CHAPTER 30-RHEUMATOID ARTHRITIS Flashcards
1
Q
What triggers the innate immune system in RA
A
An infective agent or other stimulus binding to receptors on dendritic cells (DCs)
2
Q
What happens after DCs migrate into lymph nodes in RA
A
DCs present antigen to T lymphocytes; activating them
3
Q
How are T lymphocytes activated in RA
A
By antigen presentation and costimulation through CD28
4
Q
What do activated T lymphocytes produce in RA
A
Interferon-γ (IFN-γ) and other proinflammatory cytokines
5
Q
What cells do T lymphocytes stimulate in RA
A
Macrophages and other cells+ including B lymphocytes
6
Q
Why are B cells pivotal in RA pathogenesis
A
They are 10+000 times as potent as DCs in presenting antigen
7
Q
What do B lymphocytes differentiate into in RA
A
Plasma cells that produce autoantibodies+ including rheumatoid factor (RF)
8
Q
How does rheumatoid factor contribute to RA pathology
A
It forms immune complexes in the joints+ activating complement and inflammation
9
Q
What are the key inflammatory cytokines involved in RA
A
Tumor necrosis factor-α (TNF-α)+ interleukin-1 (IL-1)+ interleukin-6 (IL-6)
10
Q
How do inflammatory cytokines contribute to RA pathology
A
They promote synovitis+ cartilage degradation+ and bone erosion
11
Q
What is the role of the pannus in RA
A
It is an abnormal layer of inflammatory granulation tissue that erodes cartilage and bone in the joints
12
Q
What are the key cells involved in the pannus formation
A
Fibroblasts+ macrophages+ and lymphocytes
13
Q
How does angiogenesis contribute to RA pathology
A
It provides nutrients and oxygen to the inflamed synovium and pannus
14
Q
What is the role of chemokines in RA
A
They attract inflammatory cells into the joint
15
Q
What are examples of chemokines involved in RA
A
IL-8+ MCP-1+ RANTES
16
Q
What is the role of matrix metalloproteinases (MMPs) in RA
A
They degrade cartilage and bone matrix
17
Q
What cells produce MMPs in RA
A
Fibroblasts+ macrophages+ and chondrocytes
18
Q
What is the role of RANKL in RA
A
It promotes osteoclast formation and bone resorption
19
Q
What cells produce RANKL in RA
A
T lymphocytes and synovial fibroblasts
20
Q
What is the role of osteoclasts in RA
A
They resorb bone+ contributing to joint damage
21
Q
What are the key components of the adaptive immune response in RA
A
T lymphocytes+ B lymphocytes+ and autoantibodies
22
Q
How do T lymphocytes contribute to RA pathogenesis
A
They produce inflammatory cytokines and activate other immune cells
23
Q
How do B lymphocytes contribute to RA pathogenesis
A
They produce autoantibodies and present antigens
24
Q
What are the major autoantibodies involved in RA
A
Rheumatoid factor (RF) and anti-citrullinated protein antibodies (ACPAs)
25
What is the significance of rheumatoid factor (RF) in RA
It is an antibody against the Fc portion of IgG+ found in about 70-80% of RA patients
26
What is the significance of anti-citrullinated protein antibodies (ACPAs) in RA
Highly specific for RA+ can be present years before clinical symptoms
27
What is the role of citrullination in RA
It is a post-translational modification of proteins that creates neoantigens targeted by ACPAs
28
What is the significance of immune complexes in RA
They deposit in the joints+ activating complement and inflammation
29
How does complement activation contribute to RA pathology
It generates inflammatory mediators that amplify the immune response
30
What is the role of synovial fibroblasts in RA
They produce inflammatory cytokines and MMPs+ contributing to joint damage
31
What is the role of chondrocytes in RA
They are cartilage cells that degrade cartilage matrix in response to inflammatory signals
32
What are the genetic factors associated with RA
HLA-DR4 and other HLA class II alleles
33
How do genetic factors contribute to RA susceptibility
They influence the presentation of antigens and T cell activation
34
What environmental factors are associated with RA
Smoking+ infections+ and certain dietary factors
35
How does smoking contribute to RA susceptibility
It promotes citrullination and increases ACPA production
36
What infectious agents have been implicated in RA
Porphyromonas gingivalis and Epstein-Barr virus (EBV)
37
How do infections contribute to RA susceptibility
They may trigger autoimmunity through molecular mimicry or bystander activation
38
What hormonal factors are associated with RA
Estrogen and other sex hormones
39
How do hormonal factors contribute to RA susceptibility
They influence immune function and inflammation
40
What is the role of dendritic cells (DCs) in RA
They present antigens to T lymphocytes and initiate the adaptive immune response
41
What are the main goals of RA treatment
Reduce pain+ inflammation+ prevent joint damage+ and improve function
42
What are the main classes of drugs used to treat RA
NSAIDs+ corticosteroids+ DMARDs+ and biologics
43
How do NSAIDs work in RA
They reduce pain and inflammation by inhibiting prostaglandin synthesis
44
How do corticosteroids work in RA
They reduce inflammation and suppress the immune system
45
What are the potential side effects of corticosteroids
Weight gain+ osteoporosis+ increased risk of infections+ and diabetes
46
What are DMARDs
Disease-modifying antirheumatic drugs that slow down disease progression
47
What are examples of DMARDs used in RA
Methotrexate+ sulfasalazine+ leflunomide+ and hydroxychloroquine
48
How does methotrexate work in RA
It inhibits dihydrofolate reductase+ reducing DNA and RNA synthesis
49
What are the potential side effects of methotrexate
Liver toxicity+ bone marrow suppression+ and lung toxicity
50
How do biologic DMARDs work in RA
They target specific molecules involved in the immune response
51
What are examples of biologic DMARDs used in RA
TNF inhibitors+ IL-6 inhibitors+ and B cell depleters
52
How do TNF inhibitors work in RA
They block the activity of tumor necrosis factor-alpha (TNF-α)
53
What are examples of TNF inhibitors
Etanercept+ infliximab+ adalimumab+ certolizumab+ and golimumab
54
What are the potential side effects of TNF inhibitors
Increased risk of infections+ including tuberculosis
55
How do IL-6 inhibitors work in RA
They block the activity of interleukin-6 (IL-6)
56
What is an example of an IL-6 inhibitor
Tocilizumab
57
What are the potential side effects of IL-6 inhibitors
Increased risk of infections+ liver toxicity+ and changes in lipid levels
58
How do B cell depleters work in RA
They eliminate B lymphocytes+ reducing autoantibody production
59
What is an example of a B cell depleter
