Rheumatology/MSK Flashcards
Define osteoarthritis
Non inflammatory, progressive synovial joint damage caused by wear and tear of most commonly used joints.
Joints commonly affected in osteoarthritis
Knees
Hips
Sarco-ileac joints
Wrist
Carpometacarpal
Interphalangeal
Risk factors for osteoarthritis
Age
Female sex
Raised BMI/obesity
Joint injury/trauma
Joint malalignment (congenital or not)
Pathophysiology of osteoarthritis
Usually, cartilage breakdown and production by chondrocytes is under balance.
In OA, chondrocytes secrete more metalloproteinases (degrading enzymes) leading to loss of Type 2 cartilage. (Type 1 has less elasticity)
IL-1 and TNF-a also stimulate metalloproteinase production and inhibit collagen production.
Causes decreased joint space, which causes damage to bones on movement. Bone attempts to repair itself with type 1 collagen but causes bony overgrowths
Signs/symptoms of osteoarthritis
Asymmetrical non inflamed joint pain, which gets worse as the day goes on
- Herbeden’s nodes (DIP Swelling)
- Bouchard’s nodes (PIP swelling)
- Fixed flexion deformity of carpometacarpal
- Joint pain worse with activity
- Mechanical locking
- Joint stiffess, tenderness, crepitus (crunching sensation when moving)
- NO EXTRA ARTICULAR MANIFESTATIONS
Typical presentation of osteoarthritis
> 45 years old
Typical activity related pain
No morning stiffness (<30 mins)
Investigations in osteoarthritis
1st - X ray (LOSS)
L - Loss of joint space
O - Osteophytes (bony overgrowths)
S - Subchondral sclerosis
S - Subchondral cysts
Non pharmacological treatments of osteoarthritis
- Weight loss
- Low impact exercise
- Physiotherapy
- Occupational therapy
- Heat/cold packs at site of pain
- Orthotics (helps with foot issues)
Pharmacological treatment of osteoarthritis
1st - Oral paracetamol, topical capsaicin, topical NSAID
Topical NSAID first for knee
Others:
- Intra articular steroid injection
- Joint replacement
Define Rheumatoid arthritis with epidemiology
Autoimmune, systemic disease causing symmetrical deforming inflammation of small joints which progresses to larger joints and organs.
More in women aged 30-50
Type 3 hypersensitivity reaction
Risk factors for Rheumatoid arthritis
- Female
- Smoking
- Family history
- Post menopause
- HLA-DR1, HLA-DR4
Pathophysiology of rheumatoid arthritis
Arginine -> Citrulline mutation of type 2 collagen. Immune cells cannot differentiate self and non-self, causing antibody formation. Anti-CCP (cyclic citrullinated peptide) antibodies formed. These bind to citrullinated peptides and form immune complexes, which accumulate in synovial fluid, causing inflammation.
Cytokines recruited by macrophages (TNF, IL1,6) proliferate, forming thick pannus containing cytokines, myofibroblasts and fibroblasts. These grow past joint margins, destroy subchondral bone and articular cartilage. T cells also express RANKL, which bind to osteoclasts, causing bone breakdown.
Inflammatory cytokines also escape joint space, causing systemic effects
Signs/symptoms of rheumatoid arthritis
Symmetrical polyarthritis
Signs
- Boutonniere deformity (PIP flexion, DIP hyperextension)
- Swan-neck deformity (PIP hyperextension, DIP flexion)
- Z thumb deformity (thumb IP hyperextension, MCP flexion)
- Ulnar deviation
- Popliteal cysts (synovial sac bulges posterior to knee)
- Rheumatoid nodules (lumps under skin and around organs)
Symptoms
- Morning stiffness, >30 mins, improves throughout day
- Carpometacarpal joint spared in rheumatoid but not psoriatic
Investigations in rheumatoid arthritis
ESR/CRP high
Autoantibodies:
- Anti CCP (more specific - can be detected 15 years before symptoms)
- Rheumatoid factor (present in other diseases e.g. Sjogren’s)
X ray- LBSP
Loss of joint space
Bone erosions
Soft tissue swelling
Periarticular osteopenia (punched out erosion)
Subluxation
Extra articular manifestations of rheumatoid arthritis
(skin, respiratory, CVD, eyes, haem, systemic)
Skin
- Rheumatoid nodules
Respiratory
- Pulmonary nodules
- Pleurisy
- Bronchiectasis
- Caplan’s syndrome
- Interstitial lung disease
Opthalmological
- Keratoconjunctivitis sicca
- Scleritis
- Corneal ulceration
CVD
- IHD and pericarditis
Anaemia, Amyloidosis, Felty syndrome
Treatment of rheumatoid arthritis
DMARD - Methotrexate (CI in pregnancy!)
NSAID
Intraarticular steroid injections
Main life threatening complication of rheumatoid arthritis
Felty’s syndrome
- Rheumatoid arthritis
- Splenomegaly
- Neutropenia
Monitoring of rheumatoid arthritis
Monitor FBC, LFT, U&E weekly until treatment stabilised
Check ESR/CRP monthly
- Check disease activity score (DAS-28) annually
- Check for comorbidities
- Assess for surgery need
What type of reaction is rheumatoid arthritis
Type 3 hypersensitivity
Define gout
Inflammatory Arthritis caused by deposition of monosodium urate crystals in joints (Most commonly first metatarsophalangeal (MTP) joint - big toe)
Risk factors for gout
- Elderly
- Male
- Purine rich foods (red meat, seafood, alcohol)
- Obesity
- Hypertension
- Impaired kidney function
- Type 2 diabetes mellitus
- Family history
Causes of gout
Increased uric acid production
- Increased cell turnover (leukaemia, haemolytic anaemia)
- Purine rich diet (shellfish, red meat, organ meat)
- Obesity/metabolic syndrome
Decreased excretion
- CKD
- Diuretics/aspirin/pyrazinamide
- Lead toxicity
What type of diet would you recommend a patient with gout switch to
High dairy diet is protective from Gout
Pathophysiology of gout
Normally, purines are broken down into uric acid by xanthine oxidase, which is then excreted by kidney. Uric acid has limited solubility in blood, in high concentrations, can become a urate ion which binds to sodium to become monosodium urate, which deposits in areas of low blood flow (joints/ kidney tubules).
