Sle Nephrology Gr

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  • Sle Nephrology Gr

    1. 1. SYSTEMIC LUPUS ERYTHEMATOSIS <ul><li>GEETA KATWA M.D., FACP. </li></ul><ul><li>Clinical Associate Professor </li></ul><ul><li>Division of Rheumatology </li></ul><ul><li>Dept. of Internal Medicine </li></ul><ul><li>Brody School of Medicine – ECU </li></ul><ul><li>March 2010 </li></ul>
    2. 2. Systemic Lupus Erythematosus <ul><li>SLE is an chronic autoimmune disorder characterized by inflammation of many organ systems </li></ul><ul><li>HALLMARK- Diversity </li></ul><ul><li>Mild, severe to life threatening </li></ul><ul><li>Severe morbidity and mortality </li></ul><ul><li>Unifying laboratory abnormality-ANA </li></ul><ul><ul><li>Ginzler EM, Rheum Dis Clin North Am 1988;14: 67-78. </li></ul></ul><ul><ul><li>Boumpas DR. Ann Int Med 1995;123:42-53 </li></ul></ul>
    3. 3. <ul><li>13 th century- Rogerices- Lupus “wolf” </li></ul><ul><li>1846- “C lassical” period- Ferdinand von Hebra- malar rash </li></ul><ul><li>1872- “Neoclassical”period – Moriz Kaposi- Lupus a systemic disease </li></ul><ul><li>1903- Osler & Jadassohn- firmly established systemic form </li></ul><ul><li>1909- Reinhart & Hauck- false +ve test for Syphilis </li></ul><ul><li>1923- Libman-Sacks Endocarditis in SLE </li></ul><ul><li>1935- Bachs- typical glomurular changes </li></ul>
    4. 4. Mordern Era <ul><li>1948- Hargraves- LE cell </li></ul><ul><li>1950- Friou (USA) & Holbora (UK) ANA </li></ul><ul><li>1950-1960’s- Dr Hughes- Sticky blood </li></ul>
    5. 5. Demographics <ul><li>Incidence: 7/100,000/yr </li></ul><ul><li>Peak incidence: 15 & 40 yrs of age </li></ul><ul><li>Prevalence: 1 in 2000 </li></ul><ul><li>Adult female:male - 6 to 10:1 </li></ul><ul><li>Children & older pts female: male – 3:1 </li></ul><ul><li>Race: African Americans female : 1/250 </li></ul><ul><li>Influence of heredity : Monozygotic concordance>>dizygotic </li></ul>
    6. 6. Etiology & Pathogenesis <ul><li>Unknown </li></ul><ul><li>Sex steroids </li></ul><ul><li>Monozygotic twins-concordance-30%, dizygotic twins & siblings-5% </li></ul><ul><li>Environmental risk factors </li></ul><ul><li>HAL-B8, DR2, DR3 </li></ul><ul><li>Complement deficiency </li></ul>
    7. 7. SLE: PREDISPOSING FACTORS <ul><li>10% have affected first- or second-degree relatives </li></ul><ul><li>Sibs 2%, Dizygotic twins 3%, Monozygotic twins 34% </li></ul><ul><li>HLA-DR2, HLA-DR3, XX </li></ul><ul><li>Deficiencies in early complement components: C1q, C1r-C1s, C2, C4 </li></ul><ul><li>C4a null alleles-deficiency high risk for SLE, </li></ul><ul><li>Deficient C3b/C4b receptors </li></ul><ul><li>Candidate genes-Classical complement, Fc gamma R, C-reactive protein,MHC, gene influencing the program cell death </li></ul>
    8. 8. Pathology <ul><li>Inflammation, vasculopathy, vasculitis, & immune-complex deposition </li></ul><ul><li>Pathogenic autoantibodies </li></ul><ul><li>Self antigens implicate immune cell dysfunction- B-cell hyperactivity </li></ul><ul><li>Genetic susceptibility - polygenic </li></ul><ul><li>Triggering events for SLE initiation & flares </li></ul>
    9. 10. ACR Criteria for Classification of SLE
    10. 11. PITFALLS IN DIAGNOSING SLE <ul><li>25 yo woman, pain all over, fatigue. Tender points over tendon insertions. FANA +. </li></ul><ul><li>35 yo woman, Raynaud’s phenomenon. Small ulcer tip of R 5 th finger. FANA +. </li></ul><ul><li>50 yo man, no signs/sx of SLE. Cr 3. Renal biopsy proliferative glomerulonephritis. </li></ul><ul><li>60 yo woman, erythema upper chest and back with red, scaly rash over extensor surfaces of MCP, PIP, and DIP joints. 30 pound weight loss. FANA +. </li></ul><ul><li>69 yo woman, joint pain. Thin scalp hair, erythema and prominent small vessels over nose and cheeks. FANA +. </li></ul>
