Downloaded 161 times
Uploaded byMiami Dade
4 Sle2009
A 22-year-old college student presents with symptoms including a malar rash, photosensitivity, arthritis, fatigue, and hair loss. Laboratory tests show a positive ANA, positive anti-Smith antibody, and low white blood cell and platelet counts. This constellation of clinical features and laboratory results makes systemic lupus erythematosus the most likely diagnosis for the patient.
More Related Content
4 Sle2009
- 1. Systemic Lupus Erythematosus SLE and APLS
- 2. Case Study • 22year old college student • New onset of red cheeks, hives in the sun, fatigue, Raynaud’s, weight loss, hair loss and stiff hands in the morning • Her cousin has JRA
- 3. What is themost likely diagnosis?
- 4. Lupus • Represent arange of disease processes characterized by the development of autoantibodies with associated manifestations and organ damage • Some forms limited to skin , or occur after exposure to a drug
- 5. SLE • Systemic lupuserythematosus: • Prototypical form of lupus • Multiorgan autoimmune disease that often presents insidiously with significant heterogeneity of expression in individuals • Severity from mild to life threatening depending on the affected organ • Medications used for treatment increase morbidity - organ damage
- 6. Chronic Cutaneous Lupus (CCL) • Limited to the skin • No systemic manifestations • Includes: – Discoid lupus – Subacute cutaneous lupus erythematosus – Lupus paniculitis • Only 5% of CCL develop SLE
- 7. Drug induced Lupus(DILE) • Triggered by certain medications • Resolution after DC of the drug • Anti-Histone ab test positive • Absence of anti-DsDNA
- 8. Drug-induced lupus: definite drug associations • Hydralazine • Procainamide • Minocycline • Chlorpromazine • Isoniazid • Penicillamine • Methyldopa • Interferon-alpha
- 9. Drug-induced lupus: possible drug associations • Anticonvulsants • Diltiazen • Quinidine • Hydrazine • Propylthiouracil • Interferon gamma • Sulfonamides • TNF inhibitors • Lithium • Beta-blockers • Nitrofurantoin • Sulfasalazine
- 10. SLE • More common in Female than male • Female : Male ratio 9:1 • Incidence of SLE in US is : • Women 9.4 per 100,000 • Men 1.54 per 100,000 • More common in African-American and Hispanic population
- 11. SLE • Disease onsetmore common in the 20s, and 30s • May occur at any age • Symptoms/disease activity “waxes and wanes” • “Flares” sometimes evident by clinical symptoms, other times only by laboratory results changes
- 12. SLE • Pathogenesis : •Exact cause is unk. • Genetic factors -10% of SLE patients have a family member with lupus • Environmental factors - UV light (most important) • Possible Also infections, smoking, and toxin exposure
- 13. SLE • Autoantibodies bindto proteins and tissues • Deposition of immune - complexes leads to an inflammatory cascade • With activation of complement system • And production of inflammatory cytokines
- 14. SLE Clinical Presentation •Most commonly affected organ systems: – Musculoskeletal – Dermatological – Renal – Hematological • Any organ can be affected
- 15. SLE Clinical Presentation •Musculoskeletal lupus – Isolated arthralgias ( more often stiffness rather than pain) – Synovitis.arthritis similar to RA – Morning stiffness – Gel phenomenon after immobility – Small joints of the hands( MTPs,PIP’s) – Wrists
- 16. SLE Clinical Presentation •Knees are less affected • Jaccoud’s arthropathy: – Progressive ulnar deviation – Swan-necking deformaties – Reversible or correctible • Typically non erosive bony changes
- 17.
- 18. SLE Dermatological • Severalskin manifestations • Malar Rash – Butterfly Rash – Erythematous – Photosensitive – Flat or raised - maculopapular – On the cheeks and Bridge of the nose – Spares naso-labial folds
- 19. Malar Rash –Butterfly Rash
- 20. Systemic lupus erythematosus: bullous lesions, palate
- 21. SLE Dermatological • Maculopapularrash also common on: – V-area of the neck, and extremities – Areas associated to sun exposure • Biopsy of the skin – demonstrate immunoglobulin and complement deposition at the dermal-epidermal junction: “lupus band sign”
- 22.