WBCs attack said crystals, causing inflammation
Signs/symptoms of gout
Generally monoarticular (can be up to 4) joint swelling, tenderness, erythema.
- Usually 1st MTP but can affect ankle, wrist, knee, small hand joints.
Gouty tophi (nodular masses of urate crystals - massive lump under skin) can appear
Flares last between 7-10 days, first 12 hours worst
Investigations in gout
Joint x ray:
- Joint effusion, preserved joint space.
- Lytic lesions
- Punched out erosions with sclerotic margins and overhanging edges
- Loss of joint space is a very late sign
Joint aspiration w/ polarised microscopy:
- Needle shaped crystals with negative birefringence
Management of gout
General life advice
Acute flares
Prevention
General life advice:
- Low purine, lose weight, avoid alcohol (especially beer)
Acute flares:
- NSAID+PPI OR colchicine OR steroid injection 2nd line
Prevention:
- Allopurinol (xanthine oxidase inhibitor)
Complication of gout caused by hyperuricaemia
Urate nephrolithiasis: Hyperuricaemia can cause urate renal stones
Define pseudogout
Pseudogout is an inflammatory arthritis caused by deposition of calcium pyrophosphatase crystals in synovium
Risk factors for pseudogout
- Increasing age
- Female
- Previous joint trauma
- Hyperparathyroidism
- Hypomagnesaemia
- Hypophosphataemia
- Haemochromatosis
- Acromegaly
Pathophysiology of pseudogout
Also known as chondrocalcinosis.
Calcium pyrophosphatase crystals trigger synovitis, most commonly in the knee, shoulder and wrist.
Acute - mainly larger joints in elderly
Chronic - Inflammatory RA-like symmetrical arthritis
Signs/symptoms of pseudogout
Usually indistinguishable from gout, except that knee, wrist, ankle are most affected
- Inflammation: warm, swelling, erythema, pain and joint stiffness
Investigations in pseudogout
X ray: Chondrocalcinosis (suggestive but not diagnostic, absence doesn’t exclude)
Joint aspiration w/ polarisation: Weakly positively birefringent rhomboid shaped crystals
Also check: Bone profile/PTH, Iron studies, serum magnesium to check cause
Management of pseudogout
Acute
- NSAID or colchicine or corticosteroid injection
- Cool packs + rest
Chronic
- DMARD (methotrexate) or joint replacement
Main differential of crystal arthropathies
Septic arthritis!
Gout vs pseudogout joint aspiration
Gout - Negative birefringent needle shaped crystals
Pseudogout - Positively birefringent rhomboid shaped crystals
Name the 2 types of infective arthritis
Septic - Infection of joints caused by either direct inoculation or haematogenous spread. Medical emergency
Osteomyelitis - Inflammatory disease of the bone marrow. Can be acute or chronic.
Define Septic arthritis
Infection of joints caused by most commonly staph aureus. occurs by direct inoculation or haematogenous spread
Causative microbes in septic arthritis
Staph Aureus - Most common
Staph epidermidis - prosthetic joints
Strep pyogenes - Children under 5
Neisseria gonorrhoeae - Sexually active
Pseudomonas aeruginosa and Ecoli in elderly, immunosuppressed or IV drugs
Risk factors for septic arthritis
- Underlying joint disease
- IV Drug use
- Immunosuppression
- Prosthetic joint
- Recent joint surgery
Pathophysiology of Septic arthritis
- Medical emergency due to risk of sepsis, permanent joint destruction and osteomyelitis.
- Direct or haematogenous spread
- 90% cases staph or strep
Signs/symptoms of septic arthritis
Mainly affects 1 joint. (Knee most common. but also hip, shoulders, wrists, elbows)
- Hot, tender, erythematous, swollen joint with very limited range of movement (weight bearing joints wont allow use its that painful/limited)
- Fever
- Distal skin lesions if gonococcal
Investigations of septic arthritis
- FBC - High WBC, high ESR/CRP
- Blood culture - Check before antibiotics!
- Urine if gonococcal
Joint aspiration GOLD
- Yellow/cloudy, high WCC, culture positive, neutrophils
- Must be sent for gram staining and culture
- Take before antibiotics!
What scoring criteria is used in Septic arthritis
Kocher criteria
(non weight bearing, temp, ESR, WCC)
Differential diagnoses of monoarticular arthritis
Gout
Pseudogout
Septic arthritis
Reactive arthritis
Treatment of septic arthritis
Empirical antibodies until cause known.
1st - Flucloxacillin and rifampicin
Joint drainage/washout
Drugs to stop in septic arthritis
Methotrexate/Anti TNF-a
Define osteomyelitis
Inflammatory condition of the bone/bone marrow, caused by infection (Staph aureus most common). Can be acute or chronic, leading to soft tissue infection, infarction and reactive new bone.
Mostly occurs in children
Causative organisms in osteomyelitis
SPSNM
Staph aureus - MC
P aeruginosa - MC (gram negative rod)
Salmonella
N gonorrhoeae
M tuberculosis
Risk factors for osteomyelitis
- Diabetes
- Old age
- PVD
- Immunocompromise
- Malnutrition
- IV drugs
- Recent invasive surgery
- Trauma
- Sickle cell anaemia
Pathophysiology of osteomyelitis
Pathogen can get into bone through
- Haematogenous spread (E.g. through cannula)
- Contiguous spread
- Direct inoculation
Disease course can be acute or chronic
Acute
- Bacteria reaches bone and proliferates. Infection fought off by immune system, however this damages bone. Osteoclasts repair damage and form new bone
Chronic
- Acute osteomyelitis can become chronic if lesion is large or if there is not enough viable bone for repair.
- Affected bone can become necrotic and separate from the healthy part of the bone (this is a Sequestrum)
- Osteoblasts from the periosteum may form new bone that wraps the sequestrum in place (this is called an involucrum)
- Cloaca (gaps in an involucrum where necrotic bone and pus can discharge) also form.
Causes of osteomyelitis
Diabetic foot ulcer/skin infection
Open fracture
Cannula
Trauma
Insect bites
Prosthetic joints contaminated during surgery
Kidney disease
Nearby infections (Contiguous spread!!)
