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Understanding Lupus

Lupus Foundation of Floridawww.lupusflorida.org

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Disclaimer

This program is not intended to dispense medical advice, directly or indirectly. The purpose of this program is to provide the public with information, not to prescribe or diagnose. Lupus is a complicated disorder that requires the regular care of a qualified physician.

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Lupus is not…

• HIV/AIDS• Leukemia• Cancer• Contagious• Your fault• All in your head

Warning Signs of LupusWhen lupus first sets in, symptoms such as fatigue and pain are often non-specific. They can be signs of so many other health problems, which can make diagnosis hard. The most common complaint people have is fatigue that is so severe it stops them from being able to function normally. This fatigue is often related to fibromyalgia. Fever, muscle and joint pain are also quite common.

Muscle & Joint Pain95% of people with lupus experience muscle and joint pain.

Fever Greater Than 100° F90% of people with lupus get a fever of more than 100 degrees Fahrenheit (38 degrees Celsius).

Prolonged or Extreme Fatigue81% of people with lupus suffer from prolonged or extreme fatigue.

Anemia71% of people with lupus simultaneously suffer from anemia.

Kidney Problems50% of people with lupus find that their kidneys are affected. Symptoms include weight gain, swollen ankles, high blood pressure, and decreased kidney function.

Pain in the Chest45% of people with lupus experience a pain in their chest upon breathing deeply. This condition is called pleurisy.

Rashes80% of people with lupus observe rashes on their skin. A butterfly-shaped rash across the cheeks and nose is especially common (42%).

Light Sensitivity30% of people with lupus become sensitive to light, a condition called photosensitivity.

Hair Loss27% of people with lupus experience hair loss resulting in patchy or bald spots.

Abnormal Blood Clotting20% of people with lupus report abnormal blood clotting problems.

Eye Disease20% of people with lupus concurrently suffer from eye complications such as dry eyes, eye inflammation, and eyelid rashes.

Seizures15% of people with lupus experience seizures.

Mouth or Nose Ulcers12% of people with lupus report ulcers on their nose or mouth.

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What is lupus?

• Chronic

• Autoimmune

• Inflammatory

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Chronic

• Lifelong-no cure• Ranges from mild to severe• Most are mild to moderate• Periods of remission and activity (flares)• Treatment goals

• Control symptoms• Prevent permanent damage

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The Immune System Defending the Body Against Invaders

Retrieved from www.lymphoma.org on 10/23/07

Retrieved from www.humanillness.com on 11/5/07

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Autoimmune & InflammatoryGenetic predisposition (5-10% risk)

+Triggers (stress, sunlight, infection)

+Inadequate suppressor T cells

Autoantibodies & surplus of antibodies B cells

Aladjem (1988)

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Immune system vs. Blood CellsAntibodies attach to blood cells

Red blood cells•Damage to cells•Accelerated spleen clearance•Can’t replace fast enough

Platelets•Damage to cells•Can’t replace fast enough

AnemiaFatigue

Thrombocytopenic anemiaClotting difficultiesBleeding into skin & organs

Treatment goal-reduce these antibodies in blood Aladjem (1988)

White blood cells•Damage to cells•Can’t replace fast enough

LeukopeniaDifficulty fighting infection

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Immune system vs. cell debrisNormal breakdown of cells

Cell debris in blood stream

Antibodies + debris=immune complexes

Defective clearance of immune complexes

Mistakenly deposit in organs other than spleen

Inflammation in organ

Immune complex + serum proteins

Activation of complement system

Complement attracts white cells to site

White cells try to eat complex

White cells release enzymes

Enzymes cause inflammation & tissue damage

Repeated attacks of inflammation, healing and scarring can result in more severe organ

impairmentAladjem (1988)

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Treatment Goals

• Prevent inflammation• Manage inflammation when it occurs• Prevent organ damage• Maintain health and well-being of patient• Intervention of acute relapses• Management of chronic problems• Medications and risk/benefit ratio