Rituximab
60
What are the potential side effects of rituximab
Infusion reactions+ increased risk of infections+ and progressive multifocal leukoencephalopathy (PML)
61
How does abatacept work in RA
It blocks T cell activation by inhibiting the interaction between CD28 and B7
62
What are the potential side effects of abatacept
Increased risk of infections
63
What is the role of physical therapy in RA management
To maintain joint mobility+ strength+ and function
64
What is the role of occupational therapy in RA management
To provide adaptive devices and strategies to improve daily activities
65
What lifestyle modifications are recommended for RA patients
Regular exercise+ healthy diet+ smoking cessation+ and stress management
66
How is RA diagnosed
Based on clinical criteria+ laboratory tests+ and imaging studies
67
What are the key laboratory tests used to diagnose RA
Rheumatoid factor (RF)+ anti-citrullinated protein antibodies (ACPAs)+ ESR+ CRP+ and CBC
68
What are the imaging studies used to evaluate RA
X-rays+ ultrasound+ and MRI
69
What are the typical radiographic findings in RA
Joint space narrowing+ bone erosions+ and periarticular osteopenia
70
What is the role of ultrasound in RA
To assess synovitis+ joint effusion+ and bone erosions
71
What is the role of MRI in RA
To detect early changes in synovium+ cartilage+ and bone
72
What are the non-pharmacological treatments of RA
Physical therapy+ occupational therapy+ and lifestyle modifications
73
What is the role of patient education in RA management
To improve adherence to treatment+ promote self-management+ and enhance quality of life
74
What is the primary goal of diagnostic evaluation in RA
To confirm the diagnosis+ assess disease activity+ and monitor treatment response
75
What is the significance of the 2010 ACR/EULAR classification criteria for RA
They provide a standardized approach to classifying patients with RA
76
What parameters are included in the 2010 ACR/EULAR classification criteria for RA
Joint involvement+ serology (RF and ACPA)+ acute-phase reactants (CRP and ESR)+ and duration of symptoms
77
How is joint involvement assessed in the 2010 ACR/EULAR criteria
By counting the number and size of affected joints
78
How is serology assessed in the 2010 ACR/EULAR criteria
By measuring rheumatoid factor (RF) and anti-citrullinated protein antibodies (ACPA)
79
How are acute-phase reactants assessed in the 2010 ACR/EULAR criteria
By measuring C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR)
80
How is the duration of symptoms assessed in the 2010 ACR/EULAR criteria
By determining if symptoms have been present for at least 6 weeks
81
What score is needed to classify a patient as having definite RA according to the 2010 ACR/EULAR criteria
A score of 6 to 10 points
82
What are the key laboratory tests used in the diagnostic evaluation of RA
Rheumatoid factor (RF)+ anti-citrullinated protein antibodies (ACPA)+ erythrocyte sedimentation rate (ESR)+ C-reactive protein (CRP)+ complete blood count (CBC)+ and comprehensive metabolic panel (CMP)
83
What is rheumatoid factor (RF)
An antibody against the Fc portion of IgG found in some autoimmune diseases
84
What is the significance of rheumatoid factor (RF) in RA
It is present in about 70-80% of RA patients but is not specific for RA
85
How is rheumatoid factor (RF) measured
By nephelometry+ ELISA+ or latex agglutination assays
86
What are the limitations of rheumatoid factor (RF) testing
It can be positive in other autoimmune diseases+ infections+ and even in healthy individuals
87
What are anti-citrullinated protein antibodies (ACPA)
Antibodies against proteins that have been citrullinated
88
What is citrullination
A post-translational modification of proteins that converts arginine to citrulline
89
What is the significance of anti-citrullinated protein antibodies (ACPA) in RA
They are highly specific for RA and can be present years before clinical symptoms
90
How are anti-citrullinated protein antibodies (ACPA) measured
By ELISA
91
What are the advantages of ACPA testing over RF testing in RA
ACPA is more specific for RA and has a higher predictive value
92
What is erythrocyte sedimentation rate (ESR)
A measure of how quickly red blood cells settle in a test tube
93
What is the significance of erythrocyte sedimentation rate (ESR) in RA
It is a marker of inflammation but is not specific for RA
94
How is erythrocyte sedimentation rate (ESR) measured
By the Westergren method
95
What are the limitations of erythrocyte sedimentation rate (ESR) testing
It can be affected by age+ gender+ anemia+ and other factors
96
What is C-reactive protein (CRP)
An acute-phase protein produced by the liver in response to inflammation
97
What is the significance of C-reactive protein (CRP) in RA
It is a marker of inflammation that correlates with disease activity
98
How is C-reactive protein (CRP) measured
By nephelometry or ELISA
99
What are the advantages of CRP testing over ESR testing in RA
CRP is more sensitive to acute changes in inflammation and is less affected by other factors
100
What is complete blood count (CBC)
A test that measures the number and types of blood cells
101
What are the typical CBC findings in RA
Anemia (low red blood cell count)+ thrombocytosis (high platelet count)+ and leukocytosis or leukopenia (abnormal white blood cell count)
102
What is comprehensive metabolic panel (CMP)
A test that measures various chemicals in the blood
103
What are the typical CMP findings in RA
Elevated liver enzymes (AST+ ALT) due to medication side effects
104
What is rheumatoid factor (RF)
An antibody against the Fc portion of IgG
105
What immunoglobulin class is RF typically
IgM+ but can also be IgG or IgA
106
What is the clinical significance of RF
It is associated with rheumatoid arthritis and other autoimmune disorders
107
What percentage of RA patients are RF positive
Approximately 70-80%
108
What is the diagnostic utility of RF for RA
It supports the diagnosis but is not specific; can be positive in other conditions
109
What other conditions can cause a positive RF
Sjögren’s syndrome+ systemic lupus erythematosus+ chronic infections+ and certain malignancies
110
How is RF measured in the laboratory
By latex agglutination+ nephelometry+ and ELISA
111
What is the principle of latex agglutination for RF
RF antibodies in the patient's serum bind to IgG-coated latex particles+ causing visible agglutination
112
What is the principle of nephelometry for RF
Measures the light scattered by immune complexes formed between RF and IgG