Signs and symptoms of Osteomyelitis
- Dull bony pain with redness and swelling at site of infection
- Joint pain
- Fever
- Reluctance to weight bear (child with limp)
- Ulcers or skin breaks
- Discharging sinus
Histopathology of Osteomyelitis
Acute
- Inflammation
- Oedema
- Vascular congestion
- Small vessel thrombosis
Chronic
- Necrotic bone (sequestrum)
- New thick sclerotic bone formation around sequestrum (Involucrum)
- Neutrophil exudate
- Tissue macrophages
Main differential of osteomyelitis
Charcot joint
- Damage to sensory nerves due to diabetic neuropathy
- Causes progressive degeneration of weight bearing joint and bony destruction
- Non infective, patient presents with Diabetic feet
Investigations in osteomyelitis
- High WBC, ESR/CRP
Imaging
X ray
- Local osteopenia
- Lytic lesions
- Cortical bone loss
- Periosteal reaction (thickening)
- Involucrum/sequestrum (“fallen leaf sign” - Sequestrum falls into medullary canal)
MRI - Most definitive imaging modality, may show signs of infection in medullary canal or surrounding soft tissue and abscesses
Microbiology
- BM biopsy + Culture GOLD
- Blood culture
- Urine MSU
-HbA1c MUST BE CHECKED
Management of Osteomyelitis with indications for surgery
- Flucloxacillin and Rifampacin empirical, give vancomycin if MRSA suspected
- Oral fusidic acid
Surgical debridement of sequestrum and necrotic bone if:
- Failure to respond to Abx
- Abscess formation
- Vertebral osteomyelitis
Main functions of bone
Haematopoiesis
Lipid/mineral storage
Support body framework
Protection (axial skeleton around major organs)
What are the cellular components of bone
Osteoblasts - Synthesise osteoid which later is calcified/mineralised into new bone
Osteocytes - As osteoid mineralises, osteoblasts become entombed between lamellae and mature into osteocytes. Monitor minerals, proteins and regulate bone mass.
Osteoclasts - Derived from monocytes, resorb bone by releasing H+ ions. Large, multinucleated cells.
What is the main component of bone ECM
Calcium hydroxyapatite crystals, main source of mineralisation of bone. Make bone hard and strong, and are organised into thin layers called lamellae
What are the main parts of bone
Cortical bone
Spongy/trabecular bone
What does cortical bone consist of
Multiple osteons, containing Haversian canals (blood supply and innervation) and lamellae, with collagen and hydroxyapatite crystals.
Gaps between lamellae, called lacunae, contain osteocytes
How does bone remodelling work
Osteoclasts resorb bone
Osteoblasts form new bone
Cortical/compact bone replaced every 10 years
Spongy/trabecular bone replaced every 3-4 years
Factors that affect bone remodelling
PTH
Calcitonin (thyroid gland hormone released in hypercalcaemia - Essentially antiPTH)
Vitamin D
What is the main difference between osteoporosis and osteomalacia
Osteoporosis refers to thin, porous bone with decreased mass and density but proper mineralisation. Usually due to increasing age and menopause
Osteomalacia refers to normal bony tissue but improper mineralisation, causing soft, weak bones, usually due to vitamin D deficiency
What bone changes increase risk of fragility fracture in osteoporosis
- Thinning of cortical bone
- Fewer trabeculae
- Widening of Haversian canals
Define osteoporosis
Skeletal disease characterised by low bone density and micro-architectural defects in bone, resulting in bone fragility and increased risk of fragility fracture.
Bone mineral density of 2.5 standard deviations below mean peak mass
Risk factors for osteoporosis
SHATTERED
S - Steroid (glucocorticoids decrease Ca2+ absorption in gut)
H - Hyperthyroid, HyperPT, hypocalcaemia/Hypercalciuria
A - Alcohol/smoking
T - Thin (low BMI)
T - Testosterone decrease
E - Early menopause
R - Renal/liver failure
E - Erosive bone disease (myeloma, RA)
D - Dietary reduced Ca2+, malabsorption, diabetes
Also, older age, female, previous fragility fracture, physical inactivity
Conditions that can cause osteoporosis
- Turner syndrome
- Hyperprolactinaemia
- Cushings
- DM
How does peak mass relate to osteoporosis
A higher peak bone mass is protective. At 25ish we have peak bone mass then begin losing bone
Signs and symptoms of osteoporosis, and most common fracture
Usually ASYMPTOMATIC TILL fracture! If symptoms likely to be something else.
- Easy fragility fracture
Most common: - Vertebral crush fracture
- Distal radius/ Colles fracture (wrist)
- Proximal femur/Femoral neck
In vertebral crush:
- Patient will have hunched posture (kyphosis), back pain and height loss (>4cm)
What are the types of osteoporosis
Type 1- Postmenopausal: Decreased oestrogen causes increased bone resorption
Type 2 - Senile: osteoblasts lose ability to form new bone.
Type 3 - Secondary: to coexisting condition
Scoring tool used in osteoporosis
FRAX Tool - Risk calculator for fragility fracture in next 10 years
Age, sex, weight, height, previous fracture, smoking, glucocorticoids, alcohol >3 units/day, femoral neck BMD.
If risk low, reassure
if intermediate - offer DEXA and recalculate
If high - Offer treatment
Investigations in osteoporosis
FRAX tool conducted first.
DEXA scan (Dual Energy Xray Absorptiometry) - measures bone mineral density. Usually measured at hip
Provides 2 readings;
- Z score - number of SDs patients BMD falls below mean for their age
- T score - number of SDs patients BMD falls below mean for young healthy adult
T score
>-1 - normal
-1 to -2.5 - Osteopenia
<-2.5 - Osteoporosis
Ca2+, phosphate and ALP should all be tested (and appear normal unless underlying cause)
Lifestyle management of osteoporosis
Activity/exercise
Maintain healthy weight
Stop smoking/alcohol
Adequate calcium/vit D
Avoid falls
Pharmacological management of osteoporosis
Bisphosphonates first line
- E.g. alendronate
If bisphosphonate CI
- Teriparatide (recombinant PTH)
- HRT (Testosterone/Oestrogen)
- Denosumab
- Raloxeifene
What are some side effects of bisphosphonates
- Reflux/oesophagitis
- Osteonecrosis of jaw
- Osteonecrosis of external auditory canal
- Oesophageal ulcers
How should bisphosphonates be taken
To be given on empty stomach, first thing in the morning with a full glass of water. Stay upright for 30 mins after taking and dont eat or drink for 30 mins after.
