Rheumatology Flashcards
1
Q
What are the characteristics of spondyloarthropathies?
A
Axial arthritis Peripheral arthritis Enthesitis Mucocutaneous lesions HLA-B27
2
Q
What patient population does ankylosing spondylitis effect most often?
A
Caucausian men between the ages of 16 and 40 years of age.
3
Q
What is the common history of someone with AS?
A
Pain > 3 moths
Prolonged morning stiffness
Improvement of pain with exercise
4
Q
What is cytokine is increased in the synovium of a patient with AS?
A
TNF-alpha
5
Q
What is enthesitis?
A
Inflammation of ligamentous-, fibrous-, and thendinous- osseous junciton
6
Q
What percent of Caucasians are HLA-B27 positive?
A
6-9%
7
Q
What is the percent chance that someone who is HLA-B27 has of developing AS?
A
2%
8
Q
What is the percent chance that someone who is HLA-B27 has of developing AS if they have a first degree relative with AS?
A
20%
9
Q
What is the incidence of AS?
A
0.1-0.2%
10
Q
Do mice with HLA-B27 develop AS?
A
Yes, unless they are raised in a sterile environment
11
Q
What patient population most often develops reactive arthritis?
A
Caucasian males between the age of 40-50.
12
Q
What would the history look like of a patient with reactive arthritis?
A
Diarrhea caused by shingella, salmonella, yersinia, campylobacter or urethritis caused by chlamydia 2-4 weeks prior to the onset of arthritis.
13
Q
What is Reiter’s syndrome?
A
Conjunctivitis- Can’t see
Urethritis- Can’t pee
Arthritis- Can’t climb a tree
14
Q
Reiter’s syndrome is commonly linked to what?
A
Reactive arthritis
15
Q
What is the common site of arthritis in reactive arthritis?
A
Lower extremities-
- —Enthesopathy- Achilles and plantar
- —Dactylitis- Sausage toes
16
Q
In what way can bacterial antigens get to the sites of arthritis?
A
Bacterial environmental triggers are transported to the joints in monocytes (Chlamydia can be latent)
17
Q
What are the four possible theories of how HLA-B27 can predispose a person to develop AS?
A
- Arthritogenic peptide hypothesis
- Molecular mimicry
- Free heavy chain hypothesis
- Unfolded protein hypothesis
18
Q
Define vasculitis.
A
Inflammation within or through the vessel wall resulting in damage to vessel intergrity flow
19
Q
Name some of the cells that infiltrate vessels in vasculitis.
A
Lymphocytes Monocytes Histiocytes Eosinophils PMNs
20
Q
Fibrinoid necrosis of vessel wall occurs secondary to what?
A
Immune complex deposition
21
Q
What is the nature of lesions in all types of vasculitis?
A
Focal and segmental
22
Q
What two vasculitis’ affect large ARTERIES?
A
Giant cell arteritis
Takayasu’s arteritis
23
Q
What two vasculitis’ affect medium ARTERIES?
A
Polyarteritis nodosa
Kawasaki’s disease
24
Q
What three vasculitis’ affect small ARTERIOLES/VENULES and are ANCA positive?
A
- Granulomatous with polyangiitis (Wegner’s) GPA
- Eosinophilic granulomatosis with polyangiitis (Churg-Strauss)
- Microscopic polyangiitis (MPA)
25
What threevasculitis' affect small ARTERIOLES/VENULES and are ANCA negative?
1. Henoch-Schonlein Purpura
2. Essential cytoglobulinemic vasculitis
3. Cutaneous leukoclastic angiitis
26
What are the five mechanisms suspected of vascular damage?
1. Immune complexes (IC)
2. Antineutrophil cytoplasmic antibodies (ANCA)
3. Antiendothelial antibodies
4. T cell dependent mediated endothelial cell injury
5. Infection of endothelial cells
27
Name four sources of antigen for immune complexes.
1. Drugs
2. Bugs: infectious agents
3. Connective tissue disease: autoimmune process
4. Malignancy
28
What are the primary granules of PMNs associated with generalized GPA?
Which antibody binds these primary granules?
Proteinase-3 (PR3)
Cytoplasmic ANCA (c-ANCA)
29
What are the primary granules of PMNs associated with microscopic polyangiitis (MPA)?