113
What is the principle of ELISA for RF
Uses enzyme-linked immunosorbent assay to detect and quantify RF antibodies
114
What are the limitations of RF testing
Moderate sensitivity and specificity; can be negative in early RA or positive in other conditions
115
What is the role of RF in the pathogenesis of RA
Contributes to immune complex formation+ complement activation+ and inflammation
116
How does RF contribute to joint damage in RA
By promoting inflammation and cartilage destruction
117
What is the relationship between RF titer and disease severity in RA
Higher RF titers may correlate with more severe disease but not always
118
What is the role of RF in extra-articular manifestations of RA
Contributes to vasculitis+ nodules+ and other systemic complications
119
What are cyclic citrullinated peptide (CCP) antibodies
Autoantibodies directed against citrullinated proteins
120
What is citrullination
A post-translational modification of arginine residues to citrulline
121
What is the clinical significance of CCP antibodies
Highly specific for rheumatoid arthritis (RA)
122
What percentage of RA patients are CCP antibody positive
Approximately 60-70%
123
What is the diagnostic utility of CCP antibodies for RA
High specificity; aids in early diagnosis
124
What are the advantages of CCP antibody testing over RF testing for RA
Higher specificity+ better predictive value for erosive disease
125
How are CCP antibodies measured in the laboratory
By enzyme-linked immunosorbent assay (ELISA)
126
What is the principle of ELISA for CCP antibodies
Patient serum is incubated with citrullinated peptides; bound antibodies are detected by enzyme-linked secondary antibody
127
What is the sensitivity of CCP antibody testing for RA
Moderate to high (60-70%)
128
What is the specificity of CCP antibody testing for RA
High (90-95%)
129
What is the relationship between CCP antibody titer and disease severity in RA
Higher CCP antibody titers may correlate with more severe or progressive disease
130
Can CCP antibodies be present before the onset of RA symptoms
Yes+ they can be detected years before clinical manifestation
131
What is the role of CCP antibodies in the pathogenesis of RA
Contribute to immune complex formation+ complement activation+ and inflammation
132
How do CCP antibodies contribute to joint damage in RA
By promoting inflammation and cartilage destruction
133
What is the association of CCP antibodies with specific HLA alleles
Strong association with HLA-DRB1 alleles
134
Can CCP antibodies be used to predict the development of RA in at-risk individuals
Yes+ they can help identify individuals at higher risk
135
What is the role of CCP antibody testing in undifferentiated arthritis
Helps in early diagnosis and prediction of progression to RA
136
How does CCP antibody testing impact the management of RA
Guides treatment decisions and helps predict prognosis
137
What is the difference between first and second generation CCP antibody assays
Second generation assays have improved sensitivity and specificity
138
What is the utility of combining CCP antibody and RF testing
Increases sensitivity and specificity for RA diagnosis
139
What is anti-nuclear antibody (ANA)
Antibodies that bind to components within the cell nucleus
140
Is ANA specific for rheumatoid arthritis (RA)
No+ it is associated with various autoimmune diseases
141
What is the clinical utility of ANA testing in RA
May indicate overlap with other autoimmune conditions like SLE
142
What ANA patterns are commonly observed in RA
Speckled and homogeneous patterns
143
What are acute phase reactants
Proteins whose serum concentrations increase or decrease in response to inflammation
144
What are common acute phase reactants measured in RA
C-reactive protein (CRP)+ erythrocyte sedimentation rate (ESR)
145
How does CRP relate to RA disease activity
CRP levels correlate with inflammation and disease activity
146
How does ESR relate to RA disease activity
ESR is an indicator of inflammation+ though less specific than CRP
147
What is the significance of C3 and C4 complement levels in RA
May be decreased in RA due to immune complex consumption
148
What are anti-modified citrullinated vimentin (anti-MCV) antibodies
Autoantibodies targeting citrullinated vimentin
149
How specific are anti-MCV antibodies for RA
Moderate specificity+ similar to RF
150
What is the utility of anti-MCV antibody testing in RA
May be helpful in RF-negative RA cases
151
What are 14-3-3η proteins
Proteins involved in intracellular signaling
152
How do 14-3-3η proteins relate to RA
Elevated levels in synovial fluid and serum of RA patients
153
What is the clinical utility of 14-3-3η protein testing in RA
May aid in early diagnosis and disease monitoring
154
What are cartilage oligomeric matrix protein (COMP) levels
A marker of cartilage turnover
155
How do COMP levels relate to RA
Elevated levels may indicate cartilage degradation in RA
156
What is the role of cytokines in RA pathogenesis
Mediate inflammation and joint destruction
157
What are key cytokines involved in RA
TNF-alpha+ IL-1+ IL-6
158
What are chemokines
Small proteins that attract immune cells to sites of inflammation
159
What is the role of chemokines in RA
Recruit inflammatory cells to the synovium
160
What are matrix metalloproteinases (MMPs)
Enzymes that degrade extracellular matrix components
161
How do MMPs relate to joint damage in RA
Contribute to cartilage and bone destruction
162
What is vascular endothelial growth factor (VEGF)
A protein that promotes angiogenesis
163
How does VEGF relate to RA
Contributes to synovial inflammation and pannus formation
164
What is the role of adipokines in RA
Influence inflammation and immune responses
165
What are examples of adipokines
Leptin and adiponectin
166
What is the significance of measuring multiple biomarkers in RA
Provides a comprehensive assessment of disease activity and prognosis
167
How do biomarkers guide treatment decisions in RA
Help tailor treatment to individual patients and monitor response
168
What are immune complexes
Antibodies bound to antigens forming complexes
169
What is the significance of immune complexes in RA
Contribute to inflammation and tissue damage
170
How do immune complexes form in RA
Rheumatoid factor (RF) binds to IgG antibodies
171
What is the role of complement in immune complex-mediated damage
Complement activation leads to inflammation and cell lysis
172
How do immune complexes deposit in RA joints
Complexes are deposited in synovial fluid and tissues
