lupus presentation final
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This document provides an overview of lupus, a chronic autoimmune disease that can affect multiple organs and tissues. It discusses the epidemiology of lupus, noting it primarily affects women and is more common in certain ethnic groups. The pathogenesis involves a genetic predisposition interacting with environmental triggers that result in an abnormal immune response attacking the body's own tissues. Symptoms and organ involvement can vary widely between patients. Diagnosis is based on meeting several criteria that may include rashes, arthritis, kidney disease, neurological issues, and positive antibody tests. Treatment depends on disease severity and organ involvement, ranging from lifestyle changes to immunosuppressive drugs and corticosteroids. Lupus nephritis, or kidney involvement,
![References
• Rahman A, Isenberg DA. Systemic lupus erythematosus. N Engl J Med. 2008;358(9):929-39.
• Bartels CM. Systemic Lupus Erythematosus (SLE). Medscape News [serial online]. November 15, 2011; Accessed December 16, 2011. Available at
http://emedicine.medscape.com/article/332244-overview
• Bernatsky S, Boivin JF, Joseph L, et. al. Mortality in systemic lupus erythematosus. Arthritis & Rheumatism 2006; 54: 2550–2557.
• Alarcón GS, McGwin G Jr, Bastian HM, Roseman J, Lisse J, Fessler BJ, et al. Systemic lupus erythematosus in three ethnic groups. VII [correction of
VIII]. Predictors of early mortality in the LUMINA cohort. LUMINA Study Group. Arthritis Rheum. 2001;45(2):191-202.
• Lupus Foundation of America. Lupus Fact Sheet. http://www.lupus.org/webmodules/webarticlesnet/templates/new_newsroomnews.aspx?articleid=351
&zoneid=59. Accessed December 16, 2011.
• Hochberg MC. Updating the American College of Rheumatology revised criteria for the classification of systemic lupus erythematosus. Arthritis
Rheum.1997;40(9):1725.
• Weening JJ, D'Agati VD, Schwartz MM, et al. The classification of glomerulonephritis in systemic lupus erythematosus revisited. J Am Soc Nephrol.
2004;15(2):241-50.
• Yazdany J, Panopalis P, Gillis JZ, Schmajuk G, MacLean CH, Wofsy D, et al. A quality indicator set for systemic lupus erythematosus. Arthritis Rheum.
2009;61(3):370-7.
• Navarra SV, Guzmán RM, Gallacher AE, Hall S, Levy RA, Jimenez RE, et al. Efficacy and safety of belimumab in patients with active systemic lupus
erythematosus: a randomised, placebo-controlled, phase 3 trial. Lancet. 2011;377(9767):721-31.
• Hill E. Belimumab Earns FDA Approval for Lupus. Medscape News [serial online]. March 15, 2011;Accessed December 16, 2011. Available at
http://www.medscape.com/viewarticle/738729.
• Appel GB, Contreras G, Dooley MA, et al. Mycophenolate mofetil versus cyclophosphamide for induction treatment of lupus nephritis. J Am Soc
Nephrol. 2009;20(5):1103-12.
• Isenberg D, Appel GB, Contreras G, et al. Influence of race/ethnicity on response to lupus nephritis treatment: the ALMS study. Rheumatology (Oxford).
2010;49(1):128-40.
• Delafuente JC, Cappuzzo KA. Systemic Lupus Erythematosus and Other Collagen-Vascular Diseases. In: Dipro JT, Talbert RL, Yee GC, Matzke GR,
Wells BG, Posey LM, eds. Pharmacotherapy: A Pathophysiologic Approach. 7th ed. New York: McGraw-Hill Companies, Inc., 2008: 1431-1445.
• Lau AH. Glomerulonephritis. In: Dipro JT, Talbert RL, Yee GC, Matzke GR, Wells BG, Posey LM, eds. Pharmacotherapy: A Pathophysiologic Approach.
7th ed. New York: McGraw-Hill Companies, Inc., 2008: 811-831
• (Chapter). Joseph T. DiPiro, Robert L. Talbert, Gary C. Yee, Gary R. Matzke, Barbara G. Wells, L. Michael Posey: Pharmacotherapy: A
Pathophysiologic Approach, 7e: http://www.accesspharmacy.com/content.aspx?aID=3187202.