What antibody binds to these primary granules?
Myeloperoxidase (MPO)
Perinuclear ANCA (p-ANCA)
30
Do antineutrophil cytoplasmic antibodies begin or amplify inclammatory vascular response?
AMPLIFY response
31
Where is the location of the muscle weakness in PM/DM?
Proximal muscle weakness
32
Identify the typical skin rashes associated with DM.
```
Gottron's papules
Heliotrope rash
V-sign and shawl-sign
Mechanic's hands
Periungual changes/erythema
```
33
What is the worst presentation associated with PM or DM?
Intersitial lung disease (ILD)
34
Name two of the anti-synthetase antibodies found in PM/DM.
Anti-aminoacyl-tRNA synthetases (cytoplasm)
Anti-Jo-1= anti-histadyl-tRNA synthetase
35
Are the anti-synthetase antibodies pathologic or myotoxic?
No
36
Polymyositis is characterized by what inflammatory cells?
Where are they located?
CD8+ T cells
Endomysial distribution surrounding and invading muscle fibers resulting in DIRECT muscle injury
37
Dermatomyositis is characterized by what inflammatory cells?
Where are they located?
CD4+ T cells
Perivascular and perifascicular inflammatory infiltrate and is complement-mediated
38
What is the potential etiology of PM/DM?
Evidence suggests a viral etiology:
- Influenza and HIV
- No live virus has been cultured but viral RNA has been detected
- Juvenile DM: coxsackie B antibodies
- Seasonal pattern: anti-Jo-1 antibodies and spring
- DM: Interferon responsive pathways
39
What is SLE?
A chronic, systemic autoimmune disease which affects multiple organ systems including the skin, joints, serosal surfaces, lungs, kidneys, CNS
40
What is the fundamental defect in systemic lupus erythematosus (SLE)?
Misdirected recognition of self as foreign, resulting in an autoimmune process; T cell AND B cell process
41
Antibody responses toward autoantigens are antigen-driven, but what do they require?
CD4+ T cells
42
What are some of the theories to explain autoimmunity in SLE?
1. Polyclonal B cell activation
2. Molecular mimicry
3. "Illicit help"
4. Sequestered antigen
5. Immunodeficiency
6. Loss of T cell tolerance
43
Is the defect that causes self-reactive lymphocytes a central or peripheral abnormality?
PERIPHERAL
44
Name some genetic predispositions of SLE.
1. HLA-DR3 and C4A null allele (C4A is the greatest risk)
2. Increase incidence of SLE among relatives
3. Concordance rate in monzygotic twins
4. More common in some ethnic groups: African Americans, Hispanic Americans, and Asians
45
What are some environmental factors that are associated with systemic lupus erythematosus?
Sex Hormones: Female more than male Increased incidence in women of childbearing age
Sun exposure: exacerbates systemic disease
46
What percent of patients with SLE are ANA+?
>95%
47
Is a positive ANA specific for SLE?
NO. they can be found in other diseases
48
Name some antibodies that are directed to multiple nuclear antigens
Anti-dsDNA antibodies: Renal disease
Anti-histone antibodies: SLE and drug-induced lupus
Antibodies to non-DNA, non-histone nuclear antigens:
- SSA
- SSB
- Smith
- Ribonuclear protein (RNP)
49
Name the specific antibody-mediated disease (Type II).
Anti-RBC antibodies >> hemolytic anemia
Anti-WBC antibodies, anti-Plt antibodies
Anti-phospholipid antibodies>>block prothrombin activation > prolonged PTT > Clotting in a way we don't know yet
50
Define osteoarthritis.
Degeneration of articular cartilage with hypertrophy of contiguous bone: joint space loss, subchondral cysts, sclerosis, osteophytes
51
Name some of the joints involved in osteoarthritis
DIP (Heberden's), PIP (Bouchard's), 1st CMC
Hips and knees
Spine: cervical and lumbar
First MTP
52
What are some predisposing factors of OA?
```
Age
Obesity
Occupational risk
Trauma
Secondary OA: Inflammatory, metabolic
SPORTS DO NOT HAVE ASSOCIATED INCREASE EXERCISE IS PROTECTIVE
```
53
What are the five components of cartilage?
