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4. HDS Multisystem > Autoimmune Diseases > Flashcards

Autoimmune Diseases Flashcards

1
Q

HLA Associations

A
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2
Q

Type I Hypersensitivity Reaction

(Anaphylactic)

A

Systemic anaphylaxis

Local anaphylaxis

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3
Q

Type II Hypersensitivity Reaction

(Cytotoxic)

A

Complement-dependent reactions

Transfusion reactions

Erythroblastosis fetalis

Autoimmune hemolytic anemia

Pemphigus vulgaris

Some drug reactions

Goodpasture syndrome

Ab-dependent cell-mediated cytotoxicity

Ab-mediated cellular dysfunction

Myasthenia gravis

Grave disease (Ab against TSH receptor)

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4
Q

Type III Hypersensitivity Reaction

(Immune Complex Mediated)

A
  • Antigens can be exogenous or endogenous
  • Systemic immune complex disease
    • Form Ag-Ab complexes in circulation
    • Deposit immune complexes in several tissues
    • Inflammatory reaction in several tissues
  • Local immune complex disease (Arthus reaction)
    • Tissue necrosis d/t acute immune complex vasculitis
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5
Q

Type IV Hypersensitivity Reaction

(Cell Mediated)

A
  • Delayed type hypersensitivity
    • E.g. Granulomatous inflammation
  • T-cell mediated cytotoxicity
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6
Q

Autoimmune Diseases

Local vs Systemic

A
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7
Q

Autoimmunity

Genetic Factors

A
  • Familial clustering of autoimmune diseases
    • SLE, autoimmune hemolytic anemia
  • Linkage of autoimmune diseases w/ HLA antigens
    • E.g. HLA B27
  • Induction of autoimmune disease in transgenic mice
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8
Q

Microbial Agents

in

Autoimmunity

A
  • Viral antigens and autoantigens may become ass. to form immunogenic units ⇒ bypass T-cell tolerance
  • Microbial infections ⇒ tissue necrosis and inflammation ⇒ ↑ co-stimulatory molecules on resting APC’S in tissue ⇒ breakdown of T-cell anergy
  • Inflammatory response ⇒ presentation of cryptic antigens ⇒ epitope spreading
  • Superantigens and other microbial products (e.g. LPS) ⇒ ⊕ large pool of T and B-cells, some of which may be autoreactive
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9
Q

Autoimmune Injury

Pathogenesis

A
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10
Q

Autoimmune Diseases to Know

A
  • Systemic lupus erythematosus
  • Sjogren’s syndrome
  • Systemic sclerosis (scleroderma)
  • Inflammatory myopathies
  • Dermatomyositis
  • Polymyositis
  • Inclusion body myositis
  • Mixed connective tissue disease
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11
Q

Systemic Lupus Erythematosus (SLE)

Overview

A
  • Chronic multi-systemic inflammatory autoimmune disease
  • Remitting and relapsing in nature
  • Characterized by production of a variety of auto-Ab
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12
Q

Systemic Lupus Erythematosus (SLE)

Epidemiology

A
  • F:M ratio is 9:1
  • Ages 15 to 45 ⇒ child-bearing age
    • Affects 1 in 700 women between ages 20-64
  • ↑ incidence in African Americans, Hispanics, and Asians
    • Incidence is particularly high in black women
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13
Q

Systemic Lupus Erythematosus (SLE)

Global Impact

A
  • Survival improved over past 50 yrs to 90% at 10 years
  • Better treatments for SLE and infections
  • Many more mild cases are dx
  • Non-fatal cumulative damage occurs in ~ 50% of survivors
  • Most often in MSK system
  • 25% with avascular necrosis and/or osteoporosis
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14
Q

SLE

Pathogenesis

A
  • Strong genetic predisposition to disease
  • 3-10x ↑ in clinical disease in MZ vs DZ twins
  • Emphasis recently on defects in apoptosis
  • Impaired removal of apoptotic cells ⇒ overload of Ag in circulating or target tissues
  • Breakdown of immunologic self-tolerance
  • Auto-antigens recognized as foreign ⇒ inflammatory response ⇒ activated complement, leukocytes, coagulation system, pro-inflammatory cytokines ⇒ local tissue damage
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15
Q