    11. 12. Manifestations of SLE <ul><li>USUAL </li></ul><ul><li>Fever </li></ul><ul><li>Joint & muscle pain </li></ul><ul><li>Skin </li></ul><ul><li>Cognitive impairment </li></ul><ul><li>Positive FANA </li></ul><ul><li>High anti-DNA </li></ul><ul><li>Low serum complement </li></ul><ul><li>LESS USUAL </li></ul><ul><li>Pleurisy </li></ul><ul><li>Lymphadenopathy </li></ul><ul><li>Pleural/pericardial effusion </li></ul><ul><li>Anemia, Leukopenia </li></ul><ul><li>Anti-phospholipid Ab </li></ul><ul><li>High immunoglobulin </li></ul><ul><li>Proteinuria </li></ul>
    12. 13. Organ systems involved <ul><li>More common </li></ul><ul><li>Mucocutaneous </li></ul><ul><li>Musculoskeletal </li></ul><ul><li>Renal </li></ul><ul><li>Nervous system </li></ul><ul><li>Cardiovascular </li></ul><ul><li>Pleura and Lungs </li></ul><ul><li>Less common </li></ul><ul><li>Gastrointestinal tract </li></ul><ul><li>Liver </li></ul><ul><li>Ocular System </li></ul>
    13. 14. Autoantibodies in SLE <ul><li>FANA </li></ul><ul><li>ANTI-DS </li></ul><ul><li>DNA </li></ul><ul><li>ANTI-Sm </li></ul><ul><li>SPECIFIC </li></ul><ul><li>+ </li></ul><ul><li>++++ </li></ul><ul><li>++++ </li></ul>COMMON ++++ +++ +
    14. 15. Conditions associated with ANA <ul><li>Other rheumatic diseases-RA, Sjogren’s syndrome, Scleroderma, Myositis </li></ul><ul><li>Drug induced </li></ul><ul><li>Hepatic-chronic hepatitis, Primary biliary cirrhosis </li></ul><ul><li>Infections </li></ul><ul><li>Malignancy </li></ul><ul><li>Neurologic- multiple sclerosis </li></ul><ul><li>Hematologic-Immune thrombocytopenic purpura, hemolytic anemia </li></ul><ul><li>Endocrine- Thyroid disease, DM </li></ul><ul><li>Pulmonary- pulmonary fibrosis, IDL </li></ul>
    15. 16. Malar Rash <ul><li>Butterfly rash </li></ul><ul><li>Involves cheeks and nose </li></ul><ul><li>Patient also has rash on chin and some telangiectasia </li></ul>Systemic lupus erythematosus
    16. 17. <ul><li>Interarticular dermatitis </li></ul><ul><li>Also has periungual erythema </li></ul><ul><li>This rash is distinct from that seen in dermatomyositis that occurs over the joints </li></ul>Systemic lupus erythematosus
    17. 18. Annular Subtype
    18. 19. Annular Subtype
    19. 20. Papulosquamous Subtype
    20. 23. Discoid lupus
    21. 26. Musculoskeletal Manifestations <ul><li>Arthralgias/arthritis </li></ul><ul><li>Jaccoud’s arthropathy </li></ul><ul><li>Myalgias </li></ul><ul><li>Inflammatory myositis </li></ul><ul><li>Osteonecrosis </li></ul><ul><li>Fibromyalgia </li></ul>
    22. 28. Renal- You are the EXPERT <ul><li>Urinary neutrophil gelatinase- associated lipocalin (uNGAL) as a novel biomarker for disease activity in lupus nephritis </li></ul><ul><li>( Rheumatology: February 9, 2010) </li></ul>
    23. 30. CNS MANIFESTATIONS OF SLE <ul><li>Headache </li></ul><ul><li>Aseptic meningitis/ encephalitis </li></ul><ul><li>Psychosis and severe depression </li></ul><ul><li>Generalized seizures </li></ul><ul><li>Organic brain syndrome </li></ul><ul><li>Focal disease- stroke syndromes, movement disorders & transverse myelitis </li></ul><ul><li>Antibodies associated with CNS-SLE: antiphospholipid, antineuronal & ant-P antibodies </li></ul>
    24. 31. HEART AND SLE <ul><li>Pericarditis </li></ul><ul><li>Myocarditis </li></ul><ul><li>Valvular disease ( Libman-Sacks atypical verrucous endocarditis ) </li></ul><ul><li>Vasculitis </li></ul><ul><li>Accelerated atherosclerosis </li></ul><ul><li>Hypertension & hypercholesterolemia </li></ul>