- 23. SLE Dermatological • Discoidlupus(chronic cutaneous) – Involve deeper Dermis, raised patches, keratotic scaling, follicular plugging – May lead to permanent loss of hair follicle – Disfiguring hyper- or hypopigmented scars may occur after resolution – Typically on face ( inside ears, above eye brows, upper palate ) – Neck, scalp and forearms
- 24.
- 25.
- 26. SLE Dermatological • SubacuteCutaneous Lupus Erythematosus (SCLE) – Photosensitive lesions – Nonscaring rash – Psoriaform form – Annular – polycyclic form • ½ of patients with SCLE have SLE
- 27.
- 28. SLE Renal Involvement • Proteinuria alone • Proteinuria and Hematuria • Cellular casts in urine : RBCs • Glomerular involvement • Elevated serum creatinine level • Possible Renal Failure • May result in Nephrotic Syndrome: – Low serum albumin, and elevated cholesterol
- 29. Renal Involvement • Internationalsociety of Nephrology Classification for lupus nephritis – I minimal mesangial – II Mesangial proliferative – III focal proliferative – IV diffuse proliferative – V membranous – VI irreversible renal sclerosis Done by Kidney Biopsy Class IV most dangerous – can rapidly progress to Renal Failure
- 30. Renal Involvement • Membranousnephritis (V) manifested by Nephrotic Syndrome
- 31. SLE Serositis • Pleurisy •Occurs most commonly as pleurisy: – Pain on deep inspiration – Sometimes associated with pleural effusion – Listen for inspiratory / expiratory rub – Exudative effusion if tapped • Differentiate from pulmonary emboli and infection pleuritic chest pain
- 32. Serositis • Pericarditis: – Positional pain – Worse with recumbency – Better leaning forward • Ascites: – Possible due to serositis – r/o infarcted bowel, infection, or Budd-Chiari syndrome (oclussion hepatic or IVC)
- 33. Hematological abnormalities • Mostcommon • Leukopenia and Lymphopenia • Medication induced cytopenias – Corticosteroids associated lymphopenia • Thrombocytopenia – Antiphospholipid antibodies – Immunosupressive drugs – Heparin administration
- 34. Hematological abnormalities • Hemolyticanemia – Coombs positive – Elevated reticulocyte count – Decreased haptoglobin • Anemia of chronic disease (inflammation) • Anemia from chronic renal disease • Iron deficiency anemia
- 35. Neurologic manifestations • Mostlikely as a result of immunecomplex deposition in small blood vessels • Rarely attributable to vasculitis • Most common neurologic complaint in SLE: – Cognitive impairment – 80%of SLE patients by 10 years after Dx. – Represents accumulated damage and not ongoing CNS SLE – Formal cognitive function testing to establish baseline
- 36. Neurologic manifestations • Mildto severe – Seizures: also from thrombosis,uremia,toxic – Psychosis: think about steroids psychosis – Encephalopathy – Coma
- 37. Neurologic manifestations – Meningitis –Stroke: vasculitis or APhospholipids Abs thrombosis, HTN, atherosclerosis – Mononeuritis multiplex – Transverse myelitis – Peripheral neuropathy – Cranial neuropathy
- 38. Organ Damage • In>50% of SLE patients over time • Significant % from corticosteroids therapy – Obesity/ Diabetes – HTN/ Hyperlipedimia – Cataracs/Glaucoma – Osteoporosis/Osteonecrosis – Infections – Depression/Psychosis
- 39. Organ Damage • AcceleratedAtherosclerosis – the major cause of death in SLE • Risk of MI – increased 50 fold • Counsel about modifiable cardiovascular risks
- 40. Organ Damage • Renaldamage occurs in at least 25% of patients with lupus nephritis in spite of maximal therapy • Recommendation for renal biopsy: – In patients with 500mg/day proteinuria – Active urinary sediment – Rising serum creatinine
- 41. Malignancy risk • Lymphomaand Solid tumors risk is increased independent to therapy • Patients with secondary Sjogren’s syndrome may have special risk of non- Hodgkin’s Lymphoma
- 42. Diagnosis • Often difficult– multiple manifestations which evolve over time / more in the early stage • Clinical diagnosis supported by Hx, Physical Exam and Laboratory tests • Make take months to years for the typical picture to unfold • ACR classification criteria for SLE is helpful but not needed for Dx
- 43.
