Upload
valentine-parsons
View
224
Download
0
Tags:
Embed Size (px)
Citation preview
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