SYSTEMIC LUPUS ERYTHEMATOSUS
(SLE)
presented by, KIRSHA.K.S 1yr MPharm
Pharmacy Practice Grace College of
Pharmacy
CONTENTS
Definition Etiology Pathophysiology Clinical manifestations Diagnosis of SLE Treatment Special groups Treatment Algorithm
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
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.
ETIOLOGY
Results from the gross disturbance of the immune system.
Etiology of abnormal autoantibody formation and development of SLE is unknown.
But…
Genetics
Hormones
Environment
• MHC• HLA• Non MHC• Mannose
binding protein genes
• Androgen
• estrogen
• Sunlight• Chemicals• virus
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
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
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.
ORGAN ORGAN INVOLVEMENT INVOLVEMENT WITH LUPUSWITH LUPUS
Kidneys Lungs Central nervous system
Blood vessels Blood Heart
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
DIAGNOSING LUPUSDIAGNOSING LUPUS
Medical history (including family history)
Complete physical examination Laboratory tests Skin or kidney biopsy
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)
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).
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
Malar Rash
Discoid Rash
Oral Ulcers
COMMON LABORATORY COMMON LABORATORY
TESTSTESTS
Antinuclear Antibody (ANA) Anti DNA Anti-Sm Anti-RNP Anti-Ro Anti-La
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
OTHER LABORATORY OTHER LABORATORY TESTSTESTS
CBC (RBC, WBC, platelets)
Urinalysis Sedimentation Rate (ESR)
Rheumatoid Factor
Skin biopsy Kidney Biopsy
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
COMMON COMMON LUPUS MEDICATIONSLUPUS MEDICATIONS
NSAIDs Anti-malarials Corticosteroids Cytotoxic drugs Investigational
(research)
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.
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
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.
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.
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
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
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.
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
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.
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.
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.
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
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
TREATMENT ALGORITHM
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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