Systemic Lupus Systemic Lupus Erythematosus (SLE)Erythematosus (SLE)

Heidi Roppelt, MDAssistant Professor of Medicine

Associate Program Director Division of RheumatologyDirector of the osteoporosis Center

History of LupusHistory of Lupus

1200 AD: Term lupus is used for the first time to describe ulcerations on the face, literally means wolf.– Skin rash, like a wolf, seems to eat away

the skin and destroy it– Skin looked like it had been bitten away by

a wolf– Frightening appearance of lupus sufferers-

thought to look like werewolves.

History of LupusHistory of Lupus 1828- First described by a British dermatologist:

– multiple cases of similar skin lesions on face 1890s- Sir William Osler noticed patients with

distinct skin lesions also had internal organ involvement

1948- LE cell seen as commonality of patients with lupus at the Mayo Clinic

1954- proteins against one’s own tissue (antibodies) were discovered specific for lupus– Steroids used for first time in these patients

1970s: Lupus Foundation Organized

SLE: Chronic, inflammatory, SLE: Chronic, inflammatory, autoimmune disease affecting autoimmune disease affecting

multiple organsmultiple organs

LUPUS

LUNGS

HEART KIDNEY

BLOOD

SKIN

BRAIN

LIVER/ PANCREAS JOINTS

Incidence of LupusIncidence of Lupus

Affects approx 1 million AmericansMore than 16,000 new cases each yearFirst degree relatives have a 3% chance

of developing the disease Identical Twins: second twin developing

disease is between 25-65%

Incidence in PopulationsIncidence in PopulationsIn America:

– Incidence of lupus between 25-64 years of age is 1 in 700 Caucasian women

– In African American women, it is 1 in 265 womenDifferent Populations are affected differently:

– Caucasians- blood and skin involvement– Hispanics- kidney involvement– African Americans- generally more aggressive

disease involving all organs

Criteria for Lupus (4 of 11)Criteria for Lupus (4 of 11)

Malar Rash Kidney Disease Discoid Rash Neurologic Disorder Positive ANA Hematologic disorder Photosensitivity Positive Antibodies Oral Ulcers Arthritis Serositis

Malar rash–Fixed erythema, flat or raised, over the face- sparing the nasolabial folds

Discoid rash–Raised patches, adherent keratotic scaling,follicular plugging; frequently causes scarring

Photosensitivity–Skin rash induced by sunlight

Oral or nasopharyngeal ulcers–Usually painless

Arthritis–Nonerosive, inflammatory in two or more peripheral joints

Serositis–Pleuritis or pericarditis

Renal disorder –Persistent proteinuria or cellular casts

Neurologic disorder–Seizures or psychosis

Hematologic–Hemolytic anemia, leukopenia (<4,000/mm3), lymphopenia (<1,500/mm3), or thrombocytopenia (<100,00/mm3)

Immunologic disorder–Antibodies to dsDNA or SM or positive antiphospholipid antibodies (IgG or IgM antibodies, lupus anticoagulant, or false-positive serologic test positive serologic test for syphilis)

Antinuclear antibody test–Positive

Epidermal LesionsEpidermal Lesions

Malar (Butterfly Rash)– 50 % of patients with lupus develop this after UV

exposure– May proceed overt SLE by months or occur as

acute manifestation– May last for hours to days and often reoccurs– Biopsy: Immunoglobulins and complements at

dermal-epidermal junction: “Lupus-Band Test”– DDx: Rosacea, facial flushing, seborrheic, atopic,

contact dermatitis

Malar Rash

                                                                                            

Systemic lupus Systemic lupus erythematosus: malar rash, erythematosus: malar rash,

faceface

Epidermal LesionsEpidermal Lesions

Discoid Lupus– Seen in 25 % of patients with systemic lupus– Can occur independent of SLE

Low titer ANA and low titer Anti-Ro antibodies 10 % of these will progress to systemic lupus erythematosus

– Usually seen on face, neck, scalp, and upper torso– Discrete, erythematosus, infiltrated plaques extending

into hair follicles– Leave depressed scars, hyper/hypo pigmentation– DDx: Psoriasis, Eczema, Lichen Planus, and Actinic

Keratosis

                                                                                            

                                                                                            

PhotosensitivityPhotosensitivity

Occurs in 60-100% of patients with SLEDevelopment of erythematous,

sometimes raised/ puritic rash approximately 24-48 hours after sun exposure– UV-B light most commonly responsible

Sunlight, fluorescent lights Glass inhibits its penetration

– UV-A (some patients)

