Brainscape's Knowledge GenomeTM

Browse over 1 million classes created by top students, professors, publishers, and experts.


See full index

RMSK > 09: Systemic Lupus Erythematosus > Flashcards

09: Systemic Lupus Erythematosus Flashcards

1
Q

What is the incidence rate of SLE?

A

5.5 per 100K

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
2
Q

What is the prevalence rate of SLE?

A

72.8 per 100K

1 per 537 black females

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
3
Q

What is the F:M ratio for SLE?

A

10-15:1

(Suggests chromosome and/or hormonal influence.)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
4
Q

What is the peak age for SLE?

A

15-44yrs

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
5
Q

What is the major health disparity in SLE?

A

Compared to whites, blacks have:

  • Earlier age at dx
  • More than 2-fold ↑ in SLE prevalence and incidence
  • ↑proportion renal dz, progression to end-stage renal dz
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
6
Q

What is the disease concordance with SLE?

A

2-5% dizygotic twins
24-58% monozygotic twins
10-12% familial prevalence if one FDR

(Genes important but not whole answer.)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
7
Q

What is the overview of pathogenesis in SLE?

A
  1. Genetic, environmental and gender factors lead to defective immune regulation
  2. Break in self-tolerance leads to the production of autoantibodies
  3. Autoantibodies lead to immune complexes –> complement activation –> tissue damage
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
8
Q

What occurs during the induction/expansion phase of SLE pathogenesis?

A
  • ↓clearance apoptotic cells
  • Deficiency of **C1q **(attachment to the complement fixing sites in immune complexed immunoglobulin)
  • Abnormalities of T cells:
    • Hyperactivation of helper cells
    • Recognition of self antigens
    • Autoreactive clones escape tolerance
    • T cell repertoire skewed toward help
    • Defective T cell regulatory circuits
  • Abnormalities of B cells:
    • Hyperactivation
    • Recognition of self antigens (RNA/protein particles)
  • Abnormalities of Ig repertoire
  • Altered cytokine production
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
9
Q

What is the role of apoptotic cells in SLE?

A
  • Surface blebs present autoAg to immune system: snRNP, SSA/Ro, SSB/La
  • ↑rates of apoptosis in lymphocytes
  • ↓rates of phagocytosis of apoptotic bodies (C1q must coat apoptotic blebs for clearance)
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
10
Q

What is the role of B cells in SLE?

A
  • Antigen presentation
  • Regulate T cell function
  • Cytokine production: TNF, IL-6, LTalpha, IL-12, IL-10
  • Regulate follicular dendritic cells and lymphoid organization
  • Antibody/autoantibody production
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
11
Q

What is BLyS (BAFF)?

A
  • B Lymphocyte Stimulator/B-cell activating factor
  • Cytokine expressed in B cell lineage cells and acts as a potent B cell activator
  • Plays role in:
    • B cell development
    • B cell proliferation
    • Ig production
  • Novel pharmaceutical/neutralizing Ab against BLys: LymphoStat-B (Benlysta)
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
12
Q

What are the clinical features (diagnostic criteria) of SLE?

A
  • Cutaneous manifestations (80-90%)
    • Butterfly/malar rash (face)
    • Discoid rash (anywhere on body)
    • Photosensitivity
  • Oral (usually hard palate) or nasal ulcers (50-75%)
  • Arthritis (76-100%)
  • Serositis:
    • Pleuritis: Convincing history of pleuritic pain or rubbing heard by a clinician or evidence of pleural effusio
    • Pericarditis
  • Kidney dz (50%)
  • Brain dz (seizures or psychosis) (30-60%)
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
13
Q

What are the laboratory features (diagnostic criteria) of SLE?

A
  • Low blood cell counts (white, red, platelets)
  • Antinuclear antibodies
  • Specific autoantibodies (anti-DNA, anti-Sm, antiphospholipid)
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
14
Q

How is SLE definitively diagnosed?

A
  • Satisfy 4 criteria:
    • At least one clinical
    • At least one immunologic

OR:

  • Have bx-proven lupus nephritis in presence of antinuclear antibodies or anti-Ds DNA antibodies
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
15
Q

What are common supporting features of SLE?

A
  • Alopecia
  • Fatigue
  • Fevers
  • Raynaud’s
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
16
Q

What is a common comorbidity with SLE?

A

Premature atherosclerosis

50x greater incidence of MIs in women w/ SLE 2/2 endothelial activation and inflammation (vasculitis)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
17
Q

What does this image show?

A

Malar (buttefly) rash: fixed erythema, flat or raised, sparing the nasolabial folds; will not cause scarring.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
18
Q

What does this image show?