How is osteoporosis monitored
Follow up in 5 years if no treatment
On treatment, FRAX/DEXA in 3-5 years. Come off treatment if BMD improves with no fragility fracture
Define Osteomalacia
Metabolic bone disease caused by incomplete mineralisation of underlying osteoid. This causes softening of bone and results in rickets in children.
Risk factors for osteomalacia
Limited sunlight exposure
Vit D deficiency
Calcium deficiency
Phosphate deficiency
Malabsorption
CKD
Dark skin
Pathophysiology of osteomalacia
Usually due to Vit D deficiency, which can be due to reduced sunlight exposure, poor nutrition, malabsorption, liver/renal failure.
Signs/symptoms of osteomalacia
Skeletal deformities
Waddling gait
Underlying hypocalcaemia/related signs
Bone pain
Muscle weakness and spasms
Investigations in osteomalacia
Vit D, Calcium and phosphate - Low
ALP, PTH - High
GOLD - Iliac bone biopsy with double tetracycline labelling
Management of osteomalacia
Correct vit D deficiency
Usually, large loading regime then smaller lifelong maintenance
Define seronegative spondyloarthropathy
Inflammatory rheumatic conditions that cause arthritis. These conditions are:
- Rheumatoid factor negative (Seronegative)
- HLA-B27 associated
- Asymmetrical
- Often affect axial skeleton (spine/sacroiliac joints)
What are the common spondyloarthropathies
Ankylosing spondylitis
Psoriatic arthritis
Reactive arthritis
Enteric arthritis
What is the current theory of pathophysiology of spondyloarthropathies
Molecular mimicry
Infection triggers immune response against infectious agent that his peptides similar to HLA-B27 proteins. Hence, autoimmunity against HLA-B27 proteins
Common spondyloarthropathy features (mnemonic)
SPINEACHE
Sausage digit (Dactylitis)
Psoriasis
Inflammatory back pain
NSAIDs work well
Enthesitis (inflammation where tendon joins bone, usually in heel - plantar fasciitis)
Arthritis
Crohns/Colitis/elevated CRP
HLA-B27
Eye (Uveitis)
Common extra-articular manifestations of spondyloarthropathies
Iritis
Uveitis
Psoriaform rashes
Oral ulcers
Aortic valve incompetence
IBD
Define ankylosing spondylitis
Progressive inflammation of spine, sacroiliac joints and vertebral column causing abnormal stiffening due to syndesmophyte formation
Pathophysiology of ankylosing spondylitis
HLA-B27 codes for a MHC class 1 molecule which sits on outside of most cells.
Key affected joints are sacroiliac joints of vertebral column. Enthesitis occurs, which heals with new bone (syndesmophyte) formation. This can progress to fusion of the spine and sacroiliac joints, causing “bamboo spine”.
Can progress to kyphosis, neck hyperextension and spino-cranial ankylosis
Signs/symptoms of ankylosing spondylitis
Typical presentation is young male with gradual onset pain and stiffening of lower back.
- Pain/stiffness is worse during night/in morning but better with exercise
- Eye irritation/photophobia/blurred vision
- Chest pain
Extra-spinal manifestations of ankylosing spondylitis
Normocytic anaemia
Iritis
Uveitis
Dactylitis
Costochondritis
Aortitis
Enthesitis
Weight loss
Fatigue
Pulmonary fibrosis
Investigations in ankylosing spondylitis
X ray - BFSSS
- Bamboo spine
- fusion of facet, sacroiliac and costovertebral joints
- Syndesmophytes
- Squaring of vertebral bodies
- subchondral sclerosis and erosions
MRI - May show bone marrow oedema and erosion of joint spaces
High ESR/CRP, HLA-B27 positive, normocytic anaemia may be present
What test can be conducted on examination for ankylosing spondylitis
Schober’s test - Assess spine mobility
Have patient stand. Locate L5 vertebrae. Mark 10cm above and 5cm below. Ask patient to bend forward as far as possible and measure distance between 2 points. <20cm distance = reduced lumbar movement.
Management of ankylosing spondylitis
1st line - NSAID (Naproxen, ibuprofen)
Steroids (Oral/IM) in flares
Anti TNF (Infliximab)
(main complication is vertebral fractures + extra articular manifestations - CBA to make new card lol)
Define reactive arthritis
Reactive arthritis (Reiter’s syndrome) refers to synovitis following a infection in other part of body.
Most commonly gastroenteritis or STIs. Affects men 30-50x more than women
Causes of reactive arthritis
STI
- Chlamydia
- Gonorrhoea
Gastroenteritis
- Salmonella
- Shigella
- Campylobacter
- Yersinia enterocolitica
Signs and symptoms of reactive arthritis
“Cant see, pee, climb a tree” Urethritis, arthritis (of lower leg), conjunctivitis
Acute, asymmetrical monoarthritis, typically of lower leg.
- Warm swollen join
- Keratoderma blennorhagica
- Mouth ulcers
Investigations of Reiter’s syndrome
“Hot joint” policy - assume warm swollen joint is septic
- Joint aspiration - Culture and gram stain. Should show no organism, excludes differential (Septic arthritis).
- ESR/CRP raised
- RF/ANA negative
Sexual health review/stool test will be diagnostic of underlying cause
X ray:
- Enthesitis
- Sacroiliitis with periosteal reaction
Management of Reactive arthritis
Give antibiotics and aspirate joint
NSAID, Steroids
Methotrexate
Define psoriatic arthritis
Chronic inflammatory joint disease associated with skin psoriasis
Types of psoriatic arthritis
Asymmetrical Oligoarthritis - asymmetrical, less than 5 joints
Symmetrical polyarthritis (rheumatoid like) - symmetrical, more than 5 joints. Hands wrists, ankles DIP joints (RA has PIP involvement)
Spondyloarthritis - Spine and sacroiliac joints involved
Distal Interphalangeal Arthritis - Only affects DIPs of fingers and toes, causes dactylitis
Athrtitis mutilans - Most severe, osteolysis of bones around joints in digits, shortening of the digit. “telescopic finger”
Signs/symptoms of psoriatic arthritis
- Joint warmth, tenderness, reduced range of motion.
