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Aneesha Flashcards BRS 2 > Rheumatoid and other inflammatory arthritis > Flashcards

Rheumatoid and other inflammatory arthritis Flashcards

1
Q

What does a synovial joint look like?

A
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2
Q

What is does the synovium, synovial fluid and articular cartilage consist. of

A

Synovium- 1-3 cell deep lining containing macrophage-like phagocytic cells (type A synoviocyte) and fibroblast-like cells that produce hyaluronic acid (type B synoviocyte), Type I collagen

Synovial fluid- Hyaluronic acid-rich viscous fluid

Articular cartilage-Type II collagen, Proteoglycan (aggrecan

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3
Q

What are the 2 major divisions of arthritis?
How does movement affect pain in each of these two types?

A

Osteoarthritis- pain usually worse on movement
Inflammatory arthritis- pain usually improves with movement

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4
Q

Radiographic signs of osteoarthritis?

A

Lossof articular cartilage leading to lack of space (bone in contact with bone)
Bony spurs (osteophytes

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5
Q

Causes of joint inflammation?

A

1) Infection- septic arthritis, tuberculosis
2) Crystal arthritis- gout, pseudo gout
3) Immune-mediated (“autoimmune”)

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6
Q

Which causes of joint inflammation are secondary in response to a noxious insult and which show primary inflammation?

Which show non-sterile and which show sterile inflammation?

A

secondary inflammation in response to a noxious insult- infection, crystal arthritis
primary inflammation- Immune-mediated (“autoimmune”)

Non-sterile- Infection
Sterile- Crystal arthritis, Immune-mediated (“autoimmune”)

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7
Q

Cause of septic arthritis (specify which organisms)

A

Bacterial infection of a joint (usually caused by spread from the blood)
Common organisms:
Staphylococcus aureus, Streptococci, Gonococcus

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8
Q

Risk factors for septic arthritis

A

immunosuppressed, pre-existing joint damage, intravenous drug use (IVDU)

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9
Q

Is septic arthritis a medical emergency?

A

Yes
Untreated, septic arthritis can rapidly destroy a joint

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10
Q

Clinical presentation of septic arthritis

A

-Acute red, hot, painful swollen joint
-Usually only 1 joint is affected* (monoarthritis)
-Typically fever. Patient often systemically unwell

Consider septic arthritis in any patient with an acute painful, red, hot, swelling of a joint, especially if there is fever

*gonococcal septic arthritis is an exception:
-It often affects multiple joints (polyarthritis)
-It is less likely to cause joint destruction

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11
Q

Diagnosis of septic arthritis

A

Joint aspiration. Send sample for urgent Gram stain and culture

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12
Q

Treatment for septic arthritis

A

Surgical wash-out (‘lavage’) and intravenous antibiotics

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13
Q

Cause of gout
Risk factor for gout
Risk factor for hyperuricaemia

A

Caused by deposition of monosodium urate (MSU) (aka uric acid) crystals in/around joints
-> inflammation

High uric acid levels (hyperuricaemia) = risk factor for gout

Causes of hyperuricaemia:
Genetic tendency
Increased intake of purine rich foods
Increased cell turn over eg chemotherapy
Reduced excretion (kidney failure)

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14
Q

Causes and risk factors for pseudo gout

A

Caused by deposition of calcium pyrophosphate dihydrate (CPPD) crystals
-> inflammation

Risk factors: background osteoarthritis, elderly patients, intercurrent infection

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15
Q

Other than gouty arthritis, what can tissue deposition of monosodium urate (MSU) crystals lead to?

A

Tophi: often develop around hands, feet, elbows, and ears

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16
Q

Clinical features of gout

A

Abrupt onset
Usually monoarthritis
Big toe 1st MTPJ (metatarsophalangeal joint) most commonly affected (podagra)
Can also affects other joints: most frequently joints in the foot, ankle, knee, wrist, finger, and elbow

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17
Q

Investigations for gout/ pseudo gout

A

Joint aspiration and synovial fluid analysis
Key investigation for any acute monoarthritis – NB SEPTIC joint!

Send to lab for
-Microbiology (gram stain, culture and sensivities)
-Polarising light microscopy to detect crystals

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18
Q

Difference between gout and pseudo gout crystals

A
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19
Q

What type of disease is rheumatoid arthritis and what is the primary site of pathology

A

RA = chronic autoimmune disease
Primary site of pathology is in the synovium
Synovitis = inflammation of the synovial membrane

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20
Q

Where is synovium found and what does inflammation at each of these sites lead to?

A
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21
Q

RA age of onset
Is it more common in females or males?

A

30-50
Females

22
Q

Key features of RA

A

Chronic arthritis
Polyarthritis
Pain, swelling and early morning stiffness in and around joints
May lead to joint damage and destruction - ‘joint erosions’ on radiographs

Systemic disease with extra-articular manifestations

Auto-antibodies usually detected in blood

23
Q

What does higher concordance of a trait in monozygotic than dizygotic twins indicate?
What would concordance rate of a purely genetic disease be in monozygotic twins?