Systemic Lupus Erythematosus (SLE)

Immunologic Factors

A
  • Failure of self-tolerance in B-cells due to:
    • Defective elimination of self-reactive B-cells in bone marrow
    • Defects in peripheral tolerance
  • CD4+ helper T-cells specific for nucleosomal antigens
    • Escape tolerance ⇒ contribute to production of high-affinity pathogenic auto-Ab
  • TLR engagement by nuclear DNA and RNA contained in immune complexes ⇒ ⊕ B-cells
  • Type I interferons ⇒ activated lymphocytes
  • Other cytokines that may play a role including TNF family member BAFF
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16
Q

SLE

Clinical Heterogeneity

A

Hypothesis to Explain Clinical Heterogeneity of SLE:

  • Environmental Etiologic Factor
  • Genetic Constitution Influences Immune Response
    • HLA Antigens
    • T-Cell Receptor Genes
    • Immunoglobulin Genes
    • Complement Component Genes
    • Complement Regulatory Genes
    • Cytokine Regulatory Genes
  • Particular Auto-Ab Arise
  • Particular set of auto-Ab present ⇒ clinical disease expression
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17
Q

Systemic Lupus Erythematosus (SLE)

Diagnosis

A

Old SLE diagnostic criteria:

Diagnosed using the criteria below

Need ≥ any 4 / 11 criteria present serially or simultaneously during any interval of observation

  1. Malar rash
  2. Discoid rash
  3. Photosensitivity
  4. Oral ulcers
  5. Arthritis of two or more peripheral joints w/ tenderness, swelling, or effusion
  6. Serositis ⇒ pleuritis or pericarditis
  7. Renal disorder ⇒ persistent proteinuria or cellular casts
  8. Neurologic disorder ⇒ seizures or psychosis in absence of offending drugs or known metabolic derangements
  9. Hematologic disorder
    • Hemolytic anemia w/ retiuculocytosis
    • Leukopenia on two or more occasions
    • Lymphopenia on two or more occasions
    • Thrombocytopenia in absence of offending drugs
  10. Immunologic disorder
    • Anti-DNA Ab to native DNA in abnormal titer
    • Anti-Sm ⇒ presence of Ab to Sm nuclear antigen
    • Positive finding of antiphospholipid Ab based on:
      • Abnormal serum level of IgG or IgM anticardiolipin Ab
      • Positive test for lupus anticoagulant
      • False positive serologic test for syphilis
      • Known to be positive for at least 6 months
      • Confirmed by a negative treponema pallidum immobilization or FTAA test
  11. Antinuclear Ab ⇒ abnormal titer in absence of drugs known to cause drug-induced Lupus syndrome

New SLE Diagnostic Criteria

Starts with presence of a positive ANA (or an equivalent test)

Includes points for many of the same criteria of old system
Uses a weighting system with different points for different sx

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18
Q

Anti-Nuclear Antigens (ANA)

Types

A
  • 4 categories of ANA:
    • Ab to DNA
    • Ab to histones
    • Ab to non-histone proteins bound to RNA
    • Ab to nucleolar antigen
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19
Q

Anti-Nuclear Antigens (ANA)

Patterns

A

See 4 patterns w/ immunofluorescence:

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20
Q

Anti-Nuclear Ab (ANA)

Test

A
  • ANA test is sensitive but not specific
    • 5-15% of normal individuals have ANAs
    • Incidence ↑ w/ age
  • Ab to double-stranded (ds) DNA and Smith Antigen are virtually diagnostic of SLE
    • Smith Antigen ⇒ particles composed of RNA and protein
  • High ds DNA Ab titer is often seen in pts w/ active renal disease
  • Lupus anticoagulant ⇒ actually is a pro-coagulant in vivo
    • Blamed for miscarriages and ischemia
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21
Q