    25. 32. SLE & Atherosclerosis <ul><li>Atherosclerosis occurred prematurely in pt with SLE & independent of traditional risk factors for SLE </li></ul><ul><li>Plaque was independently associated with age, long disease duration & less frequent with use of cytoxan and HOCl. </li></ul><ul><ul><li>(Roman MJ, N engl J Med 2003;349:2399-2406) </li></ul></ul><ul><li>SLE pt had higher coronary Ca scores independent of other risk factors </li></ul><ul><li>Coronary artery calcification at younger ages than controls </li></ul><ul><ul><li>(Asanuma Y, J Rheumatol 2006;33:539-545) </li></ul></ul>
    26. 33. Atherosclerosis in SLE <ul><li>Prompt and aggressive Rx </li></ul><ul><li>Risk factor management </li></ul><ul><li>Address traditional CV risk factor </li></ul><ul><li>Elevated homocysteine-Rx with folic acid </li></ul><ul><li>Hydroxchloroquine </li></ul><ul><li>ASA </li></ul>
    27. 34. Acute presentation <ul><li>A 25 yr hispanic female presents dizziness, fatigue, myalgias and SOB. </li></ul><ul><li>PE: pale, lethargic, mildly dyspnic, and bilateral crackles </li></ul><ul><li>Labs: Hb- 6.0 mg/dL, UA- normal, ANA-1:1280, positive anti ds-DNA, CT Chest and bronchoscopy done </li></ul>
    28. 35. Diagnosis? <ul><li>CT chest showed bilateral alveolar infiltrates </li></ul><ul><li>Bronchoscopy – pulmonary hemorrhage with few inflammtory cells. </li></ul><ul><li>Treatment – high doses of steroids initially followed by Cytoxin. </li></ul>
    29. 36. PULMONARY MANIFESTATIONS IN SLE <ul><li>Pleuritis & pleural effusion </li></ul><ul><li>Pneumonitis </li></ul><ul><li>Pulmonary hemorrhage </li></ul><ul><li>Pulmonary embolism </li></ul><ul><li>Pulmonary HTN </li></ul><ul><li>Shrinking lung syndrome </li></ul><ul><li>Chronic interstitial lung disease/fibrosis </li></ul><ul><li>Secondary infections </li></ul>
    30. 37. ALVEOLITIS
    31. 38. PULMONARY FIBROSIS
    32. 39. SHRINKING LUNG SYNDROME <ul><li>Also called “Vanishing Lung Syndrome” </li></ul><ul><li>Suspect this dx in individuals presenting dyspnea, persistent episodes of pleuritic chest pain, a progressive decrease in lung volume, with no evidence of interstitial fibrosis or pleural disease on Chest CT, but elevated diaphragms </li></ul><ul><li>Pathogenesis: Uncertain </li></ul>
    33. 40. Hematologic Abnormalities <ul><li>Anemia </li></ul><ul><li>Leukopenia ( lymphopenia) </li></ul><ul><li>Thrombocytopenia </li></ul><ul><li>Severe thrombocytopenia (5%) </li></ul><ul><li>Thrombocytopenia associated with APS </li></ul><ul><li>Elevated ESR and C-reactive protein </li></ul>
    34. 41. Antibodies associated with SLE <ul><li>Anti-dsDNA (50-70%) </li></ul><ul><li>Anti-Sm Ab (30-40%) </li></ul><ul><li>Anti-RoSSA (20-60%) </li></ul><ul><li>Anti-LaSSB (15-40%) </li></ul><ul><li>Antiphospholipid (50%) </li></ul><ul><li>Anti-RNP (30-40%) </li></ul><ul><li>Antiribosmal P protein </li></ul><ul><li>Anti-Histone </li></ul><ul><li>Ab – epitope of glutamate/N-methyl-D-aspartic acid receptors </li></ul><ul><li>Glomerulonephritis </li></ul><ul><li>IDL, GN, CNS disease </li></ul><ul><li>SCLE, SS, Neonatal lupus </li></ul><ul><li>SCLE, SS, neonatal lupus </li></ul><ul><li>Arterial & venous thrombosis, fetal loss </li></ul><ul><li>SLE & MCTD </li></ul><ul><li>Psychosis, depression </li></ul><ul><li>SLE & Drug induced SLE </li></ul><ul><li>Neuropsychiatric </li></ul>
    35. 42. Autoantibodies <ul><li>Diffuse: DNA - low titer = non-specific </li></ul><ul><ul><li>Histones – Drug-induced lupus </li></ul></ul><ul><li>Peripheral: ds-DNA -50% of SLE specific </li></ul><ul><li>Speckled: Sm -30% 0f SLE specific </li></ul><ul><ul><li>Ro (SSA) – SLE, Sjogren’s 60%, Neonatal </li></ul></ul><ul><ul><li>La (SSB) - SLE 15%, Sjogren’s 50% </li></ul></ul><ul><li>Cytoplasmic: Ro, ribosomal P - SLE psychosis </li></ul><ul><ul><li>Cardiolipin – Thrombosis, abortion, thrombocytopenia </li></ul></ul>
