staci smith do nephrology grandview hospital. overview of lupus types of lupus history common...
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Staci Smith DO
Nephrology Grandview Hospital
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Overview of LupusTypes of lupusHistory
Common manifestations SLE Nephritis
WHO classificationBiopsy IndicationsBiopsy FindingsTreatment
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hematuria proteinuria glomerulonephritis
red blood cell casts
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SLE Minimal Change Dz Membranous GN FSGS MPGN RPGN Ig A Nephropathy Anti GBM Dz
Goodpasture’s Wegener’s
Hepatitis B, C AIDS Amyloidosis HSP Cryoglobulinemia Vasculitides Poststrept/ Poststaph GN
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red cell castsvirtually diagnostic of glomerulonephritis or vasculitis
only one needed absence does not exclude diagnosis
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Systemic Lupus:most common and affects major organs
Discoid Lupus: affects only the skinnot fatal, but can cause severe scarring
Drug-induced Lupus: is systemic Lupus caused by medications
when the medicine is stopped, the disease goes away
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autoimmune disorder multisystem microvascular inflammation
defined by clinical picture and generation of autoantibodiesmostly against double stranded DNA
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autoantibodies mostly against double stranded DNA and the Smith antigen Ab to Smith (Sm) antigen is very specific for SLE
25% of patients
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not known when Lupus first appeared Hippocrates noted similar diseases in Ancient Greece
facial rash that resembles the markings of a wolf 1851 French-man named Pierre Cazenave
first clinical records more than 1.4 million Americans are affected by SLE
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Serological Tests to Aid Diagnosis of SLE
Test % positive in SLE
ANA 95%
Anti-nDNA 60%
Anti-nRNP 80%
Anti-Sm 20%
Anti-Ro 30%
Anti-La 10%
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Rim Diffuse
Nucleolar Speckled
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American College of Rheumatology presence of 4 of 11 criteria can establish SLE Dx
96% sensitive and specificupdated 1995
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Serositis –pleuritis, pericarditis
Oral ulcers - painless Arthritis – 2 or more peripheral joints
Photosensitivity
Blood Abnormalities –thrombocytopenia, lymphopenia, lymphopenia (x2),hemolytic anemia
Renal – casts, proteinuria, hematuria
ANA positive Immune Abnormalities – ANA, Anti DS DNA, Smith Ag, false (+) syphilis
Neurologic - seizures, psychosis
Malar Rash- spares nasolabial folds
Discoid Rash – scaling,scaring
SOAP BRAIN
MD
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Lupus nephritisone of the most serious manifestations of SLE
typically arises within 5 years of diagnosis commonly within the first 6 to 36 months
Renal failure rarely occurs before American College of Rheumatology classification criteria are met.
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total incidence of renal involvement among patients with SLE exceeds 90 %
abnormal urinalysis with or without an elevated Crin approximately 50% at diagnosis timeproteinuria present in 80%40% have hematuria and/or pyuria
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‘Silent’ lupus nephritisnormal urinalysisno proteinuria normal serum creatinine levels
However, renal biopsy reveals pathological changes
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Six types of renal involvement with SLE
Why do renal biopsy?to determine stage of diseasehistological evidence is present in most SLE pts even if they do not have clinical manifestations of renal disease
Pattern of glomerular injury related to the site of formation of the immune deposits
is primarily due to anti DS DNA
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Indications for Renal Biopsy with SLE Patients
Proteinuria of >1g/day
conventionally 1-2g/dayLess proteinuria does not preclude biopsy if major serologic abnormalities, especially hypocomplementemiaAt the other extreme, the presence of full-blown nephrotic and nephritic syndromes
Progressive azotemia
Decreasing renal function in assocation with active urinary sediment
Ambiguity or inconsistency of data
Lupus nephritis of indeterminate duration, severity and potential responsiveness
Overlapping clinical features
Situations where clinical and laboratory data are compatible with different classes of lupus nephritis, for which different approaches to management are warranted
Redirection of therapy
Partially treated or incompletely responsive lupus nephritis
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Morphological Classification of Lupus Nephritis(modified WHO Classification)
Class Biopsy finding
I Normal glomerulus
II Pure mesangial alteration
III Focal proliferative glomerulonephritis
IV Diffuse proliferative glomerulonephritis
V Membranous glomerulopathy
VI Advanced glomerulosclerosis
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light micrograph capillary lumens open glomerular capillary wall thickness
similar to that of the tubular basement membranes
mesangial cells and matrix are located in the central or stalk regions of the tuft
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segmental areas of increased mesangial matrix and cellularity
light micrograph
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Divided by active and/or chronic lesions:Class III (A):