• Walsh N. Predictors of renal failure in systemic lupus erythematosus. MedPageToday [serial online]. November 14, 2011; Accessed December 16,
2011. Available at http://www.medpagetoday.com/MeetingCoverage/ACR/29660.
• Gordan D. First-Time Guidelines for Lupus Nephritis. Medscape News [serial online]. November 8, 2011; Accessed December 16, 2011. Available at
http://www.medscape.com/viewarticle/753134.
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lupus presentation final
- 1. Lupus: More than Just Skin Deep Elva Angelique Van Devender, Ph.D., Pharm.D. PGY1 Pharmacy Practice Resident Providence Health and Services Portland, Oregon January 2012
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- 4. Quick Quiz: Which statement about lupus is TRUE? A.Lupus is an infectious disease. B.Lupus is curable with treatment. C.Lupus is primarily a disease of the skin. D.Lupus is more common in women. E.Lupus is often a disease of the elderly. 4
- 5. Quick Quiz: Which statement about lupus is TRUE? A.Lupus is an infectious disease. B.Lupus is curable with treatment. C.Lupus is primarily a disease of the skin. D.Lupus is more common in women. E.Lupus is often a disease of the elderly. 5
- 6. Lupus: More than Just Skin Deep Elva Angelique Van Devender, Ph.D., Pharm.D. PGY1 Pharmacy Practice Resident Providence Health and Services Portland, Oregon January 2012
- 7. Famous People with Lupus 7
- 8. Learning Objectives By the end of this lecture and learning activity, you should be able to…. - Identify the epidemiology and pathogenesis of lupus - Identify the clinical and diagnostic presentation of lupus - Recognize drugs that may induce or exacerbate lupus - Identify the potential impact of lupus to the various parts of the body - Understand the importance of lupus nephritis as a complication of lupus - Describe current drug therapy and disease management of the lupus patient - List the common side effects of the drugs used to treat lupus 8
- 9. Precipitating Factors • The number of cases of lupus in the United States is unknown. – The CDC estimates 1.5 million people may be affected with the disease. – The Lupus Foundation of America reports about 16,000 new cases are diagnosed in the United States each year. • Lupus primarily affects women (90% of lupus patients are female!). – Younger women (usually 15-45 years old) are affected more frequently. – More common in African American, Latina, Asian, and Native American women than white women • The etiology of lupus is unknown. • Theory: 9 genetic disposition toward lupus environmental “trigger” or infection “confused” immune system that attacks the body’s own tissues • Possible Triggers of Lupus • Stress • Sun Exposure • Infection • Hormones • Smoking • Surgery • Pregnancy • Drugs!!!
- 10. Drugs than Can Cause Lupus • Symptoms can include joint pain, muscle pain, and fever, and are mild for most people. • It is estimated that up to 10% of lupus may be drug induced. The following are drugs with the most evidence associated with drug-induced lupus. – Procainamide (most common) – Hydralazine – Phenytoin – Chlorpromazine – Quinidine – Methydopa – Isoniazid – Minocycline • Symptoms usually cease when the medicine is stopped. 10
- 11. Lupus: A Disease of Autoimmunity • B-cells run amok and produce antibodies that attack the body’s own tissues!!! • T-cells probably play a role in activating the errant B-cell response. • Question: Why don’t we just slam the hammer down on the immune system to smack this disease into remission? 11
- 12. Quick Quiz What is the leading cause of death in lupus patients? A. liver failure B. heart disease C. renal causes D. malignancy E. infection 12
- 13. Quick Quiz What is the leading cause of death in lupus patients? A. liver failure B. heart disease C. renal causes D. malignancy E. infection 13
- 14. Clinical and Diagnostic Presentation of SLE SLE accounts for 70% of all lupus cases. SLE Characteristics • Chronic • Inflammatory • Multisystem • Autoimmune • Fluctuating • Female: male ratio is ~9:1 14 Although we typically think of lupus as a skin disease, it can also affect many organs (i.e. heart, lungs, kidneys, joints, bone) of the body, resulting in a variety of symptoms.