Systemic Lupus Erythematosus (SLE)

Genetic Factors

A
  • ↑ incidence in families
  • 20% of clinically unaffected relatives have auto-Ab
  • 34% concordance in MZ twins
  • If discordant, twin often has auto-Ab but is clinically ok
    • This twin may lack environment needed for tissue injury
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22
Q

Systemic Lupus Erythematosus (SLE)

Non-Genetic Factors

A
  • Drugs ⇒ hydralazine, procainamide, d-penicillamine
    • Get SLE-like response
  • Ultraviolet light
  • Viruses ⇒ no hard evidence
  • Sex hormones
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23
Q

Systemic Lupus Erythematosus (SLE)

Mechanism of Tissue Injury

A
  • Most visceral lesions mediated by immune complexes
    • Type III deposit ⇒ e.g. DNA-antiDNA deposits in glomeruli
  • Auto-Ab against RBC, WBC, platelets ⇒ opsonization ⇒ phagocytosis
  • Antiphospholipid Ab syndrome ⇒ venous and arterial thromboses
    • Can see spontaneous miscarriages, etc.
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24
Q

Morphology Of SLE

A
  • Characteristic lesions result from deposition of immune complexes
    • Found in the blood vessels, kidneys, connective tissues, and skin
  • Acute necrotizing vasculitis
    • Involves small arteries and arterioles
    • May be present in any tissue
  • Fibrinoid deposits in vessel walls
  • Chronic stage ⇒ vessels undergo fibrous thickening w/ luminal narrowing
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25
Q

SLE

“Typical” Clinical Presentation

A

Young woman < 40 y/o:

  • Arthritis or arthralgia ⇒ 55%
  • Skin involvement/Malar rash ⇒ 20%
  • Nephritis/Proteinuria ⇒ 10%
  • Fever/Fatigue/Malaise/Wt Loss ⇒ 15%
  • Other ⇒ 10%
  • Most pts have sx in only 1-2 systems at onset
  • Nany accumulate organ-system involvement over several years
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26
Q

Systemic Lupus Erythematosus (SLE)

Clinical Manifestations

A
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27
Q

Renal Lupus

A
  • Up to 50% of SLE have clinically significant renal involvement
  • Manifestations may include:
    • Persistent proteinuria > 500 mg/24 hr or > 3+
    • Cellular casts (red cell, granular, tubular or mixed)
    • Nephrotic syndrome
    • End-Stage Renal Disease
  • Best studied SLE organ involvement
  • Excellent clinic-pathological correlates in SLE
  • Kidney biopsy eval. w/ LM, EM, and IF
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28
Q

SLE

Class I ‐ Minimal Mesangial Lupus Nephritis

A
  • Least common type
  • Can appear normal on LM
  • Granular mesangial deposits of Ig and complement on EM and IF
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29
Q

SLE

Class II ‐ Mesangial Proliferative Lupus Nephritis

A
  • Seen in 5-10% of biopsies in SLE
  • Clinical ⇒ microscopic hematuria and proteinuria
  • Histology:
    • Moderate ↑ in mesangial matrix and # of mesangial cells
    • Granular mesangial deposits of Ig and complement on EM and IF
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30
Q

SLE

Class III ‐ Focal Lupus Nephritis

A
  • < 50% of glomeruli involved
  • Either segmental or global lesions
  • Seen in 20% to 35% of pts
  • May see:
    • Crescent formation
    • Fibrinoid necrosis
    • Proliferation of endothelial and mesangial cells
    • Infiltrating WBCS
    • Intracapillary thrombi
  • Clinical: hematuria and proteinuria
  • Active (proliferative) inflammatory lesions can heal completely or lead to chronic glomerular scarring
31
Q

SLE

Class IV ‐ Diffuse Proliferative Lupus Nephritis

A
  • Most common and most severe form of lupus nephritis
  • Occurs in 35% to 60% of pts
  • Looks like class III but affects > 50% of glomeruli
  • Either segmental or global lesions
  • Histology:
    • Subendothelial immune complex deposits ⇒ thickened capillary wall
    • See ‘wire loops’ on LM
  • Clinical:
    • Hematuria and proteinuria along
    • Hypertension
    • Mild to severe renal insufficiency
32
Q