- Typically affects DIP, as opposed to MCP/PIP in rheumatoid arthritis
- Joint pain/stiffness
- Psoriasis: Psoriatic lesions, scalp/nail symptoms (another card)
- Telescopic finger in arthritis mutilans
Skin signs usually present before arthritis
Signs/symptoms of psoriasis
- Dry flaky scaly skin lesions
- Auspitz sign (small bleeds on scratching)
- Koebner phenomenon (psoriatic lesions to areas of trauma)
Nail signs
- Nail pitting
- Nail thickening
- Discolouration
- Ridging
- Onycholysis (Separation of nail from bed)
Investigations in psoriatic arthritis
Bloods - Negative for RF and anti CCP
X ray
- Periostitis
- Pencil in cup appearance
- Ankylosis
- Dactylitis
- Osteolysis
What criteria can be used to diagnose psoriatic arthritis
CASPAR - 2+ can be enough to diagnose PA
History of psoriasis +2 (rest are +1)
Rheumatoid factor negative
Psoriatic nail changes
History of dactylitis
Juxta-articular periostitis/Radiological evidence
What screening tool is used in psoriatic arthritis and when is it used
PEST (Psoriasis Epidemiological Screening Tool) used to screen for psoriatic arthritis in psoriasis patients
- Joint pain
- Swelling
- Arthritis
- Nail pitting
Management of psoriatic arthritis
First line: NSAIDs and physiotherapy
DMARD
Ustekinumab (treats psoriasis!)
Emollients/topical steroids
Complications of psoriatic arthritis
CVD (Increased risk)
Aortitis
Amyloidosis
Conjunctivitis
Uveitis
Patient with reactive arthritis gets dermatitis at head of penis what is this called?
Circinate balanitis
Define Enteropathic arthritis
Arthritis in patients with IBD symptoms/Coeliacs
E.g. patient presents with IBD symptoms, rash and joint pain could indicate enteropathic arthritis
Investigations and treatment of Enteropathic arthritis
Arthrocentesis
Stool culture and blood (FIT)
Colonoscopy
Treated with DMARD
Define SLE with epidemiology
Systemic Lupus Erythematous
Type 3 hypersensitivity reaction (antigen-antibody complex deposition), causing systemic autoimmune inflammation
Typically affects females in reproductive years (high oestrogen), Afro-Caribbeans and Asians.
Risk factors and environmental triggers of SLE
- 15-45 year old woman
- Afro-Caribbean descent
- Family history
- HLA association
Environmental triggers
- UV light
- Smoking
- Oestrogen
- EBV
- Drugs such as isonazid, hydralazine
Pathophysiology of SLE
Trigger such as UV light causes cell death, creating apoptotic bodies with exposed DNA. Due to genetic factors, immune system recognises these as foreign, creating antibodies against them (anti-dsDNA). Anti-Nuclear Antibodies (ANA) also produced. These antibodies bind to their antigens, forming antigen-antibody complexes which deposit around the body. Cause inflammation through compliment system on site of deposition.
Patients can also get antibodies targeting RBCs, WBCs. These kill these cells. This is a type 2 hypersensitivity reaction
What are the 4 types of hypersensitivity reaction
Type 1 - IgE antibodies, initially sensitise person to allergen before providing a quick inflammatory response on next exposure (Allergy/anaphylaxis)
Type 2 - IgG IgM antibodies bind to cell surface inducing a cascade of events leading to cell death
Type 3 - Antigen-antibody complexes are formed that deposit around body. Immunity against these causes inflammation, damaging underlying tissue. (SLE, RA)
Type 4 - T cell mediated. Delayed reactions to antigens. (chronic asthma, contact dermatitis)
What is the classic presentation of SLE
- Malar “butterfly” rash (across cheeks but not nose)
- Fatigue
- Fever,
- Widespread
- Musculoskeletal pain
- Lymphadenopathy and splenomegaly
In a middle aged, African female.
Disease follows relapsing-remitting course
Systemic effects of SLE
Skin
Pulmonary
GI
Kidney
+ random ones
(Probs dont need to know all of these but good to go over them every now and then)
Skin: Malar rash, Discoid Rash, Photosensitivity, Raynaud’s phenomenon
Pulmonary/CV: pleurisy, interstitial lung disease, pericarditis, heart block.
GI: lupus peritonitis, mesenteric artery occlusion
Kidney: Nephritis
AHA (Type 2 reaction!)
Pancytopenia
Antiphospholipid syndrome
Mouth ulcers
Sjogrens syndrome!
Investigations in SLE
FBC - Anaemia (potential pancytopenia)
ESR raised but CRP usually normal
C3/C4 low as has been used up in complex formation
Urinalysis - Proteinuria + haematuria (Nephritis)
X ray for athralgia, CXR for resp symptoms
Antibodies
- ANA - Sensitive
- Anti dsDNA - Specific
- Anti Smith (targets ribonucleoproteins) - Very specific
- Anti-histone- if drug induced
Anti-Ro, Anti-La - Sjogrens
Antibodies in SLE
ANA - Sensitive
Anti-dsDNA - Specific
Anti-Smith - most specific but low sensitivity
Anti histone - Drug induced
Anti-Ro, Anti-La - Sjogrens
Treatment of SLE
Acute therapy then maintenance
Acute
Mild - Prednisolone + hydroxychloroquine + NSAID
Moderate/severe - Prednisolone + Hydroxychloroquine + immunosuppressant (methotrexate, azathioprine)
Maintenance:
- Reduce flare up dose
- Then switch exclusively to hydroxychloroquine
Sjogren’s syndrome definition
Autoimmune condition affecting exocrine glands, leads to dry mucous membranes (dry eyes, mouth, vagina)
Can be primary or secondary to rheumatoid arthritis or SLE
HLA-B8 / HLA-DR3 association
Symptoms of Sjogrens
Dry mucous membranes
Dry eyes (keratoconjunctivitis)
Dry mouth (Xerosomia)
Dry vagina
Dry skin
Tests and examination for Sjogrens
Antibodies - Anti Ro, Anti La
Schirmer test - strip of filter paper left under eyelid for 6 mins, moisture distance measured. Tears should travel 15mm in healthy young adult, less than 10 significant.