- 15. How Will Your Patients Present? • The clinical presentation in lupus patients is variable: – Most common symptoms are fatigue and arthralgias (particularly of the hands) – Depression and headache are the most common of the neuropsychiatric symptoms. Generalized seizures and psychoses are rare. • By the numbers: – 50% of patients have cutaneous features, such as butterfly rash and discoid lupus as well as photosensitivity. – 50% of patients have nephropathy, which varies from mild proteinuria and microscopic hematuria to end-stage renal failure. – 30% of patients have oral ulcerations. – 20-30% of patients have pleurisy. – <20% of patients have pericarditis. – 10% of patients experience thromboembolic or hemorrhagic complications (antiphospholipid antibodies associated with hypercoaguable state) – 10% of patients experience peripheral neuropathy. • 15
- 16. How is Lupus Diagnosed? The American College of Rheumatology established 11 criteria to help identify the disorder. A person with lupus usually has four or more of the following symptoms: “SOAP BRAIN MD” 1. Serositis—heart, lung, peritoneum 2. Oral ulcers—painless, usually on roof or back of mouth 3. Arthritis with prolonged morning stiffness, usually up to an hour, improving as the day goes on 4. Photosensitivity 5. Blood disorders (low RBC, plt, WBC counts) 6. Renal Involvement (proteinuria/ with or without casts) 7. ANA titer> 1:160 (positive test; 93% of people with lupus have this antibody) 8. Immunologic phenomena- anti-dsDNA antibodies, anti-Smith antibodies, antiphospholipid antibodies, all of which are specific for diagnosing lupus 9. Neurological disorders – seizures, psychosis 10. Malar “butterfly” rash on the cheeks and nasal bridge 11. Discoid skin lesions (often lead to scarring) . 16
- 17. What Tests Might be Ordered? • The tests ordered upfront: – CBC to screen for leukopenia, anemia, and thrombocytopenia – Urinalysis and creatinine studies to screen for kidney disease – ANA - Screening test; sensitivity 95%; not diagnostic without clinical features; caution 5-15% of normal people have positive test! • The following are additional autoantibody tests used in the diagnosis of SLE : – Anti-dsDNA - High specificity; sensitivity only 70%; (marker of disease activity) – Anti-Sm - Most specific antibody for SLE; only 30-40% sensitivity – Anti-SSA (Ro) or Anti-SSB (La) - Present in 15% of patients with SLE (not disease specific) – Anti-RNP – often included with anti-Sm, SSA, and SSB; may indicate mixed connective- tissue disease with overlap SLE, scleroderma, and myositis (not disease specific) – Anti-ribosomal P - Uncommon antibodies that may correlate with risk for CNS disease – Anticardiolipin - used to screen for antiphospholipid antibody syndrome – Lupus anticoagulant - Multiple tests (eg, direct Russell viper venom test) to screen for inhibitors in the clotting cascade in antiphospholipid antibody syndrome – Direct Coombs test - Coombs test–positive anemia to denote antibodies on RBCs – Anti-histone - Drug-induced lupus ANA antibodies are often of this type • Biopsies of skin and kidneys (if suspected involvement) 17
- 18. How is Lupus Treated? • Desired Treatment Outcomes: – Reduce flares – Decreasing swelling and pain – Reduce/prevent damage to joints – Reduce/prevent organ damage – Maintenance of remission • There is no one size fits all treatment for lupus!!! • Joint pain: NSAIDS, hydroxychloroquine, or corticosteroids. • Skin complications: • Nonpharm: avoid sunbathing, use sunscreens • Pharm: hydroxychloroquine or corticosteroids • Organ involvement: corticosteroids and/or immunosuppressive drugs (i.e. cyclophosphamide, mycophenolate, methotrexate, azathioprine) 18
- 19. Potential Side Effects of Corticosteroids 19 Cushing’s Syndrome Osteoporosis Edema Peptic Ulcer Disease HPA axis suppression Hypokalemia & Hypomagnesemia Hyperglycemia DM Pancreatitis Psychosis Glaucoma Insomnia Increased Appetite HTN Poor Wound Healing
- 20. Overall approach to therapy • Starting at the base and moving up the pyramid with disease severity… 20 Immuno- modulators Exercise Immuno- suppressants NSAIDS Hydroxy- chloroquine Low dose Corticosteroids High dose Corticosteroids Diet Sunscreen No smoking
