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systemic lupus erythematosus


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SLE- an autoimmune disease

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systemic lupus erythematosus

  1. 1. SYSTEMIC LUPUS ERYTHEMATOSUS (SLE) presented by, KIRSHA.K.S 1yr MPharm Pharmacy Practice Grace College of Pharmacy
  2. 2. CONTENTS  Definition  Etiology  Pathophysiology  Clinical manifestations  Diagnosis of SLE  Treatment  Special groups  Treatment Algorithm
  3. 3. Definition  Systemic lupus erythematosus (SLE) is a multi-system auto-immune disease in which organs and cells undergo damage, mediated by tissue binding autoantibodies and immune complexes.  It is characterized by states of exacerbation and remission
  4. 4.  The immune system loses the ability to differentiate between foreign cells and it’s own cells and tissues  Antibodies against the immune system are formed  The immune complexes that are formed build up in the tissue causing inflammation, injury to the tissue, and pain,  Organ system commonly affected includes kidneys, CNS, PNS, heart, lungs and circulatory system.
  5. 5. ETIOLOGY  Results from the gross disturbance of the immune system.  Etiology of abnormal autoantibody formation and development of SLE is unknown.  But…
  6. 6. Genetic s Hormones Environment • MHC • HLA • Non MHC • Mannose binding protein genes • Androge n • estrogen • Sunlight • Chemicals • virus
  7. 7. SLE IS A…SLE IS A…  Major collagen disease with many clinical manifestations  Different for each person.  A disease that ranges from mild to life threatening.  Abnormal immunolgic function formation of antibodies against self antigen underlies the pathogenesis of SLE
  8. 8. PATHOPHYSIOLOGY  SLE represents a clinical syndrome rather than a discrete disease with a unique pathogenesis.  Triggering agents abnormal immune regulation T-cells B-cells autoantibody formation immune complex formation and complement activation tissue injury and damage
  9. 9. SYSTEMIC LUPUSSYSTEMIC LUPUS ERYTHEMATOSUSERYTHEMATOSUS  Can affect any organ in the body including the joints, skin, lungs, heart, blood, kidney, or nervous system.  Can range from mild to life threatening.  No two people will have identical symptoms.
  10. 10. ORGANORGAN INVOLVEMENTINVOLVEMENT WITH LUPUSWITH LUPUS  Kidneys  Lungs  Central nervous system  Blood vessels  Blood  Heart
  11. 11. CLINICAL MANIFESTATIONS  Musculoskeletal : Arthritis and Arthralgia  Constitutional : Fatigue, Fever, Weight loss  Mucocutaneous : Butterfly rash, Photosensitivity, Raynaud’s phenomenon, Discoid lesions  CNS : Psychosis, Seizures  Pulmonary : Pleuritis, Pleural effusion  CVS : Pericarditis, Myocarditis, Heart murmur, Hypertension  Renal : lupus nephritis  Gastrointestinal : Nausea, Abdominal pain, Bowel hemorrhage  Hematologic : Anemia, Leukopenia ,Thrombocytopenia  Lymphadenopathy
  12. 12. DIAGNOSING LUPUSDIAGNOSING LUPUS  Medical history (including family history)  Complete physical examination  Laboratory tests  Skin or kidney biopsy
  13. 13. DIAGNOSIS    Criterion Definition Malar Rash   Rash over the cheeks Discoid Rash   Red raised patches Photosensitivity   Reaction to sunlight, resulting in the development of or increase in skin rash Oral Ulcers   Ulcers in the nose or mouth, usually painless Arthritis   Nonerosive arthritis involving two or more peripheral joints (arthritis in which the bones around the joints do not become destroyed) Serositis   Pleuritis or pericarditis (inflammation of the lining of the lung or heart) Renal Disorder   Excessive protein in the urine (greater than 0.5 gm/day or 3+ on test sticks) and/or cellular casts (abnormal elements the urine, derived from red and/or white cells and/or kidney tubule cells)
  14. 14. DIAGNOSIS    Criterion Definition Neurologic   Disorder   Seizures (convulsions) and/or psychosis in the absence of drugs or metabolic disturbances which are known to cause such effects Hematologic   Disorder   Hemolytic anemia , leukopenia , lymphopenia or thrombocytopenia. The leukopenia and lymphopenia must be detected on two or more occasions. The thrombocytopenia must be detected in the absence of drugs known to induce it. Antinuclear   Antibody   Positive test for antinuclear antibodies (ANA) in the absence of drugs known to induce it.   Immunologic   Disorder   Positive anti-double stranded anti-DNA test, positive anti-Sm test, positive antiphospholipid antibody such as anticardiolipin, or false positive syphilis test (VDRL).
