome) are rare complications.
The kidneys are affected in 70% of cases of Systemic Lupus Erythematosis as evidenced by proteinuria, casts and microscopic hematuria. Long-standing cases present with acute nephritis syndrome, nephrosis, hypertension of renal origin and renal failure. Most patients have immune complex deposits in their kidney.
Histologic changes in kidneys consist of focal, membrano and diffuse proliferative glomerulonephritis. In addition to these there may be glomerular necrosis, cellular epithelial crescents and necrotizing vasculitis. Interstitial fibrosis and tubular atrophy lead to renal failure. Focal proliferative and membranous forms of nephritis carry poor prognosis.
Central nervous system
Neuropsychiatric disturbances in the form of convulsions (Grand Mal, Petit Mal, Focal). Psychosis organic brain syndrome, lupus headache (intractable Headache not relieved by analgesics).
Extra pyramridal disorders, cerebellar Ataxia, subarachnoid haemorrhage, aseptic meningitis and peripheral neuropathy are seen. Any part of the nervous system may be involved. Often the mental dysfunction is so mild that it may be over looked.
These include dryness of the eyes, conjunctivitis episcleritis. Optic neuritis and retinal changes (Haemorrhage & white exudates (cytoid bodies). Because of retinal vasculitis in some patients blindness may develop.
Most patients suffer from chronic form of normocytic normochronie type of anaemia, Leukopenia with lymphopenia, thrombocytopenia and autoimmune type of haemolytic anaemia.
Mild to moderate splenomegaly and lymphadenopathy mainly of cervical and axillary regions are present in more than 50% of cases.
Non-specific symptoms are seen. These include hepatomegaly, acute pancreatitis and mesenteric vasculitis which can cause acute abdominal pain with vomiting and diarrhoea. This is a serious medical emergency and may lead to perforation and death.
Late onset Systemic Lupus Erythematosis
Patients with late onset lupus have over all milder disease. There is more of polyarthritis, serositis and pulmonary involvement but less involvement of renal and central nervous system. Some may go into end stage renal disease or deterioration in mental functions.
These may be specific or non-specific. Non-specific tests include mild to moderate anaemia, leukopenia with lymphopenia and thrombocytopenia. ESR is markedly elevated. Urine examination shows proteinuria, microscopic hematuria, cellular and granular casts. Serum ceratinine levels are raised. There is increase in total serum globulins with reversal of albumin / globulin ratio.
L.E. cell phenomenon refers to the homogenization of neutrophilic nuclei and probably of lymphocyte nuclei under the influence of antinuclear antibodies and their subsequent ingestion by healthy granulocytes.
This test is reasonably specific and is positive in 80-90% cases of Systemic Lupus Erythematosis. Anti nuclear antibodies (ANA) presence confirms the diagnosis especially when present in high titres. A negative ANA excludes the diagnosis of SLE. Presence of anti-ds DNA and anti-SM antibodies are also specific (>90%t Changes in complement levels and anti-ds DNA titres serve as markers of activity of disease.
Renal biopsy can provide important information about renal involvement and prognosis about the disease.
It is mainly based upon clinical features and laboratory investigations. American college of Rheumatology has specified criteria for diagnosing Systemic Lupus Erythematosis (SLE). It was initially meant for epidemalogical purposes but now they form basis of diagnosing the disease.
Differential diagnosis should be form polymyalgia rheumatica, Rheumatoid Arthritis, Collagen disorders, Stevens Johnson syndrome etc.
Management It is mainly empirical since there is no cure. Mild cases are managed symptomatically with analgesics and NSAIDS. Patient should avoid sunlight and offending drugs which may worsen the condition. The drug treatment consists of anti-malarials, corticosteroids and immuno suppressive agents.
American College of Rheumatology criteria for the classification of SLE (1982, 1997)
1. Malarrash –
2. Discoid rash
4. Oral or nasopharyngeal ulceration
5. Serositis (pleuritis, pericarditis)
6. Renal disease (proteinuria > 0.5 g/day, cellular casts, RBCs)
7. Neuropsychiatric disorders (seizures or psychosis)
8. Haematological abnormalities (haemolytic anaemia, thronibocytopenia, leucopeniá\ lymphopenia).
9. Arthritis (non-erosive polyarthritis of small joints)
10.Antinuclear antibody (abnormal titres)
11.Immunological abnormalities (anti-ds DNA in abnormal titres, presence of anti- SM antibody and anti-phospholipid antibodies.) Abnormal serum levels of IgG or 1gM anti cardiolipin antibodies. Positive test result for lupus anticoagulant using standard method. False positive serologic tests for syphilis.
For identifying patients of SLE, at least four or more of the above criteria must be present.
These are useful for suppressing the disease. Main drugs in this groups are 4-aminoquinolones (Chloroquine and Hydroxychloroquine). Chloroquine is more effective than hydroxychoroquine (HCQ) for arthralgia and skin lesion.
Its main draw back is its toxic effect on retina which may lead to retinal damage and corneal deposits. Dose is 500 mg (250 mg chloroquine base) daily for 2 weeks followed by 250 mg daily for 3-4 months.
Recommended dose of hydroxychloroquine is 400mg daily for 4-6 weeks. Boths the drugs are useful for minor manifestations of the disease. Besides retinal toxicity other side effects include rash, neuropathy and G.I disturbances.
These are main stay of treatment in severe and disabling manifestation of Systemic Lupus Erythematosis (SLE). Dose is 1-2 mg/kg body weight of prednisolone per day. Once the acute symptoms are controlled the dosage of drug is reduced and patient maintained on a smaller dose. The activity of the disease is assessed by monitoring various parameters including ESR.
Immuno suppressive drugs
These include azathioprine and cyclophosphamide. Cyclophosphamide is probably the most effective but toxic. It can be given orally in dose of 1.5-2.5 mg/kg body weight. Main side effect is bone marrow suppression.
Azathioprine in the dose of 2- 3 mg/day orally is least toxic. In low doses it can be combined with cyclophosphamide. These drugs have steroid sparing effect and are employed in patient with advanced disease with serious manifestations.
Immunosuppressive drugs may have to be given for prolonged periods and so a watch should be kept on their side effects such as bone marrow suppression, hepatoxicity and bladder toxicity.
Patients of Systemic Lupus Erythematosis (SLE) who have fever, arthratgia, serositis and myalgia may be treated with NSAIDs. They not only provide relief but also tend to suppress the disease. Local application of creams containing hydrocortisone also helps in controlling local flare ups of the disease.
The over all management of a case of SLE shall depend on the stage at which the patient presents. Patients with severe form of disease and various systemic manifestations shall requie not only steroids but also cytotoxic agents.
Course and prognosis
Systemic Lupus Erythematosis (SLE) is characterized by periods of remission and relapses. With advances in treatment, survival rate of 100% has been seen for 5 years. In patients with uncontrolled disease and those with fulminating course, prognosis is poor.