MSK/Rheumatology Flashcards
Define crystal arthropathies and name 2
Gout and Psuedogout
Describes acute intermittent episodes of joint inflammation caused by accumulation of urate crystals within synovial joints.
What type of crystals are found in gout and describe their structure and appearance (3)
Monosodium Urate Crystals
Needle-shaped
Negatively Bifringent under polarized light
What type of crystals are found in pseudogout and describe their structure and appearance (3)
Calcium pyrophosphate crystals
Small rhomboid brick shaped
Positively bifringent under polarized light.
Where does gout most commonly affect? (2)
1st metatarsophalangeal joint (big toe = podagra)
Osteoarthritic joints (ankle, foot, hand, wrist, elbow or knee)
What is the principle driver of gout?
Hyperuricaemia (high uric acid levels)
Describe the pathophysiology of gout (3)
Purines > Hypoxanthine > Xanthine > Uric acid
Uric acid precipitates, forming monosodium urate crystals.
Urate crystals trigger acute inflammatory response (recruitment of neutrophils) causing neutrophilic synovitis.
What enzyme catalyses the conversion of xanthine to uric acid?
Xanthine oxidase
What foods/drinks contain purines? (3)
Fizzy drinks
Alcohol
Red meats
Name 1 xanthine oxidase inhibitor
Allopurinol
Where is uric acid predominantly excreted from?
Kidneys
Give 5 risk factors for gout that result from reduced urate excretion
Elderly
Male
Impaired renal function
Post-menopausal women
Drugs (Aspirin, Indapamide, Tacrolimus, Pyrazinamide)
What drug is it important to stop in patients with hypertension presenting with gout? What should be given instead?
STOP Diuretics (indapamide)
Switch to ARB (losartan) as promotes uric acid excretion
Name 4 drugs associated with gout
Aspirin (high dose)
Indapamide (diuretic)
Tacrolimus (for severe eczema)
Pyrazinamide (TB)
Give 4 clinical features of gout
Acute monoarthritis (rapid onset - severe pain - big toe)
Urate deposits (tophi in pinna, tendons or extensor surfaces)
Joint stiffness, swelling, effusion
Renal disease (hyperuricaemia > CDK = radiolucent stones/interstitial nephritis)
Give 4 differentials for gout
Septic arthritis (consider in any monoarthropathy)
Pseudogout
Reactive arthritis
Haemarthrosis (bleeding into joints - haemophilia)
What investigation is used to definitively diagnose gout?
Joint aspiration (arthrocentesis) with synovial fluid analysis.
What additional investigations is it important to conduct when investigating ? gout(4)
Synovial Fluid Culture - To exclude septic arthritis
WBC - High neutrophils
Serum urate - Raised
X-ray (shows punched out erosions in juxta-articular bone and joint space narrowing)
What drugs can be used to manage acute gout? (4)
NSAIDs - Naproxen/Ibuprofen (contraindicated in CKD)
Corticosteroids - Prednisolone
Colchicine
IL-1 inhibitors - Anakinra or Canakinumab
What drugs are used to treat recurrent episodes of gout? (2-3 weeks post acute episode) (3)
Allopurinol (xanthine oxidase inhibitor)
Probenecid (inhibits uric acid reabsorption = increased uric acid excfretion in urine)
Rasburicase (recombinant urate oxidase)
Give 3 side effects of Colchicine
Diarrhoea
Nausea
Abdominal pain
What dietary change can help reduce the risk of developing gout in the future?
Switching to a high dairy diet
Define pseudogout
Crystal arthropathy characterised by the deposition of calcium pyrophosphate crystals within joints.
Can be acute or chronic
How may acute pseudogout present?(2)
Presents with acute monoarthropathy (usually of larger joints in the elderly).
Usually occurs spontaneously and can be provoked by illness, trauma or surgery.
How may chronic pseudogout present?
Presents as an inflammatory RA-like (symmetrical) polyarthritis and synovitis (>5 joints)
What triad of pathology is typically seen in osteoarthritis?
Cartilage erosion and thickening of subchondral bone
Disordered bone repair (formation of osteophytes)
Synovial inflammation
Define osteoarthritis
Describes a degenerative joint disorder characterised by the progressive loss of hyaline cartilage, particularly of synovial joints.