- 45. Laboratory tests/Ab testingfor SLE • Tests for diagnosis • Tests for prognosis • Tests to determine appropriate treatment (What organ involvement is occurring?)
- 46. Laboratory tests/Ab testingfor SLE • CBC,diff, ESR, CRP • Creatinine, urinalysis • Chemistry Panel • ANA, anti DsDNA, anti-SM, anti-RNP anti-SSA /SSB, RF, C3,C4,total complement
- 47. Ab testing forSLE • ANA(anti-nuclear antibodies) • Positive in 95-99% of SLE • Occurs in 20% of healthy people, elderly, with drugs, thyroid disease, RA,SS, pulmonary fibrosis. • If positive + clinical symptoms continue workup
- 48. What is ANA? •Antinuclear antibody is an autoantibody against part of the cell nucleus • It is a screening test for SLE: so if negative, it makes SLE highly unlikely
- 49. Frequent ANA patterns • Speckled • Homogeneous / Diffuse • Nucleolar • Rim / Peripheral • Centromere
- 51. Positive test • Titers:stronger positive, the dilution is larger (higher denominator) – Ex. 1/1280 is a strong positive • Pattern can change depending on the dilution – Ex. 1/80 speckled and homogenous and 1/640 homogenous
- 52. Is there utilityin following the titer? • No • In general repeating the test is a waste of money • A positive test in past or at any time can count in the diagnostic criteria for SLE
- 53. When do Iorder anti DNA? • It is an auto-antibody directed against the DNA in the cells nuclei • Only order anti DNA in the presence of a positive ANA, when you are clinically suspecting SLE • It is very specific for SLE, but very insensitive
- 54. What does antiDNA correlate with? • It is highly specific for SLE • It correlates with renal SLE (but not 100%) • Thus, it can be a bad prognosticator and it is part of the diagnostic criteria
- 55. What is anENA • ENA is extractable nuclear antigens • The lab will do a screen to see if it is positive or negative • If positive, more assays are done to determine which antibody is positive
- 56. ENA examples • AntiRo, (anti SSA) • Anti La, (anti SSB) • Anti Sm (Smith – fairly sensitive for SLE) • Anti RNP (goes with MCTD and SLE) • Anti Scl 70 (Topoisomerase 1) – goes with diffuse scleroderma esp with interstitial lung disease • Other: anti Jo1(myositis)
- 57. Anti-Ro(anti-SSA) and La(anti-SSB) • + Anti Ro: – is associated with cutaneous SLE features including rash and photosensitivity – is often + in ANA negative SLE – can go with anti La in Sjogren’s S. – can increase the risk of congenital heart block in babies whose moms are +
- 58. The results ofthe college student • WBC 2.8, Hbg 11.1, Plt 43 • Creatinine 1.0, urine neg for protein and blood • ANA 1/320 speckled • ENA: + for anti Smith (Sm) • antiDNA negative
- 59. Does she haveSLE? • + ANA • Low WBC and plt • + anti Sm • Malar rash • Photosensitivity • Possible inflammatory arthritis • She has at least 5 criteria
- 60. Laboratory tests/Ab testingfor SLE
- 61. Antiphospholipid antibody syndrome (APS) • Half are associated with SLE • Occurs in 10-20% of SLE patients • Syndrome of arterial and or venous clotting (CVA, DVT, PE), recurrent abortions and often livedo reticularis, low platelets
- 62. Antiphospholipid antibody syndrome (APS) • Positive tests may include – Lupus anticoagulant (false prolongation of PTT) – Anticardiolipin antibody (aCL) or other antiphospholipid antibodies – False positive VDRL – Abnormal RVV time (Russel venon viper time)
- 63. APS • Treatment varieson symptoms and signs • ASA or LMW heparin in pregnancy • Warfarin if DVT • ASA and possibly warfarin if CVA (Cerebro-vascular-accident)
- 64. SLE Management -treatment • No cure – chronic condition • TTo aimed at: – Reducing inflammation – Suppressing immune system – Closely monitoring patients to ID and to treat disease features as early as possible – Minimize therapy adverse effects