Management of Sjogrens
Pilocarpine - increases exocrine secretion
Hydroxychloroquine
Artificial tears saliva and lubricant
Define vasculitis
Group of autoimmune conditions that cause inflammation of the blood vessel walls. Can be primary (autoimmune) or secondary to SLE, RA, hepatitis, HIV, polymyositis. Affect small, medium and large vessels.
Types of vasculitis
Large vessels:
- Giant cell arteritis ☆
- Takayasu’s arteritis
Medium vessels:
- Polyarteritis nodosa ☆
- Kawasaki disease
Small vessels (capillaries/arterioles)
ANCA +ve
- Wegener’s granulomatosis (granulomatosis with polyangiitis) ☆
- Eosinophilic granulomatosis with polyangiitis
- Microscopic polyangiitis
ANCA -ve
- Henoch-Schonlein purpura
(the ones with stars are covered in more detail)
Define Giant cell arteritis
Temporal arteritis, affects branches of the carotid artery. Most common vasculitis. Often associated with polymyalgia rheumatica.
Pathophysiology of GCA
Granulomatous vasculitis of large/medium arteries. Arteries become inflamed, intima is thickened and vascular lumen is narrowed. Usually cerebral (temporal) arteries affected:
- Superficial temporal artery: Headache/scalp tenderness
- Mandibular artery: jaw claudication
- Ophthalmic artery: visual loss (retinal ischaemia)
Signs/symptoms of GCA
- Severe unilateral headache around temple/forehead
- Diminished/absent temporal artery pulse
- Reduced visual acuity
- Optic disc pallor
- Scalp tenderness (painful to comb)
- Jaw claudication
- Blurred/double vision
Fever, muscle aches, weight loss, loss of appetite
Complete loss of sight is an emergency
GCA typical presentation
50+ white female with unilateral temple headache, scalp tenderness (painful to comb), jaw claudication and vision changes.
Investigations in GCA
ESR/CRP high
Normocytic anaemia
Duplex ultrasound
- Halo sign of temporal artery
Temporal artery biopsy GOLD
- Presence of granuloma (multinucleated giant cells)
- Intimal thickening and narrowed lumen
- Large biopsy should be taken as lesions are skip lesions.
Diagnostic criteria in GCA
3 of:
- Over 50
- New headache
- Temporal artery tenderness/diminished pulse
- ESR Raised
- Abnormal temporal artery biopsy
Management and possible complications of GCA
High dose prednisolone
- Sight loss (amaurosis fugax!)
Should be dealt with ASAP or could lead to permanent blindness - Ischaemic cranial complications (Visual loss/stroke)
- Aortic aneurysm
In cases where long term steroids are given, what 2 systems should be protected and how is this done?
GI (stomach and oesophagus) and Bones
- PPI (omeprazole)
- Alendronate (bisphosphonate)
- Ca2+ and vitamin D
Rules in patients taking steroids
DONT STOP
Dont - Stop taking abruptly; due to adrenal crisis risk
S - Sick day rules (Take extra when unwell - prevent adrenal crisis)
T - Treatment card given to patient (if dose above 100mcg a day)
O - Osteoporosis and oesophagitis prevention with PPI Calcium and vit D
P - PPI for gastric protection
Define polymyalgia rheumatica
Condition that causes pain stiffness and inflammation in neck, shoulders and hips. Limits range of motion. Occurs alongside GCA often.
Morning pain/stiffness in shoulders etc. Leads to fatigue, fever, weight loss, anorexia and depression
Managed with prednisolone
Define Takayasu’s arteritis
The other large vessel vasculitis.
- Affects branch points of aortic arch, leads to weak or no pulse. If it affects branches serving head, can cause visual and neurological symptoms.
- Asian women under 40
- Weak/absent pulse and arm claudication + systemic symptoms
Give the types of medium vessel vasculitis
- Polyarteritis Nodosa (Hep B associated, affects skin, GI tract, kidney, heart supplying vessels)
- Kawasaki disease (Affects coronary arteries, usually boys under 5 with Japanese descent)
Define polyarteritis nodosa
Hep B associated inflammation of several arteries as a result of body confusing hep B infection and fighting vessels as a result. Typically affects skin, GI tract, kidneys, heart.
- Causes range of symptoms including skin ulcers, renal failure (haematuria, HTN, proteinuria), neurological symptoms.
- Renal angiogram: String of beads pattern
- Biopsy: Transmural fibrinoid necrosis and inflammation.
Define Kawasaki disease
Coronary artery medium vessel vasculitis affecting japanese boys under 5.
CRASH
- Conjunctivitis
- Rash (which peels)
- Adenopathy (lymph nodes enlargened)
- Strawberry tongue
- Hands and feet (swollen and rashy)
Treated with IV immunoglobulins and aspirin
Define Wegners granulomatosis
AKA Granulomatosis with polyangiitis
Necrotising granulomatous inflammation of many small and medium sized vessels at once.
Affects ears, nose, kidneys, sinuses, lungs
Pathophysiology of Granulomatosis with polyangiitis
B cells release cANCA (Cytoplasmic Anti-Neutrophilic Cystoplasmic antibodies) which target the granules of the hosts own neutrophils. Causes them to release free radicals.
Affects nasopharynx, lungs and kidneys
Signs and symptoms of Granulomatosis with polyangiitis
Nasopharynx
- Chronic pain from sinusitis
- Nose bleeding (epsitaxis)
- Saddle shaped nose
Lungs
- SOB, cough, wheeze
- Bloody cough
Kidneys
- Proteinuria
- Haematuria
- HTN
Investigations in Granulomatosis with polyangiitis
cANCA positive
ESR CRP raised
Urinalysis to look for proteinuria and haematuria
CXR may show fluffy infiltrates of pulmonary haemorrhage and nodules.
Renal biopsy will show granulomatous inflammation on vessel walls
Management of Granulomatosis with polyangiitis
Steroids and cyclophosphamide (immunosuppressant)
Methotrexate for maintenance
Complications of Granulomatosis with polyangiitis
Glomerulonephritis!