173
What is the effect of immune complex deposition on the synovium
Triggers inflammation+ angiogenesis+ and pannus formation
174
What cell types are activated by immune complex deposition
Macrophages+ neutrophils+ and mast cells
175
What inflammatory mediators are released upon immune complex activation
Cytokines+ chemokines+ and reactive oxygen species
176
How do cytokines contribute to immune complex-mediated damage
Promote inflammation+ cartilage degradation+ and bone erosion
177
What is the role of Fc receptors in immune complex-mediated damage
Fc receptors on immune cells bind to immune complexes+ activating the cells
178
How do neutrophils contribute to immune complex-mediated damage
Release enzymes and reactive oxygen species that damage tissues
179
How do macrophages contribute to immune complex-mediated damage
Release cytokines and MMPs that promote inflammation and tissue destruction
180
What is the effect of immune complexes on cartilage degradation
Promote chondrocyte activation and MMP production
181
How do immune complexes contribute to bone erosion
Stimulate osteoclast formation and activity
182
What is the role of vascular endothelial growth factor (VEGF) in immune complex-mediated damage
Promotes angiogenesis and synovial hyperplasia
183
What is the effect of immune complex deposition on synovial fluid
Increases viscosity+ turbidity+ and inflammatory cell counts
184
What is the role of immune complexes in extra-articular manifestations of RA
Contribute to vasculitis+ nodules+ and other systemic complications
185
How do immune complexes contribute to vasculitis in RA
Deposition in blood vessel walls activates complement and inflammation
186
How do immune complexes contribute to rheumatoid nodules
Formation of granulomas with central necrosis
187
What is the role of immune complexes in the pathogenesis of Felty’s syndrome
Contribute to splenomegaly and neutropenia
188
What is the effect of immune complex-mediated inflammation on joint function
Causes pain+ swelling+ stiffness+ and limited range of motion
189
How do therapeutic strategies target immune complexes in RA
DMARDs and biologics reduce autoantibody production and inflammation
190
What is the role of B cell depletion in reducing immune complex formation
Reduces the production of rheumatoid factor (RF) and other autoantibodies
191
How do TNF inhibitors reduce immune complex-mediated damage
Block the activity of TNF-alpha+ a key cytokine involved in inflammation
192
What is the complement system
A group of serum proteins that mediate immune and inflammatory responses
193
What is the role of the complement system in RA
Contributes to inflammation and joint damage
194
How are complement levels affected in RA
May be decreased due to immune complex formation and consumption
195
Which complement components are commonly measured in RA
C3+ C4+ and CH50
196
What is the significance of decreased C3 and C4 levels in RA
Indicates active disease and immune complex-mediated inflammation
197
What is the classical pathway of complement activation
Initiated by antibody-antigen complexes (immune complexes)
198
How are immune complexes involved in complement activation in RA
Rheumatoid factor (RF) binds to IgG+ activating the classical pathway
199
What is the alternative pathway of complement activation
Activated by microbial surfaces and other non-antibody triggers
200
What is the lectin pathway of complement activation
Activated by mannose-binding lectin (MBL) binding to carbohydrates on microbial surfaces
201
How does complement activation contribute to inflammation in RA
Generates inflammatory mediators like C3a and C5a
202
What are the functions of C3a and C5a in RA
They are anaphylatoxins that promote inflammation+ vasodilation+ and immune cell recruitment
203
What is the role of the membrane attack complex (MAC) in RA
Can cause cell lysis and tissue damage
204
How does complement activation affect synovial cells
Stimulates synovial cell proliferation and cytokine production
205
What is the effect of complement activation on neutrophils
Recruits neutrophils to the joints and activates their inflammatory functions
206
What is the role of complement in cartilage degradation
Promotes chondrocyte activation and MMP production
207
What is the role of complement in bone erosion
Stimulates osteoclast formation and activity
208
How do complement inhibitors regulate complement activation
Prevent excessive inflammation and tissue damage
209
What is the effect of complement deficiencies on RA
May increase susceptibility to infections
210
How do therapeutic strategies target complement in RA
Some DMARDs and biologics can indirectly reduce complement activation
211
What is the relationship between complement levels and disease activity in RA
Lower complement levels generally correlate with higher disease activity
212
How does complement activation relate to extra-articular manifestations of RA
Contributes to vasculitis+ nodules+ and other systemic complications
213
What is the role of complement in the pathogenesis of Felty’s syndrome
Contributes to splenomegaly and neutropenia
214
What is the effect of complement-mediated inflammation on joint function
Causes pain+ swelling+ stiffness+ and limited range of motion
215
What are antinuclear antibodies (ANA)
Autoantibodies that bind to components within the cell nucleus
216
What is the clinical significance of ANA
Associated with various autoimmune diseases+ including SLE+ scleroderma+ and RA
217
How is ANA detected in the laboratory
By indirect immunofluorescence assay (IFA) on HEp-2 cells
218
What is the principle of IFA for ANA
Patient serum is incubated with HEp-2 cells; bound antibodies are detected by fluorescently labeled secondary antibody
219
What are common ANA patterns observed in IFA
Homogeneous+ speckled+ nucleolar+ and centromere patterns
220
What ANA patterns are most commonly associated with SLE
Homogeneous and speckled patterns
221
What ANA patterns are most commonly associated with scleroderma
Nucleolar and centromere patterns
222
What is the significance of a homogeneous ANA pattern
Associated with antibodies to dsDNA+ histones+ and nucleosomes
223
What is the significance of a speckled ANA pattern
Associated with antibodies to extractable nuclear antigens (ENAs)
224
What is the significance of a nucleolar ANA pattern
Associated with antibodies to nucleolar RNA and proteins
225
What is the significance of a centromere ANA pattern
Associated with antibodies to centromere proteins
