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Systemic Lupus
Erythematosus SLE
    and APLS
Case Study
• 22 year old college student
• New onset of red cheeks, hives in the
  sun, fatigue, Raynaud’s, weight loss,
 ...
What is the most likely
     diagnosis?
Lupus
• Represent a range of disease
  processes characterized by the
  development of autoantibodies with
  associated ma...
SLE
• Systemic lupus erythematosus:
• Prototypical form of lupus
• Multiorgan autoimmune disease that often
  presents ins...
Chronic Cutaneous Lupus
           (CCL)
• Limited to the skin
• No systemic manifestations
• Includes:
  – Discoid lupus
...
Drug induced Lupus (DILE)
•   Triggered by certain medications
•   Resolution after DC of the drug
•   Anti-Histone ab tes...
Drug-induced lupus: definite
        drug associations
•   Hydralazine
•   Procainamide
•   Minocycline
•   Chlorpromazine...
Drug-induced lupus: possible
         drug associations
•   Anticonvulsants     • Diltiazen
•   Quinidine           • Hydr...
SLE
•   More common in Female than male
•   Female : Male ratio 9:1
•   Incidence of SLE in US is :
•   Women 9.4 per 100,...
SLE
• Disease onset more common in the 20s,
  and 30s
• May occur at any age
• Symptoms/disease activity “waxes and
  wane...
SLE
• Pathogenesis :
• Exact cause is unk.
• Genetic factors -10% of SLE patients
  have a family member with lupus
• Envi...
SLE
• Autoantibodies bind to proteins and
  tissues
• Deposition of immune - complexes
  leads to an inflammatory cascade
...
SLE Clinical Presentation
• Most commonly affected organ
  systems:
  – Musculoskeletal
  – Dermatological
  – Renal
  – H...
SLE Clinical Presentation
• Musculoskeletal lupus
  – Isolated arthralgias ( more often stiffness
    rather than pain)
  ...
SLE Clinical Presentation
• Knees are less affected
• Jaccoud’s arthropathy:
  – Progressive ulnar deviation
  – Swan-neck...
Jaccoud’s Arthropathy
SLE Dermatological
• Several skin manifestations
• Malar Rash – Butterfly Rash
  – Erythematous
  – Photosensitive
  – Fla...
Malar Rash – Butterfly Rash
Systemic lupus erythematosus:
    bullous lesions, palate
SLE Dermatological
• Maculopapular rash also common on:
  – V-area of the neck, and extremities
  – Areas associated to su...
SLE Dermatological-neck rash
SLE Dermatological
• Discoid lupus(chronic cutaneous)
  – Involve deeper Dermis, raised patches,
    keratotic scaling, fo...
Discoid Lupus
Discoid Lupus
SLE Dermatological
• Subacute Cutaneous Lupus
  Erythematosus (SCLE)
  – Photosensitive lesions
  – Nonscaring rash
  – Ps...
SCLE- Annular rash
SLE Renal Involvement
•   Proteinuria alone
•   Proteinuria and Hematuria
•   Cellular casts in urine : RBCs
•   Glomerula...
Renal Involvement
• International society of Nephrology
  Classification for lupus nephritis
  – I minimal mesangial
  – I...
Renal Involvement
• Membranous nephritis (V) manifested by
  Nephrotic Syndrome
SLE Serositis
• Pleurisy
• Occurs most commonly as pleurisy:
  – Pain on deep inspiration
  – Sometimes associated with pl...
Serositis
• Pericarditis:
  – Positional pain
  – Worse with recumbency
  – Better leaning forward
• Ascites:
  – Possible...
Hematological abnormalities
• Most common
• Leukopenia and Lymphopenia
• Medication induced cytopenias
  – Corticosteroids...
Hematological abnormalities
• Hemolytic anemia
  – Coombs positive
  – Elevated reticulocyte count
  – Decreased haptoglob...
Neurologic manifestations
• Most likely as a result of immunecomplex
  deposition in small blood vessels
• Rarely attribut...
Neurologic manifestations
• Mild to severe
  – Seizures: also from thrombosis,uremia,toxic
  – Psychosis: think about ster...
Neurologic manifestations
– Meningitis
– Stroke: vasculitis or APhospholipids Abs
  thrombosis, HTN, atherosclerosis
– Mon...
Organ Damage
• In >50% of SLE patients over time
• Significant % from corticosteroids therapy
  – Obesity/ Diabetes
  – HT...
Organ Damage
• Accelerated Atherosclerosis – the major
  cause of death in SLE
• Risk of MI – increased 50 fold
• Counsel ...
Organ Damage
• Renal damage occurs in at least 25% of
  patients with lupus nephritis in spite of
  maximal therapy
• Reco...