A

If the concordance rate for monozygotic twins > dizygotic twins, this indicates a genetic component.
If the disease was purely genetic, the concordance rate would be 100% for monozygotic twins.

24
Q

Risk factors for rheumatoid arthritis

A

Genetics- higher concordance in monozygotic than dizygotic twins (but not 100%), therefore mix of genes and environment
Strongest genetic risk factor = HLA-DR
HLA-DRb chain amino acids 70-74 (‘shared epitope’). Smoking & shared epitope synergistically increase risk
Genome-wide association studies (GWAS):
>100 other genetic loci that contribute to RA risk (polygenic)
E.g. PTPN22, IL6R

Environment:
Smoking
Microbiome
Porphyromonas gingivalis
Poor oral health

Female sex

25
Q

Rheumatoid arthritis: pattern of joint involvement

A

Symmetrical

Affects multiple joints (polyarthritis)

Affects small and large joints, but particularly hands, wrists and feet

Commonest affected joints:
Metacarpophalangeal joints (MCP)
Proximal interphalangeal joints (PIP)
Wrists
Knees
Ankles
Metatarsophalangeal joints (MTP)

26
Q

Rheumatoid arthritis: extra-articular features

A

Common
Fever, weight loss
Subcutaneous nodules
Uncommon
Lung disease – nodules, fibrosis, pleuritis
Ocular inflammation e.g. episcleritis
Vasculitis
Neuropathies
Felty’s syndrome – triad of splenomegaly, leukopenia and rheumatoid arthritis
Amyloidosis

27
Q

Rheumatoid arthritis: subcutaneous nodules
Describe the nodule
How common is it in RA
What is it associated with

A

Central area of fibrinoid necrosis surrounded by histiocytes and peripheral layer of connective tissue
Occur in ~30% of patients
Associated with:
Severe disease
Extra-articular manifestations
Rheumatoid factor

28
Q

Rheumatoid arthritis: pathogenesis

A

Synovial membrane is abnormal in rheumatoid arthritis:
The synovium becomes a proliferated mass of tissue (pannus) due to:

Neovascularisation
Lymphangiogenesis
inflammatory cells:
activated B and T cells
plasma cells
mast cells
activated macrophages

Recruitment, activation and effector functions of these cells is controlled by a cytokine network
There is an excess of pro-inflammatory vs. anti-inflammatory cytokines (‘cytokine imbalance’)

The cytokine tumour necrosis factor-alpha (TNFα) is the dominant pro-inflammatory cytokine in the rheumatoid synovium
Its pleotropic actions are detrimental in this setting:
Osteoclasts - activate bone resorptions to cause bone erosion
Synoviocytes - activates joint inflammation to cause pain and joint swelling
Chondrocytes- hypertrophy and its expression of proteolytic enzymes leads to cartilage degradation to cause joint space narrowing

29
Q

Can TNF alpha inhibition be used to treat RA?
How is this administered and what is administered?

A

Yes
Most commonly achieved through parenteral administration (most commonly sub-cutaneous injection) of antibodies or fusion proteins

30
Q

How would blood Hb, MCV, white cell count, platelet count, ESRand CRP differ in RA, osteoarthritis and septic arthritis?

A
31
Q

What antibodies are found in the blood of RA patients

A
  1. Rheumatoid factor
    Antibodies that recognize the Fc portion of IgG as their target antigen
    typically IgM antibodies i.e. IgM anti-IgG antibody
    Positive in 70% at disease onset and further 10-15% become positive over the first 2 years of diagnosis
  2. Antibodies to citrullinated protein antigens (Anti-citrullinated protein Antibodies ACPA)
    Antibodies to citrullinated peptides are highly specific for rheumatoid arthritis
    Citrullination of peptides is mediated by enzymes termed:
    Peptidyl arginine deiminases (PADs)
    Smoking causes citrullination of proteins in the lung epithelium therefore risk factor for RA
    ACPAs predate first clinical symptoms of RA by a median of 4.5 years
32
Q

X-ray features of RA
What is the limitation of this

A

Radiographic features of RA:
Soft tissue swelling
Peri-articular osteopenia
Bony erosions

NB erosions occur only in established disease. The aim of modern therapy is to treat EARLY before erosions (permanent damage) has occurred

Information from X-rays is limited to bony structures

33
Q

Ultrasound features of RA

When is this performed

Disadvantage of using MRI

A

Ultrasound (US) is a much better test for detecting synovitis. US changes in RA:
Synovial hypertrophy (thickening)
Increased blood flow (seen as doppler signal)
May detect erosions not seen on plain X-ray

US (usually of hands and wrists) can be performed alongside clinical assessment in a dedicated early arthritis clinic

MRI can also be used but expensive and time-consuming

34
Q

Principles of RA management

A

Treatment goal: prevent joint damage

Requires:
Early recognition of symptoms, referral and diagnosis
Prompt initiation of treatment: joint destruction = inflammation x time
Aggressive pharmacological treatment to suppress inflammation

Multidisciplinary input where needed e.g. physiotherapy, occupational therapy, surgery

35
Q

Rheumatoid arthritis: pharmacological treatment

A

Glucocorticoid therapy (‘steroids’) useful acutely but avoid long-term use because of side-effects.