SLE

Class V - Membranous GN

A
  • Seen in 10-15% of lupus nephritis pts
  • See diffuse thickening of the capillary walls
  • Similar to idiopathic membranous glomerulonephritis
  • Severe proteinuria or nephrotic syndrome
  • Can occur concurrently w/ focal or diffuse lupus nephritis
33
Q

SLE

Class VI – Advanced Sclerosing

A
  • Sclerosis of > 90% of glomeruli
  • Represents end-stage renal disease
  • Can also see changes in interstitum and tubules
  • Immune complexes in tubular or peritubular capillary basement membranes
34
Q

Mucocutaneous Lupus

A
  • Rashes:
    • Malar/butterfly rash ⇒ spares nasolabial folds
      • Seen in 50% of pts
    • Discoid ⇒ peripheral hyperpigmentation with central atrophy/scarring, usually on face, scalp, ears, neck and extensor surfaces of the arms
    • Subacute cutaneous (SCLE) ⇒ raised erythematous lesions (annular or serpiginous) usually on chest, back and outer arms
  • Oral/nasopharyngeal ulcers ⇒ usually painless
  • Alopecia
    • Scarring (discoid)
    • Non-scarring (active systemic disease and drugs)
  • Vasculitic lesions
    • Nail fold infarcts
    • Frank digital ulcers
  • Livedo Reticularis ⇒ netlike pattern of reddish-blue skin discoloration
  • Photosensitivity ⇒ worse in sunlight
    • Sunlight can incite or accentuate erythema
35
Q

SLE

Skin Histology

A
  • Liquefactive degeneration of basal layer of epidermis
  • Edema at D-E junction
  • Perivascular mononuclear infiltrates
  • Fibrinoid vasculitis
  • See Ig and complement along D-E junction w/ IF
36
Q

Lupus Arthritis

A
  • Arthralgias ⇒ common (89-90%) ⇒ MCP/IP and wrist joints
  • Non-erosive arthritis ⇒ Joint deformities unusual
    • Polys and fibrin seen in the synovium
    • Secondary to ligament loosening/reducible (Jaccoud’s arthritis)
    • Differential Dx ⇒ Rheumatoid arthritis
  • Osteonecrosis common (~5-15 %)
37
Q

CNS Lupus

Clinical Manifestations

A
  • Cognitive disorder
  • Headaches
  • Depression, Psychosis
  • Seizures - in the absence of offending drugs or metabolic derangements
  • Stroke/TIA
  • Aseptic Meningitis
  • Mono/Poly-neuropathy, Transverse Myelitis
38
Q

CNS Lupus

Pathogenesis

A
  • Acute vasculitis ⇒ focal neurologic symptoms
    • Not histologically proven
  • Non-inflammatory occlusion of small vessels by intimal proliferation
  • Antiphospholipid Ab may cause damage to endothelium of vessel
39
Q

Cardiopulmonary SLE

A
  • Accelerated atherosclerosis
  • Pleuro-pericarditis/Effusions
    • Seen in vast majority of SLE pts
  • Valve can be affected by non-bacterial verrucous endocarditis (Libman-sacks)
  • Pneumonitis with or without pulmonary hemorrhage
  • Interstitial fibrosis
  • Pulmonary Hypertension
  • Pulmonary embolism/Secondary infection
  • “Shrinking lung syndrome”
40
Q

Hematologic SLE

A
  • Anemia (of chronic disease)
  • Leukopenia (<4000/L)
  • Lymphopenia (<1500/L)
  • Thrombocytopenia (<100,000/L) Lymphadenopathy
  • Splenomegaly
  • Hemolytic anemia with reticulocytosis
41
Q