226
Is ANA specific for rheumatoid arthritis (RA)
No+ but it can be present in some RA patients
227
What percentage of RA patients have positive ANA
Approximately 30-50%
228
What is the clinical utility of ANA testing in RA
May indicate overlap with other autoimmune conditions+ particularly if atypical features are present
229
What is the significance of ANA positivity in RA without other autoimmune features
May be associated with more severe disease or extra-articular manifestations
230
What is the relationship between ANA titer and disease activity in RA
Higher titers may correlate with more severe disease but not always
231
What ENAs are commonly tested in ANA-positive RA patients
Anti-Ro/SSA+ anti-La/SSB+ anti-RNP+ anti-Sm+ and anti-Scl-70
232
What is the clinical significance of anti-Ro/SSA antibodies
Associated with Sjögren's syndrome and neonatal lupus
233
What is the clinical significance of anti-La/SSB antibodies
Also associated with Sjögren's syndrome
234
What is the clinical significance of anti-RNP antibodies
Associated with mixed connective tissue disease (MCTD)
235
What is the clinical significance of anti-Sm antibodies
Highly specific for systemic lupus erythematosus (SLE)
236
What is the clinical significance of anti-Scl-70 antibodies
Associated with systemic sclerosis (scleroderma)
237
Does ANA positivity alter the treatment approach for RA
Not typically+ unless there is evidence of overlap with other autoimmune conditions
238
What is the role of ANA testing in differentiating RA from other arthropathies
Helps identify patients with overlapping autoimmune features
239
What is juvenile idiopathic arthritis (JIA)
Chronic arthritis of unknown etiology in children
240
What is the diagnostic criteria for JIA
Arthritis lasting at least 6 weeks+ with onset before 16 years of age+ excluding other known causes
241
What are the subtypes of JIA
Oligoarticular+ polyarticular+ systemic+ enthesitis-related+ psoriatic+ and undifferentiated
242
What is oligoarticular JIA
Involvement of ≤4 joints during the first 6 months of disease
243
What is polyarticular JIA
Involvement of ≥5 joints during the first 6 months of disease
244
What is systemic JIA
Arthritis with systemic features such as fever+ rash+ and organ involvement
245
What is enthesitis-related arthritis (ERA)
Arthritis with enthesitis (inflammation at tendon or ligament insertions)
246
What is psoriatic arthritis (PsA)
Arthritis associated with psoriasis or family history of psoriasis
247
What is undifferentiated arthritis
Arthritis that does not meet criteria for any other subtype
248
What are common symptoms of oligoarticular JIA
Joint pain+ swelling+ and stiffness; often affects large joints like knees
249
What are common symptoms of polyarticular JIA
Symmetrical arthritis affecting small and large joints; may resemble adult RA
250
What are common symptoms of systemic JIA
Daily fever+ salmon-colored rash+ arthritis+ and organ involvement (e.g.+ hepatosplenomegaly)
251
What are common symptoms of enthesitis-related arthritis (ERA)
Joint pain+ enthesitis+ and sacroiliitis; often affects lower extremities and spine
252
What are common symptoms of psoriatic arthritis (PsA)
Joint pain+ psoriasis+ nail changes+ and dactylitis (sausage fingers)
253
What are the laboratory findings in JIA
Elevated ESR and CRP+ positive ANA (more common in oligoarticular)+ positive RF (more common in polyarticular RF+)+ and positive anti-CCP (less common)
254
What is the significance of ANA in JIA
More common in oligoarticular JIA; associated with increased risk of uveitis
255
What is the significance of RF in JIA
More common in polyarticular JIA; may indicate a more aggressive disease course
256
What is the significance of anti-CCP in JIA
Less common; may indicate a more erosive disease course
257
What is the role of imaging studies in JIA
X-rays to assess joint damage; MRI to detect early synovitis and cartilage changes
258
What is the treatment for JIA
NSAIDs+ corticosteroids+ DMARDs (methotrexate)+ and biologics (TNF inhibitors+ IL-6 inhibitors)
259
What is the role of NSAIDs in JIA
Reduce pain and inflammation
260
What is the role of corticosteroids in JIA
Reduce inflammation and suppress the immune system; used for short-term control
261
What is the role of methotrexate in JIA
DMARD that slows down disease progression and reduces joint damage
262
What is the role of TNF inhibitors in JIA
Block the activity of tumor necrosis factor-alpha (TNF-α)+ reducing inflammation
263
What is the role of IL-6 inhibitors in JIA
Block the activity of interleukin-6 (IL-6)+ reducing inflammation
264
What is the role of physical and occupational therapy in JIA
Maintain joint mobility+ strength+ and function; provide adaptive strategies
265
What is the prognosis for JIA
Variable; some children achieve remission+ while others have chronic active disease
266
What are potential complications of JIA
Joint damage+ growth disturbances+ uveitis+ and functional disability
267
What is the importance of early diagnosis and treatment of JIA
To prevent joint damage+ preserve function+ and improve long-term outcomes
268
What is the role of intra-articular corticosteroid injections in JIA
Reduce inflammation and pain in specific joints
269
What are the primary goals of RA treatment
Reduce pain+ inflammation+ slow disease progression+ and improve quality of life
270
What are the main categories of drugs used to treat RA
NSAIDs+ corticosteroids+ DMARDs+ and biologics
271
What are NSAIDs+ and how do they help treat RA
Nonsteroidal anti-inflammatory drugs that reduce pain and inflammation by inhibiting prostaglandin synthesis
272
What are common side effects of NSAIDs
Gastrointestinal ulcers+ cardiovascular risks+ and kidney damage
273
What are corticosteroids+ and how do they help treat RA
Potent anti-inflammatory drugs that suppress the immune system
274
What are common side effects of long-term corticosteroid use
Weight gain+ osteoporosis+ increased risk of infections+ diabetes+ and adrenal suppression
275
What are DMARDs+ and how do they help treat RA
Disease-modifying antirheumatic drugs that slow down disease progression and prevent joint damage
276
What are conventional synthetic DMARDs (csDMARDs)
Traditional DMARDs like methotrexate+ sulfasalazine+ leflunomide+ and hydroxychloroquine
277
What is methotrexate+ and how does it work
A csDMARD that inhibits dihydrofolate reductase+ reducing DNA and RNA synthesis
278
What are common side effects of methotrexate
Liver toxicity+ bone marrow suppression+ mouth sores+ and lung toxicity