Malignancy risk
• Lymphoma and Solid tumors risk is
  increased independent to therapy
• Patients with secondary Sjogren’s...
Diagnosis
• Often difficult – multiple manifestations
  which evolve over time / more in the early
  stage
• Clinical diag...
Clinical Manifestations of SLE
Laboratory tests/Ab testing for
               SLE
• Tests for diagnosis
• Tests for prognosis
• Tests to determine approp...
Laboratory tests/Ab testing for
                 SLE
•   CBC,diff, ESR, CRP
•   Creatinine, urinalysis
•   Chemistry Panel...
Ab testing for SLE

• ANA(anti-nuclear antibodies)
• Positive in 95-99% of SLE
• Occurs in 20% of healthy people,
  elderl...
What is ANA?
• Antinuclear antibody is an autoantibody
  against part of the cell nucleus
• It is a screening test for SLE...
Frequent ANA patterns
•   Speckled
•   Homogeneous / Diffuse
•   Nucleolar
•   Rim / Peripheral
•   Centromere
Positive test
• Titers: stronger positive, the dilution is
  larger (higher denominator)
  – Ex. 1/1280 is a strong positi...
Is there utility in following the
                titer?
• No
• In general repeating the test is a waste
  of money
• A po...
When do I order anti DNA?
• It is an auto-antibody directed against
  the DNA in the cells nuclei
• Only order anti DNA in...
What does anti DNA correlate
           with?
• It is highly specific for SLE
• It correlates with renal SLE (but not
  10...
What is an ENA
• ENA is extractable nuclear antigens
• The lab will do a screen to see if it is
  positive or negative
• I...
ENA examples
• Anti Ro, (anti SSA)
• Anti La, (anti SSB)
• Anti Sm (Smith – fairly sensitive for SLE)
• Anti RNP (goes wit...
Anti-Ro(anti-SSA) and
          La(anti-SSB)
• + Anti Ro:
  – is associated with cutaneous SLE features
    including rash...
The results of the college
           student
• WBC 2.8, Hbg 11.1, Plt 43
• Creatinine 1.0, urine neg for protein and
  bl...
Does she have SLE?
•   + ANA
•   Low WBC and plt
•   + anti Sm
•   Malar rash
•   Photosensitivity
•   Possible inflammato...
Laboratory tests/Ab testing for
             SLE
Antiphospholipid antibody
          syndrome (APS)
• Half are associated with SLE
• Occurs in 10-20% of SLE patients
• Syn...
Antiphospholipid antibody
          syndrome (APS)
• Positive tests may include
  – Lupus anticoagulant (false prolongatio...
APS
• Treatment varies on symptoms and
  signs
• ASA or LMW heparin in pregnancy
• Warfarin if DVT
• ASA and possibly warf...
SLE Management - treatment
• No cure – chronic condition
• TTo aimed at:
  – Reducing inflammation
  – Suppressing immune ...
Management - treatment
• Patient Education and prophylactic measures
  to avoid flares :
• Sunscreens SPF >30 and protecti...
Management – treatment
• Low dose ASA for patients with
  +Antiphospholipid Abs
  – Potentially avoid thrombosis
• Psychol...
Management – treatment
• Enforce regularly scheduled:
  – Colonoscopy
  – Pap smears
  – Mammograms
  – Increased risk of ...
Management – treatment
• Baseline and periodic bone
  densitometry
• Biphosphonates – not given to patients
  with renal i...
Management – treatment
• Pregnancy
  – High risk
  – 90 % successful
  – Flares can occur
  – High disease activity with i...
Management – treatment
• Risk of Neonatal Lupus in + Ro(anti SSA) AB
• Cross placenta
• 2-5 % risk of congenital heart blo...
Management – treatment
• Cutaneous Lupus:
• Hydroxychloroquine (Plaquenil)
  – 200 mg PO BID
  – Risk for retinopathy (<1 ...
Management – treatment
• Musculoskeletal symptoms
    – NSAIDS – mild arthralgias
    – COX 2 inhibitors
•   Do not use fo...
Management – treatment
• Persistent Synovitis
  – Methotrexate
  – Leflunomide
  – Abatacet
  – Rituximab
Management – treatment
• Serositis
• Mild serositis: may respond to NSAIDS
• Moderate S: Triamcinolone 100mg IMx1
• Severe...
Management – treatment
• Lupus Nephritis
• Mycophenolate Mofetil (Cellcept)
  induction and maintenance therapy
• Recent s...
Neprhitis (cont)
• Cyclophosphamide (Cytoxan)
  induction therapy- IV pulse
• Induction IV 500-750 mg/m2 body
  surface, m...
Management – treatment
• CNS Lupus
• IV Methylprednisolone pulse
• IV monthly Cyclophosphamide
• Additional antiepileptic ...
