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SYSTEMIC LUPUS ERYTHEMATOSUS (SLE) Gergely Péter dr Definition: The clinical picture of SLE is variable. The most common form of the disease: young female.

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Presentation on theme: "SYSTEMIC LUPUS ERYTHEMATOSUS (SLE) Gergely Péter dr Definition: The clinical picture of SLE is variable. The most common form of the disease: young female."— Presentation transcript:

1 SYSTEMIC LUPUS ERYTHEMATOSUS (SLE) Gergely Péter dr Definition: 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. SYSTEMIC LUPUS ERYTHEMATOSUS (SLE)

2 Prevalence of SLE

3 Pathomechanism of SLE Endogeneous factors: genetic hormonal Exogeneic factors: infections, UV radiation drugs (hydralazine, INH, quinidine, procainamide) B cell hyperreactivity  enhanced autoantibody production, in particular antinuclear antibody (ANA) production  immune complex formation and deposition  tussue inflammation (skin, joints, kidney)  organ lesion/regeneration

4 Lupus band test = IC deposition in the skin

5 ANA

6

7 Clinical features of SLE Clinical picture: The well known butterfly (malar) rash is relatively uncommon, but the diagnosis is in most cases easy, if we base it on the criteria of American Rheumatism Association (ARA). General symptoms: fever, lymphadenomegaly, weight loss are always present, their severity depends on the intensity of the disease. At first sight, such patient seem to be suffering of an infectious disease.

8 Joints: 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. Joints

9 Hand

10 Jaccoud arthropathy in SLE

11 Skin involvement is frequent. Beside butterfly and discoid rash, chronic (IC-mediated) urticaria, livedo reticularis, skin vasculitis, biphasic Raynaud’s phenomenon, hair thickening and alopecia areata may be present. Skin involvement is frequent

12 Malar (butterfly) rash in SLE Malar (butterfly) rash in SLE

13 Malar rash in SLE Malar rash in SLE

14 Malar rash in SLE Malar rash in SLE

15 Discoid lesion

16 Chronic DLE on the face Chronic DLE on the face

17 Discoid on the scalp

18 DLE on the scalp

19 SCLE

20

21 Raynaud phenomenon

22 Perinugual vasculitis

23 Periungual vasculitis Perinugual vasculitis

24 Vasculitis on the feet

25 Livedo reticularis

26 Lupus pernio

27 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. Renal involvement is observed in 60% of patients

28 Generalized edema in nephrotic syndrome

29 Lupus nephritis (WHO I)

30 Lupus nephritis (WHO II)

31 Lupus nephritis (WHO III)

32 Lupus nephritis (WHO IV)

33 IC deposition in the glomeruli - SLE

34 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. Hematological disorders are very common

35 ACR criteria of CNS involvement: acute inflammatory demyelinizing polyradiculopathy (Guillain- Barré syndrome) aseptic meningitis autonomous nervous system alterations (e.g. orthostatic hypotension) cerebrovascular disease (e.g. stroke) demyelinization syndrome lupus headache mononeuropathy myasthenia gravis cranial neuropathy plexopathy convulsions acute confusion state anxiety cognitive dysfunction mood disorders ACR criteria of CNS involvement

36 Multiple infarcerations in SLE –APS (MRI) Multiple infarcerations in SLE –APS (MRI)

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. Antiphospholipid syndrome (Hughes’s syndrome)

38 Diagnostic criteria of SLE (ARA, 1982, modified in 1997) 1.Malar rash (or: vespertilio, butterfly rash) 2.Discoid rash 3.Photosensitivity 4.Oral ulcers: oral or nasopharyngeal ulceration 5.Arthritis: nonerosive athritis 6.Serositis: (at least one of the following) a) pleuritis b) pericarditis 7. 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) seizures b) b) psychosis 9. Hematologic disorder (at least one of the following): a) a) hemolytic anemia (with reticulocytosis), or b) b) leukopenia (<4.0 on 2 or more occasions), or c) c) lymphopenia (<1.5 on 2 or more occasions), or d) 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, or b) b) antibody to Sm nuclear antigen, or c) c) abnormal titer of anticardiolipin antibody 11.ANA positivity If 4 criteria are present serially or simultaneously, the diagnosis = SLE Diagnostic criteria of SLE (ARA, 1982, modified in 1997)