```
Collagen
Proteoglycans
Matrix proteins
Chondrocytes
Water
```
54
What type of collagen is damaged in osteoarthritis?
Type II
55
What two proteoglycans are linked to hyaluronic acid?
Chondroitin and keratin sulfate
56
Name tow matrix proteins found in cartilage.
Metalloproteinases (MMPs) and Tissue inhibitors of metalloproteinases (TIMPS)
57
What percentage of cartilage is made up of water?
70%
58
Does cartilage have a blood supply or nerve supply?
Neither
59
What are the following changes you see in cartilage in early osteoarthritis?
- Chrondroccytes
- Proteoglycans
- Metalloproteinases
- TIMP
- Water content
```
Increase of chondrocytes
Decrease of proteoglycan
Increase metalloproteinases
Decrease in TIMP
Increase in water content
```
Lack so systemic features
Synovial fluid is noninflammatory in type I (200-2000 WBC)
60
What two structures produce cytokines and inflammatory mediators implicated in articular cartilage destruction?
Chrondrocytes and synovium
61
Name three cytokines and inflammatory mediators implicated in articular cartilage destruction.
1. Interleukin-1
2. Nitric oxide
3. Prostaglandins
- Other cytokines: TNF, IL-6, IL-17 and IL-18
>>>>>Complement activation and adipokines
62
Define: Rheumatoid arthritis
A systemic, inflammatory, autoimmune disorder of unknown etiology that results predominantly in a peripheral, SYMMETRIC SYNOVITIS which can result in cartilage and bone destruction
63
What are the joints most commonly involved in rheumatoid arthritis?
Bilateral, symmetric-small joints of the hands and feel sparing the DIPs
Medium and large joints can be involved
X-rays: marginal joint erosions and deformities
64
What is the etiology of rheumatoid arthritis?
Arthritogenic peptide/s in the genetically susceptible host
Disease susceptibility and severity associated with shared epitope (QKRAA; in antigen binding groove) in subtypes of HLA-DR4 and HLA-DR1
65
What is the rheumatoid factor?
Antibody directed against the Fc portion of IgG; RF usually IgM, can be IgG or IgA
In 85% of patients with RA
Produced locally in the synovial tissue
RF-IgG immune compleses are PATHOGENIC
66
What two autoantibodies when found in the same patient have a 98-100% specificity for RA?
Anti-CCP and RF
67
What are the major lymphocytes found in the synovium of RA patients?
CD4+ T cells and Th17
Plasma cells
NO PMNs
68
What is the role of CD4+ memory T cells in rheumatoid arthritis?
Modulation and amplificaiton of local immune response through antigen recognition
69
What causes vasculitis in RA?
| What causes rheumatoid nodule formation in the tissue of patients with RA?
RF-IgG immune complex
70
What is the cause of gout?
The result of tissue deposition of monosodium urate (MSU) crystals due to hyperuricemia supersaturation
71
What joints are commonly involved in gout?
1st MTP
| Cool, peripheral joints of lower and upper extremities
72
What is more common over-production or underextretors?
Underexcretors
73
Uric acid is a product of ________ metabolism.
Purine
74
Humans lack ________ which oxidizes uric acid into allantoin
Uricase
75
Overproduction of uric acid is associated with what two X-linked disorders?
```
PRPP synthetase overactivity
HGPRT deficiency (complete: Lesch-Nyhan)
```
76
How are crystal arthropathies diagnosed?
Arthrocentesis to look for needle-shaped, negatively birefringent
77
What two drugs inhibit xanthine oxidase?
Allopurinol and Febuxostat
78
How does MSU crystals induce inflammation?
1. Naked MSU crystals bind TLR2/ TLR4
| 2. MSU crytals engage the caspase-1 activating NLRP3 inflammasome resulting in IL-1Beta production
79
What does IgG-coating of crystals promote?
Phagocytosis by PMNs but IgG is NOT specific anti-crystal antibodies
80
What does the coating of crystals by apolipoprotein B do?
Inhibits phagocytosis
81
PPi perceipitates with calcium forming CPPD crystals in mid-zonal cartilage layers. These crystals are released into the joint space called
-"shedding phenomenon
-"enzymatic strip mining"
Describe CPPD crystals
Rhomboid, positively birefringent
