LUPUS DISABILITY

1. LUPUS & DISABILITY

2. Connective Tissue Disorders

3. LUPUS: What is it? It is a SYSTEMIC disease NOT localized It is a MULTI-ORGAN (multi-system) disease not single organ � eg skin, joints, kidneys It is an AUTOIMMUNE INFLAMMATORY disease, but not an infection � the normally �protective� immune system is hyperactive and inward looking and �hurtful� [Single organ autoimmune diseases � thyroid, diabetes, multiple sclerosis, myasthenia gravis] Lupus=Systemic Lupus Erythematosus=SLE

4. How Rare is Lupus? It is not! 0.15 % - 150-250/100,000 >500,000 in the USA >10,000 in MD 9X commoner women than men 3x commoner AA vs Cauc�s also commoner in Asians and Hispanics

5. LUPUS & Women, Minorities and Children: An unfair and discriminatory disease increased in women increased in AA women peak incidence in women of childbearing years - a serious disease of young people more severe in AA, Hispanics more severe, more renal disease in children higher cardiovascular mortality in women, AA women

6. How Can Lupus Affect the Body? Systemic lupus erythematosus (SLE) affects multiple organ systems. This is due to the ubiquitous nature of the autoantibodies against DNA, RNA, and associated proteins. Antigen-autoantibody complexes form immune complexes that damage small vessels. Although the kidney is most commonly affected, all organs can be affected. Some of the affected organs in SLE1 Most SLE patients report some CNS-related symptoms such as irritability, anxiety, depression, mild impairment of concentration and memory, and headache. Inflammation of the blood vessels in the brain or even sudden temporary blindness may also occur. Abnormalities of the blood are associated with SLE in almost 85% of patients. The lungs are affected in about 60% of SLE patients. Inflammation of the tissue surrounding the heart (pericarditis) is reported in about 30% of patients. About 45% of SLE patients suffer gastrointestinal problems. Lupus nephritis occurs in about 50% of SLE patients. SLE afflicts women 9 times more than men, suggesting that sex hormones may be involved in the pathogenesis. This is further supported by the observation that this ratio is greatest between menarche and menopause, when sex hormone levels are greatest.2 The influence of estrogen is unclear, although several models have been proposed. For example, it has been suggested that in women with SLE, estrogen mediates an increase in the expression of CD40L, leading to stimulated T-cell activation. Subsequently, T cell-B cell interactions, B-cell activation, and autoantibody production are also amplified in response to estrogen.3 References 1. http://www.ucdmc.ucdavis.edu/health/a-z/63SystemicLupus/doc63severity.html. 2. Janeway CA et al. Immunobiology. New York, NY: Garland Publishing; 2001:505. 3. Rider V and Abdou NI. Gender differences in autoimmunity: molecular basis for estrogen effects in systemic lupus erythematosus. Int Immunopharmacol. 2001;1:1009-1024. Systemic lupus erythematosus (SLE) affects multiple organ systems. This is due to the ubiquitous nature of the autoantibodies against DNA, RNA, and associated proteins. Antigen-autoantibody complexes form immune complexes that damage small vessels. Although the kidney is most commonly affected, all organs can be affected. Some of the affected organs in SLE1 Most SLE patients report some CNS-related symptoms such as irritability, anxiety, depression, mild impairment of concentration and memory, and headache. Inflammation of the blood vessels in the brain or even sudden temporary blindness may also occur. Abnormalities of the blood are associated with SLE in almost 85% of patients. The lungs are affected in about 60% of SLE patients. Inflammation of the tissue surrounding the heart (pericarditis) is reported in about 30% of patients. About 45% of SLE patients suffer gastrointestinal problems. Lupus nephritis occurs in about 50% of SLE patients. SLE afflicts women 9 times more than men, suggesting that sex hormones may be involved in the pathogenesis. This is further supported by the observation that this ratio is greatest between menarche and menopause, when sex hormone levels are greatest.2 The influence of estrogen is unclear, although several models have been proposed. For example, it has been suggested that in women with SLE, estrogen mediates an increase in the expression of CD40L, leading to stimulated T-cell activation. Subsequently, T cell-B cell interactions, B-cell activation, and autoantibody production are also amplified in response to estrogen.3 References 1. http://www.ucdmc.ucdavis.edu/health/a-z/63SystemicLupus/doc63severity.html. 2. Janeway CA et al. Immunobiology. New York, NY: Garland Publishing; 2001:505. 3. Rider V and Abdou NI. Gender differences in autoimmunity: molecular basis for estrogen effects in systemic lupus erythematosus. Int Immunopharmacol. 2001;1:1009-1024.

7. Is Lupus Difficult to Diagnose? Yes and No Often starts as a �flu�- fever, aches and pains, fatigue but persists Mild rash harder to spot in dark skin or may not be present Often abnormalities in the routine blood tests - anemia, low WBC (like viral infection) Key Question: Could I have Lupus? Blood tests (autoantibodies- ANA, anti-DNA and others are good diagnostic markers) What about lupus flares? Lupus is chronic with recurrent mild or severe flares Current biomarkers helpful but imperfect Is it active lupus, is it comorbidity such as infection, is it both?