279
What is sulfasalazine+ and how does it work
A csDMARD with anti-inflammatory and immunomodulatory effects
280
What are common side effects of sulfasalazine
Gastrointestinal upset+ skin rash+ and liver abnormalities
281
What is leflunomide+ and how does it work
A csDMARD that inhibits pyrimidine synthesis+ reducing lymphocyte proliferation
282
What are common side effects of leflunomide
Liver toxicity+ hair loss+ and gastrointestinal upset
283
What is hydroxychloroquine+ and how does it work
A csDMARD with anti-inflammatory and immunomodulatory effects+ often used for mild RA
284
What are common side effects of hydroxychloroquine
Eye damage (retinopathy)+ skin rash+ and gastrointestinal upset
285
What are biologic DMARDs (bDMARDs)
DMARDs derived from living organisms that target specific components of the immune system
286
What are TNF inhibitors+ and how do they work
bDMARDs that block the activity of tumor necrosis factor-alpha (TNF-α)+ a key inflammatory cytokine
287
What are common TNF inhibitors used in RA
Etanercept+ infliximab+ adalimumab+ certolizumab+ and golimumab
288
What are common side effects of TNF inhibitors
Increased risk of infections+ injection site reactions+ and rarely+ lymphoma
289
What is abatacept+ and how does it work
A bDMARD that inhibits T cell activation by blocking the interaction between CD28 and B7
290
What are common side effects of abatacept
Increased risk of infections and infusion reactions
291
What is rituximab+ and how does it work
A bDMARD that depletes B cells+ reducing autoantibody production
292
What are common side effects of rituximab
Infusion reactions+ increased risk of infections+ and progressive multifocal leukoencephalopathy (PML)
293
What is tocilizumab+ and how does it work
A bDMARD that blocks the activity of interleukin-6 (IL-6)+ a pro-inflammatory cytokine
294
What are common side effects of tocilizumab
Increased risk of infections+ liver toxicity+ and changes in lipid levels
295
What are targeted synthetic DMARDs (tsDMARDs)
Small molecule DMARDs that target specific intracellular signaling pathways
296
What is tofacitinib+ and how does it work
A tsDMARD that inhibits Janus kinases (JAKs)+ key enzymes in cytokine signaling
297
What are common side effects of tofacitinib
Increased risk of infections+ changes in lipid levels+ and blood clots
298
What is baricitinib+ and how does it work
A tsDMARD that inhibits Janus kinases (JAKs)+ similar to tofacitinib
299
What are common side effects of baricitinib
Similar to tofacitinib+ including increased risk of infections and blood clots
300
What are non-pharmacological treatments for RA
Physical therapy+ occupational therapy+ lifestyle modifications+ and surgery
301
What is the role of physical therapy in RA treatment
To maintain joint mobility+ strength+ and function through exercise and other modalities
302
What is the role of occupational therapy in RA treatment
To provide adaptive devices and strategies to protect joints and improve daily activities
303
What lifestyle modifications are recommended for RA patients
Regular exercise+ healthy diet+ smoking cessation+ and stress management
304
What is the role of surgery in RA treatment
To repair or replace damaged joints in severe cases
305
What are common surgical procedures for RA
Joint replacement+ arthrodesis (joint fusion)+ and synovectomy (removal of inflamed synovium)
306
How is RA treatment tailored to individual patients
Based on disease severity+ symptoms+ lab results+ and patient preferences
307
What is the treat-to-target approach in RA
A strategy that aims to achieve specific goals+ such as remission or low disease activity+ through regular monitoring and treatment adjustments
308
What are the key goals of treat-to-target in RA
Remission or low disease activity+ as measured by validated disease activity scores
309
How is disease activity monitored in RA
Using composite measures such as the Disease Activity Score 28 (DAS28)+ Clinical Disease Activity Index (CDAI)+ or Simplified Disease Activity Index (SDAI)
310
What is remission in RA
Absence of significant disease activity+ defined by specific criteria
311
What is low disease activity in RA
Minimal disease activity+ allowing for improved function and quality of life
312
What is the role of shared decision-making in RA treatment
Encourages patients and providers to collaborate on treatment plans based on the patient’s values and preferences
313
What is arthrocentesis
A procedure to aspirate fluid from a joint
314
What is the purpose of arthrocentesis in RA
To diagnose and evaluate joint inflammation and infection
315
What are the indications for arthrocentesis
Joint effusion+ suspected infection+ crystal-induced arthritis+ or undiagnosed joint pain
316
What contraindications exist for arthrocentesis
Overlying skin infection+ bleeding disorders+ or joint prosthesis
317
How is arthrocentesis performed
Sterilize the skin+ anesthetize locally+ insert needle into joint space+ aspirate fluid
318
What is synovial fluid analysis
Laboratory examination of joint fluid
319
What tests are performed on synovial fluid
Cell count and differential+ crystal examination+ Gram stain and culture+ glucose+ protein
320
What is the normal appearance of synovial fluid
Clear and colorless or straw-colored
321
What does turbid or opaque synovial fluid indicate
Inflammation or infection
322
What is the normal white blood cell (WBC) count in synovial fluid
Less than 200 cells/µL
323
What does an elevated WBC count in synovial fluid indicate
Inflammation or infection
324
What types of cells are seen in synovial fluid
Neutrophils+ lymphocytes+ monocytes+ and synovial lining cells
325
What is the significance of neutrophils in synovial fluid
Increased in bacterial infections and inflammatory conditions
326
What is the significance of lymphocytes in synovial fluid
Increased in viral infections and autoimmune conditions
327
How are crystals identified in synovial fluid
By polarized light microscopy
328
What crystals are commonly found in synovial fluid
Monosodium urate (gout)+ calcium pyrophosphate dihydrate (CPPD)+ and cholesterol crystals
329
What does the presence of monosodium urate crystals indicate
Gout
330
What does the presence of calcium pyrophosphate dihydrate (CPPD) crystals indicate
Pseudogout
331
What is Gram stain+ and how is it used in synovial fluid analysis
A staining technique to identify bacteria; used to detect bacterial infections
332
What can lead to the initiation of Synovitis?
