Systemic Lupus Erythematosus PDF

SYSTEMIC LUPUS ERYTHROMATOSIS DR: HEMN MAHMOOD AGHA FIBMS RHEUMATOLOGY MRCP (UK) RHEUMATOLOGY  Systemic lupus erythematosus (SLE, ‘lupus’) is a rare disease with a prevalence that ranges from about 0.03% in Caucasians to 0.2% in Afro-Caribbeans. 90% of affected patients are fema...

SYSTEMIC LUPUS ERYTHROMATOSIS DR: HEMN MAHMOOD AGHA FIBMS RHEUMATOLOGY MRCP (UK) RHEUMATOLOGY  Systemic lupus erythematosus (SLE, ‘lupus’) is a rare disease with a prevalence that ranges from about 0.03% in Caucasians to 0.2% in Afro-Caribbeans. 90% of affected patients are female and the peak age at onset is between 20 and 30 years. SLE is associated with considerable morbidity and a fivefold increase in mortality compared to age- and gender-matched controls. mainly because of an increased risk of premature cardiovascular disease.  Pathophysiology The cause of SLE is incompletely understood but genetic factors play an important role.the disease is strongly associated with polymorphic variants at the HLA locus. environmental factors that cause flares of lupus, such as ultraviolet light and infections, increase oxidative stress and cause cell damage. autoantibody production and immune complex formation are thought to be important mechanisms of tissue damage in active SLE, leading to vasculitis and organ damage. SLE may occur because of defects in apoptosis or in the clearance of apoptotic cells, which causes inappropriate exposure of intracellular antigens on the cell surface, leading to polyclonal B- and T-cell activation and autoantibody production.  Pathophysiology cont. From an immunological standpoint, the characteristic feature of SLE is autoantibody production. These autoantibodies have specificity for a wide range of targets but many are directed against antigens present within the cell or within the nucleus. SLE is also associated with inherited mutations in complement components C1q, C2, C3 and C4, in the immunoglobulin Fc receptor or in the DNA exonuclease TREX1. Clinical features  Clinical features Symptoms such as fever, weight loss and mild lymphadenopathy may occur during flares of disease activity, whereas others such as fatigue and low-grade joint pains can be constant and not particularly associated with active inflammatory disease. Arthralgia is a common symptom, occurring in 90% of patients, and is often associated with early morning stiffness. Tenosynovitis may also occur but clinically apparent synovitis with joint swelling is rare. Joint deformities may arise (Jaccoud’s arthropathy) as the result of tendon damage but joint erosions are not a feature.  Clinical features cont. Raynaud’s phenomenon is common and may antedate other symptoms by months or years. SLE can present with Raynaud’s phenomenon, along with arthralgia or arthritis. Secondary Raynaud’s phenomenon associated with SLE and other AICTDs needs to be differentiated from primary Raynaud’s phenomenon, which is common in the general population (up to 5%). Features in favor of secondary Raynaud’s phenomenon include age at onset of over 25 years, absence of a family history of Raynaud’s phenomenon, male sex and ulceration Examination of capillary nail-fold loops using an ophthalmoscope. Clinical features cont. Skin manifestation The skin is commonly involved in SLE, and many SLE skin eruptions are precipitated by exposure to ultraviolet light. The main types of skin involvement are: The classic facial rash (up to 20% of patients). This is erythematous, raised and painful or itchy, and occurs over the cheeks with sparing of the nasolabial folds. A discoid rash characterized by hyperkeratosis and follicular plugging, with scarring alopecia if it occurs on the scalp. Diffuse, usually non-scarring alopecia, which may also occur with active disease. Urticarial eruptions. Livedo reticularis and can become frankly vasculitic, if severe. Discoid rash MALAR RASH Raynaud’s phenomenon SCLE Discoid rash and scary alopecia  Clinical features cont. Kidney Renal involvement is one of the main determinants of prognosis and regular monitoring of urinalysis and blood pressure is essential. The typical renal lesion is a proliferative glomerulonephritis characterized by heavy hematuria, proteinuria and casts on urine microscopy. Cardiovascular The most common manifestation is pericarditis. Myocarditis and Libman–Sacks endocarditis.The risk of atherosclerosis is greatly increased. This is thought to be due to the adverse effects of inflammation on the endothelium, chronic glucocorticoid therapy and the procoagulant effects of antiphospholipid antibodies.  Clinical features cont. Lung Lung involvement is common and most frequently manifests as pleuritic pain (serositis) or pleural effusion. Other features include pneumonitis, atelectasis, reduced lung volume and pulmonary fibrosis that leads to breathlessness. The risk of thromboembolism is increased, especially in patients with antiphospholipid antibodies. Neurological Fatigue, headache and poor concentration are common and often occur in the absence of laboratory evidence of active disease. More specific features of cerebral lupus include visual hallucinations, chorea, organic psychosis, transverse myelitis and lymphocytic meningitis.  