Management – treatment
• Hematological Lupus
• Plt count < 30,000 bleeding may occur
• Severe hemolytic anemia /
  thrombo...
Case study
Patient Name: Melisa T.
Age: 19

Sex: Female

Description: Melisa, a young Latina student, is taking
mycophenol...
• 19-year-old Latina patient with systemic
  lupus erythematosus (SLE) is seen today
  for a routine follow-up visit. She ...
• Eventually, prednisone was tapered down to
  10 mg.Today she denies significant joint pain
  or swelling, rashes, chest ...
•   Current Conditions
•   Lupus nephritis
•   Obesity
•   Systemic lupus erythematosus

•   Current Medications
•   10 mg...
Original Lab results
• Anticardiolipin antibodies: medium
  positive titer
• Lupus Anticoagulant: not detected
• Beta2 Gly...
Renal Biopsy
•   24 Apr 07 - Renal biopsy from 13 months ago was consistent with lupus nephritis
    Class IV (no crescent...
•   anti-CCP      2 IU/mL
•   Note:
•   0-19 (negative)
•   20-39 (weak positive)
•   40-59 (moderate positive)
•   >60 (s...
AB testing
• Anti-Sm (Smith): Positive
• ANA positive at 320 in a homogeneous
  pattern
• DsDNA Positive at 1:80
• C3 Comp...
•   Glucose (FPG) 92 mg/dL
•   70 - 110
•   Creatinine 0.8 mg/dL
•   0.6 - 1.3
•   Albumin 3.7 g/dL
•   3.4 - 5.0
•   Bili...
Current lab tests
• A CBC should be ordered several
  times a year in patients with SLE
  (every 3 months if taking MMF) t...
• Hb (Hemoglobin) 9.8 g/dL
• 9.6 - 18.0
• HCT (Hematocrit) 29 %
• 37 - 47
• Platelet Count   214 1000/mm3
• 50 - 350
• WBC...
• A chemistry panel that checks
  fasting glucose, creatinine, lipids,
  and hepatic enzymes should be
  ordered several t...
•   Glucose (FPG) 82 mg/dL
•   70 - 110
•   Creatinine 1.2 mg/dL
•   0.6 - 1.3
•   Albumin 3.6 g/dL
•   3.4 - 5.0
•   Bili...
In anticipation of obtaining a renal
    biopsy, coagulation studies are
               indicated.
• Prothrombin Time     ...
Dyslipidemia is a potential consequence of
      proteinuria; LDL-C levels should be checked
    regularly. Abnormal lipid...
Renal biopsy:
Class IV lupus nephritis with a high level of activity
                   (crescents)




                  ...
•   Color     yellow
•   Turbidity cloudy
•   Specific Gravity 1.013 1.006 - 1.030
•   Urine Glucose negative
•   Ketones ...
• A urine protein/creatinine ratio is an efficient
  and reasonably accurate method to quantitate
  proteinuria. Values > ...
• Antiphospholipid Antibodies: With her
  repeatedly positive anticardiolipin
                      .
  antibody determina...
Possible options
• Due to the failure of MMF for decreasing
  proteinuria to below 500-1,000 mg/day in this
  patient, dis...
• Patients with lupus nephritis and this degree
  of ongoing pathologic activity require use of
  an immunosuppressive age...
• Some success has been reported in
  open-label series using rituximab ,which
  peripherally depletes B-lymphocytes
  and...
• Azathioprine has been shown to have
  equivalent efficacy to MMF in
  maintenance trials, but patients are
  unlikely to...
• Standard Dosing Ranges
• 1,000-1,500 mg of mycophenolate mofetil 500
  mg oral tablet BID maximum, 2,000-3,000 mg
  dail...
4 Sle2009
4 Sle2009
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Transcript of "4 Sle2009"

  1. 1. Systemic Lupus Erythematosus SLE and APLS
  2. 2. Case Study • 22 year old college student • New onset of red cheeks, hives in the sun, fatigue, Raynaud’s, weight loss, hair loss and stiff hands in the morning • Her cousin has JRA
  3. 3. What is the most likely diagnosis?