Systemic lupus erythematosus: photosensitive Systemic lupus erythematosus: photosensitive erythematosus rash, upper backerythematosus rash, upper back

Epidermal LesionsEpidermal Lesions

Subacute Cutaneous Lupus– 10 % of systemic lupus patients will develop this

lesion– 50 % of patients with this lesion will develop

systemic lupus– Associated with more photosensitivity than

systemic lupus patients– Affected areas: shoulders, neck, forearms, and

upper torso– Face is generally spared– Scarring does not occur

AlopeciaAlopecia Occurs in majority of SLE patients Scarring

– Discoid Lupus Non-scarring

– Lupus Hair Thinning and breakage of hair at times of increased

disease activity. Returns to normal once disease is quiescent

– Telogen Effluvium (Premature Hair Loss) 3 months after stressful event- hair loss Glucocorticoids, Emotional Stress, Pregnancy, etc. Will grow back to normal

Raynaud’s PhenomenonRaynaud’s Phenomenon

Triphasic color change in fingers:– White Blue Red

Occurs upon exposure to cold or even to emotional stress

If begins later in life, can be a clue to underlying autoimmune disease which may develop in months- years

Raynauds Picture

                                                                                                                    

Systemic lupus erythematosis: vasculitis, Systemic lupus erythematosis: vasculitis, handshands

Musculoskeletal Musculoskeletal Manifestations and LupusManifestations and Lupus

ArthralgiasArthritisOsteonecrosisMyalgiaOsteoporosis

                                                                                                                                      

Systemic lupus erythematosus: Jaccoud’s arthropathy

Systemic lupus erythematosus: Systemic lupus erythematosus: interarticular dermatitis, handsinterarticular dermatitis, hands

Hematologic Manifestations of Hematologic Manifestations of SLESLE

Anemia– Autoimmune

Leukopenia– WBC < 4,000

Autoimmune thrombocytopenia– Usually correlates with disease activity

Increased risk of clotting– Anticardiolpin antibodies– Lupus Anticoagulant

Antiphospholipid antibody syndrome: Antiphospholipid antibody syndrome: clinical manifestationsclinical manifestations

Arterial thrombosis

Venous thrombosis

Valvular abnormalities

Pregnancy loss and infertility

Livedo reticularis

Neurologic complications– cerebrovascular

thrombosis– Chorea

Catastrophic APS syndrome

Thrombocytopenia

Clinical criteria•Vascular thrombosis•Pregnancy morbidity(a) One or more unexplained deaths of a fetus at or beyond the 10th week of gestation, or(b) One or > premature births at or before the 34th week of gestation because of severe preeclampsia or eclampsia, or severe placental insufficiency, or(c) Three or > unexplained consecutive spontaneous abortions before the 10th week of gestation

Laboratory criteria• Anticardiolipin antibody (IgG and/or IgM)

medium or high titer, on 2 or more occasions, at least 12 weeks apart

• Lupus anticoagulant present in plasma, on 2 or more occasions at least 12 weeks apart

• Anti-b2 glycoprotein-I antibody (IgG and/or IgM) present on two or more occasions, at least 12 weeks apart

Definite APS if at least 1 clinical criteria and 1 laboratory criteria are met

Kidney Disease and SLEKidney Disease and SLEAbnormal urinalysis +/- proteinuria present

in 50% at diagnosis, eventually 70%Most renal disease occurs within the first

6-36 months6 Classes of renal disease:

Class I Minimal mesangial LNClass II Mesangial proliferative LNClass III Focal LN* (50% of glomeruli)III (A): active lesionsIII (A/C): active and chronic lesionsIII (C): chronic lesions

Kidney Disease and SLEKidney Disease and SLE

6 Classes of renal disease cont:Class IV Diffuse LN

– Diffuse segmental (IV-S) or global (IV-G) LN

– IV (A): active lesions– IV (A/C): active and chronic lesions– IV (C): chronic lesions

Class V Membranous LNClass VI Advanced sclerosing LN

Heart Disease and SLEHeart Disease and SLE

Increased incidence of Myocardial Infarctions– Higher cholesterol- need to monitor! Target

LDL<100 even <80– Can get direct involvement of blood

vesselsPericarditisValvular disease

Lung Disease and SLELung Disease and SLE

Pleuritis– Pleuritic Chest Pain

Acute PneumonitisAcute Lung HemorrhageInterstitial lung disease

Systemic lupus erythematosus: nervous Systemic lupus erythematosus: nervous

system manifestationssystem manifestations Seizures Headache Stroke syndromes Transverse myelitis (may be

associated with APS) Aseptic meningitis Peripheral neuropathy Cranial neuropathy Mononeuritis multiplex Ataxia Psychiatric disorders

