Immune Dysfunction - Connective Tissue Diseases

Front 1

What are the 2 common findings in Connective Tissue Diseases? What is their origin often?

Back 1

-Fibrinoid changes
-ANA's
-Autoimmune origin

Front 2

What are 6 CT diseases?

Back 2

-Systemic lupus - SLE
-Progressive systemic sclerosis - PSS/Scleroderma
-Sjogren syndrome SS
-Polymyositis
-Mixed CT disease MCTD
-Polyarteritis nodosa

Front 3

For which 2 diseases is the ANA most sensitive?

Back 3

-SLE - 93%
-PSS - 85%

Front 4

What are the 4 categories of ANA antibodies?

Back 4

-Anti-DNA
-Anti-histone
-Anti-other proteins bound to DNA but not histones
-Anti-nucleolar antigens

Front 5

What do you do when a person has a positive ANA?

Back 5

Other assays for more specific antibodies

Front 6

What are the other more specific assays?

Back 6

Anti-dsDNA
Anti-Sm
Anti-RNP
Anti-Ro/La (SSA/SSB)

Front 7

What 2 antibodies are commonly seen in SLE?

Back 7

-Anti-dsDNA
-Anti-Sm

Front 8

What antibody is commonly seen in DLE?

Back 8

Anti-histone

Front 9

What is Anticentromere a marker of?

Back 9

Limited scleroderma (crest)

Front 10

Does Progressive scleroderma (PSS) have a antibody marker?

Back 10

no

Front 11

What are the Sjogren's antibody markers?

Back 11

Anti-SSA ro
Anti-SSB la

Front 12

Which of the CT diseases are Multisystemic and which are Organ-specific?

Back 12

Multi: SLE, PSS, SS, MCTD
Spcfc: Polymyositis, Polyarteritis nodosa

Front 13

What is the prototype CTD?

Back 13

Systemic lupus erythematosus

Front 14

What sex/age does SLE most often affect?

Back 14

Women of childbearing age

Front 15

What type of lesions are involved in the organs of patients with SLE?

Back 15

Extensive Immune-complex mediated inflammatory lesions

Front 16

What are 5 sites at which these inflammatory lesions develop in SLE? Which is the most clinically significant?

Back 16

-Skin
-Serosal membranes
-Joints
-Lungs
-Kidneys - most important

Front 17

What test is often falsely positive in patients with SLE?

Back 17

VDRL for syphilis

Front 18

What test is almost always positive in SLE patients?

Back 18

The ANA test - with a diffuse spectrum of patterns

Front 19

What was an old lab test that is not done much anymore for SLE?

Back 19

LE test

Front 20

What is the basis of the LE test?

Back 20

-Put patient serum containing autoantibody into mix with damaged neutrophils
-Forms LE cells

Front 21

What are LE cells?

Back 21

Cells with a certain morphologic characteristic

Front 22

What type of ANA tests for SLE are positive?

Back 22

-Anti-dsDNA
-AntiSm

Front 23

What do HIGH titers of Anti-dsDNA in patients with SLE indicate?

Back 23

Active glomerulonephritis

Front 24

If you see a positive Anti-HISTONE think:

Back 24

DRUG-induced SLE!!!

Front 25

What is the characteristic pattern of Anti-dsDNA in SLE patients?

Back 25

Rim pattern - peripheral nuclear staining

Front 26

What lab finding is often greatly DECREASED in SLE patients?

Back 26

Serum Complement

Front 27

What is often seen in skin biopsies of patients with SLE?

Back 27

Immune complex deposition at the dermal-epidermal junction

Front 28

Why is the VDRL test positive in some patients with SLE?

Back 28

Because they have Anti-cardiolipin antibody which cross-reacts.

Front 29

What are the 2 types of skin findings in LE? Which has a better prognosis?

Back 29

-Cutaneous LE
-Discoid LE - better; only 5-10% progress to systemic dis.

Front 30

And what is the worst complication in SLE?

Back 30

Kidney changes

Front 31

So the most clinically important lesions in SLE are:

Back 31

The kidney lesions

Front 32

What are 4 common symptoms in women with SLE?