  4. 4. Lupus • Represent a range of disease processes characterized by the development of autoantibodies with associated manifestations and organ damage • Some forms limited to skin , or occur after exposure to a drug
  5. 5. SLE • Systemic lupus erythematosus: • Prototypical form of lupus • Multiorgan autoimmune disease that often presents insidiously with significant heterogeneity of expression in individuals • Severity from mild to life threatening depending on the affected organ • Medications used for treatment increase morbidity - organ damage
  6. 6. Chronic Cutaneous Lupus (CCL) • Limited to the skin • No systemic manifestations • Includes: – Discoid lupus – Subacute cutaneous lupus erythematosus – Lupus paniculitis • Only 5% of CCL develop SLE
  7. 7. Drug induced Lupus (DILE) • Triggered by certain medications • Resolution after DC of the drug • Anti-Histone ab test positive • Absence of anti-DsDNA
  8. 8. Drug-induced lupus: definite drug associations • Hydralazine • Procainamide • Minocycline • Chlorpromazine • Isoniazid • Penicillamine • Methyldopa • Interferon-alpha
  9. 9. Drug-induced lupus: possible drug associations • Anticonvulsants • Diltiazen • Quinidine • Hydrazine • Propylthiouracil • Interferon gamma • Sulfonamides • TNF inhibitors • Lithium • Beta-blockers • Nitrofurantoin • Sulfasalazine
  10. 10. SLE • More common in Female than male • Female : Male ratio 9:1 • Incidence of SLE in US is : • Women 9.4 per 100,000 • Men 1.54 per 100,000 • More common in African-American and Hispanic population
  11. 11. SLE • Disease onset more common in the 20s, and 30s • May occur at any age • Symptoms/disease activity “waxes and wanes” • “Flares” sometimes evident by clinical symptoms, other times only by laboratory results changes
  12. 12. SLE • Pathogenesis : • Exact cause is unk. • Genetic factors -10% of SLE patients have a family member with lupus • Environmental factors - UV light (most important) • Possible Also infections, smoking, and toxin exposure
  13. 13. SLE • Autoantibodies bind to proteins and tissues • Deposition of immune - complexes leads to an inflammatory cascade • With activation of complement system • And production of inflammatory cytokines
  14. 14. SLE Clinical Presentation • Most commonly affected organ systems: – Musculoskeletal – Dermatological – Renal – Hematological • Any organ can be affected
  15. 15. SLE Clinical Presentation • Musculoskeletal lupus – Isolated arthralgias ( more often stiffness rather than pain) – Synovitis.arthritis similar to RA – Morning stiffness – Gel phenomenon after immobility – Small joints of the hands( MTPs,PIP’s) – Wrists
  16. 16. SLE Clinical Presentation • Knees are less affected • Jaccoud’s arthropathy: – Progressive ulnar deviation – Swan-necking deformaties – Reversible or correctible • Typically non erosive bony changes
  17. 17. Jaccoud’s Arthropathy
  18. 18. SLE Dermatological • Several skin manifestations • Malar Rash – Butterfly Rash – Erythematous – Photosensitive – Flat or raised - maculopapular – On the cheeks and Bridge of the nose – Spares naso-labial folds
  19. 19. Malar Rash – Butterfly Rash
  20. 20. Systemic lupus erythematosus: bullous lesions, palate
  21. 21. SLE Dermatological • Maculopapular rash also common on: – V-area of the neck, and extremities – Areas associated to sun exposure • Biopsy of the skin – demonstrate immunoglobulin and complement deposition at the dermal-epidermal junction: “lupus band sign”
  22. 22. SLE Dermatological-neck rash
  23. 23. SLE Dermatological • Discoid lupus(chronic cutaneous) – Involve deeper Dermis, raised patches, keratotic scaling, follicular plugging – May lead to permanent loss of hair follicle – Disfiguring hyper- or hypopigmented scars may occur after resolution – Typically on face ( inside ears, above eye brows, upper palate ) – Neck, scalp and forearms
  24. 24. Discoid Lupus
  25. 25. Discoid Lupus
  26. 26. SLE Dermatological • Subacute Cutaneous Lupus Erythematosus (SCLE) – Photosensitive lesions – Nonscaring rash – Psoriaform form – Annular – polycyclic form • ½ of patients with SCLE have SLE
  27. 27. SCLE- Annular rash
  28. 28. SLE Renal Involvement • Proteinuria alone • Proteinuria and Hematuria • Cellular casts in urine : RBCs • Glomerular involvement • Elevated serum creatinine level • Possible Renal Failure • May result in Nephrotic Syndrome: – Low serum albumin, and elevated cholesterol