39 Autoantibodies in SLE AntigenNatureFrequency (%) Native DNA(double-stranded DNA)40 Denatured DNA(single-stranded DNA)70 HistonH1, H2A, H2B, H3, H4) 70* SmRNA-protein complexes30 nuclear-RNP(U1-nRNP)32 SS-A (Ro)RNA-protein complexes35 SS-B (La)RNA-protein complexes15 Kuprotein10 ribosomal-RNPphosphoproteins10 Ki/S1protein6 * >90% in drug-induced SLE Autoantibodies in SLE

40 LE cell phenomenon

41 Homogenous ANA positivity on HEp-2 cells

42 Peripheral ANA positivity

43 Speckled ANA positivity

44 Nucleolar ANA positivity

45 Anti-DNA positivity (Crithidia luciliae test)

46 Differential diagnosis. In all cases SLE should be clearly differentiated from: 1. other systemic autoimmune diseases 2. infections 3. malignancies, especially lymphomas. Differential diagnosis

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). The activity of the disease (monitoring) can be assessed by the followings

48 SLEDAI Score Symptom 8acute convulsion 8psychosis 8"organic brain" syndrome 8visual disturbances (retinal vasculitis) 8cranial nerve sign (sensory, motor) 8lupus cephalalgia 8cerebrovascular laesion (excluded: atherosclerosis) 8vasculitis (ulcus, gangrena, skin vasculitis) 4myositis 4arthritis (> 2 joints) 4granular or erythrocyte casts 4hematuria (>5 red cells/field) 4new proteinuria (>0.5 g/day), or >+0.5 g/day increase 4pyuria (>5 leukocytes/field) (excluded: infection) 2new exanthema 2alopecia, new or recurrent 2mucous membrane ulcer 2pleuritis 2pericarditis 2low complement (CH50, C3, etc.) 2high anti-DNA 1fever (>38 o C) (excluded: infection) 1thrombocytopenia (<100,0) 1leucopenia (<3,0) (wxcluded: drug-induced) TOTALSLEDAI SCORE SLEDAI

49 Therapy of SLE 1) Inactive Check-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 serositis NSAID and/or (hydroxy)chloroquine RESPONSE continue chloroquine for at least 6 mo (fundus control after 2 months, then every 6 months) NSAID as required NO 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 15 mg/week) Therapy of SLE

50 b) hematology: leucopenia: no treatment anemia: only hemolysis should be treated if HTC<0.3 hemolysis: 30 mg or more prednisolone/day, maintenance dose, and/or MTX added thrombocytopenia: if >50: no treatment if <20 prednisolone 30 mg or more/day, then maintenance dose if 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 hematology

51 3) Active (according to both clinical, and laboratory tests) a) skin and/or arthritis and/or serositis: 30 mg prednisolon/day (see above) NO RESPONSE: 64 mg methylprednisolone/day, maintenance RESPONSE BUT HIGH MAINTENANCE DOSE: 100 mg Imuran or MTX added b) progressive nephritis, either diffuse and/or proliferative histology: 250 mg methylprednisolone/day cca. 1 g cumulative dose, then tapering to maintenance dose, OR 6 x 1 g bolus steroid slowly tapered to maintenance plus 600 mg cyclophosphamide (CTX) infusion once a month 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/day maintenance dose (corticosteroid therapy continued). Oral mycophenolate may substitute for CTX. Active (according to both clinical, and laboratory tests)

52 c) APS with thrombosis: 2 mg/kg/day prednisolone + LMW heparin, then maintenence dose + warfarin, In arterial thrombosis: aspirin in severe cases: high dose IVIG d) severe hemolysis, or CNS involvement: high dose (250 mg-1 g/day) corticosteroid alternative: IVIG, apheresis APS with thrombosis

53 Drug induced exanthema Drug induced exanthema

54 Avascular bone-necrosis

55 Retinopathia due to chloroquine

56 Neonatal lupus (caused by trasfer of SS-A antibodies)


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