Chronic Discoid Lupus

A
  • Rarely see systemic manifestations
  • 5-10% get multisystem disease after many years
  • Characterized by skin plaques which can have:
    • Edema
    • Erythema
    • Scaliness
    • Follicle plugging
    • Skin atrophy
    • Surrounding erythematous border
  • 35% of these pts ANA positive
  • Rarely positive for dsDNA
42
Q

SLE Management

General Principles

A
  • Monitoring every 3-6 months for disease activity
  • Photoprotection
  • Avoid possible triggers ⇒ sulfa drugs, birth control, alfalfa sprouts
  • Prevent atherosclerosis ⇒ stop smoking, control BP and cholesterol
  • Prevent osteoporosis ⇒ Calcium, Vit D, Bisphosphonates
  • Infection Control
    • Pneumococcal/Influenza Immunization
    • Antibiotic Prophylaxis
  • Planned Pregnancy
43
Q

SLE

Acute Treatment

A
  • Monitoring every 3-6 months for disease activity for those who are doing well
  • Corticosteroids ⇒ for acute issues
  • Can be given in very high doses (“pulse steroids”) for life-threatening complications
  • Non-steroid treatment options
  • “Steroid sparing” agents (i.e. disease modifying drugs)
    • Hydroxychloroquine
    • Methotrexate
    • Azathioprine
    • Leflunomide
    • Mycophenylate Mofetil
  • Biologicals ⇒ Rituximab (B-cell depletion)
  • Cyclophosphamide ⇒ standard for steroid resistant SLE
44
Q

SLE Mortality

A

Common Causes:

  • Infections
  • Lupus nephritis, renal failure
  • Cardiovascular disease
  • CNS lupus
45
Q

Neonatal Lupus Syndromes

46
Q

Drug-Induced Lupus

Etiologies

A
  • Drugs:
    • Hydralazine ⇒ HLA DR4 has greater risk
    • Procainamide
    • Isoniazid
    • D-penicillamine
  • Pts develop ANAs while taking these meds
  • Rarely see renal and CNS involvement
  • Anti-dsDNA Ab rarely develops
  • High frequency of anti-histone positivity
47
Q

Drug-Induced Lupus

Manifestations

48
Q

Sjogren’s Syndrome

Overview

A
  • Immune destruction of lacrimal and salivary glands
    • Primary form ⇒ Sicca syndrome
  • Results in:
    • Keratoconjunctivitis sicca (dry eyes) ⇒ blurring, burning, itching, thick secretions
    • Xerostomia (dry mouth) ⇒ swallowing difficulty, ↓ sense of taste, dry mucosa
  • If these develop in a pt w/ another autoimmune disease (most often RA) ⇒ secondary form of Sjogren’s syndrome
49
Q

Sjogren’s Syndrome

Labs

A
  • Lymphoid infiltration of lacrimal and salivary glands by activated CD4+ T-cells and B-cells
  • 75% ⇒ ⊕ Rheumatoid factor
  • 50-80% ⇒ ⊕ ANA
  • 25% ⇒ ⊕ LE test
50
Q

Sjogren’s Syndrome

Antibodies

A
  • Ab vs two RNP antigens ⇒ SS-A (Ro) and SS-B (La)
    • Detected in up to 90% of pts
  • High titers of anti SS-A Ab are more likely to have extra-glandular manifestations
  • Ab can also be seen in SLE pts
  • Certain HLA types predominate
  • EBV may play a role
51
Q

Sjogren’s Syndrome

Clinical Characteristics

A
  • Monoclonal B-cell population in salivary gland
  • Can be a precursor of lymphoma
    • 40x higher incidence of lymphoma vs those w/o Sjogren’s
    • Often B-cell, marginal zone type
52
Q

Mikulicz’s Syndrome

A

Lacrimal and salivary gland enlargement

Can be secondary to sarcoid, leukemia, lymphoma, Sjogren’s

53
Q

Sjogren’s Diagnose

A

By lip biopsy to examine minor salivary glands

Presence of periductal and perivascular inflammation and lymphoid follicles w/ germinal centers

54
Q

Systemic Sclerosis

(Scleroderma)