  29. 29. Renal Involvement • International society of Nephrology Classification for lupus nephritis – I minimal mesangial – II Mesangial proliferative – III focal proliferative – IV diffuse proliferative – V membranous – VI irreversible renal sclerosis Done by Kidney Biopsy Class IV most dangerous – can rapidly progress to Renal Failure
  30. 30. Renal Involvement • Membranous nephritis (V) manifested by Nephrotic Syndrome
  31. 31. SLE Serositis • Pleurisy • Occurs most commonly as pleurisy: – Pain on deep inspiration – Sometimes associated with pleural effusion – Listen for inspiratory / expiratory rub – Exudative effusion if tapped • Differentiate from pulmonary emboli and infection pleuritic chest pain
  32. 32. Serositis • Pericarditis: – Positional pain – Worse with recumbency – Better leaning forward • Ascites: – Possible due to serositis – r/o infarcted bowel, infection, or Budd-Chiari syndrome (oclussion hepatic or IVC)
  33. 33. Hematological abnormalities • Most common • Leukopenia and Lymphopenia • Medication induced cytopenias – Corticosteroids associated lymphopenia • Thrombocytopenia – Antiphospholipid antibodies – Immunosupressive drugs – Heparin administration
  34. 34. Hematological abnormalities • Hemolytic anemia – Coombs positive – Elevated reticulocyte count – Decreased haptoglobin • Anemia of chronic disease (inflammation) • Anemia from chronic renal disease • Iron deficiency anemia
  35. 35. Neurologic manifestations • Most likely as a result of immunecomplex deposition in small blood vessels • Rarely attributable to vasculitis • Most common neurologic complaint in SLE: – Cognitive impairment – 80%of SLE patients by 10 years after Dx. – Represents accumulated damage and not ongoing CNS SLE – Formal cognitive function testing to establish baseline
  36. 36. Neurologic manifestations • Mild to severe – Seizures: also from thrombosis,uremia,toxic – Psychosis: think about steroids psychosis – Encephalopathy – Coma
  37. 37. Neurologic manifestations – Meningitis – Stroke: vasculitis or APhospholipids Abs thrombosis, HTN, atherosclerosis – Mononeuritis multiplex – Transverse myelitis – Peripheral neuropathy – Cranial neuropathy
  38. 38. Organ Damage • In >50% of SLE patients over time • Significant % from corticosteroids therapy – Obesity/ Diabetes – HTN/ Hyperlipedimia – Cataracs/Glaucoma – Osteoporosis/Osteonecrosis – Infections – Depression/Psychosis
  39. 39. Organ Damage • Accelerated Atherosclerosis – the major cause of death in SLE • Risk of MI – increased 50 fold • Counsel about modifiable cardiovascular risks
  40. 40. Organ Damage • Renal damage occurs in at least 25% of patients with lupus nephritis in spite of maximal therapy • Recommendation for renal biopsy: – In patients with 500mg/day proteinuria – Active urinary sediment – Rising serum creatinine
  41. 41. Malignancy risk • Lymphoma and Solid tumors risk is increased independent to therapy • Patients with secondary Sjogren’s syndrome may have special risk of non- Hodgkin’s Lymphoma
  42. 42. Diagnosis • Often difficult – multiple manifestations which evolve over time / more in the early stage • Clinical diagnosis supported by Hx, Physical Exam and Laboratory tests • Make take months to years for the typical picture to unfold • ACR classification criteria for SLE is helpful but not needed for Dx
  43. 43. Clinical Manifestations of SLE
  44. 44. Laboratory tests/Ab testing for SLE • Tests for diagnosis • Tests for prognosis • Tests to determine appropriate treatment (What organ involvement is occurring?)
  45. 45. Laboratory tests/Ab testing for SLE • CBC,diff, ESR, CRP • Creatinine, urinalysis • Chemistry Panel • ANA, anti DsDNA, anti-SM, anti-RNP anti-SSA /SSB, RF, C3,C4,total complement
  46. 46. Ab testing for SLE • ANA(anti-nuclear antibodies) • Positive in 95-99% of SLE • Occurs in 20% of healthy people, elderly, with drugs, thyroid disease, RA,SS, pulmonary fibrosis. • If positive + clinical symptoms continue workup
  47. 47. What is ANA? • Antinuclear antibody is an autoantibody against part of the cell nucleus • It is a screening test for SLE: so if negative, it makes SLE highly unlikely
  48. 48. Frequent ANA patterns • Speckled • Homogeneous / Diffuse • Nucleolar • Rim / Peripheral • Centromere
  49. 49. Positive test • Titers: stronger positive, the dilution is larger (higher denominator) – Ex. 1/1280 is a strong positive • Pattern can change depending on the dilution – Ex. 1/80 speckled and homogenous and 1/640 homogenous
