Transcript
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SYSTEMIC LUPUS ERYTHEMATOSUS

(SLE)

presented by, KIRSHA.K.S 1yr MPharm

Pharmacy Practice Grace College of

Pharmacy

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CONTENTS

Definition Etiology Pathophysiology Clinical manifestations Diagnosis of SLE Treatment Special groups Treatment Algorithm

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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

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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.

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ETIOLOGY

Results from the gross disturbance of the immune system.

Etiology of abnormal autoantibody formation and development of SLE is unknown.

But…

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Genetics

Hormones

Environment

• MHC• HLA• Non MHC• Mannose

binding protein genes

• Androgen

• estrogen

• Sunlight• Chemicals• virus

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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

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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

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SYSTEMIC LUPUS SYSTEMIC LUPUS ERYTHEMATOSUS ERYTHEMATOSUS

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.

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ORGAN ORGAN INVOLVEMENT INVOLVEMENT WITH LUPUSWITH LUPUS

Kidneys Lungs Central nervous system

Blood vessels Blood Heart

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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

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DIAGNOSING LUPUSDIAGNOSING LUPUS

Medical history (including family history)

Complete physical examination Laboratory tests Skin or kidney biopsy

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DIAGNOSIS

   Criterion DefinitionMalar 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)

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DIAGNOSIS

   Criterion DefinitionNeurologic  

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).

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ACR DIAGNOSTIC ACR DIAGNOSTIC CRITERIACRITERIA

Skin criteria1. Butterfly rash2. Discoid rash3. Photosensitivity4. Oral ulcers

Systemic criteria5. Arthritis6. Serositis7. Kidney disorder8. Neurologic disorder

Laboratory criteria 9. Hematologic abnormalities10. Immunologic disorder11. Antinuclear antibody

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Malar Rash

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Discoid Rash

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Oral Ulcers

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COMMON LABORATORY COMMON LABORATORY

TESTSTESTS

Antinuclear Antibody (ANA) Anti DNA Anti-Sm Anti-RNP Anti-Ro Anti-La

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FLUORESCENT ANA TEST Nearly all SLE patients are ANA positive.

PATTERN ANTIGEN DISEASEPeripheral • dsDNA • SLESpeckled • 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

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OTHER LABORATORY OTHER LABORATORY TESTSTESTS

CBC (RBC, WBC, platelets)

Urinalysis Sedimentation Rate (ESR)

Rheumatoid Factor

Skin biopsy Kidney Biopsy

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EFFECT OF LABORATORY TESTS EFFECT OF LABORATORY TESTS WITH INCREASED LUPUS WITH 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

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COMMON COMMON LUPUS MEDICATIONSLUPUS MEDICATIONS

NSAIDs Anti-malarials Corticosteroids Cytotoxic drugs Investigational

(research)

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DRUG CLASS DRUG AND DOSE MAJOR INDICATIONSNSAIDs Various agents

Anti-inflammatory doseMild 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 diseaseControl of mild disease or maintenance after diseaseSuppression 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.

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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

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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.

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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.

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Medications implemented in drug induced lupusAcebutolol Clonidine Interleuki

n 2Minocycline

Pindolol Sulfasalazine

Amiodarone Clozapine Isoniazid

Nifedipine Primidone Tetracycline

Anti-TNF therapies

Diltiazem Labetalol Oral contraceptives

Procainamide

Thiazide diuretics

Atenolol Ethosuximide

Lisinopril Para-amino salicylate

Propranolol Ticlopidine

Captopril Gold salts Lithium Penicillamine

Propylthiouracil

Timolol

Carbamazepine Griseofulvin Mephenytoin

Penicillin Quinidine Tocainide

Chlorpromazine

Hydralazine

Methimazole

Phenytoin Reserpine Valproate

Ciprofloxacin hydroxyurea Methyldopa

Phenylbutazone

Simvastatin

Verapamil

Clobazam Interferon (alpha, gamma)

Metoprolol

phenelzine

Streptomycin

Zafirlukast 

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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

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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.

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Medication use during SLE pregnancy

Medication to continue in pregnancy

Medication to discontinue prior to

pregnancyPrenatal multivitamin Cyclophosphamide

Low-dose Aspirin Mycophenolate mofetil

Hydroxychloroquine Methotrexate

Prednisone (moderate dose)

Leflunomide

Azathioprine  Aspirin 81 mg  

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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.

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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.

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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.

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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

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Immunosuppressive therapy: This is generally guided by the WHO Class of lupus nephritisClass I: Immunosuppressive therapy is not indicated. Class IIa: -doClass 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

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TREATMENT ALGORITHM

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Monitoring the toxicities of drugs used in SLEDrug Toxicities to monitor Baseline

evaluationMonitoring

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

Hydroxychloroquine

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 earlyPAP 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

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Thank YouThank You


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