A

Discoid rash: raised patches, adherent keratotic scaling, folicular plugging; older lesions may cause scarring.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
19
Q

What are the characteristics of arthritis in SLE?

A
  • Non-erosive, non-deforming (correctable)
    • 2/2 ligament loosening
  • Frequently precedes other manifestations of SLE
  • Morning stiffness
  • Evanescent (quickly fading) or persistent
  • Knees, small joints of hands (PIPs)
  • Objective evidence of inflammation (tenderness, swelling, effusion)
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
20
Q

What are the cardiac manifestations in SLE?

A
  • Primary lupus carditis:
    • Pericarditis (ACR criterion for SLE dx)
    • Myocarditis
    • Endocarditis
    • Conduction defects
  • Secondary heart disease:
    • Ischemic
    • HTN:
      • Systemic
      • Pulmonary
    • Infecive

NB: Seen in 25% of SLE pts.

NB: Pericarditis p/w chest pain worse w/ deep breath or lying down

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
21
Q

What are the pulmonary manifestations in SLE?

A
  • Pleuritis/pleural effusion (ACR criterion for SLE dx)
  • Pneumonitis
  • Pulmonary hemorrhage
  • Pulmonary HTN
  • Pulmonary embolism
  • Shrinking lung syndrome (unexplained dyspnea, a restrictive pattern on pulmonary function tests, and an elevated hemidiaphragm)

NB: Seen in >30% of SLE pts.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
22
Q

What histologies are present in renal involvement of SLE, and waht are their clinical manifestations?

A
  • Predominantly mesangial: nl U/A, nl function
  • Predominantly membranous: U/A >2+ protein, no sediment; nl function
  • Predominantly proliferative:
    • Focal: U/A >2+, active sediment; nl function
    • Diffuse: U/A >2+, active sediment; abnl BUN/creatinine, ↑BP
  • ​Sclerosis: markedly abnl BUN/creatinine
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
23
Q

What are the classes of lupus nephritis?

A
  • Class I: Minimal mesangial LN
  • Class II: Mesangial proliferative LN
  • Class III: Focal LN
    • A: active lesions (focal proliferative)
    • B: active + chronic lesions
    • C: chronic (inactive) lesions + scars
  • Class IV: Diffuse LN (>50% of glomeruli)
    • S: Segmental
    • G: Global
  • Class V: Membranous LN
    • If proliferative lesions present, “V + III” or “V + IV”
  • Class VI: Advanced sclerotic LN

NB: Proliferative lesions dictate therapy

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
24
Q

What does this image show?

A
  • Diffuse proliferative LN (class IV)
  • Extensive immune complex deposition in mesangium and subendothelial side of capillary BM
25
Q

What does this image show?

A
  • Membranous LN (class V)
  • Immune complex deposition confined to intramembranous and subepithelial area of capillary BM
  • Thickening of capillary walls and irregularity due to “spikes” in the external aspect of the BM
26
Q

What are the indications for renal biopsy?

A
  1. Clinical parameters misleading (low C, high DNA Abs, inactive sediment, protein excretion abnl but <1g/24hr)
  2. Tx issues
  3. Evaluation of tx response
  4. Research
27
Q

What are the primary neuropsychiatric manifestations of SLE?

A
  • Organic mental syndrome (psychosis) (20%)
  • Seizure (15%)
  • Cranial neuropathy
  • Peripheral neuropathy
  • Stroke
  • Movement disorder
  • Transverse myelitis
  • Aseptic meningitis
28
Q

What are the hematologic abnormalities in SLE?

A
  • Anemia (Hct <35%):
    • Of chronic dz: 57-78%
    • Hemolytic: 5-40%
  • Leukopenia (<4K/mm)** **(60%)
    • **Lymphopenia **(<1.5K/mm) (60-84%)
    • Neutropenia
  • Thrombocytopenia (<100K/mm) (60%)
    • Spontaneous bleeding at <10K
29
Q

What are the features of natural antibodies?

A
  • IgM
  • Polyreactive (bind to a variety of different and structurally unrelated self and non-self foreign antigens)
  • Low affinity
  • Germline-encoded
  • Protective
30
Q

What are the features of pathogenic autoantibodies?

A
  • IgG
  • Monospecific
  • High affinity
  • Somatically mutated
31
Q

What are the common autoantibodies in SLE? What is their frequency? What are their clinical associations?

A
  • Anti-dsDNA (40-70%): SLE-specific, renal dz
  • Anti-Sm (14-55%): SLE-specific, CNS dz
  • Anti-RNP (30-80%): Also seen in MCTD, PSS, arthritis
  • Anti-SSA/Ro (35-60%): Also seen in SS, dry eyes + mouth, neonatal lupus
  • Anti-SSB/La (10-15%): Also seen in SS, dry eyes + mouth, neonatal lupus
  • Antiphospholipid (25-50%): Associated w/ thrombosis, stroke, fetal loss, thrombocytopenia
32
Q

Where are the various SLE AAbs found?

