ALU 301, Ch. 15 Rheumatoid Arthritis |Complete Questions
with 100% Correct Solutions
Rheumatoid arthritis (RA)
is a chronic inflammatory polyarthritis of unknown etiology that targets the synovial tissue of
moveable joints.
Epidemiology of RA
-prevalence of approximately 1%
-30-45 cases per 100,000 of the general population
-more common in women than men with a ratio of 3:1. Although rheumatoid arthritis can present at
any age, women usually develop symptoms between their second and fifth decades
-incidence peaks about age 55
-44% disabled within 10 years onset
Etiology of RA
-multifactorial
-Genetics, presence of HLA-DR4
-other genes, including metalloproteinase-3
-production of RF is under genetic control and linked to RA in the role of autoantigen
-Infectious cause - no bacterial or viral source identified, but EBV has been studied
-Other causes - smoking, decaf coffee
Pathogenesis of RA. There are two theories of the mechanism of generating and maintaining the
inflammatory response in RA:
1. "T cell centric" theory
2. "macrophage-fibroblast" theory
"T cell centric" theory
In this scenario, endogenous or exogenous antigen is presented to CD4+ (helper) T cells by major
histocompatibility complex (MHC) class II molecules, such as HLA-DR4, on antigen presenting cells
(APCs).26,27,28 (For an illustration of this, a recommended resource is Dr. Bathon's article at
http://www.hopkins-arthritis.org/ rheumatoid/ rheum_clin_path.html.) Upon recognition of the
antigen, the now "activated" T cell initiates the host response by secreting cytokines that drive the
inflammatory process.
"macrophage-fibroblast" theory
This theory proposes that T cells may be significant in initiating the disease, but that macrophages and
fibroblasts act independently of T cells to perpetuate the inflammatory process.
A synovial joint
also called a diarthrodial joint, is composed of two bones held together by a fibrous capsule that is
lined with synovium. The bones are capped with cartilage and are separated by a thin layer of synovial
fluid. Together they permit frictionless movement of the joint.
The synovium provides nutrients to the avascular cartilage and produces hyaluronic acid that
lubricates the joint. It also produces collagen and fibronectin used for the synovial matrix. It is
composed of two layers and the synovial cavity
1. The synovial intimal layer is normally one or two cells thick and forms an interface between the
synovium and the synovial fluid space. The lining has two major cell types, a macrophage type cell
, (Type A synoviocyte) and a fibroblast type cell (Type B synoviocyte). Both cell types increase in
number with rheumatoid synovitis.
2. The subintimal area of the synovium is the source of blood vessels. In RA, it becomes infiltrated
with T and B lymphocytes and macrophages that promote angiogenesis (proliferation of blood
vessels) that support the inflammatory process.
3. The synovial cavity is a "potential" space that contains a small amount of hyaluronic acid that
allows free movement of the joint. In RA, this potential space becomes filled with a large amount of
neutrophil containing fluid (effusion). These effusions are highly inflammatory
Five stages have been identified in the development of chronic synovitis:
1. Stage 1 - antigen is presented to T cells causing proliferation of the synovial intimal cells
2. Stage II - inflammatory cells (including T lymphocytes, B lymphocytes, macrophages, plasma cells,
mast cells, neutrophils, and granulocytes) join the immune response causing tissue damage
3. Stage III - synovial proliferation and hypertrophy, with onset of pain, swelling, and morning stiffness
4. Stage IV - pannus formation and periarticular osteopenia (discussed further in the next section)
5. Stage V - initiation of cartilage destruction and subchondral bone erosions.
Whatever triggers the onset of RA, once the inflammatory process is initiated, cascades of cellular
factors and soluble inflammatory mediators are expressed in the RA synovium and synovial fluid that
perpetuate the condition.
T lymphocytes, particularly Th1 cells (CD4+ helper T cells), are present in large numbers in the
synovium and act as inflammatory cells. When activated, T cells stimulate the production of pro-
inflammatory cytokines.
Cytokines are mediators of cell-to-cell communication that act locally on surrounding tissues and are
potent mediators of inflammation.
In RA, there is an imbalance of pro-inflammatory and anti-inflammatory cytokines, with pro-
inflammatory cytokines dominating
ANTI-INFLAMMATORY CYTOKINES
Soluble tumor necrosis factor receptor Interleukin-1 receptor antagonist (IL-1ra) Transforming growth
factor ß (TGF- ß) Interleukin-10 (IL-10)
PRO-INFLAMMATORY CYTOKINES
tumor necrosis factor alpha (TNF-α) Interleukin 1 (IL-1)
Interleukin 6 (IL-6)
Interleukin-8 (IL-8)
Granulocyte macrophage-colony stimulating factor (GM-CSF)
T cells, macrophages, and fibroblasts are the synovial cells believed to perpetuate the inflammatory
process by producing cytokines.
They cause the production of tumor necrosis factor alpha (TNF-α), interleukin-1 (IL-1), IL-6, IL-8, and
granulocyte macrophage-colony stimulating factor (GM-CSF), to name just a few.