- 65. Management - treatment •Patient Education and prophylactic measures to avoid flares : • Sunscreens SPF >30 and protective clothing – Photosensitivity, Raynaud’s Phen. • Avoid estrogen containing oral contraceptives – Lupus flares, hyperthrombotic states • Avoid medications such as: – Sulfonamides, Echinacea, and Melatonin
- 66. Management – treatment •Low dose ASA for patients with +Antiphospholipid Abs – Potentially avoid thrombosis • Psychological support – Depression and anxiety • Routine immunizations – Influenza (yearly) and pneumococcus vaccine (every 5-10 years) - Live virus vaccines not recommended
- 67. Management – treatment •Enforce regularly scheduled: – Colonoscopy – Pap smears – Mammograms – Increased risk of cancer
- 68. Management – treatment •Baseline and periodic bone densitometry • Biphosphonates – not given to patients with renal insufficiency or potential to have pregnancies • Osteopenic patients: Biphosphonates, CaCO3 and Vit D • Management of HTN and Lipid levels
- 69. Management – treatment •Pregnancy – High risk – 90 % successful – Flares can occur – High disease activity with increased DsDNA level and decreased complement levels – Increased pre-eclampsia, preterm births, and fewer live births
- 70. Management – treatment •Risk of Neonatal Lupus in + Ro(anti SSA) AB • Cross placenta • 2-5 % risk of congenital heart block in the baby, hemolytic anemia, and rashes • Women with medium to high titer anticardiolipin /anti-B2 glycoprotein, hx of pregnancy loss or severe preeclampsia – ASA and Heparin during pregnancy and 6 months after.
- 71. Management – treatment •Cutaneous Lupus: • Hydroxychloroquine (Plaquenil) – 200 mg PO BID – Risk for retinopathy (<1 of 5000 exposed) – Eye exam once a year • Alternate: Quinacrine 100mg PO QD – Higher ocular toxicity • If no response: Cellcept, Methotrexate,or Imuran
- 72. Management – treatment •Musculoskeletal symptoms – NSAIDS – mild arthralgias – COX 2 inhibitors • Do not use for long periods of time • Proton pump inhibitors- PRN • Hydroxychloroquine – 200mg PO BID • Low – Dose Prednisone <7.5mg/day
- 73. Management – treatment •Persistent Synovitis – Methotrexate – Leflunomide – Abatacet – Rituximab
- 74. Management – treatment •Serositis • Mild serositis: may respond to NSAIDS • Moderate S: Triamcinolone 100mg IMx1 • Severe : Methylprednisolone IV pulse (1000mg over 90minutes x 3days ) followed by oral Prednisone tapering dose • Maintenance immunosupressive regimen if persistent / recurrent serositis
- 75. Management – treatment •Lupus Nephritis • Mycophenolate Mofetil (Cellcept) induction and maintenance therapy • Recent studies show potential superiority of Cellcept as induction and safety profile when compared to Cytoxan
- 76. Neprhitis (cont) • Cyclophosphamide(Cytoxan) induction therapy- IV pulse • Induction IV 500-750 mg/m2 body surface, monthly, for 6 months • Maintenance IV quaterly for 2 years • Hemorrhagic Cystitis • Long term risk for Urinary Bladder malignancy
- 77. Management – treatment •CNS Lupus • IV Methylprednisolone pulse • IV monthly Cyclophosphamide • Additional antiepileptic medication in the case of seizures/ Neuro-consult • Psychosis-antipsychotic drugs and mood stabilizers
- 78. Management – treatment •Hematological Lupus • Plt count < 30,000 bleeding may occur • Severe hemolytic anemia / thrombocytopenia • High dose steroids, if no improvement intravenous immunoglobulin • Rituximab
- 79. Case study Patient Name:Melisa T. Age: 19 Sex: Female Description: Melisa, a young Latina student, is taking mycophenolate mofetil (MMF) for lupus nephritis (LN) has come in for a routine follow-up visit. How would you monitor progress, and, based on the lab results, are there any changes you would make to her regimen?