A
  • Nuclear (screen w/ ANA)
    • dsDNA
    • Smith
    • nRNP
  • Cytoplasmic
    • SSA/Ro
    • SSB/La
  • Membrane
    • Phospholipids
33
Q

How do AAbs cause tissue damage?

A
  1. AAbs form immune complexes w/ their antigen
    1. Activation of classical (C1) or alternative (C3) pathway produces complement products
    2. C3a, C5a: chemotactic factor, anaphylotoxin
    3. Leads to glomerulonephritis and fetal loss
34
Q

How do AAb and complement protein levels vary over the course of SLE and its treatment?

A
  • Emerging dz: ↑levels of AAbs, ↓levels of complement proteins
  • Tx of dz: ↑levels of complement proteins, ↓levels AAbs
35
Q

What are the widespread vascular manifestations of SLE?

A
  • Vasculitis
  • Vasospasm
  • Vasculopathy (microvascular leuko-occlusive dz)
  • Thromboembolism
  • Accelerated atherosclerosis

NB: Demonstrates that endothelium is active participant in SLE pathology.

36
Q

Hydroxychloroquine:

  1. Pharma
  2. Efficacy
  3. Toxicity
  4. MOA
A
  1. PO
  2. Mild-moderate
  3. Rare retinal dz (schedule biannual retinal exams)
  4. Unknown; may a) alter lysosomal granule pH, b) modify antigen presentation, c) alter TLRs
37
Q

What drugs are used in the treatment of SLE?

A
  • Glucocorticoids
  • Hydroxychloroquine
  • Methotrexate
  • Azathioprine (use in place of long-term steroids)
  • Cyclophosphamide
  • Mycophenolate mofetil
  • Belimumab
  • Rituximab (Ab against CD20, primarily found on surface of B cells)
  • Cyclosporine (lower activity of T cells and their immune response)
38
Q

Cyclophosphamide

  1. Pharma
  2. Efficacy
  3. Toxicity
  4. MOA
A
  1. IV for lupus, PO for other uses (Wegener’s dz, granulomatosus dz)
  2. High rate of remission in combo w/ prednisone; T cells particularly sensitive
  3. N/V, severe immunosupp, infx, infertility/sterility, marrow failure, bladder toxicity, bladder Ca, other malignancies (including lymphoma)
  4. Alkylating agent: effective in rapidly dividing cells
39
Q

Mycophenolate Mofetil (MMF)

  1. Pharma
  2. Efficacy
  3. Toxicity
  4. MOA
A
  1. Fungal derivative; prodrug converted in liver
  2. Comparable to other drugs
  3. (Not mentioned)
  4. Inhibits guanine synthesis, targeting lymphocytes
40
Q

What is the treatment regimen for an SLE pt p/w malar rash, fatigue and arthralgia?

A
  • Hydroxychloroquine
  • NSAIDS
  • Prednisone (if necessary; try to avoid if possible)
41
Q

What is the treatment regimen for an SLE pt p/w renal dz?

A
  • Hydroxychloroquine
  • High dose prednisone
  • Cyclophosphamide IV
  • MMF
  • Biologics/rituxamab
42
Q

What is the treatment regimen for an SLE pt p/w severe skin rash and alopecia?

A
  • High dose hydroxychloroquine or switch to chloroquine
  • Quinacrine
  • Prednisone
  • Methotrexate
  • Azathioprine (steroid sparing if need cont’d prednisone)
43
Q

What is the treatment regimen for an SLE pt p/w arthritis w/ moderate loss of function?

A
  • Hydroxychloroquine
  • NSAIDS
  • Prednisone
  • Methotrexate
  • Azathioprine or MMF (steroid sparing if need cont’d prednisone)
  • Belimumab
44
Q

What is the mortality risk for 15-25yo pts w/ SLE?

A

20x more than sex/age-matched individuals.

45
Q

What is the risk of mortality in a pt diagnosed w/ SLE at 20yo?

A

1-in-6 by age 35 (by lupus or infx)

46
Q

What is Sjogren’s Syndrome?

A

Chronic, slowly progressive autoimmune disease characterized by lymphocytic infiltration & destruction of the exocrine glands resulting in xerostomia and dry eyes.

47
Q

What are the clinical signs of Sjogren’s syndrome?