NSAIDs (non-steroidal anti-inflammatory drugs e.g. ibuprofen): symptom relief but increasingly less important and unfavourable long-term safety profile ((renal function, cardiovascular risk))

‘DMARDs’ (disease-modifying anti-rheumatic drugs) =
drugs that control the disease process (usually immunosuppressive)

1st line treatment regime:
IM or short course of oral steroids
Start combination DMARD therapy (usually Methotrexate + hydroxychloroquine &/or sulfasalazine)

2nd line regime:
Biological therapies: potent and targeted
New therapies include Janus Kinase (JAK) inhibitors : Tofacitinib & Baricitinib

36
Q

What receptor does glucocorticoids bind
Where is this receptor
what happen on binding

A

Glucocorticoids bind the glucocorticoid receptor (GR)
GR resides in cytoplasm
On binding by glucocorticoids, steroid-GR complex translocates to the nucleus and binds DNA response elements, affecting transcription

37
Q

Methods of steroid administration

A

Oral prednisolone
Intramuscular (IM) methyl prednisolone
Intravenous (IV)
Intra-articular (IA)

38
Q

Methotrexate mechanism of action

A

Inhibits dihydrofolate reductase (”folate antagonist”)
Immunosuppressive/anti-inflammatory

39
Q

Methotrexate side effects

A

Nausea
Hair loss
Fall in WCC
Abnormal liver function
Pneumonitis
Infection risk

40
Q

Biologicaltherapies for RA

A

Biological therapies are proteins (usually antibodies) that specifically target a protein such as an inflammatory cytokine

  1. Inhibition of tumour necrosis factor-alpha (‘anti-TNF’)
    antibodies (infliximab, adalimumab, golimumab, certolizumab)
    fusion proteins (etanercept)
  2. B cell depletion
    Rituximab – antibody against the B cell antigen, CD20
  3. Modulation of T cell co-stimulation
    Abatacept - fusion protein - extracellular domain of human cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4) linked to modified Fc (hinge, CH2, and CH3 domains) of human immunoglobulin G1
  4. Inhibition of interleukin-6 signalling
    Tocilizumab (RoActemra) – antibody against interleukin-6 receptor.
    Sarilumab (Kevzara) – antibody against interleukin-6 receptor.
41
Q

What is psoriasis?

A

Psoriasis is an immune-mediated disease affecting the skin
Scaly red plaques on extensor surfaces (eg elbows and knees)

~10% of psoriasis patients also have joint inflammation

42
Q

Is psoriatic arthritis seronegative?

A

Yes

43
Q

Dominant pathogenic pathway for psoriatic arthritis

A

Interleukin-17/interleukin-23
(IL17-IL23)

44
Q

Clinical presentation of psoriatic arthritis

A

Varied clinical presentations:
-Classically asymmetrical arthritis affecting IPJs

But also can manifest as:
-Symmetrical involvement of small joints (rheumatoid pattern)
-Oligoarthritis of large joints
-Arthritis mutilans
-Spinal and sacroiliac joint inflammation

45
Q

What is reative arthritis?
What infections does it usually follow?

A

Sterile inflammation in joints following infection elsewhere in the body
Symptoms follow 1-4 weeks after infection and this infection may be mild

Common infections:
urogenital (e.g. Chlamydia trachomatis)
gastrointestinal (e.g. Salmonella, Shigella, Campylobacter infections)

Reactive arthritis may be first manifestation of HIV or hepatitis C infection

46
Q

Extra-articular manifestations of reactive arthritis?

A

Enthesitis (tendon inflammation)
Skin inflammation
Eye inflammation

47
Q

Who does this commonly occur in?

A

Commonly young adults with genetic predisposition (e.g. HLA-B27) and environmental trigger (e.g. Salmonella infection)

48
Q

Septic arthritis vs. reactive arthritis

A
49
Q

Inflammatory spondyloarthrits example
What other diseases can manifest as this
How does IS present

A

Classic example is Ankylosing spondylitis (AS)
SpA can also occur as a manifestation of psoriatic arthritis and inflammatory bowel disease (IBD)

Primarily inflammation of the spine (spondylitis) and sacro-iliac joints (sacro-iliitis)
Peripheral joints, esp. tendon insertions (entheses), can also be affected
Extra-articular manifestations including anterior uveitis (iritis)

50
Q

Classification of RA and key history/ examination points

A

Aneesha Flashcards BRS 2 (47 decks)

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