- 21. Mild to Moderate Disease • In a patient presenting without life or organ-threatening symptoms, conservative measures can be used. 21 Exercise NSAIDS Hydroxy- chloroquine Low dose Corticosteroids Diet Sunscreen No smoking
- 22. Treatments at a Glance • Nonsteroidal Anti-inflammatory Drugs (NSAIDs) – Examples: ibuprofen, naproxen, diclofenac – MOA: Decrease inflammation through prostaglandin inhibition – Use: Provide symptomatic relief for arthralgias, fever, and mild serositis – AE: GI bleeding (concomitant administration with prednisone may increase risk of GI ulceration), acute kidney injury, hepatotoxicity • Antimalarials – Example: hydroxychloroquine (Plaquenil) – MOA: Thought to inhibit chemotaxis of eosinophils and locomotion of neutrophils and impairs complement-dependent antigen-antibody reactions without causing overt immunosuppression. – Use: • Treating lupus skin rashes, constitutional symptoms, arthralgias, and arthritis • Prevention of lupus flares (associated with reduced morbidity and mortality in SLE patients) • Renally protective – AE: retinopathy 22
- 23. Treatments at a Glance • Corticosteroids – Examples: methylprednisolone, prednisone – MOA: decrease inflammation by suppressing migration of polymorphonuclear leukocytes and reversing increased capillary permeability – Use/place in therapy: in mild, moderate, and severe lupus whenever immunosuppression is required – AE: Cushing’s syndrome, osteoporosis, edema, peptic ulcer disease, HPA axis suppression, hypokalemia and hypomagnesemia, hyperglycemia, decreased wound healing, pancreatitis, psychosis, glaucoma, insomnia, increased appetite, HTN, and DM 23
- 24. Moderate to Severe Disease • When SLE can’t be controlled by conservative measures alone, more extreme treatment is needed. This involves the use of high dose corticosteroids and immunosuppressive agents (i.e. azathioprine, cyclophosphamide, and mycophenolate mofetil). 24 Immuno- modulators Exercise Immuno- suppressants NSAIDS Hydroxy- chloroquine Low dose Corticosteroids High dose Corticosteroids Diet Sunscreen No smoking
- 25. • Immunosuppressive (cytotoxic) Agents – Examples: cyclophosphamide, mycophenolate, azathioprine, methotrexate – MOA: interfere with DNA synthesis or replication (cytotoxic) – Use: Immunosuppression in cases of serious SLE organ involvement (especially severe CNS involvement, vasculitis, and lupus nephritis); cyclophosphamide is reserved for severe organ-threatening disease. At the other end of the spectrum, methotrexate or azathioprine may be helpful for milder arthritis or skin disease. – Place in therapy: in moderate/severe disease when antimalarials and corticosteroids have failed – AE: infection, myelosuppression, heptatotoxicity, malignancy • Immunomodulators – Examples: rituximab (Rituxan), belimumab (Benlysta) – MOA: B-cell depletion (rituximab) and B-cell inhibition (belimumab) – Use/place in therapy: Immunomodulation in patients who have failed antimalarials, corticosteriods, and immunosuppresion with cytotoxic agents – AE: infection!!! (also nausea, diarrhea, fever, infusion-site reactions, pharyngitis, bronchitis, insomnia, extremity pain, depression, and migraine) 25 Treatments at a Glance
- 26. Belimumab (Benlysta): the first new lupus treatment in 50 years • The monoclonal antibody belimumab (Benlysta) is a B-lymphocyte stimulator protein inhibitor (BLyS) thought to decrease the amount of abnormal B cells contributing to lupus. • Approved by the FDA in March 2011 for use in combination with standard therapies to treat active autoantibody-positive SLE. – Reduced disease – Decreased the number of severe flares – Decreased steroid use • Should NOT be used in patients – With mild disease (20%-30% of lupus patients) who respond to NSAIDs, short courses of steroids, and antimalarial drugs. – With severe, life-threatening disease (not tested in trials) – Of African American or African descent (lack of response in trials) • Place in therapy – Patients with moderately severe disease who have failed stronger medications including high dose/long courses of steroids and immunosuppressive agents (like cyclophosphamide and mycophenylate) 26