  15. 15. ACR DIAGNOSTIC CRITERIAACR DIAGNOSTIC CRITERIA Skin criteria 1. Butterfly rash 2. Discoid rash 3. Photosensitivity 4. Oral ulcers Systemic criteria 5. Arthritis 6. Serositis 7. Kidney disorder 8. Neurologic disorder Laboratory criteria 9. Hematologic abnormalities 10. Immunologic disorder 11. Antinuclear antibody
  16. 16. Malar Rash
  17. 17. Discoid Rash
  18. 18. Oral Ulcers
  19. 19. COMMON LABORATORYCOMMON LABORATORY TESTSTESTS  Antinuclear Antibody (ANA)  Anti DNA  Anti-Sm  Anti-RNP  Anti-Ro  Anti-La
  20. 20. FLUORESCENT ANA TEST  Nearly all SLE patients are ANA positive. PATTERN ANTIGEN DISEASE Peripheral • dsDNA • SLE Speckled • Acidic nuclear protein • Ribonucleoprotein • Extractable nuclear antigen • RA • SLE • Scleroderma, mixed connective tissue disease Homogenous • dsDNA, ssDNA • Histones • RA • SLE, DI lupus nucleolar • Nucleolar RNA • Progressive systemic sclerosis
  21. 21. OTHER LABORATORYOTHER LABORATORY TESTSTESTS  CBC (RBC, WBC, platelets)  Urinalysis  Sedimentation Rate (ESR)  Rheumatoid Factor  Skin biopsy  Kidney Biopsy
  22. 22. EFFECT OF LABORATORY TESTSEFFECT OF LABORATORY TESTS WITH INCREASED LUPUSWITH INCREASED LUPUS ACTIVITYACTIVITY C reactive protein (CRP)  Sedimentation rate (ESR)  Anti DNA  Liver and Kidney Function tests  CPK  Urine protein or cell casts CBC (WBC, RBC, platelets) Serum albumin
  23. 23. COMMONCOMMON LUPUS MEDICATIONSLUPUS MEDICATIONS  NSAIDs  Anti-malarials  Corticosteroids  Cytotoxic drugs  Investigational (research)
  24. 24. DRUG CLASS DRUG AND DOSE MAJOR INDICATIONS NSAIDs • Various agents • Anti-inflammatory dose Mild disease: fever, arthritis ,skin rash, serositis Antimalarial • Hydroxychloroquine, 200-400mg, PO daily • Chloroquine, 250-500mg, PO daily   Mild disease: arthritis, skin rash, serositis Corticosteroid • Prednisone, 1-2mg/kg/d, PO daily (or equivalent) <1mg/kg/d (or equivalent)       • Methyl prednisolone, 500-600mg IV daily * 3-6 days   Initial control of severe disease Control of mild disease or maintenance after disease Suppression with higher doses. Life threatening disease Cytotoxic • Cyclophosphamide, 0.5-1.0g/m2 IV monthly for 6 months, then every 3 months for 2 years or 1 year after remission. • Azathioprine 1-3mg/kg PO daily • Cyclophosphamide, 1-3mg/kg PO daily • Mycophenolate mofetil, 1-3g PO daily Most commonly used in severe lupus nephritis: may be necessary for other severe disease manifestations.
  25. 25. NON PHARMACOLGIC THERAPY  Balanced routine of rest and exercise while avoiding overexertion is essential in managing fatigue.  Avoidance of smoking  Fish oil derivatives in pregnant women  Limit exposure to sunlight
  26. 26. DRUG INDUCED LUPUSDRUG INDUCED LUPUS  Develops after long-term use of certain medications.  To meet the criteria for DIL, a patient should have exposure to a suspected drug, no prior history of idiopathic SLE prior to the use of drug, development of ANAs (anti-histone antibody), and at least one clinical feature of SLE and rapid improvement of symptoms with a gradual decline in ANAs following drug discontinuation.  Most common in men over 50 years old.  Symptoms are similar to SLE.
  27. 27.  Musculoskeletal symptoms, fever, fatigue, pericarditis, pleurisy and weight loss.  +ve ANA test (>90%)  Antibodies are primarily against ssDNA and not dsDNA as in idiopathic SLE.  Most important treatment is to recognize medication and discontinue use.  Once medication is stopped, symptoms usually disappear completely within 6 months.