  50. 50. Is there utility in following the titer? • No • In general repeating the test is a waste of money • A positive test in past or at any time can count in the diagnostic criteria for SLE
  51. 51. When do I order anti DNA? • It is an auto-antibody directed against the DNA in the cells nuclei • Only order anti DNA in the presence of a positive ANA, when you are clinically suspecting SLE • It is very specific for SLE, but very insensitive
  52. 52. What does anti DNA correlate with? • It is highly specific for SLE • It correlates with renal SLE (but not 100%) • Thus, it can be a bad prognosticator and it is part of the diagnostic criteria
  53. 53. What is an ENA • ENA is extractable nuclear antigens • The lab will do a screen to see if it is positive or negative • If positive, more assays are done to determine which antibody is positive
  54. 54. ENA examples • Anti Ro, (anti SSA) • Anti La, (anti SSB) • Anti Sm (Smith – fairly sensitive for SLE) • Anti RNP (goes with MCTD and SLE) • Anti Scl 70 (Topoisomerase 1) – goes with diffuse scleroderma esp with interstitial lung disease • Other: anti Jo1(myositis)
  55. 55. Anti-Ro(anti-SSA) and La(anti-SSB) • + Anti Ro: – is associated with cutaneous SLE features including rash and photosensitivity – is often + in ANA negative SLE – can go with anti La in Sjogren’s S. – can increase the risk of congenital heart block in babies whose moms are +
  56. 56. The results of the college student • WBC 2.8, Hbg 11.1, Plt 43 • Creatinine 1.0, urine neg for protein and blood • ANA 1/320 speckled • ENA: + for anti Smith (Sm) • antiDNA negative
  57. 57. Does she have SLE? • + ANA • Low WBC and plt • + anti Sm • Malar rash • Photosensitivity • Possible inflammatory arthritis • She has at least 5 criteria
  58. 58. Laboratory tests/Ab testing for SLE
  59. 59. Antiphospholipid antibody syndrome (APS) • Half are associated with SLE • Occurs in 10-20% of SLE patients • Syndrome of arterial and or venous clotting (CVA, DVT, PE), recurrent abortions and often livedo reticularis, low platelets
  60. 60. Antiphospholipid antibody syndrome (APS) • Positive tests may include – Lupus anticoagulant (false prolongation of PTT) – Anticardiolipin antibody (aCL) or other antiphospholipid antibodies – False positive VDRL – Abnormal RVV time (Russel venon viper time)
  61. 61. APS • Treatment varies on symptoms and signs • ASA or LMW heparin in pregnancy • Warfarin if DVT • ASA and possibly warfarin if CVA (Cerebro-vascular-accident)
  62. 62. SLE Management - treatment • No cure – chronic condition • TTo aimed at: – Reducing inflammation – Suppressing immune system – Closely monitoring patients to ID and to treat disease features as early as possible – Minimize therapy adverse effects
  63. 63. Management - treatment • Patient Education and prophylactic measures to avoid flares : • Sunscreens SPF >30 and protective clothing – Photosensitivity, Raynaud’s Phen. • Avoid estrogen containing oral contraceptives – Lupus flares, hyperthrombotic states • Avoid medications such as: – Sulfonamides, Echinacea, and Melatonin
  64. 64. Management – treatment • Low dose ASA for patients with +Antiphospholipid Abs – Potentially avoid thrombosis • Psychological support – Depression and anxiety • Routine immunizations – Influenza (yearly) and pneumococcus vaccine (every 5-10 years) - Live virus vaccines not recommended
  65. 65. Management – treatment • Enforce regularly scheduled: – Colonoscopy – Pap smears – Mammograms – Increased risk of cancer
  66. 66. Management – treatment • Baseline and periodic bone densitometry • Biphosphonates – not given to patients with renal insufficiency or potential to have pregnancies • Osteopenic patients: Biphosphonates, CaCO3 and Vit D • Management of HTN and Lipid levels
  67. 67. Management – treatment • Pregnancy – High risk – 90 % successful – Flares can occur – High disease activity with increased DsDNA level and decreased complement levels – Increased pre-eclampsia, preterm births, and fewer live births
  68. 68. Management – treatment • Risk of Neonatal Lupus in + Ro(anti SSA) AB • Cross placenta • 2-5 % risk of congenital heart block in the baby, hemolytic anemia, and rashes • Women with medium to high titer anticardiolipin /anti-B2 glycoprotein, hx of pregnancy loss or severe preeclampsia – ASA and Heparin during pregnancy and 6 months after.