- 27. Side Effects of Commonly Used Drugs in SLE 27
- 28. Quick Quiz: Patients with lupus are at risk for all of the following complications from drug therapy EXCEPT A.myelosuppression B.hepatotoxicity C.malignancy D.osteoporosis E.hypotension 28
- 29. Quick Quiz: Patients with lupus are at risk for all of the following complications from drug therapy EXCEPT A.myelosuppression B.hepatotoxicity C.malignancy D.osteoporosis E.hypotension 29
- 30. Lupus Nephritis • Kidney disease – One of the most serious complications of SLE – Mortality reduced with medical interventions in recent years but morbidity on the rise – Commonly seen within first four years of diagnosis of SLE – NOT drug induced • Biopsy required to diagnose – Assesses the severity of disease – Predicts short term and long term therapeutic outcomes – Dictates treatment • Presentation can range from minimal hematuria and proteinuria to severe diffuse glomerulonephritis. – Hypertension in 25-45% of patients – Elevated SCr – Anemia 30
- 31. First-Time Guidelines for Lupus Nephritis (ETA Spring 2012) • Biopsy all patients to classify and manage the disease International Society of Nephrology 2003 Revised Classification of SLE Nephritis • Maintenance therapy – All patients should receive hydroxychloroquine, given the data demonstrating its ability to reduce long-term kidney damage. – Patients with proteinuria of at least 0.5 g/day should also receive ACEI or ARB – Azathioprine alone is no longer recommended for maintenance therapy. • Additional recommendations: – Maintenance of blood pressure <130/80 mm Hg – statin therapy for patients with LDL > 100 mg/dL (CKD is coronary equivalent!) 31
- 32. First-Time Guidelines for Lupus Nephritis (ETA Spring 2012) • Induction therapy for class III/IV lupus nephritis: – Choice between mycophenolate mofetil (MMF) or cyclophosphamide for induction therapy in patients with class III/IV lupus nephritis. • Note: MMF (2 to 3 g/day for 6 months) is preferred over cyclophosphamide in black and Hispanic patients. • In those of Caucasian or European background), cyclophosphamide can be used in either – the low-dose Euro-Lupus regimen (500 mg IV every 2 weeks for 6 weeks) – or the high-dose National Institutes of Health regimen (500 to 1000 mg/m² body surface area monthly for 6 months is recommended – All patients should also receive an intravenous (IV) glucocorticoid pulse for 3 days, followed by prednisone at 0.5 to 1.0 mg/kg per day and then tapered after a few weeks to the lowest effective dose. – Patients who fail the first induction should be switched to the other option. – Patients who fail both MMF and cyclophosphamide should be started on rituximab or calcineurin inhibitors. – Patients who improve can be maintained on either MMF (1 to 2 g/day) or azathioprine (2 mg/kg per day). 32
- 33. First-Time Guidelines for Lupus Nephritis (ETA Spring 2012) • Induction therapy for class V membranous lupus nephritis: – MMF (2 to 3 g/day for 6 months) plus prednisone (0.5 mg/kg per day for 6 months). – If improvement, patients should receive maintenance therapy with MMF or azathioprine. – If no improvement, patients should be started on cyclophosphamide (500 to 1000 mg/m² monthly for 6 months) plus a glucocorticoid pulse, followed by daily prednisone (0.5 to 1.0 mg/kg per day). • The guidelines also address management in pregnant women. – Pregnancy counseling – Women with a history of class III or higher disease do not require treatment if there is no evidence of disease activity. • Those with mild disease activity should receive hydroxychloroquine (200 to 400 mg/day) • Those with clinically active disease should receive prednisone at doses required to suppress activity and, if necessary, azathioprine (not to exceed 2 mg/kg per day). 33
- 34. SLE and Pregnancy • Women with lupus can safely become pregnant. – Lupus should be under control or in remission for six months before getting pregnant. • Antiphospholipid antibodies may be associated with increased likelihood of spontaneous abortion • Pregnancy in women with lupus can result in – Disease flares – Greater incidence of miscarriage – Greater chance of developing preeclampsia • Discuss risks versus benefits with patients 34 Ok in pregnancy prednisone, hydroxychloroquine, and low-dose aspirin Ok, but use carefully in pregnancy azathioprine (not to exceed 2 mg/kg per day). Not ok in pregnancy mycophenolate mofetil, cyclophosphamide, and methotrexate (all cytotoxic)