Overview

A
  • Characterized by the presence of excess fibrosis throughout the body
    • Skin most commonly affected
    • Also GI tract, kidneys, heart, muscles, and lungs
  • F:M = 3:1
  • Peak from age 50-60
  • Most severe in black pts, particularly black women
  • In a majority of pts (diffuse scleroderma), the disease progresses to visceral involvement
  • Death from renal failure, cardiac failure, pulmonary insufficiency, or intestinal involvement
55
Q

Scleroderma

Epidemiology

A
  • About 150,000 people in the U.S.
  • Women > men (7-9:1)
  • Usu. 4th/5th decade of life
56
Q

Scleroderma

Pathogenesis

A

Progressive fibrosis

Three interrelated processes:

  1. Autoimmune response
    • Unclear triggers: some pts have environmental exposure to silica dust
    • Not clearly an autoimmune disease although associated w/ autoantibodies
    • Other autoantibodies, specifically anti-epithelial cell Ab, may be pathogenic by triggering apoptosis of endothelial cells
  2. Vascular damage
  3. Fibrosis
57
Q

Scleroderma

Autoimmunity

A

Unknown Ag ⇒ T-cells response ⇒ cytokine and other mediator release ⇒ ⊕ collagen synthesis by fibroblasts

Also see inappropriate activation of humoral immunity

58
Q

Scleroderma

Antibodies

A

Disordered humoral immunity also seen

Two ANAs unique to systemic sclerosis:

  • Anti-Sc170 Ab: anti-DNA topoisomerase I
    • Highly specific
    • More likely to have pulmonary fibrosis and peripheral vascular disease if Ab present
  • Anti-centromere Ab
    • 96% w/ this Ab have crest syndrome (limited systemic sclerosis)
59
Q

Scleroderma

Diagnosis

A
  • Skin biopsy can be done although the dx is often based on exam
    • Biopsy revealing dermal fibrosis, ↑ collagen deposition tests
  • Blood tests:
    • Antinuclear Ab (80-95% + depending on how the test is done)
      • Scl-70 Ab: topoisomerase Ab
        • Mainly in diffuse scleroderma, less commonly in limited)
        • Can predict interstitial lung disease
      • Anti-centromere Ab
        • Mainly in limited scleroderma
        • Less commonly in diffuse scleroderma
        • Usu. Present early in disease course
        • Predicts limited cutaneous involvement and less aggressive disease
    • Anti-PM-Scl Ab
      • Can be seen in pts w/ polymyositis/ scleroderma overlap syndrome
    • Generally ESR/CRP are not elevated
  • Raynaud’s phenomenon is nearly universal
    • Can occur w/o Scleroderma
60
Q

Scleroderma

Vascular Injury

A
  • Endothelial injury (cause unknown) ⇒ platelet aggregation ⇒ release of platelet
  • Factors ⇒ periadventitial fibrosis
  • Activated endothelial cells ⇒ release PDGF and fibroblasts chemotactic factors
  • Narrowed microvasculature ⇒ ischemic injury
  • See e/o capillary dilatation and destruction
61
Q

Scleroderma

Fibrosis

A

Multiple factors:

  • Accumulation of alternatively activated macrophages
  • Actions of fibrogenic cytokines produced by infiltrating leukocytes
  • Hyperresponsiveness of fibroblasts to cytokines
  • Vascular lesions ⇒ ischemic damage ⇒ scarring
62
Q

Diffuse Scleroderma

Clinical Manifestations

A

Skin thickening and tightening

Usu. Starts in hands/feet and progresses centrally

Rapid progression is associated w/ worse disease

Raynaud’s: affects nearly all pts w/ scleroderma

Esophageal dysmotility

Digital ischemia and gangrene

Pulmonary fibrosis and interstitial lung disease: higher risk in pts w/ anti-Scl-70 Ab