  69. 69. Management – treatment • Cutaneous Lupus: • Hydroxychloroquine (Plaquenil) – 200 mg PO BID – Risk for retinopathy (<1 of 5000 exposed) – Eye exam once a year • Alternate: Quinacrine 100mg PO QD – Higher ocular toxicity • If no response: Cellcept, Methotrexate,or Imuran
  70. 70. Management – treatment • Musculoskeletal symptoms – NSAIDS – mild arthralgias – COX 2 inhibitors • Do not use for long periods of time • Proton pump inhibitors- PRN • Hydroxychloroquine – 200mg PO BID • Low – Dose Prednisone <7.5mg/day
  71. 71. Management – treatment • Persistent Synovitis – Methotrexate – Leflunomide – Abatacet – Rituximab
  72. 72. Management – treatment • Serositis • Mild serositis: may respond to NSAIDS • Moderate S: Triamcinolone 100mg IMx1 • Severe : Methylprednisolone IV pulse (1000mg over 90minutes x 3days ) followed by oral Prednisone tapering dose • Maintenance immunosupressive regimen if persistent / recurrent serositis
  73. 73. Management – treatment • Lupus Nephritis • Mycophenolate Mofetil (Cellcept) induction and maintenance therapy • Recent studies show potential superiority of Cellcept as induction and safety profile when compared to Cytoxan
  74. 74. Neprhitis (cont) • Cyclophosphamide (Cytoxan) induction therapy- IV pulse • Induction IV 500-750 mg/m2 body surface, monthly, for 6 months • Maintenance IV quaterly for 2 years • Hemorrhagic Cystitis • Long term risk for Urinary Bladder malignancy
  75. 75. Management – treatment • CNS Lupus • IV Methylprednisolone pulse • IV monthly Cyclophosphamide • Additional antiepileptic medication in the case of seizures/ Neuro-consult • Psychosis-antipsychotic drugs and mood stabilizers
  76. 76. Management – treatment • Hematological Lupus • Plt count < 30,000 bleeding may occur • Severe hemolytic anemia / thrombocytopenia • High dose steroids, if no improvement intravenous immunoglobulin • Rituximab
  77. 77. Case study Patient Name: Melisa T. Age: 19 Sex: Female Description: Melisa, a young Latina student, is taking mycophenolate mofetil (MMF) for lupus nephritis (LN) has come in for a routine follow-up visit. How would you monitor progress, and, based on the lab results, are there any changes you would make to her regimen?
  78. 78. • 19-year-old Latina patient with systemic lupus erythematosus (SLE) is seen today for a routine follow-up visit. She was referred 1 year ago with polyarthritis, thought by her primary care provider to be due to rheumatoid arthritis (RA). After confirmation of SLE, she was found to have 3+ proteinuria, 10 RBCs/HPF, and class IV diffuse proliferative nephritis seen on renal biopsy. Treatment with high-dose prednisone plus mycophenolate mofetil (MMF; first 2 g/day, then 3 g/day) stabilized her lupus nephritis (LN): urine protein decreased to 0.3 g/day and revealed no RBCs.
  79. 79. • Eventually, prednisone was tapered down to 10 mg.Today she denies significant joint pain or swelling, rashes, chest pains, skin or mucous membrane abnormalities, or neurological symptoms. Past history and family history are unremarkable. She has never been pregnant, but is determined to have children with her fiance in the future. At present she uses barrier methods (estimated 90% of the time). She is willing to use other forms of contraception for a period of time, but despite her present monogamy she rejects use of an IUD due to prior pelvic inflammatory disease. Review of systems is otherwise normal. Physical exam reveals obesity without evidence of malar or other rash.
  80. 80. • Current Conditions • Lupus nephritis • Obesity • Systemic lupus erythematosus • Current Medications • 10 mg prednisone daily • 1500 mg mycophenolate mofetil bid • 600 mg-200 units calcium-vitamin D bid • Daily multivitamin
  81. 81. Original Lab results • Anticardiolipin antibodies: medium positive titer • Lupus Anticoagulant: not detected • Beta2 Glycoprotein I: negative • Urine hCG Negative • Urine protein/creatinine ratio = 0.3, which correlates with 300 mg proteinuria/day.
  82. 82. Renal Biopsy • 24 Apr 07 - Renal biopsy from 13 months ago was consistent with lupus nephritis Class IV (no crescents noted). QuickTime™ and a decompressor are needed to see this picture.
  83. 83. • anti-CCP 2 IU/mL • Note: • 0-19 (negative) • 20-39 (weak positive) • 40-59 (moderate positive) • >60 (strong positive)
  84. 84. AB testing • Anti-Sm (Smith): Positive • ANA positive at 320 in a homogeneous pattern • DsDNA Positive at 1:80 • C3 Complement 61 mg/dL • 82 - 235 • C4 Complement 44 mg/dL • 16 - 70
  85. 85. • Glucose (FPG) 92 mg/dL • 70 - 110 • Creatinine 0.8 mg/dL • 0.6 - 1.3 • Albumin 3.7 g/dL • 3.4 - 5.0 • Bilirubin, Total 0.7 mg/dL • 0.0 - 1.0 • Alkaline Phosphatase 121 IU/L • 50 - 136 • AST (SGOT) 23 IU/L • 15 - 37 • ALT (SGPT) 18 IU/L • 15 - 37
  86. 86. Current lab tests • A CBC should be ordered several times a year in patients with SLE (every 3 months if taking MMF) to screen for leukopenia, thrombocytopenia, and/or anemia.