Clinical features cont. Hematological Neutropenia, lymphopenia, thrombocytopenia and hemolytic anemia may occur, due to antibody-mediated destruction of peripheral blood cells. The degree of lymphopenia is a good guide to disease activity. Gastrointestinal Mouth ulcers may occur and may or may not be painful. Peritoneal serositis can cause acute pain. Mesenteric vasculitis is a serious complication, which can present with abdominal pain, bowel infarction or perforation. Hepatitis is a recognized, though rare, feature.  Pediatric disease Renal disease and cutaneous manifestations are more frequent in juvenile-onset SLE compared to disease in adults. Similarly, there is subsequently a higher incidence of renal disease, malar rash, Raynaud’s phenomenon, cutaneous vasculitis and neuropsychiatric manifestations than in adults.  Investigations Checking of ANAs, antibodies to extractable nuclear antibody ENAs and complement, routine hematology, biochemistry and urinalysis are mandatory. Patients with active SLE test positive for ANA. Some authorities believe that ANA-negative SLE occurs (e.g. in the presence of antibodies to Ro) Anti-dsDNA antibodies are positive in many, but not all. Patients with active disease tend to have low levels of C3 due to complement consumption high titer of Anti-dsDNA antibodies. A raised ESR, leucopenia and lymphopenia are typical of active SLE, along with anemia, hemolytic anemia and thrombocytopenia. CRP is often normal in active SLE, except in the presence of serositis or infection. The classification criteria for SLE The diagnosis is based on a combination of clinical features and laboratory abnormalities. To fulfil the classification criteria for SLE, at least 4 of the 11 factors must be present or have occurred in the past  Management The therapeutic goals are to educate the patient about the nature of the illness, to control symptoms and to prevent organ damage and maintain normal function. Patients should be advised to avoid sun and ultraviolet light exposure and to employ sun blocks (sun protection factor 25–50).  Mild to moderate disease Patients with mild disease restricted to skin and joints can sometimes be managed with analgesics and hydroxychloroquine. Frequently, glucocorticoids are necessary (prednisolone 5–20 mg/day), often in combination with immunosuppressants such as methotrexate, azathioprine or mycophenolate mofetil (MMF). Increased doses of glucocorticoids may be required for flares in activity or complications such as pleurisy or pericarditis. The monoclonal antibody belimumab, which targets the β-cell growth factor, has recently been shown to be effective in patients with active SLE who have responded inadequately to  Severe and life-threatening disease therapy High-dose glucocorticoids and immunosuppressants are required for the treatment of renal, CNS and cardiac involvement. A commonly used regimen is pulsed methylprednisolone (10 mg/kg IV) plus cyclophosphamide (15 mg/kg IV), repeated at 2–3-weekly intervals for six cycles. Cyclophosphamide may cause hemorrhagic cystitis but the risk can be minimised by good hydration and co-prescription of mesna (2-mercaptoethane sulfonate), which binds its urotoxic metabolites. Because of the risk of azoospermia and premature menopause, sperm or oocyte collection and storage need to be considered prior to treatment with cyclophosphamide. Severe and life-threatening disease therapy cont. MMF has been used successfully with high-dose glucocorticoids for renal involvement with results similar to those of pulsed cyclophosphamide but fewer adverse effects. Belimumab in combination with standard therapy significantly decreases disease activity in SLE patients and is safe and well tolerated. Its role in patients with renal and neurological disease is still under investigation. Rituximab has been reported as being effective in selected cases. SLE TREATMENT ALGORITHM  Maintenance therapy Following control of acute disease, a typical maintenance regimen is oral prednisolone in a dose of 40–60 mg daily, gradually reducing to 10–15 mg/day or 5mg or less by 3 months. Azathioprine (2–2.5 mg/kg/day), methotrexate (10–25 mg/week) or MMF (2–3 g/day) should also be prescribed. The long-term aim is to continue the lowest dose of glucocorticoid and immunosuppressant to maintain remission. Cardiovascular risk factors, such as hypertension and hyperlipidemia, should be controlled and patients should be advised to stop smoking. Patients with SLE and the antiphospholipid antibody syndrome, who have had previous thrombosis, require life-long warfarin therapy. SLE patients are at risk of osteoporosis and hypovitaminosis D, and should be screened with biochemistry and DXA scanning accordingly.