9. Can Lupus Be Fatal? YES! 1950 � 50% mortality in 3yrs 2010 � 10% mortality in >5yrs BUT these are young women and men and sometimes children more severe illness and higher mortality in AA, Hispanics, children

10. Do the Drugs Work for Lupus? Treatments can be life saving Treatments do not cure lupus In general, high risk treatments do better in the short term (treating severe flares) than over long periods In general, the most potent treatments have the highest risk of side effects

11. Medications Approved by FDA for Treatment of SLE 2010 St Joseph Aspirin Ecotrin Hydroxychloroquine Corticosteroids Prednisolone Dexamethasone Solu-Medrol

12. What Drugs are Used to Treat Lupus ? prednisone � low (<0.5mg/kg/day) to moderate to high dose (>1mg/kg/day) hydroxychloroquine (Plaquenil) � rash, fatigue, joint, muscle pains immunosuppressives methotrexate, azathioprine (Imuran), mycophenolate (CellCept) cyclophosphamide (Cytoxan) I.V. � remission induction - renal, brain inflammation

13. Is there anything new? Yes! NEW Biologic Agents � �designer drugs� belimumab (Benlysta) Human Genome Sciences, Rockville, MD **Nov 16,2010 - Arthritis Panel of the FDA voted 13 to 2 to approve Benlysta for Lupus** epratuzumab rituximab (Rituxan) And others � directed against elements (B cells/proteins) in the hyperactive immune system of Lupus

14. SLE and Connective Tissue DisordersClinical Features related to disability Constitutional and multisystem effects Chronic, no cure Exacerbations (flares) and remissions unpredictable but usually treatable Treated with immunosuppressive medications � side effects Comorbidities due to organ damage, to medication side effects, to long term disease/treatment effects and to other factors (eg psychological)

15. Work Disability in SLEExtent of the Problem Cohort of 159 patients with SLE working since diagnosis (Partridge et al: Arthritis Rheum 1997; 40:2199) 40% quit work completely average of 3.4 years after diagnosis substantial job modifications predictors of early work disability � lower education status (no college), physical rather than mental job, greater disease activity at time of diagnosis

17. Time to the occurrence of self-reported work disability in the LUMINA cohort: (A) entire cohort and (B) by ethnic group. H-TX, Hispanics from Texas (green line); H-PR, Hispanics from Puerto Rico (black line); AA, African Americans (purple line); and Caucasians (blue line). Time to the occurrence of self-reported work disability in the LUMINA cohort: (A) entire cohort and (B) by ethnic group. H-TX, Hispanics from Texas (green line); H-PR, Hispanics from Puerto Rico (black line); AA, African Americans (purple line); and Caucasians (blue line).

18. How Can Lupus Cause Disability?Severe organ disease Renal (50-60% adult; 70-80% children) CNS Lungs Heart acute and chronic kidney failure (app 5%), hemodialysis, kidney transplantation encephalitis, spinal cord inflammation, strokes lung hemorrhage, pulmonary hypertension valvular disease, myocardial infarction

19. End Stage Renal Disease � women, AAs, childrenUS Renal Data System

20. Lupus and DisabilityEffects of Medications Cortisone toxicity � diabetes, hypertension, obesity, cataracts, osteoporosis, avascular necrosis (need hip and knee replacements), infections leading to acute and chronic disability (shingles) Other immunosuppressive medications - serious infections, sometimes fatal Sterility (cyclophosphamide)

21. Cognitive Changes in SLE Acute: lupus cerebritis medication � steroid psychosis CNS infection Chronic: stroke multi-infarct dementia chronic cognitive impairment of uncertain cause

22. The Cruelty of Coronary Artery Disease in Lupushigher risk than diabetes 498 women with SLE - 33 developed CAD (6.6%) (f/u 13 years, ages 15-74) 2208 women in Framingham study - 36 developed CAD (1.6% 35-44 age group up to 50X increased incidence compared to normal in Framingham youngest 34 - in SLE group any age � even in the 20�s 36% deaths in lupus due to cardiovascular (CV) disease - heart attacks and strokes Black women with SLE were 20 years younger than black women matched controls at time of CV death American journal of epidemiyology 55-64 decreased incidence to compare 35-44??? Rate ratio=52.43, 95% CI 21.6- 98.5American journal of epidemiyology 55-64 decreased incidence to compare 35-44??? Rate ratio=52.43, 95% CI 21.6- 98.5

23. Disability in LupusSummary Depends on Disease-specific Factors: disease severity specific organ involvement and damage medications used and complications long term morbidity, including cardiovascular disease Depends on demographic factors: race and gender socioeconmoic status education level and type of work (eg physical vs sedentary)