Give 5 risk factors for pseudogout
Hyperparathyroidism
Haemochromatosis
Hypothyroidism
Age
Hypophosphataemia (may be 2nd to hyperparathyroidism)
Describe the clinical presentation of pseudogout
Osteoarthritis/RA live involvement of joints (wrists, shoulders, knee ect)
Symptoms of gout (swelling, effusion, pain ect)
What may be seen on an x-ray of a patient with pseudogout?
Chondrocalcinosis (soft tissue Ca deposits)
Other than joint aspiration (atherocentesis) what additional investigations are important to conduct in a patient with pseudogout? (2)
Serum calcium levels (to exclude hyperparathyroidism - low)
Serum parathyroid hormone (to exclude hyperparathyroidism - low)
How does osteoarthritis typically present (4)
Joint pain, Stiffness, Deformity and loss off function.
Where anatomically is the most common presentation of osteoarthritis?
OA of the knee
What cells produce cartilage? And from what substance makes cartilage resistant to compression?
Chondrocytes
Chondroitin sulfate
Name 3 types of cartilage and give examples of where they are found.
Hyaline cartilage (most widespread types - articular surfaces of long bones, rib tips, rings of trachea)
Fibrous cartilage (pubic symphysis, intervertebral discs, menisci)
Elastic cartilage (Epiglottis and pinnae of ear)
What are the main components of fibrous cartilage?
Type I and Type II collagen
What are the main components of elastic cartilage?
Elastin and Type II collagen
What type of cartilage is found in the pubic symphysis, intervertebral discs and menisci?
Fibrous cartilage
What type of cartilage is the most widespread cartilage found on the articular surfaces of long bones, rib tips and rings of the trachea?
Hyaline cartilage
What ultimately drives the progression of osteoarthritis? name 3 factors that influence this.
Reduced formation and increased breakdown of articular hyaline cartilage;
Metalloproteinase over production (enzymes catalyse collagen)
Production of IL-1 and TNF-a (stimulates chondrocytes to produce metalloproteinases)
Production of NO (NO activates metalloproteinases)
Give 3 clinical features of osteoarthritis
Pain (Worse with prolonged activity)
Joint stiffness (<30mins morning stiffness - improves through the day)
Bouchard’s (PIP) and Heberden’s (DIP) Nodes
What is the primary investigation for osteoarthritis? What would it likely show?
X-Ray of affected joint
LOSS;
- Loss of joint space (joint space narrowing)
- Osteophyte formation
- Subchondral sclerosis
- Subchondral cysts
What blood tests would be conducted when investigating osteoarthritis? (4)
CRP (Normal)
ESR (Normal)
Rheumatoid Factor (Negative)
Anti-CCP (Negative)
What investigation can be used to assess osteoarthritic damage to the knee?
Arthroscopy
How is osteoarthritis managed? (3)
Exercise (improve muscle strength) (weight loss if overweight)
Patient Education
Analgesia (Oral/Topical)
Describe the 1th to 4th line analgesic treatments for osteoarthritis (5)
1st - Topical analgesia (Diclofenac/Ibuprofen gel/Capsaicin)
2nd - Paracetamol + Topical Analgesia
3rd - NSAID + Paracetamol + Topical Analgesia
4th - Opioid (codeine) + Paracetamol + Topical Analgesia
Adjunct - Intra-articular steroid injections (Methylprednisolone acetate)
Describe 3 surgical methods of treating osteoarthritis
Arthroscopy
Osteotomy (removing bone)
Arthroplasty (joint replacement)
Give 3 indications for conducting an arthroplasty in a case of osteoarthritis
Uncontrolled pain (particularly at night)
Significant limitation of function
Patient age
Define Rheumatoid Arthritis and describe how it is characterised.
Describes a chronic systemic inflammatory disease primarily affecting synovial joints of the hands and feet.
Characterised by symmetrical, deforming peripheral polyarthritis (>5 joints).
What is Rheumatoid Arthritis associated with and why?
An increased risk of cardiovascular and cerebrovascular disease as atherosclerosis is accelerated
Give 3 risk factors for rheumatoid arthritis
Smoking
Genetics - HLA-DR1/DR4
Female
What is the main driver of rheumatoid arthritis? What factors drive this? (3)
Synovial inflammation (synovitis)
Driven by; TNF, IL-1 and IL-6
What 4 processes occur during the development of Rheumatoid Arthritis?