Gastrointestinal Gastrointestinal Manifestations of SLEManifestations of SLE

Abdominal Pain (30%)– Serositis/ Peritonitis– Mesenteric Ischemia

DyspepsiaPancreatitisAbnormal Liver Enzymes

Menstrual Function, Menstrual Function, Menopause in SLEMenopause in SLE

Menstrual Function– Menorrhagia- heavy menstrual flow (15%)– Amennorhea- autoimmune activity against ovaries

or from immunosuppressive agents Menopause

– Symptoms of SLE seem to lessen– Higher risk of osteoporosis– Higher risk of heart disease

Oral Contraceptive Use– No increased risk of disease flares– Avoid in those with antiphospholipid positivity

Pregnancy and SLEPregnancy and SLE

Pregnancy is NOT advised during active disease

Patient should be in remission for at least 6 months

Disease can become very aggressive during pregnancy– Renal involvement– Neurologic

Premature birth

Neonatal LupusNeonatal Lupus

Rash that occurs in newbornsMothers are positive for specific

antibodies seen in lupus (and also in Sjogren’s syndrome)– Anti-Ro/ SSA and Anti-La/ SSB antibodies

Resolves in 6-8 monthsChild does NOT have lupus

Subacute cutaneous lupus

Autoantibody-disease associations: Autoantibody-disease associations: SLE and drug-induced lupusSLE and drug-induced lupus

Antigen SLE Drug-Induced LE

dsDNA 40% No

Histone 70% >95%

Sm antigen 30% No

RNP 30% No

SS-A/Ro 35% No

SS-B/La 15% No

Drug-induced lupus: definite Drug-induced lupus: definite drug associationsdrug associations

Hydralazine Procainamide Minocycline Chlorpromazine Isoniazid Penicillamine Methyldopa Interferon-alpha

Laboratory DataLaboratory Data

Non-specific Tests– ANA – Complement C3/ C4– ESR

Specific Tests (Antibodies)– Anti-double stranded DNA– Anti- Smith– Anti-ENA Ab (Anti-Ro/ Anti-La/ Anti-RNP)

ANA (Anti-Nuclear antibody)ANA (Anti-Nuclear antibody) Studies have shown that 10-25% of normal, healthy people

have a positive ANA Other situations in which ANA is positive

– Autoimmune Diseases Rheumatoid Arthritis Scleroderma Thyroid Disease Autoimmune Hepatitis Sjogren’s syndrome

– Infections– Certain medications– Advanced age

Can I have SLE without a positive ANA?– Yes, but extremely rare

                                                                                                                                             

TreatmentTreatment

General management–Fatigue–Support groups–Avoid sun exposure–Minimize risk factors for

cardiovascular disease–osteoporosis

TreatmentTreatment

NSAIDS–May cause aseptic meningitis and

cognitive dysfunction–Monitor for renal, hepatic, GI side

effects–monitor CBC, LFT’s, BUN/CR,

urinalysis

TreatmentTreatment

Corticosteroids– Relatively low doses for treatment of

Constitutional sx, arthritis, cutaneous manifestations, serositis

– High doses for treating nephritis, cerebritis, hematologic abnl, vasculitis

– Mainstay of therapy during pregnancy– Side effects: osteonecrosis, hyperglycemia,

HTN, hyperlipidemia, osteoporosis

TreatmentTreatment

Hydroxychloroquine (plaquenil)– Prevent flares– Effective for rx of mild skin disease,

arthritis, mild serositis, constitutional sx– May have antithrombotic effects, lipid

lowering effects– Monitor for macular damage;

fundoscopic/ visual field checks q6months

TreatmentTreatment

Azathioprine (Imuran)–Purine analogue inhibiting nucleic

acid synthesis; affects humoral and cellular immunity

–Steroid sparing agent for rx of non-renal manifestations of SLE, or nephritis

–Bone marrow and GI toxicity

TreatmentTreatment

Cyclophosphamide– Most commonly used for treatment for

severe organ system disease, and nephritis

– Hemmorrhagic cystitis, bladder ca, gonadal toxicity

Use of GNRH agonists, Mesna to prevent

– Most commonly given monthly IV for six months

TreatmentTreatment

Other:–Mycophenylate mofetil (Cellcept)–Methotrexate– IVIG