Back 32

-Fever
-Malaise
-Lymph node enlargement
-Weight loss

Front 33

What does the joint inflammation in SLE cause?

Back 33

Nonerosive synovial inflammation without deformity but with pain

Front 34

What are the 2 types of skin findings that can be seen in SLE? Which has better prognosis?

Back 34

-Cutaneous LE
-Discoid LE - better prognosis - fewer progress to systemic SLE.

Front 35

What accompanies the classic malar erythema of acute cutaneous LE?

Back 35

Photsensitivity

Front 36

What is seen in the fingers of patients with SLE often?

Back 36

Raynaud phenomenon

Front 37

Where does the serosal inflammation manifest the most severely in SLE? As what?

Back 37

Cardiac - pericarditis
Lungs - pleuritis

Front 38

What other lung manifestation develops in some SLE cases?

Back 38

Diffuse interstitial pneumonitis

Front 39

How often is endocarditis seen in SLE and why?

Back 39

Not as often anymore - because we treat with corticosteroids

Front 40

What type of endocarditis used to be seen more in SLE?

Back 40

The Atypical Nonbacterial Verrucuous form

Front 41

What is another name for this Atypical Nonbacterial Verrucuous form of endocarditis?

Back 41

Libman-Sacks

Front 42

Where are the vegetations seen on which heart valve in SLE patients with Libman Sacks endocarditis?

Back 42

On BOTH sides of the MITRAL valve leaflet

Front 43

What is the most severe glomerular lesion that develops in SLE?

Back 43

Diffuse proliferative glomerulonephritis

Front 44

What is the classic term for the H/E appearance of the diffuse proliferative glomerulonephritis?

Back 44

Wire loop appearance

Front 45

Where are the immune complexes deposited in membranous glomerulonephritis in SLE?

Back 45

Subendothelially

Front 46

Why do neurologic and psychiatric manifestations develop in SLE?

Back 46

Because of perivascular inflammation in CNS small vessels and intimal proliferation

Front 47

What does the intimal proliferation lead to and manifest as?

Back 47

-Leads to vessel occlusion
-Manifests as headache and mental disturbance

Front 48

What is drug-induced LE?

Back 48

Just a positive ANA in patients on some certain meds

Front 49

How is DLE different from SLE?

Back 49

It rarely has the symptoms

Front 50

What is almost diagnostic for DLE?

Back 50

A positive Anti-histone Antibody test!

Front 51

Felty's syndrome triad:

Back 51

-RA
-Splenomegaly
-Neutropenia

Front 52

What is the age of women affected by Sjogren's syndrome in contrast to those with SLE?

Back 52

OLDER - not a whole lot, but late middle age instead of childbearing age.

Front 53

What is the TRIAD of Sjogren syndrome?

Back 53

-Presence of a CTD or autoimmune disease (like RA)
-Keratoconjunctivitis sicca
-Xerostomia

Front 54

What are Keratoconjunctivitis sicca and Xerostomia?

Back 54

Dry eyes and dry mouth

Front 55

What is Dry eyes and Dry mouth without a CTD or autoimmune disease?

Back 55

Sicca syndrome

Front 56

What is the autoimmune disease that most often accompanies Sjogren syndrome?

Back 56

Rheumatoid arthritis

Front 57

What are the lab findings in Sjogren syndrome? (2)

Back 57

-Significant polyclonal Hypergammaglobulinemia
-Positive Anti-SS A/B

Front 58

Which is more specific; Anti-SSB or Anti-SSA?

Back 58

B (la)

Front 59

What is a common finding in women with Sjogrens due to the salivary gland involvement?

Back 59

Parotid gland enlargement

Front 60

What organ is more likely to be involved in patients with high titers of Anti-SS-A?

Back 60

Renal

Front 61

What type of renal lesion will be seen if involved in Sjogren's syndrome?

Back 61

Tubulointerstitial nephritis - the TUBULES

Front 62

Why are the lymph nodes so enlarged in patients with Sjogren's?

Back 62

Because of the dramatic polyclonal B-cell activation producing hypergammaglobulinemia!

