L04 - Introduction to inflammatory joint disorders Flashcards
Define Rheumatoid arthritis?
Rheumatoid arthritis (RA)= systemic, chronic inflammatory autoimmune disease principally attacking the joints.
What is the epidemiology of RA?
relatively common condition
prevalence 1%;
3 - 5x women > men
Peak @ 20-40 years old
pathogenesis of RA?
susceptibility genes + trigger CD4+ T cells by arthritogenic agent (e.g. microbial infection or self-antigen CCP)
> > T and B cell responses to self-antigens
> > Proliferation of Fibroblasts, Chondrocytes, Synovial cells
> > Release of enzymes collagenase, Stromelysin**, elastase … etc
> > Pannus formation and destruction of bone, cartilage
List the AutoAb in RA
cytokine-mediated inflammation (CD4+ T cell)
AutoAb vs cyclic citrullinated peptides (CCPs)
+
AutoAb vs citrullinated fibrinogen, type II collagen, Vimentin***
What genetic factors predispose RA?
HLA- DRB1
PTPN-22
What is the typical manifestation of RA?
symmetric arthritis - Polyarticular
small joints of the hands and feet
ankles, knees, wrists, elbows, and shoulders
Which joints in the hands are affected by RA?
proximal interphalangeal and
metacarpophalangeal joints are affected
distal interphalangeal joints are spared.
Which axial joints are affected in RA?
limited to the upper cervical spine***
hip joint involvement is extremely uncommon
Define “Pannus formation” in RA.
Pannus = chronic papillary synovitis: edematous, villous
+ inflammatory cells, granulation tissue, fibrosis
5 histological features of Rheumatoid synovium?
- synovial hyperplasia
- dense perivascular inflammatory cell infiltrates
- increased vascularity
- aggregates of fibrin on synovium
- periarticular bone erosion
How does RA lead to ankylosis?
Juxta-articular bone erosion by pannus
> pannus fills the joint space
> fibrosis and ossification
> ankylosis
What are the radiological hallmarks of RA?
joint effusions*
juxtaarticular osteopenia/ erosions*
narrowing of the joint space
loss of articular cartilage
deformations of the digits seen in RA?
1) Radial deviation of the wrist
2) Ulnar deviation of fingers
3) swan-neck deformity of fingers
4 extra-articular features of RA?
- Rheumatoid nodules
- Lung fibrosis
- Vasculitis
- Amyloidosis
List some drugs for RA?
Symptom-modifying anti-rheumatic drugs
• Non steroidal antiinflammatory drugs (NSAIDs)
• Cycloxygenase 2 (COX II) inhibitor
Disease-modifying anti-rheumatic drugs (DMARDs)
• Conventional DMARDs (cDMARDs)
• Biological DMARDs (bDMARDs)
• Target synthetic DMARDs (tsDMARDs)
3 Dx tests for RA?
(1) X-ray: characteristic findings
(2) Synovial fluid aspriation:
- sterile, turbid synovial fluid
- decreased viscosity
- inclusion-bearing neutrophils
(3) Blood test:
antiCCP and rheumatoid factor**
What causes gout?
excessive uric acid within tissues and body fluids
Monosodium urate crystals precipitate = acute inflammatory reaction
Elevated uric acid levels must always lead to gout. True or False?
False
elevated level of uric acid is an essential component of gout, not all such persons develop gout
genetic and environmental factors also contribute to its pathogenesis.
What metabolic imbalance causes gout?
Over production of uric acid
Under excretion of uric acid
What are the 2 categories of gout and what is the difference?
Primary and secondary
Primary = Idiopathic or inborn metabolic enzymatic defect
Secondary = known dominant cause
What are some causes of secondary gout?
Diseases with increased nucleic acid turnover—e.g., leukemias
Chronic renal disease (reduce excretion of urate)
Inborn metabolic disease e.g. Lesch- Nyhan syndrome or HGPRT deficiency
histological morphology of acute gouty arthritis?
Dense NEUTROPHILIC infiltrate at synovium
Long, slender needle-shaped monosodium urate crystals
Edema
What is the histological morphology of chroni tophaceous arthritis due to gout?
Repetitive precipitation of urate crystals during acute attacks :
- Articular surface ENCRUSTED with urate crystal
- Heavy urate deposit in synovium
- Pannus formation*: hyperplastic, fibrotic, juxtaarticular bone erosion
How does gout affect the kidneys?
Gouty neuphropathy
Renal Calculi
Pyelonephritis due to urinary obstruction
What is are the normal metabolic pathways that produce uric acid?
Uric acid = end product of purine catabolism
• de novo pathway = synthesis of
purine nucleotides from nonpurine precursors.
• salvage pathway = synthesis of
purine nucleotides from free purine bases from
diet and purine nucleotides
What are some predisposing factors of gout?
Male sex
After age 30
obesity, alcoholism, purine-rich foods, diabetes
renal failure
What are the 4 stages of gout?
(1) asymptomatic hyperuricemia, (2) acute gouty arthritis, (3) “intercritical” gout, (4) chronic tophaceous gout.
What are the symptoms of acute gouty arthritis?
sudden onset
monoarticular joint pain
localized erythema, and warmth
Definitive Dx of gouty arthritis?
urate crystals in the joint (by arthrocentesis)
Genetic risk, Tissue affected, Joints affected in Ankylosing spondylitis?
- HLA- B27
- Pathologic changes in LIGAMENTS to spine
- Involvement of SACROILIAC JOINT + arthritis in peripheral joints
- XR BAMBOO SPINE
Bamboo spine due to hyperintense inflammation and spinal bone formation
Apart from RA, name another type of autoimmune joint disease?
Psoriatic arthritis
Name a type of infective joint disease?
Dactylitis
What causes Dactylitis?
1) infection of the fatty pad of a single finger or toe, arise from skin infection
2) Spondyloarthritis causing joint swelling (RA doesn’t cause Dactylitis)
3) Advanced psoriatic arthritis
4) Syphilis
5) Sickle cell disease
6) TB & Sarcoidosis (extremely rare)
Which types of arthritis are linked to enthesitis?
Psoriatic arthritis
Ankylosing spondylitis
juvenile RA
Not linked to Osteoarthritis or RA
extra-articular conditions caused by spondyloathropathy?
- Eye: uveitis
- Cardiac: aortic regurgitation
- Lung: apical fibrosis
What are the treatment options for Spondyloarthropathies?
1) NSAIDs
2) Conventional DMARDs for peripheral arthritis
3) Biological DMARDs for axial joints
4) Physiotherapy
How to DDx different types of arthritis?
Poly-, oligo- or monoarthritis
Symmetrical or Asymmetrical
Large or small joints
Blood test, synovial fluid aspiration, Xray, MRI results