  28. 28. Medications implemented in drug induced lupus Acebutolol Clonidine Interleukin 2 Minocycline Pindolol Sulfasalazi ne Amiodarone Clozapine Isoniazid Nifedipine Primidone Tetracyclin e Anti-TNF therapies Diltiazem Labetalol Oral contraceptiv es Procainami de Thiazide diuretics Atenolol Ethosuximide Lisinopril Para-amino salicylate Propranolol Ticlopidine Captopril Gold salts Lithium Penicillamin e Propylthioura cil Timolol Carbamazepine Griseofulvin Mephenyto in Penicillin Quinidine Tocainide Chlorpromazine Hydralazine Methimazo le Phenytoin Reserpine Valproate Ciprofloxacin hydroxyurea Methyldo pa Phenylbuta zone Simvastatin Verapamil Clobazam Interferon (alpha, gamma) Metoprolol phenelzine Streptomycin Zafirlukast  
  29. 29. SLE in pregnancy  Exacerbation is likely, if the disease is in remission at conception.  Hydroxychloroquine is safer to use in pregnancy.  There is increased risk of abortions (2-3 times), intrauterine growth retardation and stillbirth. Pregnancy increases the risk of disease flare (40%-50% probability).  The risk of flare is doubled in women who have active disease at the time of conception
  30. 30. Laboratory monitoring during pregnancy  Initial evaluation: Hb, WBC, DLC, platelets, urinalysis with microscopy, 24-hour urinary estimation of protein and creatinine, blood urea, glucose and serum creatinine, serum lipids if patient is nephrotic or on steroids, Coombs’ test, aPL VDRL, anti-dsDNA, C3. Anti-Ro and anti-La should be done if there is a past history of giving birth to a baby with neonatal lupus.  Monthly Laboratory assessment includes Hb, WBC, DLC, platelets, urinalysis (with 24-hr analysis if nephritis), chemistry panel as above, anti-dsDNA and C3. Elevated anti-dsDNA and low C3 indicate active SLE or impending flare in over 80% of patients  In case anaemia develops, peripheral smear should be reviewed and Coombs’ test repeated.
  31. 31. Medication use during SLE pregnancy Medication to continue in pregnancy Medication to discontinue prior to pregnancy Prenatal multivitamin Cyclophosphamide Low-dose Aspirin Mycophenolate mofetil Hydroxychloroquine Methotrexate Prednisone (moderate dose) Leflunomide Azathioprine   Aspirin 81 mg  
  32. 32. NEONATAL LUPUSNEONATAL LUPUS  Occurs when the mother’s antibodies cross over the placenta to the baby.  Can affect the skin, heart, liver and/or blood of the fetus and newborn.  Good prenatal care can prevent most problems.
  33. 33. CONTRACEPTION  Estrogen containing oral contraceptives are avoided in women with SLE.  Combined oral contraceptives ,progestin only contraceptives and IU devices are suggested for women with SLE.
  34. 34. ANTI-PHOSPHOLIPID SYNDROME & THROMBOSIS  Presence of anti-phospholipid antibodies may lead to thrombosis.  Low dose Aspirin (81-325mg/day)  Patient with acute thrombotic event – standard treatment with anti-coagulants like Heparin.
  35. 35. LUPUS NEPHRITIS  Lupus nephritis is currently defined as the presence of more than +++ or 0.5 gram/24 hr proteinuria or presence of cellular casts of any type.  Principles of treatment of lupus nephritis General measures: It is advisable to restrict salt if hypertension is present, fat if hyperlipidemia or nephrotic syndrome is present, protein should be restricted if azotemia is present and calcium should be supplemented with steroid therapy. Meticulous control of hypertension is desirable. Pregnancy should be avoided during active lupus nephritis with suitable contraception (vide infra). NSAIDs should be avoided in the presence of impaired renal function
  36. 36. Immunosuppressive therapy: This is generally guided by the WHO Class of lupus nephritis Class I: Immunosuppressive therapy is not indicated. Class IIa: -do Class IIb: If proteinuria is > 1 gram/24 hours, anti- dsDNA is high and C3 is low, prednisolone should be administered at a dose of 20 mg daily for 6-12 weeks, followed by tapering over next 3 months
  38. 38. Monitoring the toxicities of drugs used in SLE Drug Toxicities to monitor Baseline evaluation Monitoring System review Laboratory Salicylates, NSAIDs GI bleeding, hepatic and renal toxicity, hypertension CBC, creatinine, urinalysis, AST, ALT Dark/black stool, dyspepsia, nausea, vomiting, abdominal pain, shortness of breath, edema CBC yearly, Creatinine yearly Corticosteroids Hypertension, hyperglycemia, hyperlipidemia, hypokalemia, osteoporosis, avascular necrosis, cataract, weight gain, infections, fluid retention BP, bone densitometry, glucose, potassium, cholesterol, triglycerides, HDL, LDL Polyuria, polydipsia, edema, shortness of breath, BP, visual changes, bone pain Urinary dipstick for glucose every 3-6 months, total cholesterol yearly, bone densitometry yearly to assess osteoporosis Hydroxychloroquin e Macular damage None unless patient is over 40 years of age or has previous eye disease Visual changes Funduscopic and visual fields every 6-12 months Azathioprine Myelosuppression, hepatotoxicity, lymphoprolipherative disorders CBC, platelet count, creatinine, AST, ALT Symptoms of myelosuppression CBC and platelet count every 1-2weeks with changes in dose (every 1-3 months thereafter), AST early PAP test at regular intervals Cyclophosphamide Myelosuppression, myeloproliferative disorders, malignancy, immunosuppression, hemorrhage, cystitis, secondary infertility CBC and differential and platelet count, urinalysis Symptoms of myelosuppression, hematuria, infertility CBC and urinalysis monthly ,urine cytology, and PAP test yearly for life
  39. 39. Thank YouThank You