- 80. • 19-year-old Latinapatient with systemic lupus erythematosus (SLE) is seen today for a routine follow-up visit. She was referred 1 year ago with polyarthritis, thought by her primary care provider to be due to rheumatoid arthritis (RA). After confirmation of SLE, she was found to have 3+ proteinuria, 10 RBCs/HPF, and class IV diffuse proliferative nephritis seen on renal biopsy. Treatment with high-dose prednisone plus mycophenolate mofetil (MMF; first 2 g/day, then 3 g/day) stabilized her lupus nephritis (LN): urine protein decreased to 0.3 g/day and revealed no RBCs.
- 81. • Eventually, prednisonewas tapered down to 10 mg.Today she denies significant joint pain or swelling, rashes, chest pains, skin or mucous membrane abnormalities, or neurological symptoms. Past history and family history are unremarkable. She has never been pregnant, but is determined to have children with her fiance in the future. At present she uses barrier methods (estimated 90% of the time). She is willing to use other forms of contraception for a period of time, but despite her present monogamy she rejects use of an IUD due to prior pelvic inflammatory disease. Review of systems is otherwise normal. Physical exam reveals obesity without evidence of malar or other rash.
- 82. • Current Conditions • Lupus nephritis • Obesity • Systemic lupus erythematosus • Current Medications • 10 mg prednisone daily • 1500 mg mycophenolate mofetil bid • 600 mg-200 units calcium-vitamin D bid • Daily multivitamin
- 83. Original Lab results •Anticardiolipin antibodies: medium positive titer • Lupus Anticoagulant: not detected • Beta2 Glycoprotein I: negative • Urine hCG Negative • Urine protein/creatinine ratio = 0.3, which correlates with 300 mg proteinuria/day.
- 84. Renal Biopsy • 24 Apr 07 - Renal biopsy from 13 months ago was consistent with lupus nephritis Class IV (no crescents noted). QuickTime™ and a decompressor are needed to see this picture.
- 85. • anti-CCP 2 IU/mL • Note: • 0-19 (negative) • 20-39 (weak positive) • 40-59 (moderate positive) • >60 (strong positive)
- 86. AB testing • Anti-Sm(Smith): Positive • ANA positive at 320 in a homogeneous pattern • DsDNA Positive at 1:80 • C3 Complement 61 mg/dL • 82 - 235 • C4 Complement 44 mg/dL • 16 - 70
- 87. • Glucose (FPG) 92 mg/dL • 70 - 110 • Creatinine 0.8 mg/dL • 0.6 - 1.3 • Albumin 3.7 g/dL • 3.4 - 5.0 • Bilirubin, Total 0.7 mg/dL • 0.0 - 1.0 • Alkaline Phosphatase 121 IU/L • 50 - 136 • AST (SGOT) 23 IU/L • 15 - 37 • ALT (SGPT) 18 IU/L • 15 - 37
- 88. Current lab tests •A CBC should be ordered several times a year in patients with SLE (every 3 months if taking MMF) to screen for leukopenia, thrombocytopenia, and/or anemia.
- 89. • Hb (Hemoglobin)9.8 g/dL • 9.6 - 18.0 • HCT (Hematocrit) 29 % • 37 - 47 • Platelet Count 214 1000/mm3 • 50 - 350 • WBC (White Blood Cell Count) 3.2 1000/mm3 • 4.0 - 10.8
- 90. • A chemistrypanel that checks fasting glucose, creatinine, lipids, and hepatic enzymes should be ordered several times a year (every 3 months if taking MMF) in patients with SLE.