    36. 44. Drug induced SLE <ul><li>Procainamide </li></ul><ul><li>Hydralzine </li></ul><ul><li>Quinidine </li></ul><ul><li>Sulfasalazine </li></ul><ul><li>Minocycline </li></ul><ul><li>Isoniazid </li></ul><ul><li>Chlorpromazine </li></ul><ul><li>TNF inhibitors </li></ul>
    37. 45. TREATMENT <ul><li>Patient education </li></ul><ul><li>Identify & treat conditions that contribute to fatigue </li></ul><ul><li>Adequate rest & energy conservation </li></ul><ul><li>Avoid sunlight, routine use of sunscreen & protective clothing </li></ul><ul><li>Immunizations </li></ul><ul><li>Minimize the risk factors for premature CAD </li></ul><ul><li>Effective birth control. </li></ul>
    38. 46. TREATMENT (cont.) <ul><li>NSAID’s </li></ul><ul><li>Corticosteroids </li></ul><ul><li>Antimalarials </li></ul><ul><li>Thalidomide </li></ul><ul><li>Azathioprine </li></ul><ul><li>Cyclophosphamide </li></ul><ul><li>Methotrexate </li></ul><ul><li>Cyclosporine </li></ul><ul><li>Mycophenylate Mofetil </li></ul>
    39. 47. “ Ideal” immunomodulatory Rx <ul><li>HOCl-rebirth (pleiotrophic effects) </li></ul><ul><ul><li>Prevents severe flares </li></ul></ul><ul><ul><li>Reduces the risk of nephritis </li></ul></ul><ul><ul><li>Organ damage </li></ul></ul><ul><ul><li>Cardiovascular risk factors-lipid profile </li></ul></ul><ul><ul><li>Thrombosis </li></ul></ul><ul><ul><li>Survival </li></ul></ul>
    40. 48. When should immunosuppressive Rx be added to minimize prednisone use ? ( J. Rheumatol.2009;36:560-4 ) <ul><li>Hopkins Lupus Cohort (525 pt’s) </li></ul><ul><ul><li>Cumulitive dose of prednisone(0-180mg/mth)- hazard ratio, 1.16 </li></ul></ul><ul><ul><li>Dose of180-360 mg/mth- hazard ratio,1.50 </li></ul></ul><ul><ul><li>Dose of 360-540 mg/mth- harzard ratio, 1.64 </li></ul></ul><ul><ul><li>Dose of >540 mg/mth- harzard ratio, 2.51 </li></ul></ul><ul><ul><li>(risk of organ damage) </li></ul></ul>
    41. 49. INDICATIONS FOR HIGH DOSE STEROIDS <ul><li>Severe lupus nephritis </li></ul><ul><li>CNS lupus with severe manifestation </li></ul><ul><li>Autoimmune thrombocytopenia(<30,000) </li></ul><ul><li>Autoimmune hemolytic anemia </li></ul><ul><li>Acute pneumonitis </li></ul><ul><li>Severe vasculitis with visceral organ involvement </li></ul>
    42. 50. Mycophenolate Motefil Trial Schanz S, et al. Successful treatment of subacute cutaneous lupus erythematosus with mycophenolate mofetil. Br J Dermatol. 2002 Jul;147(1):174-8.
    43. 51. Mycophenolate Motefil Trial Schanz S, et al. Successful treatment of subacute cutaneous lupus erythematosus with mycophenolate mofetil. Br J Dermatol. 2002 Jul;147(1):174-8.
    44. 52. New Developments in SLE Landscape <ul><li>B-cell depletion - Rituximab, Epratuzumab </li></ul><ul><ul><li>(J. Rheumatol 2008 May; 35(5):826 ) </li></ul></ul><ul><li>Inhibition of B-cell survival – Belimumab (LymphoStat-B) </li></ul><ul><li>B-cell-specific Toleragen: Abestimus Na (LJP 394) decreases ds-DNA </li></ul><ul><li>Inhibition of Costimulatory Interaction- Abatacept & RG2077 </li></ul><ul><li>Cytokine blockade- anti TNF alpha, Ab against IL-10, IL-6, IFN-alpha modulation </li></ul>
    45. 53. Conclusions <ul><li>SLE is a compositeof clinically unrelated manifestations, acummulates overtime associated with autoantibodies </li></ul><ul><li>Greater awareness to both physician & pt </li></ul><ul><li>Physicians maintain high vigilance </li></ul><ul><li>Accurate prediction of flares & premptive treatment </li></ul><ul><li>Search for biomarkers & biologic offers promise </li></ul>

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