  • Alimentary Tract
    • Affected in > 90% of pts
    • Most severe in esophagus
    • Muscle atrophies and is replaced w/ collagen
    • Mucosa thin and prone to ulceration
  • Musculoskeletal
    • Synovitis w/ progression to fibrosis, no joint destruction
  • Lungs
    • Pulmonary fibrosis and interstitial lung disease
    • Can get cyst-like cavities and thickening of small pulmonary vessels
    • Higher risk in pts w/ anti-Scl-70 Ab
  • Heart
    • Pericarditis or myocardial fibrosis can occur
  • Kidneys
    • 2/3 have renal abnormalities
    • See intimal thickening w/ collagen deposition in the walls of interlobular arteries and concentric proliferation of intimal cells
63
Q

CREST Syndrome

A
  • Localized scleroderma
    • Relatively limited skin involvement w/ later visceral involvement
  • Ass. w/ anti-centromere Ab
  • Pts have a higher incidence of CREST
    • Calcinosis
    • Raynaud’s phenomenon ⇒ episodic vasoconstriction of arteries and arterioles of extremities, often precedes other symptoms)
    • Esophageal dysmotility
    • Sclerodactyly: tightened skin of fingers and toes causing joint contractures
    • Telangiectasia: visible small linear red blood vessels
  • Often coincides w/ pulmonary HTN, especially in pts w/ anti-centromere Ab
64
Q

Scleroderma

Renal Crisis

A
  • Malignant HTN, ↓ kidney function
  • More common in diffuse scleroderma than limited although can happen in both
  • Less common than previously w/ improved recognition and treatment
65
Q

Scleroderma

Prognosis

A
  • Most common cause of death is related to pulmonary fibrosis in diffuse scleroderma
  • Pts w/ limited scleroderma may have normal life expectancy, especially if the cutaneous disease is mild
66
Q

Scleroderma

Differential Diagnosis

A
  • Nephrogenic systemic fibrosis
  • Eosinophilic fasciitis
  • Medication reaction or environmental exposure
67
Q

Scleroderma

Treatment

A
  • No proven effective treatments although many have been tried
  • Treatment of organ-specific symptoms in limited scleroderma
  • Early recognition/treatment/prevention of scleroderma renal crisis: ACE-inhibitors
68
Q

Inflammatory Myopathies

A
  • ANA Ab can be present in some cases
    • Anti-Jo-1 ⇒ Ab vs tRNA synthetase
      • Somewhat specific for inflammatory myopathies
      • Present in 15-25% of pts w/ inflammatory myopathy
      • Also a marker of coexisting interstitial pulmonary fibrosis
  • Diagnosis made by study of the clinical picture, EMG, enzyme levels, and muscle biopsy
69
Q

Dermatomyositis

Overview

A

Seen in adults and children

Clinical manifestations:

  • Distinctive lilac (heliotrope) skin rash
  • Discoloration of the upper eyelids
  • Periorbital edema
  • Grotton’s lesion ⇒ scaling red eruption on knuckles, elbows, and knees
  • Muscle weakness ⇒ bilaterally symmetric and first affects proximal muscles
  • Children can also get GI ulcers, soft tissue calcification
70
Q

Dermatomyositis

Pathogenesis & Histology

A

Mechanism involves capillary attack by Ab and complement ⇒ myocyte necrosis

Women w/ dermatomyositis have ↑ incidence of some visceral cancers

71
Q

Polymyositis

A
  • Mainly seen in adults
  • Lacks cutaneous involvement
  • Mechanism involves cell-mediated immunity w/ CD8+ T-cells
  • Microscopically see endomysial inflammation w/o evidence of vascular injury
72
Q

Inclusion Body Myositis

A
  • Involves distal muscles first
  • May be asymmetric
  • Pts usually over age 50
  • Mechanism involves cell-mediated immunity w/ CD8+ T-cells
  • Micro: rimmed vacuoles in myocytes on frozen section
73
Q

Mixed Connective Tissue Disease

A
  • Clinically has elements of SLE, polymyositis, and systemic sclerosis
  • High titers of Ab to RNP-particle-containing U1 RNP
  • Pts show little renal disease and a good response to steroids

4. HDS Multisystem (43 decks)

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