active lesionsClass III (A/C):
active and chronic pathologyClass III (C):
chronic inactive lesions with scarring a.k.a. focal sclerosing lupus nephritis
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usually associated with subsubendothelialendothelial deposits
areas of cellular proliferation
thickening of glomerular capillary “wire loop”
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subendothelial deposits deposition of immunoglobulins and complement results in thickening of the glomerular capillary wall
subsetssegmental = < 50% of glomerulidiffuse = >50% of glomeruli
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subendothelial deposits
thickening of glomerular capillary wall
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Class five the one form of lupus nephritis that may present with no other clinical or serologic manifestations of SLE
typically presents with signs of nephrotic syndrome
microscopic hematuria and hypertension also may be seen
Cr concentration is usually normal or only slightly elevated
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sclerosis of more than 90% of glomeruli
represents healing of previous inflammatory injury as well as the advanced stage of chronic class III, IV, or V lupus nephritis
immunosuppressive therapy is NOT likely to be beneficial
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diffuse (class IV) or severe focal (class III) proliferative glomerulonephritis,
severe or progressive membranous lupus (class V)
marked nephrotic syndrome rising serum creatinine membranous in association with class III or class IV diseasemixed disease
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No internal organ involvement First line: NSAID’s Cyclooxygenase-2 specific inhibitor
may induce thrombotic risk in patients with antiphospholipid antibodies
Low dose hydroxychloroquine200mg twice a day
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Manifestations not often responsive to glucocorticoidsThrombosis—includes strokesGlomerulonephritis Resistant thrombocytopenia or hemolytic anemia
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Previously untreated patients Active lupus nephritis or severe manifestationsdecreased renal function and /or high-grade proteinuria
First line: high doses of corticosteroidsabout 1mg/kg/day
Cytotoxic drugs or other immunosuppressive drugs
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Active and severe GN depsit high dose steroids
Responded to corticosteroids but require an unacceptably high dose to maintain a response.
Side effects from corticosteroids
Chronic damage on a renal biopsy
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requires 6–12 months to work well 1–3 mg/kg/day(initial dose) 1–2 mg/kg/day(maintenance dose) Advantage:probably reduces flares, reduces renal scarring, reduces glucocorticoid dose requirement
Side effects: Bone marrow suppression, leukopenia, infection(herpes zoster), infertility, malignancy, early menopause, hepatic damage, nausea
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Advantagereduces flares, reduces renal scarring, reduces glucocorticoid doses
Side effectsbone marrow suppression, leukopenia, infection, malignancy, nausea,etc
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requires 2–16 weeks to work well Initial dose:1-3 mg/kg/day orally or 8–20 mg/kg intravenously once a month plus mesna
Maintenance dose:0.5–2 mg/kg/day orally or 8–20mg/kg intravenously every 4–12 wks
Mesna
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mycophenoalte mofetil may be an alternative to cyclophosphamide as initial therapy
particularly among patients who refuse or cannot tolerate cyclophosphamide
Biggest side effect is diarrhea, also myelosuppression
fewer side effects than cyclophosphamide
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interferes with the activation and differentiation of B cells
lysis mediated by:ComplementFc receptor-bearing cytotoxic cellInducing apoptosis
selective transient depletion of the CD20+ B-cell subpopulation
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Avoid possible disease triggers-sulfa antibiotics, sun, high estrogen-containing birth control pills,alfalfa sprouts
Prevent atherosclerosis Prevent osteoporosis Prevent infection Prevent progression of renal disease
Prevent clots in patients with antiphospholipid antibodies
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hematuria proteinuria glomerulonephritis
red blood cell casts
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autoimmune disorder multisystem microvascular inflammation
defined by clinical picture and generation of autoantibodiesmostly against double stranded DNA
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Serositis –pleuritis, pericarditis
Oral ulcers - painless Arthritis – 2 or more peripheral joints
Photosensitivity
Blood Abnormalities –thrombocytopenia, lymphopenia, lymphopenia (x2),hemolytic anemia
Renal – casts, proteinuria, hematuria
ANA positive Immune Abnormalities – ANA, Anti DS DNA, Smith Ag, false (+) syphilis
Neurologic - seizures, psychosis
Malar Rash- spares nasolabial folds
Discoid Rash – scaling,scaring
SOAP BRAIN
MD
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Morphological Classification of Lupus Nephritis(modified WHO Classification)
Class Biopsy finding
I Normal glomerulus
II Pure mesangial alteration
III Focal proliferative glomerulonephritis
IV Diffuse proliferative glomerulonephritis
V Membranous glomerulopathy
VI Advanced glomerulosclerosis
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Happy Thanksgiving !