Relapse as cANCA still present
Pulmonary fibrosis
Main differentials of Granulomatosis with polyangiitis
Eosinophilic Granulomatosis with Polyangiitis (Churg-Strauss Syndrome)
- High eosinophils on FBC
- Presents as severe asthma, doesnt affect kidneys
- p-ANCA present
- Treated with ICS
Microscopic polyangiitis
- Doesnt affect nose, only lungs and kidney
- No granuloma, pANCA present
Define Henoch-Schonlein purpura
Small vessel vasculitis in kids under 10.
No ANCA involvement
Purpuric rash on buttocks and thighs as well as joint pain, haematuria, abdominal pain.
Treated supportively
Normal pain conduction
Pinprick will cause nociceptors to generate electrical signal. This goes to dorsal root ganglion, which releases substance P. This binds to 2nd order neuron.
Inhibitory neurons in dorsal horn dampen pain response by releasing serotonin and Nad.
If nociceptor signal greater than inhibition, AP fired
Mast cells release NGF which boosts growth of nociceptors, more pain.
Define fibromyalgia
Syndrome characterised by widespread pain, sleep disturbances, fatigue and depression. (Essentially MSK equivalent of IBS)
Pathophysiology of fibromyalgia
Hypersensitivity to pain, due to excess substance P and NGF or low serotonin.
More common in females 20-60 years, with low socioeconomic status. Associated with RA, SLE etc.
Key presentation of fibromyalgia
Woman with chronic (>3 months) severe pain all over, cant sleep, depressed and stressed.
Pain aggravated by stress, cold, activity
Investigations in fibromyalgia
All tests normal, done to exclude
TFT (hypothyroid), ANA/dsDNA (SLE), ESR/CRP (Inflammation), Vit D (Deficiency), RF and anti-CCP (exclude RA)
Diagnostic criteria of fibromyalgia
Chronic pain >3 months
Widespread pain all over (left and right sides, above and below waist)
On digital palpation of tender points, mild pain in at least 7 areas, and severe in at least 5
Management of fibromyalgia
Regular exercise, physiotherapy, CBT
Amitriptyline (increase serotonin levels)
Define antiphospholipid syndrome
Disease of excess clotting associated with antiphospholipid antibodies (lupus anticoagulant, anticardiolipin antibody and anti-beta2-glycoprotein 1), as well as excess thromboses and miscarriage
Can occur on its own or secondary to autoimmune conditions such as SLE
What do antiphospholipid antibodies cause
CLOT
Coagulopathy
Livedo reticularis (purple discolouration of skin)
Obstetric issues (recurrent miscarriages etc)
Thrombocytopenia (low platelet)
Antibodies involved in antiphospholipid syndrome
Lupus anticoagulant antibodies
Anti-cardiolipin antibodies
Anti-beta-2 glycoprotein 1 antibodies
Signs of antiphospholipid syndrome
Thrombosis
Miscarriage
Purple skin (livedo-reticularis)
Thrombocytopenia
(Ischaemic stroke TIA MI (Arteries)
DVT, PAD, Budd-Chiari syndrome (Veins))
Management of Antiphospholipid syndrome
Warfarin to minimise thrombosis (CI if pregnant)
If pregnant, LMWH and Aspirin
Define polymyositis (and Dermatomyositis)
Autoimmune inflammation and necrosis of skeletal muscle. Where skin is involved this becomes dermatomyositis
HLA B8
HLA DR3
Signs and symptoms of polymyositis and dermatomyositis
Bilateral muscle pain, fatigue and wasting
Proximal muscles (shoulders/hips) most affected
(Difficulty squatting or raising hands above head)
Skin:
- Gottron Lesions - Scaly, red patches on backs of fingers elbows and knees. PHOTOSENSITIVE, itchy, painful, bleeds.
- Heliotrope rash
- Periorbital oedema
- Subcutaneous calcinosis
Investigations in polymyositis and dermatomyositis
Antibodies:
- Anti-Jo-1: Polymyositis
- Anti-Mi-2: Dermatomyositis
Creatinine Kinase (enzyme found in muscle cells) - Raised
(aldolase and LDH also raised)
Muscle biopsy GOLD: Inflammatory cell infiltrates
Other causes of raised creatinine kinase
Rhabdomyolysis
AKI
MI
Statin use
Strenuous exercise
Management of polymyositis and dermatomyositis
Corticosteroid (prednisolone)
Hydroxychloroquine if skin rashes
Immunosuppressants if other treatment doesnt work
Define scleroderma
Multisystem, autoimmune disease characterised by fibrosis of skin and visceral organs
- Sclerqoderma - hardening of skin
- Systemic sclerosis - when it affects rest of body and visceral organs as well
CREST used for symptoms
Both types of scleroderma
Limited Cutaneous Systemic Sclerosis (Most common) - CREST features and Raynaud’s Phenomenon early
Diffuse Cutaneous Systemic Sclerosis - CREST and other internal organs
Signs/symptoms of scleroderma
CREST
- Calcinosis (deposits in skin, esp hands) - Renal Failure!!
- Raynaud’s (fingers go white then blue in response to mild cold, due to vasoconstriction)
- oEsophageal dysmotility - Dysphagia, acid reflux, oesophagitis
- Sclerodactyly and scleroderma (skin tightening and hardening, restricts motion and causes fingers to be clawed)
- Telangiectasia - Dilated small blood vessels with thin, thready appearance.
Beaked nose, small mouth, pulmonary HTN, fibrosis and heart failure possible
Investigations in scleroderma
FBC - Anaemia, high Urea/Creatinine due to AKI
Autoantibodies
- Anti-centromere: Limited (MC)
- Anti-SCL 70: Diffuse
- ANA (positive but non specific)
X Ray - Calcinosis
Barium swallow - Impaired oesophageal motility
CT chest to check for fibrotic lung
Management of scleroderma
No cure, can just help symptoms
Raynauds - Hand warmers, CCB (to allow vasodilation)
Immunosuppression
PPI for oesophagus
ACEi to prevent renal crisis
Analgesia
Complications of scleroderma
- Skin ulcers
- Hypothyroid
- Osteomyelitis
- Malabsorption
- Digital amputation
What cancers metastasise to bone
BLKTP
Breast
Lung
Kidney
Thyroid
Prostate
BL - Osteolytic
KTP - Osteosclerotic
Name 4 primary bone tumours
Osteosarcoma - Bone cancer, associated with Pagets!