- 91. • Glucose (FPG) 82 mg/dL • 70 - 110 • Creatinine 1.2 mg/dL • 0.6 - 1.3 • Albumin 3.6 g/dL • 3.4 - 5.0 • Bilirubin, Total 0.6 mg/dL • 0.0 - 1.0 • Alkaline Phosphatase 113 IU/L • 50 - 136 • AST (SGOT) 28 IU/L • 15 - 37 • ALT (SGPT) 18 IU/L • 15 - 37
- 92. In anticipation ofobtaining a renal biopsy, coagulation studies are indicated. • Prothrombin Time 12 seconds • 11 - 15 • Partial Thromboplastin Time 29 seconds • 25 - 40 • International Normalized Ratio 1.0 • 0.8 - 1.2
- 93. Dyslipidemia is apotential consequence of proteinuria; LDL-C levels should be checked regularly. Abnormal lipid levels deserve vigorous treatment. • Triglycerides 173 mg/dL • 0 - 150 • Total Cholesterol 225 mg/dL • 0 - 200 • LDL Cholesterol 110 mg/dL • 62 - 130 • HDL Cholesterol 79 mg/dL • 50 - 60
- 94. Renal biopsy: Class IVlupus nephritis with a high level of activity (crescents) QuickTime™ and a decompressor are needed to see this picture.
- 95. • Color yellow • Turbidity cloudy • Specific Gravity 1.013 1.006 - 1.030 • Urine Glucose negative • Ketones negative • Blood negative • Protein 2+ • Bilirubin negative • Urobilinogen negative • Nitrites negative • Leukocyte Esterase negative • Casts negative • RBCs negative • Crystals negative • WBCs negative
- 96. • A urineprotein/creatinine ratio is an efficient and reasonably accurate method to quantitate proteinuria. Values > 0.5 (correlating to > 0.5 g (500 mg)/24 h) suggest the need for a renal biopsy to stage possible lupus nephritis (3659 ). • Urine protein/creatinine ratio = 2.0
- 97. • Antiphospholipid Antibodies:With her repeatedly positive anticardiolipin . antibody determinations and intrinsic high risk for thrombotic complications, continued monitoring is prudent. • Anticardiolipin antibodies: 80 GPL U/mL (high positive) • Lupus anticoagulant: not present • Beta2 Glycoprotein I: negative
- 98. Possible options • Dueto the failure of MMF for decreasing proteinuria to below 500-1,000 mg/day in this patient, discontinuation of its use and substitution of rituximab, or the combination of cyclophosphamide with leuprolide premedication, or perhaps azathioprine is a reasonable next step.
- 99. • Patients withlupus nephritis and this degree of ongoing pathologic activity require use of an immunosuppressive agent, such as cyclophosphamide lyophilized, azathioprine, tacrolimus, or an experimental therapy such as rituximab • Although cyclophosphamide remains the standard for use in rapidly-progressive crescentic lupus nephritis, its use is highly associated with infertility noted in about 50% of patients using this drug. The incidence of infertility can be decreased to approximately 15%, however, with leuprolide injections 2 weeks prior to the monthly cyclophosphamide
- 100. • Some successhas been reported in open-label series using rituximab ,which peripherally depletes B-lymphocytes and is approved for use in rheumatoid arthritis. • While not FDA-approved for use in lupus nephritis, the anti-rejection agent tacrolimus has been associated with some degree of success in a small number of patients
- 101. • Azathioprine hasbeen shown to have equivalent efficacy to MMF in maintenance trials, but patients are unlikely to have a better response to azathioprine than they had to MMF.
- 102. • Standard DosingRanges • 1,000-1,500 mg of mycophenolate mofetil 500 mg oral tablet BID maximum, 2,000-3,000 mg daily maximum • 1-80 mg of predniSONE 10 mg oral tablet QID maximum, 1-80 mg daily maximum • 1-4 ea of calcium-vitamin D 600 mg-200 units oral tablet QID maximum, 1-4 ea daily maximum • 1 ea of Multiple Vitamins oral capsule once a day maximum