Aladjem (1988)

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Therapy Aimed at Multiple Sites in Cycle

• Prevention of excessive antibody production• Prevention of complement binding or activation• Prevention of white blood cell enzyme release• Blocking of enzyme action• Prevention of scar formation

No one medication can accomplish all these

tasks.Aladjem (1988)

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Other Autoimmune Disorders23.5 million Americans

Multiple sclerosisCrohn’s Disease-ulcerative colitisInsulin dependent diabetes (type I)Fibromyalgia-fibromyositisCeliac Sprue-Dermatitis HerpetiformusGrave’s diseaseMixed connective tissue diseasePsoriasisRheumatoid arthritisMyasthenia gravisVitiligoAlopecia areataRaynaud’sScleroderma

www.aarda.org

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How many people have lupus?

• 1.5-2 million Americans• 90,000 Floridians• 16,000 Americans develop lupus annually• Between 1,500,000 and 2,000,000 people in the

United States have been diagnosed with lupus, making lupus more prevalent than AIDS, sickle-cell anemia, cerebral palsy, multiple sclerosis, and cystic fibrosis combined.

• A word about statistics

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Who gets lupus?• 90% of lupus patients are women• 80% are diagnosed between 14 and 45• 70% have systemic lupus erythematosus (SLE)• Asians, Hispanics, African Americans and Native

Americans have 2-3 times the incidence of lupus as Caucasians

• Lupus can develop in any person regardless of age, gender or ethnicity

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How Is Lupus Diagnosed?• Symptoms• Medical history-review of systems• Elimination of other disorders• Laboratory tests• American College of Rheumatology Criteria

Typical adult •Consults 3 to 5 physicians before diagnosis•Waits 2-3 years for diagnosis•Over age 60 up to 4 years for diagnosis

Wallace (1988)

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American College of Rheumatology (ACR) Revised Criteria for the Classification of Systemic Lupus Erythematosus (1996)

Skin Criteria• Butterfly rash• Discoid rash• Sun sensitivity• Oral ulcerations

Systemic Criteria• Arthritis• Serositis• Kidney disorder• Neurologic disorder

Laboratory Criteria• Blood abnormalities• Immunologic disorder• Positive ANA blood test

American College of Rheumatology www.rheumatology.org

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Diagnosis of Systemic Lupus Erythematosus

Patients presenting with disease manifestations involving two or more organ systems

ANA testing

Titer > 1:40 Titer<1:40Consider referral to rheumatologist

for full SLE evaluation including 1. ACR diagnostic criteria2. Laboratory tests

Strong argument against SLE-alternative explanation for organ system manifestations should be pursued

Zero to three ACR criteria

Four or more ACR criteria

No SLE or incomplete SLE

SLE

Explanation found

Sufficient to rule out SLE

No explanation found

Consider referral to rheumatologist if question of SLE or incomplete SLE remains American Family Physician retrieved from www.aafp.org/afp/20031201/2179.htmlon 10/23/07

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“Routine” Lab Work• Complete blood count (CBC)

• Red blood cells• Platelets• White blood cells

• Neutrophils • Lymphocytes• Monocytes • Basophils • Eosinophils

Retrieved from www.rmlonline.com/patientCen.asp?id=ss160 on 10/23/07

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“Routine” Lab Work

Blood Chemistry (7 to 25 tests)• Blood sugar• Kidney function• Liver function• Electrolytes• Lipids• Proteins• Thyroid function

Wallace (2005)

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Other Tests Relevant to SLE

• Creatine phosphokinase (CPK)-muscle inflammation

• Westergren sedimentation rate or C-reactive protein (CRP)-quantitates

levels of inflammation• Prothrombin time (PT) and partial

thromboplastin time (PTT)-clotting tests

Wallace (2005)

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Antibody Panels and Screens• Antinuclear antibody (ANA)• Anti-double-stranded DNA• Serum complement• Rheumatoid factor