Presentation of Rheumatoid Arthritis
Joint pain, inflammation, positive RF, effusions, and even nodule formation can be presenting
symptoms
Table 2. Differential Diagnoses of Rheumatoid Arthritis
with 100% Correct Solutions
Rheumatoid arthritis (RA)
is a chronic inflammatory polyarthritis of unknown etiology that targets the synovial tissue of
moveable joints.
Epidemiology of RA
-prevalence of approximately 1%
-30-45 cases per 100,000 of the general population
-more common in women than men with a ratio of 3:1. Although rheumatoid arthritis can present at
any age, women usually develop symptoms between their second and fifth decades
-incidence peaks about age 55
-44% disabled within 10 years onset
Etiology of RA
-multifactorial
-Genetics, presence of HLA-DR4
-other genes, including metalloproteinase-3
-production of RF is under genetic control and linked to RA in the role of autoantigen
-Infectious cause - no bacterial or viral source identified, but EBV has been studied
-Other causes - smoking, decaf coffee
Pathogenesis of RA. There are two theories of the mechanism of generating and maintaining the
inflammatory response in RA:
1. "T cell centric" theory
2. "macrophage-fibroblast" theory
"T cell centric" theory
In this scenario, endogenous or exogenous antigen is presented to CD4+ (helper) T cells by major
histocompatibility complex (MHC) class II molecules, such as HLA-DR4, on antigen presenting cells
(APCs).26,27,28 (For an illustration of this, a recommended resource is Dr. Bathon's article at
http://www.hopkins-arthritis.org/ rheumatoid/ rheum_clin_path.html.) Upon recognition of the
antigen, the now "activated" T cell initiates the host response by secreting cytokines that drive the
inflammatory process.
"macrophage-fibroblast" theory
This theory proposes that T cells may be significant in initiating the disease, but that macrophages and
fibroblasts act independently of T cells to perpetuate the inflammatory process.
A synovial joint
also called a diarthrodial joint, is composed of two bones held together by a fibrous capsule that is
lined with synovium. The bones are capped with cartilage and are separated by a thin layer of synovial
fluid. Together they permit frictionless movement of the joint.
The synovium provides nutrients to the avascular cartilage and produces hyaluronic acid that
lubricates the joint. It also produces collagen and fibronectin used for the synovial matrix. It is
composed of two layers and the synovial cavity
1. The synovial intimal layer is normally one or two cells thick and forms an interface between the
synovium and the synovial fluid space. The lining has two major cell types, a macrophage type cell
, (Type A synoviocyte) and a fibroblast type cell (Type B synoviocyte). Both cell types increase in
number with rheumatoid synovitis.
2. The subintimal area of the synovium is the source of blood vessels. In RA, it becomes infiltrated
with T and B lymphocytes and macrophages that promote angiogenesis (proliferation of blood
vessels) that support the inflammatory process.
3. The synovial cavity is a "potential" space that contains a small amount of hyaluronic acid that
allows free movement of the joint. In RA, this potential space becomes filled with a large amount of
neutrophil containing fluid (effusion). These effusions are highly inflammatory
Five stages have been identified in the development of chronic synovitis:
1. Stage 1 - antigen is presented to T cells causing proliferation of the synovial intimal cells
2. Stage II - inflammatory cells (including T lymphocytes, B lymphocytes, macrophages, plasma cells,
mast cells, neutrophils, and granulocytes) join the immune response causing tissue damage
3. Stage III - synovial proliferation and hypertrophy, with onset of pain, swelling, and morning stiffness
4. Stage IV - pannus formation and periarticular osteopenia (discussed further in the next section)
5. Stage V - initiation of cartilage destruction and subchondral bone erosions.
Whatever triggers the onset of RA, once the inflammatory process is initiated, cascades of cellular
factors and soluble inflammatory mediators are expressed in the RA synovium and synovial fluid that
perpetuate the condition.
T lymphocytes, particularly Th1 cells (CD4+ helper T cells), are present in large numbers in the
synovium and act as inflammatory cells. When activated, T cells stimulate the production of pro-
inflammatory cytokines.
Cytokines are mediators of cell-to-cell communication that act locally on surrounding tissues and are
potent mediators of inflammation.
In RA, there is an imbalance of pro-inflammatory and anti-inflammatory cytokines, with pro-
inflammatory cytokines dominating
ANTI-INFLAMMATORY CYTOKINES
Soluble tumor necrosis factor receptor Interleukin-1 receptor antagonist (IL-1ra) Transforming growth
factor ß (TGF- ß) Interleukin-10 (IL-10)
PRO-INFLAMMATORY CYTOKINES
tumor necrosis factor alpha (TNF-α) Interleukin 1 (IL-1)
Interleukin 6 (IL-6)
Interleukin-8 (IL-8)
Granulocyte macrophage-colony stimulating factor (GM-CSF)
T cells, macrophages, and fibroblasts are the synovial cells believed to perpetuate the inflammatory
process by producing cytokines.
They cause the production of tumor necrosis factor alpha (TNF-α), interleukin-1 (IL-1), IL-6, IL-8, and
granulocyte macrophage-colony stimulating factor (GM-CSF), to name just a few.
Presentation of Rheumatoid Arthritis
Joint pain, inflammation, positive RF, effusions, and even nodule formation can be presenting
symptoms
Table 2. Differential Diagnoses of Rheumatoid Arthritis