Front 63

What are patients with Sjogren's at risk for developing and by how much?

Back 63

LYMPHOMA - by 40X

Front 64

What is Progressive Systemic Sclerosis?

Back 64

Widespread fibrosis and degenerative changes of unknown etiology

Front 65

What are the most commonly affected organs in PSS?

Back 65

-Skin
-GI tract - esophagus
-Heart
-Muscle

Front 66

In what age group does PSS predominantly present?

Back 66

Young women

Front 67

What are the initial presenting symptoms of PSS usually?

Back 67

-Raynaud's phenomenon (precedes all others usually)
-Skin changes
-Esophageal symptoms/Pain

Front 68

What will cause death in PSS?

Back 68

The involvement of visceral organs - myocardial fibrosis, pulmonary HTN/fibrosis, and HTN leading to renal failure.

Front 69

What are the skin symptoms of PSS?

Back 69

-Tight face skin leads to FIXED FACE appearance
-Claw hands
-Raynaud phenomenon

Front 70

What causes the fixed face appearance in PSS?

Back 70

Hypertrophy of Collagen fibers in the subcutaneous tissues.

Front 71

What is Clawed hand called?

Back 71

Sclerodactyly

Front 72

What are the 2 subcategories of systemic sclerosis?

Back 72

-Diffuse (PSS)
-Limited

Front 73

How are Diffuse and Limited scleroderma differentiated?

Back 73

Based on the degree of skin involvement at disease onset, and how rapidly it progresses to visceral involvement

Front 74

What do some patients with limited scleroderma actually have?

Back 74

Just CREST syndrome

Front 75

What is the development of visceral involvement in Diffuse scleroderma like?

Back 75

Rapidly progressive and seen early in disease.

Front 76

What is it like in Limited?

Back 76

Late visceral involvement

Front 77

What is the pathogenesis that leads to PSS?

Back 77

Activation of Tcells in response to an unknown Ag leads to cytokine release that stimulates excessive Collagen synthesis/Fibrosis

Front 78

What is the ANA associated with actual PSS, systemic sclerosis?

Back 78

Anti Scl-70 (DNA topo I)

Front 79

And what 2 complications are associated with patients who are positive for Anti-Scl70?

Back 79

-Pulmonary fibrosis
-Peripheral vasc disease (visceral involvement)

Front 80

What is Anticentromere antibody found in?

Back 80

CREST syndrome

Front 81

What does CREST stand for?

Back 81

-Calcinosis
-Raynaud phenomenon
-Esophageal dysfunction
-Sclerodactyly
-Telangiectasia

Front 82

What is the major cause of death in patients with PSS?

Back 82

Pulmonary hypertension and Interstitial fibrosis

Front 83

What are the 2 inflammatory myopathies to know about?

Back 83

-Polymyositis
-Dermatomyositis

Front 84

What is Polymyositis?

Back 84

Chronic inflammation causeing necrosis of the Proximal muscles of extremities

Front 85

What is Dermatomyositis?

Back 85

Polymyositis plus skin involvement resulting in marked discoloration

Front 86

How are Dermatomyositis and Polymyositis diagnosed?

Back 86

By measure CK-MM and muscle biopsy

Front 87

Which inflammatory myopathy is associated with increased risk of cancer?

Back 87

Dermatomyositis

Front 88

What is MCTD?

Back 88

The mixed hodgepodge of symptoms of ALL the CTD's together

Front 89

Ironically what is a rare finding in MCTD?

Back 89

Renal involvement

Front 90

What is the most unique feature of MCTD?

Back 90

Its specific ANA patterns:
-High titer anti-U1RNP
-Speckled pattern

Front 91

What is a CTD that affects small and medium arteries of almost any organ?

Back 91

Polyarteritis nodosa

Front 92

What is PAN an example of?

Back 92

Vasculitis

Front 93

What is the unique difference of Polyarteritis nodosa in contrast to all the other CTD's?

Back 93

It is predominantly in MEN!

Front 94

What type of inflammation is characteristicly seen in PAN?

Back 94

Fibrinoid necrosis in the walls of small-med arteries