• 80% positive in RA• 20-30% positive in SLE

• Antiphospholipid antibodies • Anticardiolipin• Lupus anticoagulant

Wallace (2005)

www.bindingsite.uk.co

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Antinuclear Antibody Test

• Positive in 95-98% of SLE patients• 68% positive with Sjogren’s• 40-75% positive with scleroderma (especially

with speckled ANA)• 16% positive juvenile rheumatoid arthritis• 25-50% positive in rheumatoid arthritis

(especially with diffuse pattern)

Aladjem (1988)

Other Diagnostic Tests

•Chest X-ray•Kidney biopsy•Neurological exam•Skin biopsy•Bone marrow biopsy

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Different Forms of Lupus

• Neonatal• Drug induced• Cutaneous or discoid• Systemic lupus erythematosus (SLE)

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Neonatal Lupus• Very rare• Affects fetus or newborn• Mother passes auto-antibodies to

baby• Affects skin, heart, and blood of baby• Rash appears in first weeks-disappears

by six months• Can cause congenital heart block• Neonatal lupus is not systemic lupus

erythematosus

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Drug Induced Lupus• Long term use of certain medications• Symptoms of SLE• Stopping medications reduces symptoms

within weeks• Some implicated medications

•Chloropromazine•Methyldopa•Hydralazine•Precainamide•Isoniazid•Dilantin•Penicillamine•Quinidine•Certain antibiotics•Allupurinol

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Lupus and the Skin

• 60-70% of lupus patients report some skin complaint• Ultraviolet light

• UVA & UVB damage DNA deposits near skin surface• Altered DNA leads to formation of anti-DNA• UV light induces production of anti-Ro (SSA), anti-La (SSB)

and anti-RNP• Patients who are positive for anti-Ro are very sun-sensitive• Immune complexes may be deposited in organs • Some medications increase photosensitivity

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Cutaneous Features of Lupus

Mouth or nose sores

www.hss.edu

www.hss.edu

Alopecia-hair loss

Oral thrush

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Cutaneous Features of Lupus

Butterfly (malar) rash Changes in pigmentation

Hives or welts (urticaria)

www.humanillnesses.com

www.medstudents.com.

br

www.answers.comwww.users.globalnet.co.uk

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Vascular Rashes

Raynaud’s Phenomenon• 1/3 of lupus patients• Autonomic system

malfunction • Dilate or constrict small

blood vessels

www.immunologyclinic.com

www.pdrhealth.com

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Vascular Rashes

Levido reticularis www.londonlupuscentre.co.uk

Cutaneous vasculitis

www.aclaic.or

g

Purpura & ecchymoses

www.medscape.com

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Other Skin Disorders in LupusLupus panniculitis (profundus)• Inflamed fat pads in skin• Rare• Responds to treatment• 1 in 200 www.merckmedicus.com

www.accessmedicine.com

Blisters (bullous lupus)•Fluid filled blisters or blebs•Biopsy required to determine treatment•1 in 500 lupus patients

www.merckmedicus.com

Source: Wallace (2005)

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Musculoskeletal System

• Joints• Muscles• Bone• Supporting structures-

tendons, ligaments, bursae

www.msnbc.msn.com

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Joints and Soft Tissues• Arthralgia-joint pain• Arthritis-visible joint

inflammation• Synovium-thin membrane lining

certain joints• Inflammation of synovium causes

pain and damage over time

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Heart and Lungs

Lungs•Pleurisy/pleural effusion•Acute lupus pneumonitis•Diffuse interstitial lung disease•Pulmonary embolism

Heart•Endocardium-inside•Myocardium-heart muscle•Pericardium-outside lining

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AtherosclerosisHardening of the Arteries

“Atherosclerotic heart disease…is the third most common cause of death in lupus patients, following complications of kidney disease and infection.” Wallace (2005)

•High blood pressure•Diabetes•High cholesterol•Premature atherosclerosis

Long term moderate to high dose steroid use

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Nervous System

• CNS vasculitis-inflammation of blood vessels in brain (10%)