- 35. Future Therapies • Targeted anti-B cell therapies (i.e. atacicept, epratuzumab) • T cell inhibition therapy (i.e. abatacept, cyclosporine) • Cytokine manipulation • Bone marrow transplant 35
- 36. References • Rahman A, Isenberg DA. Systemic lupus erythematosus. N Engl J Med. 2008;358(9):929-39. • Bartels CM. Systemic Lupus Erythematosus (SLE). Medscape News [serial online]. November 15, 2011; Accessed December 16, 2011. Available at http://emedicine.medscape.com/article/332244-overview • Bernatsky S, Boivin JF, Joseph L, et. al. Mortality in systemic lupus erythematosus. Arthritis & Rheumatism 2006; 54: 2550–2557. • Alarcón GS, McGwin G Jr, Bastian HM, Roseman J, Lisse J, Fessler BJ, et al. Systemic lupus erythematosus in three ethnic groups. VII [correction of VIII]. Predictors of early mortality in the LUMINA cohort. LUMINA Study Group. Arthritis Rheum. 2001;45(2):191-202. • Lupus Foundation of America. Lupus Fact Sheet. http://www.lupus.org/webmodules/webarticlesnet/templates/new_newsroomnews.aspx?articleid=351 &zoneid=59. Accessed December 16, 2011. • Hochberg MC. Updating the American College of Rheumatology revised criteria for the classification of systemic lupus erythematosus. Arthritis Rheum.1997;40(9):1725. • Weening JJ, D'Agati VD, Schwartz MM, et al. The classification of glomerulonephritis in systemic lupus erythematosus revisited. J Am Soc Nephrol. 2004;15(2):241-50. • Yazdany J, Panopalis P, Gillis JZ, Schmajuk G, MacLean CH, Wofsy D, et al. A quality indicator set for systemic lupus erythematosus. Arthritis Rheum. 2009;61(3):370-7. • Navarra SV, Guzmán RM, Gallacher AE, Hall S, Levy RA, Jimenez RE, et al. Efficacy and safety of belimumab in patients with active systemic lupus erythematosus: a randomised, placebo-controlled, phase 3 trial. Lancet. 2011;377(9767):721-31. • Hill E. Belimumab Earns FDA Approval for Lupus. Medscape News [serial online]. March 15, 2011;Accessed December 16, 2011. Available at http://www.medscape.com/viewarticle/738729. • Appel GB, Contreras G, Dooley MA, et al. Mycophenolate mofetil versus cyclophosphamide for induction treatment of lupus nephritis. J Am Soc Nephrol. 2009;20(5):1103-12. • Isenberg D, Appel GB, Contreras G, et al. Influence of race/ethnicity on response to lupus nephritis treatment: the ALMS study. Rheumatology (Oxford). 2010;49(1):128-40. • Delafuente JC, Cappuzzo KA. Systemic Lupus Erythematosus and Other Collagen-Vascular Diseases. In: Dipro JT, Talbert RL, Yee GC, Matzke GR, Wells BG, Posey LM, eds. Pharmacotherapy: A Pathophysiologic Approach. 7th ed. New York: McGraw-Hill Companies, Inc., 2008: 1431-1445. • Lau AH. Glomerulonephritis. In: Dipro JT, Talbert RL, Yee GC, Matzke GR, Wells BG, Posey LM, eds. Pharmacotherapy: A Pathophysiologic Approach. 7th ed. New York: McGraw-Hill Companies, Inc., 2008: 811-831 • (Chapter). Joseph T. DiPiro, Robert L. Talbert, Gary C. Yee, Gary R. Matzke, Barbara G. Wells, L. Michael Posey: Pharmacotherapy: A Pathophysiologic Approach, 7e: http://www.accesspharmacy.com/content.aspx?aID=3187202. • Walsh N. Predictors of renal failure in systemic lupus erythematosus. MedPageToday [serial online]. November 14, 2011; Accessed December 16, 2011. Available at http://www.medpagetoday.com/MeetingCoverage/ACR/29660. • Gordan D. First-Time Guidelines for Lupus Nephritis. Medscape News [serial online]. November 8, 2011; Accessed December 16, 2011. Available at http://www.medscape.com/viewarticle/753134. 36
- 37. Time for a Case! • We will break into your 14 assigned groups to work on a case. • Please work through the entire case. You will present on the specific question your group is given, but you are expected to contribute to the discussion of the other points as well. • There will be no answer key distributed for this case. • You will have about 30 minutes to work up the case. We will then discuss the case together as a class. 37