Recruitment of inflammatory Cells (T-cells, B-cells, Macrophages)
Synovial Hyperplasia
Increased angiogenesis
Joint effusion (swelling from excess synovial fluid)
What joints are primarily affected in Rheumatoid Arthritis? How does this differ to Osteoarthritis?
RA = MCP and PIP Joints of the hands and feet
OA = PIP and DIP joints (not MCP)
Give 3 clinical features of rheumatoid arthritis
Symmetrical Arthritic of MCP and POP joints lasting >6 weeks
Pain/stiffness worse in the morning (relieved with exercise)
Systemic illness (fatigue, weightloss, carpal tunnel syndrome)
Give 5 systemic, extra articular symptoms of rheumatoid arthritis
Carpal Tunnel Syndrome/Frozen Shoulder/Quervains tenosynovitis
Fatigue/Weight loss
Heart - Pericarditis/Pericardial effusion
Eyes - Sceleritis/Uveitis
Lungs - Pleural effusions/Fibrosing alveolitis
Name and describe 1 rare complication of rheumatoid arthritis
Felty’s syndrome
SANTA;
- Splenomegaly
- Anaemia
- Neutropenia
- Thrombocytopenia
- Arthritis (rheumatoid)
What clinical signs may be seen in rheumatoid arthritis? (4)
Boutonniere’s/Swan Neck Deformities
Ulnar deviation and subluxation
Raynauds
Signs of inflammation (hot, red, swelling, pain, loss of function)
What blood tests may be ordered to investigate rheumatoid arthritis?
ESR/CRP (Raised)
Rheumatoid Factor (Positive)
Anti-CCP (Positive - Useful if RF is negative)
What imaging investigation is useful to use to investigate rheumatoid arthritis? What may it show?
X-ray
Shows periarticular erosions at joint margins. May later progress to joint space narrowing.
Describe the management of rheumatoid arthritis
1st line;
DMARDs - Methotrexate/Sulfasalazine (Pregnancy)
Analgesia - NSAIDs/Aspirin
Corticosteroids - Prednisolone
2nd line
Anti-TNF medications - Infliximab (if unresponsive to DMARD)
3rd line
Rituximab (If unresponsive to Anti-TNF)
Give 4 possible side effects of methotrexate
Hepatotoxicity
Anaemia (Macrocytic)
Pulmonary fibrosis
Pancytopenia
Describe spondyloarthropathies
A group of chronic inflammatory conditions affecting the spine and peripheral joints
Spondyloarthropathies are associated with what allele?
HLA-B27
Name 4 types of seronegative spondyloarthropathies
Ankylosing spondylitis
Psoriatic arthritis
Reactive arthritis
Enteric arthropathy
What common clinical features are seen in seronegative spondyloarthropathies? (SPINEACHE)
S - Sausage Digit (Dactylitis)
P - Psoriasis
I - Inflammatory back pain
N - NSAID good response
E - Enthesitis (achilies tendon, costochondritis)
A - Arthritis (axial - spine/sacroiliac joints)
C - Crohn’s /Colitis/Raised CRP
H - HLA-B27
E - Eye (Uveitis)
How do spondyloarthropathies tend to present? (3)
Asymmetrical
Large joint oligoarthritis (<5 joints) or monoarthritis
Seronegative (RF negative)
Define ankylosing spondylitis
Chronic inflammatory disease characterized by stiffening and inflammation of the spine and sacroiliac joints
How does ankylosing spondylitis differ to rheumatoid arthritis?
In contrast to RA, where inflammation and erosion are the only pathological processes present, AS also involves subsequent repair (ossification).
Inflammation in AS patients is dominated by inflammatory cells and an increased number of osteoclasts.
Give 3 epidemiological features of ankylosing spondylitis
More common in men
Early presentation (late teens/early 20s)
Gradual onset lower back pain
Describe the typical presentation of ankylosing spondylitis. (5)
Typical presentation is a man <30 yrs with gradual onset of lower back pain, worse in the morning relieved with exercise.
