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LUPUS & DISABILITY

Arthur Weinstein, MD, FACR, MACP

Professor of Medicine, Georgetown University Medical School

Director of Rheumatology, Washington Hospital Center

SSA Panel on Compassionate Allowances for Autoimmune Disease 03/16/2011

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Connective Tissue Disorders SLE

Dermatomyositis

PolymyositisUndifferentiated CTD

Sjogren’s syndrome

Scleroderma

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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

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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

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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

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Central Nervous SystemSeizures, Psychosis, Strokes, HeadachesCognitive dysfunction, Neuropathies, Myelopathy, Depression, Fatigue

Eyes and MucousMembranesUlcers in the Eyes, Nose, Mouthor Vagina, Sjogren’s Syndrome

Heart and LungsPericarditis, MyocarditisEndocarditis, Pleuritis, Heart attacks

KidneysEdema, Hypertension, ProteinuriaCell Casts, Renal Failure, Dialysis

MusculoskeletalArthralgia, Myalgia, Arthritis,Jaccoud’s Arthropathy, Myositis

BloodAnemia, ThromobocytopeniaLeukopenia, Thromobosis, TTP,Circulating Autoantibodies and Immune Complexes

SkinButterfly Rash, Cutaneous Lesions,Photosensitivity, Alopecia, VasculitisRaynaud’s Phenomenon

How Can Lupus Affect the Body?

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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?

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SLESLE

GenesGenes

Immune Immune DysregulationDysregulation

EnvironmentEnvironment

DO WE KNOW WHAT CAUSES LUPUS?

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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

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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

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Medications Approved by FDA for Treatment of SLE 2010

• St Joseph Aspirin

• Ecotrin

• Hydroxychloroquine

• Corticosteroids

– Prednisolone

– Dexamethasone

– Solu-Medrol

Nothing Approved for Lupus in >50 years!!(President Dwight D Eisenhower)

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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

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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)

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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

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Feature Odds ratio 95% confidence

interval p Value*

Age 1.068 1.018–1.119 0.007

Sex (male) 4.489 1.277–15.783 0.019

Poverty 2.860 1.167–7.004 0.021

Total disease duration

1.211 1.061–1.380 0.004

SLAM-R average 1.248 1.129–1.379 <0.001

SDI at the last visit 1.362 1.115–1.663 0.002

Systemic lupus erythematosus in a multiethnic US cohort LUMINA Factors predictive of work disability by multivariable logistic regression analysis

Only p = 0.05 are recorded.SLAM-R, Systemic Lupus Activity Measure—Revised SDI, Systemic Lupus International Collaborating Clinics Damage Index; .

Inception cohort of 273 SLE patients (C, AA, H) (Bertoli et al: Ann Rheum Dis 2007; 66:12)

19% self-report of disability at 5 years (25% in AA)

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 Time to the occurrence of self-reported work disability in the LUMINA cohort: (A) entire cohort and (B) by ethnic group.

Bertoli A M et al. Ann Rheum Dis 2007;66:12-17

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Most disability within 2-3 years

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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

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End Stage Renal Disease – women, AAs, childrenUS Renal Data System

Ped SLE

171 (5%)

Adult SLE

1342 (1.4%)

Ped Other

3276

Adult Other

93, 694

Mean age at HD 15.2 39 11.6 58.5

% Female 79 83 44 47

% Black 66 55 35 38

Sule et, Pediatr Nephrol 2010

Higher mortality in Pediatric and Adult SLE ESRD than others

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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)

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Cognitive Changes in SLE

Acute:

• lupus cerebritis

• medication – steroid psychosis

• CNS infection

Chronic:

• stroke

• multi-infarct dementia

• chronic cognitive impairment of uncertain cause

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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

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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)