Ewing sarcoma - Mesenchymal stem cell
Fibrosarcoma
Chondrosarcoma - Cartilage cancer
(Primary less common, more common are secondary)
General local and systemic signs and symptoms of bone cancer
Local
- Severe, deep pain worst at night
- Fractures
- Decreased range of motion of long bones/vertebrae
Systemic
- Weight loss
- Fatigue
- Fever
- Malaise
Investigations in bone cancer
Skeletal isotope scan
X ray - Osteolysis, metastasis etc
Increased ALP alone!
Hypercalcaemia
How does bone remodelling work
Osteoblasts release RANKL which binds to osteoclasts and activates them
Osteoclasts resorb bone by secreting lysosomal enzymes e.g. collagenase and HCl, digesting collagen and dissolving minerals in bone matrix
Osteoblasts secrete osteoprotegerin which stops activity of osteoclasts by binding to RANKL
Osteoblasts release osteoid seam which builds scaffold upon which calcium and phosphate can get deposited on, forming new bone
Define Paget’s disease
Chronic increased bone remodelling, resulting in overgrowth of poorly organised bone.
Also known as Osteitis deformans
Associated with Osteosarcoma!
Pathophysiology of Pagets
Phase 1 - lytic phase
- Osteoclasts with up to 100 nuclei aggressively demineralise bone
Phase 2 - Mixed (lytic and blastic)
- Blastic - rapid, disorganised proliferation of new bone tissue by large number of osteoblasts
Phase 3 - Sclerotic phase
- New bone formation exceeds bone resorption. Bone disorganised and weak.
Signs/symptoms of pagets
Bone pain
Growth signs in skull
- Leontiasis
- Hearing loss/ deafness (bone narrows auditory foramen, impinge on auditor nerve)
- Vision loss
Kyphosis (spine curve)
Bowlegs (if tibia affected)
Bone enlargement
Investigations in Pagets
LFT and bone profile
- ALP raised, others normal
- Calcium and phosphate normal
X ray
- Bone enlargement and deformity
- Osteoporosis circumscripta (lytic lesions in lytic phase)
- Cotton wool appearance of skull
- V shaped defects of long bones
- Thickened bone cortices
Management of Pagets
NSAIDs, bisphosphonates, surgery to decompress nerve impingement, correct bone deformities
Complications of pagets
Pagets sarcoma (osteosarcoma)
Spinal stenosis/spinal cord decompression
Fractures
Vision loss
Hearing loss
Arthritis
Cardiac failure
Define Marfans
Autosomal dominant FB1 (fibrillin 1 protein) (chromosome 15) mutation causing defective connective tissue.
Causes fewer microfibrils, so less integrity and elasticity. TGF beta signalling excessive so excess growth in bones
Signs/symptoms of Marfans
Tall stature, long arms, long legs
Long fingers
Scoliosis
Flexible joints
Stretch marks
Investigations of Marfans
Diagnose based on features
- Lens dislocation
- Aortic dissection/dilation
- Dural ectasia
- Long arms, fingers etc
- Scoliosis
- Flat feet
Complications of Marfans
- Retinal detachment
- Joint dislocations and pain
- Bulla formation on lungs causing pneumothorax
CVD effects
- Aortic dilation
- Aortic dissection, aneurysm, rupture
- Mitral valve prolapse
- Aortic valve prolapse
Define Ehlers Danlos syndrome with joint and skin effects
Group of 13 connective tissue disorders caused by mutations of connective tissue proteins, with collagen most affected.
Causes joint hypermobility, pain, dislocation and scoliosis.
Causes Hyper elasticity, Easy bruising, Atrophic skin
Complications of Ehlers Danlos
Subarachnoid haemorrhage
Abdominal hernia
GORD
Degenerative arthritis
CVD
- Mitral valve prolapse
- Aortic dissection
- AAA
- Organ rupture
Causes of mechanical back pain
- Strain
- Heavy manual handling
- Pregnancy
- Trauma
- Lumbar disc prolapse
- Osteoarthritis
- Spondylolisthesis (vertebral disc slip)
- Lumbar disc prolapse
- Fracture
Syndromes causing mechanical back pain
Lumbar spondylosis
Facet joint syndrome
Fibrositic nodulosis
Postural back pain/”swayback” of pregnancy
Symptoms caused by mechanical back pain
Stiff back
Scoliosis
Muscular spasm
Pain worse in evening, worse with exertion
Relieved by stress and morning stiffness absent
Sudden onset
Usually self limiting
What artery causes erectile dysfunction
Interior Pudendal Artery
Define cellulitis
Bacterial infection of the dermal and sub-cutaneous tissues. Infection enters through break in skin and can occur anywhere but usually affects legs.
Usually caused by:
- Staph aureus
- Beta-haemolytic streptococcus (pyogenes, agalacticae)
Risk factors for cellulitis
History of cellulitis
Cutaneous tissue break (ulcer, wound, puncture from IV drug use)
Immunocompromise (Diabetes, HIV, leukaemia)
Venous insufficiency
Eczema
Obesity
Pregnancy
Where does cellulitis normally affect and spread to?
Typically affects lower leg or arm and spreads proximally. Other sites usually affected include abdomen, perianal and periorbital! areas.
Signs/symptoms of cellulitis
Red hot painful area, typically shin
Macular erythema with indistinct borders
Shiny skin
Oedema
Investigations of Cellulitis
Swab and gram stain to identify bacteria
Diagnosis is clinical
Classification of Cellulitis
Eron’s classification used.
1 - no systemic toxicity
2 - Systemically unwell or comorbidity that may delay resolution (e.g. PAD)
3 - Significant systemic upset (confusion, tachycardia, hypotension)
4 - Sepsis or severe infection (e.g. necrotising fasciitis)
Management of Cellulitis
Flucloxacillin first line
Co amoxiclav if periorbital or severe
What are factors for hospital admission/IV antibiotics in cases of cellulitis?
- Eron 3 or 4
- Severely deteriorating cellulitis
- Under 1 or frail
- Immunocompromise
- Facial cellulitis including periorbital
- Lymphoedema
Complications of cellulitis
- Sepsis
- Necrotising fasciitis
- Lymphoedema (chronic swelling in tissues)
- Abscess formation
