Presentation on theme: "SYSTEMIC LUPUS ERYTHEMATOSUS (SLE)"— Presentation transcript:
1 SYSTEMIC LUPUS ERYTHEMATOSUS (SLE) Gergely Péter drDefinition: The clinical picture of SLE is variable. The most common form of the disease: young female with non-erosive arthritis, (low grade) fever, elevated ESR, leucopenia (with or without skin and kidney involvement).Epidemiology: Incidence: 0.7/100,000, prevalence 23-50/100,000. In Hungary the expected number of SLE cases may be between 2500 and Female dominance (male: female ratio: 1:9). Familial aggregation is known.
7 Clinical features of SLE Clinical picture: The well known butterfly (malar) rash is relativelyuncommon, but the diagnosis is in most cases easy, if we base it onthe criteria of American Rheumatism Association (ARA).General symptoms: fever, lymphadenomegaly, weight loss are alwayspresent, their severity depends on the intensity of the disease.At first sight, such patient seem to be suffering of an infectious disease.
8 JointsJoints: are frequently involved, moderate swelling and morning stiffness are the dominant features. Unlike in RA, no erosions and deformity is seen. Subluxation and Jaccoud type arthropathy are rare forms of SLE.
27 Renal involvement is observed in 60% of patients Renal involvement is observed in 60% of patients. SLE may manifest as a monosystemic glomerulonephritis, but usually other organs are also involved. Glomerulonephritis is an IC-mediated inflammation with various histological and clinical signs: from mild proteinuria to rapidly progressive glomerulonephritis. Nephrosis syndrome is very common.According to histology, nephritis can be classified. WHO classification is shown below (in parentheses: clinical manifestations)I. normal (no alterations)II. mesangial (mild proteinuria)III. focal segmental (marked proteinuria, positive sediment)IV. diffuse (acute nephritis or nephrosis)V. membranous (nephrosis)VI. sclerosis/end stage.
34 Hematological disorders are very common Hematological disorders are very common. A mild anemia (anemia of chronic disease) is always almost present in active disease, frank hemolysis is rare. Leucopenia is common, but even patients with leukocyte count <2.0 have no problems at all. Lymphopenia can be profound (0.5), granulocytopenia rarely results in infections. Thrombocytopenia is more common in patients with APS.Central nervous system involvement is common, in particular in patients with APS. One of the most reliable method to detect CNS involvement is MRI (however, some foci, seen in MRI may be asymptomatic, therefore the correlation between MRI changes and clinical picture is weak). Psychosis due to corticosteroid treatment is much less frequent that caused by the disease itself. In cuch cases, when in doubt, a bolus corticosteroid is more likely of benefit then withdawal. There are also minor signs: headache, cognitive and emotional disturbances, e.d. depression, etc.
37 Antiphospholipid syndrome (Hughes’s syndrome) A relatively recently decribed syndrome characterized by recurrent venous (or arterial) thromboses, thrombocytopenia, stroke, and in women, recurrent fetal loss. Less frequently other thromboembolic complications may also occur. The syndrome is caused by autoantibodies directed against phospholipid – glycoprotein complexes interfering with normal clotting mechanism.
38 Diagnostic criteria of SLE (ARA, 1982, modified in 1997) Malar rash (or: vespertilio, butterfly rash)Discoid rashPhotosensitivityOral ulcers: oral or nasopharyngeal ulcerationArthritis: nonerosive athritisSerositis: (at least one of the following)a) pleuritisb) pericarditis7. Renal disorder (at least one of the following): a) persistent proteinuria (>0.5g/day or 3+)b) cellular casts (erythrocyte, hemoglobin, granular, tubular or mixed)8. Neurological disorder (at least one of the following):a) a) seizuresb) b) psychosis9. Hematologic disorder (at least one of the following):a) a) hemolytic anemia (with reticulocytosis), orb) b) leukopenia (<4.0 on 2 or more occasions), orc) c) lymphopenia (<1.5 on 2 or more occasions), ord) d) thrombocytopenia (<100 in the absence of offending drug)10. Immunologic disorder (at least one of the following):a) a) abnormal titer anti-dsDNA antibody, orb) b) antibody to Sm nuclear antigen, orc) c) abnormal titer of anticardiolipin antibodyANA positivityIf 4 criteria are present serially or simultaneously, the diagnosis = SLE
39 Autoantibodies in SLE Autoantibodies in SLE Antigen Nature Frequency (%)Native DNA (double-stranded DNA) 40Denatured DNA (single-stranded DNA) 70Histon H1, H2A, H2B, H3, H4) 70*Sm RNA-protein complexes 30nuclear-RNP (U1-nRNP) 32SS-A (Ro) RNA-protein complexes 35SS-B (La) RNA-protein complexes 15Ku protein 10ribosomal-RNP phosphoproteins 10Ki/S1 protein 6* >90% in drug-induced SLE
46 Differential diagnosis In all cases SLE should be clearly differentiated from:1. other systemic autoimmune diseases2. infections3. malignancies, especially lymphomas.