Primary causative factor
333
What are the subsequent immunologic events that perpetuate the initial inflammatory reaction called?
Transition of an inflammatory reaction in the synovium
334
What does a Transition of an inflammatory reaction in the synovium cause?
Proliferative+ destructive tissue process
335
What kind of symptoms do Rheumatoid arthritis often begin with?
Prodromal symptoms
336
What kind of prodromal symptoms does Rheumatoid arthritis begin with?
Fatigue+ anorexia+ weakness+ and generalized aching and stiffness not localized to articular structures
337
If conditions are present for at least 6 weeks+ what does the patient designated as?
Having classic RA
338
What kind of markers may help identify patients with more severe RA who are still in the early stages of the disease?
Prognostic markers
339
Name examples of Prognostic markers?
persistently high number of swollen joints+ high serum levels of acute-phase reactants of immunoglobulin M (IgM) rheumatoid factor+ early radiographic and functional abnormalities+ and the presence of certain HLA class II alleles
340
What is the joints lined by at their margins?
Synovial membrane (synovium)
341
What do Synovial (joint) fluid lubricate?
The joint space and transport nutrients to the articular cartilage
342
What does Arthrocentesis constitute?
A liquid biopsy of the joint
343
Name observations and procedures that can include for Routine analysis of synovial fluid?
volume and appearance+ viscosity+ mucin test+ chemical analysis for protein+ and glucose
344
What can be seen when Rheumatoid synovium is examined by the immunofluorescent technique?
large amounts of immunoglobulin G (IgG) and IgM+ alone or together
345
Where can Immunoglobulins also be seen?
Synovial lining cells+ blood vessels+ and interstitial connective tissues
346
What do current model of the pathogenesis of RA propose?
infective agent or other stimulus binds to receptors on dendritic cells (DCs)
347
What does Dendritic cells migrate into?
lymph nodes
348
What are the 2 signals that T lymphocytes is activated by?
presentation of antigen and costimulation through CD28
349
After been stimulated+ what do T lymphocytes produce?
Interferon-γ (IFN-γ) and other proinflammatory cytokines
350
What stimulates macrophages and other cells+ including B lymphocytes?
T lymphocytes
351
Which cell appears to be pivotal in the pathogenesis of RA?
B cells
352
What term is used to describe joint inflammation?
Arthritis
353
What refers to a disease involving multiple joints?
Polyarthritis
354
What refers to chronic+ systemic autoimmune disorder characterized by inflammation of the synovium?
Rheumatoid arthritis (RA)
355
What term refers to inflammation of the synovial membrane?
Synovitis
356
What does it describe the tissue lining the inner surface of a joint?
Synovium
357
What is a procedure to aspirate fluid from a joint?
Arthrocentesis
358
What word describes something relating to a joint?
Articular
359
What word describes something occurring outside the joints?
Extra-articular
360
What are abnormal antibodies produced by the immune system that can cause inflammation in the joints and other tissues in rheumatoid arthritis?
Rheumatoid factor (RF)
361
What refers to a progressive autoimmune disease that causes thickening and scarring of the skin and internal organs?
Scleroderma
362
What term refers to a systemic inflammatory condition characterized by fusion of the spine and sacroiliac joints?
Ankylosing spondylitis
363
What is a type of arthritis that affects children+ characterized by joint pain+ swelling+ and stiffness?
Juvenile idiopathic arthritis
364
What are inflammatory mediators involved in allergic reactions and inflammation?
Leukotrienes
365
What is the process by which a disease develops and progresses?
Pathogenesis
366
What are abnormal proteins found in the blood that precipitate at low temperatures?
Cryoglobulins
367
What is the goal of Nonsteroidal Antiinflammatory Drugs (NSAIDs) when treating Rheumatoid Arthritis?
To provide Analgesia(Pain relief) and reduce inflammation
368
What is the goal of Corticosteroids and Glucocorticoids when treating Rheumatoid Arthritis?
Provide Powerful anti-inflammatory agents that influence function of lymphocytes
369
What is the goal of Disease-Modifying Antirheumatic Drugs(DMARDS) when treating Rheumatoid Arthritis?
To Slow progression of joint destruction
370
What type of Other drugs does Rheumatoid Arthritis have?
Gold salts+ D-penicillamine+ cytotoxic agents (azathioprine and cyclophosphamide)+ and cyclosporine
371
What is a liquid biopsy of the joint?