Asymmetrical involvement
Morning stiffness/pain relieved by exercise
Iritisis/uveitis
Enthesitis
Kyphosis/Lumbar lordosis
What may an pelvic x-ray show in a patient with ankylosing spondylitis? (3)
Sacroiliitis (erosions, irregularities, sclerosis)
Syndesmophytes (bony proliferations)
Bamboo spine (fusion of spinal joints)
How is ankylosing spondylitis managed? (5)
Exercise
Analgesia - NSAIDs/Paracetamol
Intra-articular corticosteroid injections - Hydrocortisone (if peripheral joint involvement)
DMARDs - Sulfasalazine/Methotrexate
Surgery (hip replacement)
Describe psoriatic arthritis
Describes an chronic inflammatory joint disease associated with psoriasis.
What joint is commonly affected in psoriatic arthritis?
Distal Interphalangeal Joint (DIP)
What deformities may be seen on an x-ray of a patient with psoriatic arthritis? (3)
Pencil cup deformity (Erosion of DIP joint)
Fluffy periostitis (peri-articular new bone formation)
Osteolysis
Give 4 clinical features of psoriatic arthritis
Psoriatic skin symptoms (Psoriasic plaques on scalp/legs, onycholysis - detachment of nail from nail bed)
Prolonged morning stiffness/pain (>30 mins) that improves with use
DIP joint involvement
Dactylitis
Describe reactive arthritis
Reactive arthritis describes an inflammatory arthritis that occurs after exposure to certain gastrointestinal (dysentery) or genitourinary infections (urethritis).
Give 3 gastro-intestinal causes of reactive arthritis
Salmonella
Shigella
Yersinia enterocolitica
Give 1 genitourinary cause of reactive arthritis
Chlamydia
Describe Systemic Lupus Erythematosus
Describes a multisystemic autoimmune disease characterized by the generation of antibodies against autoantigens (such as Anti-Nuclear Antibody -ANA) which form immune complexes.
What type of hypersensitivity reaction is SLE? and why?
Type 3 hypersensitivity reaction
Forms immune complexes
Give 3 epidemiological factors of SLE
Female
Afro-caribbean/asian
Genetics - HLA-B8, DR2 and DR3/Compliment deficiency (C3/C4)
Give 5 clinical features of SLE
Malar rash (butterfly rash)
Photosensitive rash (after sunlight exposure)
Discoid rash (keratotic rash - chronic SLE)
Arthralgia/arthritis (presents similar to RA)
Organ specific features (kidney, eyes, CS, GI, Heart)
What immunological tests should be performed when investigating SLE? (4)
ANA (Most sensitive - useful rule out test)
dsDNA antibody (Most specific)
Anti-Smith
Low Cs and C4
Give 3 additional tests (non-immunological) to perform when investigating SLE
ESR/CRP (ESR elevated due to systemic inflammation, CRP normal as condition is chronic)
Urinalysis (Assess renal involvement)
Coombs test (order if pt has features of anaemia)
Describe the management of SLE (3)
Analgesia - NSAIDs
Suncream
Hydroxychloroquine
Give 2 potential musculoskeletal features of SLE
Arthralgia
Non-erosive arthritis
Give 2 potential cardiovascular features of SLE
Pericarditis (most common cardiac symptom)
Myocarditis
Give 2 potential respiratory features of SLE
Pleurisy
Fibrosing alveolitis
Give 2 potential renal features of SLE
Proteinuria
Glomerulonephritis (diffuse proliferative glomerulonephritis is most common)
How is diffuse proliferative glomerulonephritis (caused by SLE) treated? (2)
Treat hypertension
Glucocorticoids (prednisolone) with Mycophenolate/Cyclophosphamide
Give 2 potential neuropsychiatric features of SLE
Anxiety/Depression
Seizures
Describe osteoporosis
Osteoporosis is a systemic skeletal disease characterized by low bone mass and structural deterioration in bone microarchitecture.
Making bones more susceptible to fracture
What is a fragility fracture?
Describes an osteoporotic fracture that occurs as a result of increased bone fragility due to osteoporosis.
Typically occurring from the patient falling from a standing height or less.
Name 3 common sites for fragility fractures to occur
Wrist, Hip, Spine
What cell type drives bone resorption?
Osteoclasts
What cell type drives bone formation?
Osteoblasts
How does osteoporosis occur?
Occurs as a consequence of imbalances in bone resorption (osteoclasts) and bone formation (osteoblasts), in which bone resorption is favoured, resulting in a net loss of bone density.