47 The activity of the disease (monitoring) can be assessed by the followings 1. Clinical signs and symptoms are of utmost importance.2. Blood count: leukopenia cannot be used, but thrombocyto- penia and hemolysis are of importance.3. ESR may reflect disease activity, high value usually indicates acivity, but it remains high in many cases in remission.4. Renal functions (serum creatinine) and proteinuria should be checked regularly. High creatinine and an increase in daily proteinuria usually indicate an activation.5. Anti-DNA level runs parallel with activity, but it may remain elevated in remission.6. Complement activity and C3, C4 levels also indicate activity, they decrease during activity, and tend to normalize in remission.7. CRP usually remains normal, an increase may indicate bacterial infection.8. There are indices to measure overall disease activity, e.g. SLEDAI (SLE disease activity index).
49 Therapy of SLE Therapy of SLE 1) Inactive Therapy of SLETherapy of SLE1) InactiveCheck-up: 3 months: blood count, urine, creatinine,blood pressure, once a year: immunology (anti-DNA complement, anti-cardiolipin etc.2) moderately active (complaints, laboratory abnormalities, no general signs)Organ involvement:a) skin and/or joints and/or moderate serositisNSAID and/or (hydroxy)chloroquineRESPONSE continue chloroquine for at least 6 mo (fundus control after 2 months, then every 6 months)NSAID as requiredNO RESPONSE 30 mg prednisolone/day (24 mg methyl-prednisolone) for 1 week, then slowly (during 2 weeks)taper to 5-10 mg maintenance dose;discontinue if possible.OR: 7.5 mg methotrexate (MTX) per week (up to 15mg/week)
50 hematology b) hematology: leucopenia: no treatment anemia: only hemolysis should be treated if HTC<0.3hemolysis: 30 mg or more prednisolone/day, maintenancedose, and/or MTX addedthrombocytopenia: if >50: no treatment if <20 prednisolone 30 mg or more/day, then maintenance doseif instable: danazole, vincristine c) kidney:normal creatinine, moderate (0.2-1 g/day) proteinuria, minimal sediment; if stable only observation, biopsy = treatment options according to WHO grade.d) ACL positivity without clinical APS: only observation
51 Active (according to both clinical, and laboratory tests) a) skin and/or arthritis and/or serositis: 30 mgprednisolon/day (see above)NO RESPONSE: 64 mg methylprednisolone/day, maintenanceRESPONSE BUT HIGH MAINTENANCE DOSE: 100 mg Imuran orMTX addedb) progressive nephritis, either diffuse and/or proliferativehistology: 250 mg methylprednisolone/day cca. 1 gcumulative dose, then tapering to maintenance dose, OR 6 x 1 g bolus steroid slowly tapered to maintenanceplus 600 mg cyclophosphamide (CTX) infusion once amonth for 1-2 years(or 100 mg orally for 1-2 years – not used any more!) If CTX cannot be given or proteinuria is refractory:4 mg/kg/day cyclosporine A for 3-6 mo, then 2 mg/kg/daymaintenance dose (corticosteroid therapy continued).Oral mycophenolate may substitute for CTX.
52 APS with thrombosis c) APS with thrombosis: 2 mg/kg/day prednisolone + LMW heparin, thenmaintenence dose + warfarin,In arterial thrombosis: aspirinin severe cases: high dose IVIGd) severe hemolysis, or CNS involvement:high dose (250 mg-1 g/day) corticosteroidalternative: IVIG, apheresis