Arthrocentesis
372
Why would Arthrocentesis may alleviate elevated intra-articular
Elevated intra-articular pressure
373
What does the Aspiration of synovial fluid allow?
analysis that supports the diagnosis of various joint diseases
374
What is Analysis of aspirated synovial fluid?
Essential in the evaluation of any patient with joint disease because it is a better reflection of the events in the articular cavity than abnormal blood test results
375
What type of analysis should include Wet preparation examination for cell count and differential+ crystals+ Gram stain+ and microbiologic culture?
Routine analysis of synovial fluid
376
What is the purpose of examining Very turbid fluids in routine analysis?
to perform Gram staining and culture
377
When do observations and procedures can include volume and appearance+ viscosity+ mucin test+ chemical analysis for protein+ and glucose?
Routine analysis
378
What can be seen when Rheumatoid synovium is examined by the immunofluorescent technique?
large amounts of immunoglobulin G (IgG) and IgM+ alone or together
379
Where can Immunoglobulins also be seen?
Synovial lining cells+ blood vessels+ and interstitial connective tissues
380
What does B cells make in the synovium of patients with RA?
Immunoglobulin
381
A:
382
What cells that can be located in the synovium secrete an IgG RF that combines with similar IgG molecules (self-associating IgG) in the cytoplasm?
Plasma cells
383
Case 1= A 65-year-old woman presents with symmetrical joint pain+ stiffness+ and swelling in her hands and feet for the past 6 months. She also experiences morning stiffness lasting over an hour. Lab results show elevated ESR and CRP+ and positive rheumatoid factor (RF) and anti-CCP antibodies - What is the most likely diagnosis?
Rheumatoid Arthritis
384
Case 1= What are the important diagnostic features in this case?
Symmetrical polyarthritis+ morning stiffness+ elevated inflammatory markers+ and positive RF and anti-CCP antibodies
385
Case 1= What treatment options are suitable for this patient?
DMARDs (e.g.+ methotrexate)+ biologics (e.g.+ TNF inhibitors)+ and NSAIDs for symptomatic relief
386
387
Case 2= A 40-year-old man reports lower back pain+ stiffness+ and limited spinal mobility that has been worsening over the past 2 years. He also complains of pain in his heels. Imaging shows sacroiliitis - What is the most likely diagnosis?
Ankylosing Spondylitis
388
Case 2= What are the key diagnostic features in this case?
Lower back pain and stiffness+ limited spinal mobility+ heel pain+ and sacroiliitis
389
Case 2= What are the treatment options for this patient?
NSAIDs+ physical therapy+ TNF inhibitors
390
391
Case 3= An 8-year-old girl presents with joint pain+ swelling+ and stiffness in her knees and ankles for over 6 weeks. She also has a persistent fever and a salmon-colored rash that comes and goes. Lab tests show elevated ESR and CRP - What is the most likely diagnosis?
Systemic Juvenile Idiopathic Arthritis (sJIA)
392
Case 3= What are the characteristic diagnostic features of this case?
Persistent fever+ salmon-colored rash+ arthritis+ and elevated inflammatory markers
393
Case 3= What are the treatment options for this patient?
NSAIDs+ corticosteroids+ DMARDs (e.g.+ methotrexate)+ and biologics (e.g.+ IL-1 or IL-6 inhibitors)
394
395
Case 4= A 50-year-old woman has a history of rheumatoid arthritis for 15 years. She presents with decreased white blood cell count+ enlarged spleen+ and recurrent infections - What is the most likely diagnosis?
Felty’s Syndrome
396
Case 4= What are the important diagnostic features of this case?
RA+ splenomegaly+ neutropenia+ and recurrent infections
397
Case 4= How to manage this patient's conditions?
Manage with DMARDs+ G-CSF (granulocyte colony-stimulating factor) for neutropenia+ and consider splenectomy if other treatments fail
398
What is a key characteristic feature of Rheumatoid Arthritis?
Chronic inflammatory disease characterized by joint pain+ swelling+ and stiffness
399
What autoantibodies that is associated with Rheumatoid Arthritis?
Rheumatoid factor (RF) and anti-citrullinated protein antibodies (ACPA)
400
What are the main goals of Rheumatoid Arthritis treatment?
Reduce pain+ inflammation+ slow disease progression+ and improve quality of life
401
What is the purpose of the Rapid Agglutination procedure
To detect the presence of rheumatoid factor (RF) in patient serum
402
What specimen is required for the Rapid Agglutination procedure
Serum or plasma
403
How is the Rapid Agglutination procedure performed
Mix patient serum with reagent latex particles coated with IgG; observe for agglutination
404
What indicates a positive test result in the Rapid Agglutination procedure
Visible clumping or agglutination
405
What are common sources of error in the Rapid Agglutination procedure
Incorrect technique+ contamination+ or outdated reagents
406
How to confirm a positive Rapid Agglutination test result
By using more specific assays such as nephelometry or ELISA
407
What are limitations of the Rapid Agglutination procedure
Low specificity; can be positive in other conditions besides RA
408
What are clinical applications of the Rapid Agglutination procedure
Screening for RF in patients with suspected RA
409
What is the name of The disease characterized by chronic inflammation of the joints?
Rheumatoid arthritis
410
What are The key diagnostic markers in Rheumatoid arthritis
Rheumatoid factor (RF) and anti-citrullinated protein antibodies (ACPA)
411
What should treatment for Rheumatoid arthritis focus on?
Reducing pain+ inflammation+ slowing disease progression+ and improving quality of life
412
What are the diagnostic criteria for RA
According to the 2010 ACR/EULAR classification criteria: joint involvement+ serology+ acute-phase reactants+ and duration of symptoms
413
What is the significance of ACPA in RA
Highly specific for RA; aids in early diagnosis and predicting erosive disease
414
What are the non-pharmacological treatments of RA
Physical therapy+ occupational therapy+ and lifestyle modifications