A
  • Sicca symptoms:
    • Dry eyes (keratoconjuctivitis sicca)
    • Xerostomia (may cause periodontal dz)
  • Extraglandular involvement:
    • Skin:
      • Xerosis
      • Cutaneous vasculitis
      • Raynaud’s
      • Photosensitivity
      • Annular erythematous lesions
    • MSK:
      • Arthralgias
      • Inflammatory myopathy
    • Pulm:
      • ILD
      • Lymphocytic interstitial pneumonitis
    • GU:
      • Vaginal dryness
      • Interstitial cystitis
    • GI:
      • Dysphagia
      • GERD
      • Gastritis
      • Constipation
      • Celiac dz
      • Hepatitis, PBC
      • Pancreatitis
    • Renal:
      • RTA, interstital nephritis
    • Neuro:
      • Neuropathy
      • CNS vasculitis
48
Q

What does this image show?

A

Parotid swelling 2/2 Sjogren’s syndrome

49
Q

What is the Schrimer test?

A

Measure of amount of tears produced; used in the dx of Sjogren’s sydnrome.

50
Q

What does this image show?

A

Rose bengal stain: stains damaged corneal and conjuctival cells purple (2/2 decreased tear formation –> corneal abrasions in Sjogren’s syndrome)

51
Q

What labs and histology are useful in the diagnosis of Sjogren’s syndrome?

A
  • ANA
  • Anti-ENA
  • SSA/SSB
  • RF (40% of SS pts)
  • Hypergammaglobulinemia
  • Lip bx/minor salivary glands: focal lymphocytic sialoadenitis
  • Salivary gland (parotid/submandibular) bx only useful in severe cases
52
Q

What is the treatment for Sjogren’s syndrome?

A
  • Replace saliva/tears
  • Stimulate saliva/tear flow via secretagogues
    • Pilocarpine
    • Cevimeline
  • Immunomodulation/suppression:
    • Plaquenil
    • Methotrexate
    • If life-threatening systemic manifestations:
      • Cytoxan
      • Cellcept
      • Imuran
      • Rituxan
      • Orencia
53
Q

What is antiphospholipid syndrome?

A

Autoantibody-mediated acquired thrombophilia characterized by recurrent arterial or venous thrombosis and/or pregnancy morbidity in the presence of autoantibodies against phospholipid (PL)-binding plasma proteins, mainly a plasma apolipoprotein known as β2 glycoprotein I (β2GPI) and prothrombin

54
Q

How is antiphospholipid syndrome diagnosed?

A

One clinical and one laboratory manifestation:

CLINICAL:

  • Clot (arterial/venous/small vessel thrombosis)
  • Pregnancy pathology:
    • 1 or more unexplained fetal death of morphologically normal fetus at 10th week of gestation or later
    • 3 or more unexplained consecutive spontaneous abortions before 10th week of gestation (r/o maternal/paternal abnl)
    • 1 premature birth of morphologically normal neonate before 34 weeks 2/2 eclampsia or severe pre-eclampsia or placental insufficiency

LABORATORY:

  • **Anti-cardiolipin IgG **and/or IgM on 2+ occasions not less than 12 weeks apart w/ medium/high titer
  • **Anti-B2 glycoprotein I IgG **and/or IgM on 2+ occasions not less than 12 weeks apart w/ medium/high titer
  • Lupus anticoagulant on 2+ occasions not less than 12 weeks apart
55
Q

What are the three distinct types of APS?

A
  1. **Primary **(absence of any comorbidity)
  2. **Secondary **(pre-existing autoimmune condition, most frequently SLE)
  3. Catastrophic: (simultaneous multi-organ failure w/ small vessel occlusion)
56
Q

How is catastrophic APS diagnosed?

A

Must have all four of the following:

  1. Evidence of involvement of three or more organs, systems, and/or tissues
  2. Development of manifestations simultaneously or in less than a week
  3. Confirmation by histopathology of small vessel occlusion in at least one organ or tissue
  4. Laboratory confirmation of the presence of antiphospholipid antibodies (lupus anticoagulant and/or anticardiolipin antibodies)
57
Q

What is the VDRL test, and why is it important in APS?

A

Test which detects Abs against syphilis; aPL binds to lipid in the test, thus APS patients will have a false positive (resolve by using more specific **FTA-Abs **test).

58
Q

What is the treatment for APS?

A
  • Prophylaxis: aspirin (inhibit platelet activation)
    • efficacy debated
  • Treatment:
    • **warfarin **(anticoagulant)
      • must be kept on for life
      • rx after thrombotic event
      • teratogenic
    • **LMW heparin **(in pregnancy)
      • prevents miscarriage when taken in conjunction w/ low-dose aspirin
  • For CAPS:
    • Plasmapheresis/IVIG/rituxan

RMSK (16 decks)

Brainscape helps you reach your goals faster, through stronger study habits.
© 2024 Bold Learning Solutions. Terms and Conditions