• Seizures• Strokes & transient ischemic

attacks (TIA’s) clots caused by antiphospholipid antibodies

• Neuropathy-numbness, tingling, local palsies

• Lupus headachewww.nlm.nih.go

v

Wallace (2005)

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Lupus in the Kidney and Urinary Tract

Lupus primarily affects the glomerulus•Usually no specific complaints traceable to kidney•Other causes of “kidney” pain-pleurisy, kidney stone, kidney infection, muscle spasm in lumbar spine

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Lupus in the Kidney

Patient awareness of kidney problem• Nephrotic or uremic-kidney spills large

amounts of protein• Swelling in ankles and abdomen• General sense of bloating and

discomfort• Pleural and pericardial effusion

www.clevelandclinic.org

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Lupus in the KidneyBlood and urine tests• Blood urea nitrogen (BUN)• Creatinine clearance• Casts (cellular debris)• ProteinBiopsy 1. No disease2. Mesangial3. Focal proliferative4. Diffuse proliferative5. Membranous6. Glomeruloscleroisis

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Lupus and Pregnancy• 10-15 % of all pregnancies end in miscarriage• Slightly higher miscarriage rate in lupus• Exacerbation may occur during or shortly after delivery• Fertility affected by disease activity, dialysis or medications• Chances baby will have lupus-fewer than 10% of patients

who carry a lupus gene will ever develop the disease• Patients with anti-Ro (SSA) and anti-La (SSB)

• Neonatal lupus• Congenital heart dysfunction or block

Wallace (2005)

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Antiphospholipid Syndrome

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Fatigue

• What is the cause? Other factors?• What are the implications for treatment?• What is normal vs. abnormal fatigue?• The role of inflammatory cytokines.

“Abnormality is when the number of bad days exceed the number of good ones or when there are more bad days than there used to be.” Peter H. Schur, M.D. (Aladjem, 1988)

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Other Causes of Fatigue• Increased work load (home, work, family)• Lack of sleep• Depression• Unhealthful habits (smoking drinking, drugs, fad diets, sedentary lifestyle)• Internal conflicts• Deconditioning-being out of shape• Anemia• Mononucleosis• Certain medications• Inflammatory disease• Systemic infections

Medications

Only 4 medications approved by the FDA specifically for the treatment of lupus

• Aspirin• Corticosteroids (1955)• Hydroxychloroquine (1955)• Belimumab (Benlysta) (2011)

Off Label Medications

• Prescription anti-inflammatories• Neurological medications (Lyrica, Neurontin,

etc.)• Anti-depressants (Lexapro, Cymbalta, etc. )• Chemotherapies (cytoxan, azathioprine, etc.)• Anti-rejection medications (Cellcept)• DMARDs (Disease Modifying Anti-Rheumatic

Drugs-monoclonal antibodies-Rituximab, belimimumab.)

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Lupus

www.sdmines.sdsmt.edu

Lupus can strike any person regardless

of gender or ethnicity

www.juliaswartz.com

Lupus can develop at any age

Lupus can affect every part of the body. Lupus affects each patient differently.

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The Lupus Foundation of Florida

• Educational Seminars• Support groups with trained facilitators• Funding for research• Advocacy at National and State levels• Patient referrals

www.lupusflorida.org

SourcesAmerican College of Rheumatology http://www.rheumatology.org/

Medscape http://www.medscape.com/

Could I Have Lupus http://www.couldihavelupus.gov/

National Institute of Arthritis Musculoskeletal and Skin Diseaseshttp://www.niams.nih.gov/

Lupus Initiative www.thelupusinitiative.org/

Lupus Research Institute http://www.lupusresearch.org/

Lahita, Robert, ed. Systemic Lupus Erythematosus: Fourth Edition. San Diego, CA: Academic Press 2004.

Wallace, Daniel. The Lupus Book: A Guide for Patients and Their Families, 4th ed. Oxford: Oxford University Press (2009).