  87. 87. • Hb (Hemoglobin) 9.8 g/dL • 9.6 - 18.0 • HCT (Hematocrit) 29 % • 37 - 47 • Platelet Count 214 1000/mm3 • 50 - 350 • WBC (White Blood Cell Count) 3.2 1000/mm3 • 4.0 - 10.8
  88. 88. • A chemistry panel that checks fasting glucose, creatinine, lipids, and hepatic enzymes should be ordered several times a year (every 3 months if taking MMF) in patients with SLE.
  89. 89. • Glucose (FPG) 82 mg/dL • 70 - 110 • Creatinine 1.2 mg/dL • 0.6 - 1.3 • Albumin 3.6 g/dL • 3.4 - 5.0 • Bilirubin, Total 0.6 mg/dL • 0.0 - 1.0 • Alkaline Phosphatase 113 IU/L • 50 - 136 • AST (SGOT) 28 IU/L • 15 - 37 • ALT (SGPT) 18 IU/L • 15 - 37
  90. 90. In anticipation of obtaining a renal biopsy, coagulation studies are indicated. • Prothrombin Time 12 seconds • 11 - 15 • Partial Thromboplastin Time 29 seconds • 25 - 40 • International Normalized Ratio 1.0 • 0.8 - 1.2
  91. 91. Dyslipidemia is a potential consequence of proteinuria; LDL-C levels should be checked regularly. Abnormal lipid levels deserve vigorous treatment. • Triglycerides 173 mg/dL • 0 - 150 • Total Cholesterol 225 mg/dL • 0 - 200 • LDL Cholesterol 110 mg/dL • 62 - 130 • HDL Cholesterol 79 mg/dL • 50 - 60
  92. 92. Renal biopsy: Class IV lupus nephritis with a high level of activity (crescents) QuickTime™ and a decompressor are needed to see this picture.
  93. 93. • Color yellow • Turbidity cloudy • Specific Gravity 1.013 1.006 - 1.030 • Urine Glucose negative • Ketones negative • Blood negative • Protein 2+ • Bilirubin negative • Urobilinogen negative • Nitrites negative • Leukocyte Esterase negative • Casts negative • RBCs negative • Crystals negative • WBCs negative
  94. 94. • A urine protein/creatinine ratio is an efficient and reasonably accurate method to quantitate proteinuria. Values > 0.5 (correlating to > 0.5 g (500 mg)/24 h) suggest the need for a renal biopsy to stage possible lupus nephritis (3659 ). • Urine protein/creatinine ratio = 2.0
  95. 95. • Antiphospholipid Antibodies: With her repeatedly positive anticardiolipin . antibody determinations and intrinsic high risk for thrombotic complications, continued monitoring is prudent. • Anticardiolipin antibodies: 80 GPL U/mL (high positive) • Lupus anticoagulant: not present • Beta2 Glycoprotein I: negative
  96. 96. Possible options • Due to the failure of MMF for decreasing proteinuria to below 500-1,000 mg/day in this patient, discontinuation of its use and substitution of rituximab, or the combination of cyclophosphamide with leuprolide premedication, or perhaps azathioprine is a reasonable next step.
  97. 97. • Patients with lupus nephritis and this degree of ongoing pathologic activity require use of an immunosuppressive agent, such as cyclophosphamide lyophilized, azathioprine, tacrolimus, or an experimental therapy such as rituximab • Although cyclophosphamide remains the standard for use in rapidly-progressive crescentic lupus nephritis, its use is highly associated with infertility noted in about 50% of patients using this drug. The incidence of infertility can be decreased to approximately 15%, however, with leuprolide injections 2 weeks prior to the monthly cyclophosphamide
  98. 98. • Some success has been reported in open-label series using rituximab ,which peripherally depletes B-lymphocytes and is approved for use in rheumatoid arthritis. • While not FDA-approved for use in lupus nephritis, the anti-rejection agent tacrolimus has been associated with some degree of success in a small number of patients
  99. 99. • Azathioprine has been shown to have equivalent efficacy to MMF in maintenance trials, but patients are unlikely to have a better response to azathioprine than they had to MMF.
  100. 100. • Standard Dosing Ranges • 1,000-1,500 mg of mycophenolate mofetil 500 mg oral tablet BID maximum, 2,000-3,000 mg daily maximum • 1-80 mg of predniSONE 10 mg oral tablet QID maximum, 1-80 mg daily maximum • 1-4 ea of calcium-vitamin D 600 mg-200 units oral tablet QID maximum, 1-4 ea daily maximum • 1 ea of Multiple Vitamins oral capsule once a day maximum
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