Name 3 biochemical factors involved in regulating bone remodelling
Parathyroid hormone (increases blood Ca levels by promoting bone resportion)
1,25 dihydroxy vitamin D (Calcitriol) (increases blood Ca levels by promoting bone resorption and renal phosphate resorption)
Calcitonin (opposes PTH) (Acts to decrease blood calcium levels by inhibiting bone resorption)
Give risk factors for osteoporosis (SHATTERED)
S - Steroid use (>5mg/d prednisolone)
H - Hyperthyroidism, hyperparathyroidism, hypercalciuria
A -Alcohol and smoking
T - Thin (<18.5 BMI)
T - Testosterone reduction
E - Early Menopause
R - Renal or Liver failure (Chronic Kidney Disease associated w/ tertiary hyperparathyroidism)
E -Erosive/inflammatory bone disease (myeloma/RA)
D - Dietary (reduced calcium intake, malabsorption, diabetes mellitus type 1)
What is the gold standard investigation for osteoporosis?
DEXA bone densitometry
(T-score <-2.5 = osteoporosis)
What assessment tool is used in osteoporosis? What does it estimate?
FRAX (Fracture risk assessment tool)
Estimates 10yr risk of osteoporotic fracture in untreated patients
FRAX should be conducted in ALL patients before a DEXA except for? (3)
> 50 with hx of fragility fractures
<40 with major risk factor for fragility fractors
With vertebral or hip fractures
What metabolite tests would be useful to perform on a patient with osteoporosis?
Calcium (hypocalcemia)
Phosphate (low - osteomalacia)
PTH
Vitamin D
TFTs
Describe how T-scores used in a DEXA scan are used to assess severity (4)
> -1.0 = Normal
-1.0 to -2.5 = Osteopenia
< -2.5 = Osteoporosis
< -2.5 + fracture = Severe osteoporosis
What does a T score of <-2.5 mean?
This means that the patient’s bone density is >2.5 standard deviations below the young adult mean value
What does a Z-score compare your bone density to?
to the average values for a person of the same;
age, gender and ethnicity.
Give 4 pieces of general management advice for managing osteoporosis
Reduce smoking and alcohol intake
Increase dietary intake of calcium and phosphate (dairy)
Encourage weight bearing or balancing exercises (Tai Chi)
Home based fall prevention
Give 3 pharmacological managements for osteoporosis
1st line - Alendronic Acid (bisphosphonates)
Calcium + Vitamin D supplementation
Strontium Ranelate (stimulates bone formation)
Give 4 drugs used in the secondary prevention of osteoporosis
Raloxifene (Selective oestrogen receptor modulator)
Teriparatide (PTH analogue)
Denosumab (RANK Ligand MAB)
HRT (Oestrogen)
How is osteomalacia characterised?
Osteomalacia is characterised by a normal amount of bone but it has a decreased mineral content (as there is excess unmineralized osteoid and cartilage).
What is the difference between rickets and osteomalacia?
Rickets occurs DURING the period of bone growth (before fusion of the epiphysis),this can result in growth retardation and skeletal deformities.
Osteomalacia is when this occurs AFTER fusion of the epiphysis.
What is the primary cause of osteomalacia?
Vitamin D deficiency
Give 4 causes of vitamin D deficiency
Sub-optimal exposure to UV-B (biggest factor)
Insufficient dietary intake
Insufficient absorption of vitamin D in the smal intestine
Liver/Renal failure
What is the primary role of vitamin D and how does it achieve this? (3)
Primary role is to maintain blood calcium and phosphate levels.
Does this by;
Promoting calcium reabsorption in the distal tubule.
Promoting intestinal (duodenal) calcium and phosphate absorption.
Stimulating osteoclast activity (stimulates bone reabsorption)
Give 3 clinical features of osteomalacia
Bone pain
Proximal muscle weakness (myopathy) and tenderness
Malabsorption syndromes (coeliac, chronic alcoholism, chronic pancreatitis)
Give 4 clinical features of Rickets (children)
Bone pain
Growth retardation
Developmental delay
Bony deformities (pigeon chest, bowed legs)
What metabolite levels would be seen in the blood of a patient with osteomalacia? (3)
Low calcium
Low Vitamin D
Low Phosphate
How is osteomalacia treated? (2)
Calcium carbonate/citrate
Ergocalciferol (Vitamin D)
