MSK Flashcards
Define osteoarthritis
Degenerative joint disorder, not inflammatory. Osteoarthritis is ‘wear and tear’ of synovial joints, resulting from mechanical and biological events that destabilise the normal degradation and synthesis of cartilage.
Describe the aetiology of osteoarthritis
Arthritis
Describe the risk factors for osteoarthritis
High intensity labour, old age, obesity, occupation/sports, genetic
Describe the pathophysiology of osteoarthritis
Non-inflammatory degenerative destruction of cartilage from repeated mechanical forces. Disruption of chondrocytes prevents rebuilding. Imbalanced cartilage breakdown > repair causing increased chondrocyte metalloproteinase secretion which degrades T2 collagen and causes cysts. Bone attempts to overcome this with T1 collagen which leads to abnormal bony growths (osteophytes) and cysts
Commonly affected joints: hips, knees, fingers, thumb, cervical spine
Describe the key presentations of osteoarthritis
Transient painful joints stiff for <30 mins in morning, worse throughout day. Proximal Bouchard nodes and distal Heberden nodes on fingers.
Describe the clinical manifestations of osteoarthritis
Signs: Hard asymmetrical bulky non-inflamed joint, squaring at the base of thumb (carpometacarpal saddle joint)
Symptoms: Restricted motion, crepitus on moving (popping/clicking), no extra-articular sx
What is the gold standard investigation for osteoarthritis
x-ray: loss of joint space, osteophyte formation (bony lumps), subchondral sclerosis, subchondral cysts.
Describe the first line investigations for osteoarthritis
x-ray. FBC (normal)
What are the differential diagnosis for osteoarthritis
Bursitis, gout, pseudo-gout, rheumatoid arthritis, psoriatic arthritis
Describe the management for osteoarthritis
1st line - lifestyle (less weight-bearing, physio), topical analgesics (capsaicin, NSAIDs – diclofenac, methyl salicylate), + paracetamol, + opioid (PPI for gastric protection)
joint replacement surgery (arthroplasty)
Describe the complications of osteoarthritis
Destruction of joint, loss of joint function, NSAID related GI bleeding/renal dysfunction
Define rheumatoid arthritis
Autoimmune condition causing inflammation of the synovial lining of joints, tendon sheaths and bursa. Inflammatory symmetrical polyarthritis
Describe the epidemiology of rheumatoid arthritis
Women 30-50 (3x more likely than men premenopausal)
Describe the aetiology of rheumatoid arthritis
Autoimmune, genetic (HLA DR4/DR1)
Describe the risk factors for rheumatoid arthritis
Young, female, FHx, other autoimmune conditions
Describe the pathophysiology of rheumatoid arthritis
Autoimmune destruction of the synovium. Inflammation causes damage to tendons, bone cartilage and ligaments.
Rheumatoid factor is an autoantibody which targets IgG antibodies causing activation of the immune system against IgG causing systemic inflammation.
Cyclic citrullinated peptide antibodies (anti-CCP) are autoantibodies which target healthy joint tissues.
Describe the key presentations of rheumatoid arthritis
Joint pain worse in morning (>30mins) gets better as day goes on. Symmetrical distal Polyarthropathy, hot inflamed joints, most common in wrist/hand + feet, knee, hip.
Describe the clinical manifestations of rheumatoid arthritis
Signs: Swan neck thumb, ulnar deviation, boutonniere deformity, Z shaped thumb deformity. DIP joint often spared. Extra-articular complications
Symptoms: Painful, swollen, stiff joints for more than 1hour in the morning, get better as the day goes on and with movement. Fatigue, weight loss, malaise, aches and cramps
What is the gold standard investigation for rheumatoid arthritis
Clinical diagnosis, serology, inflammatory markers
Describe the first line investigations for rheumatoid arthritis
Serology: anti CCP positive, rheumatoid factor positive
Bloods: anaemia, CRP/ESR raised
x-ray: less lost joint space, erosion, soft tissue swelling, soft bones
What are the differential diagnosis for rheumatoid arthritis
Osteoarthritis, psoriatic arthritis, gout, pseudo-gout
Describe the management for rheumatoid arthritis
1st line – DMARDs (disease modifying anti-rheumatic drugs) e.g., methotrexate, leflunomide, sulfasalazine
2nd – Add biological agent (infliximab, adalimumab, etanercept, rituximab)
3rd – corticosteroid (prednisolone), NSAIDs (ibuprofen)
Pregnant: prednisolone, sulfasalazine, hydroxychloroquine
Describe the complications for rheumatoid arthritis
Cervical spine cord compression (weakness and loss of sensation), lung involvement (interstitial lung disease, fibrosis), ischemic heart disease, vision problems, CKD. Work disability
Define Gout
Type of crystal arthropathy associated with high blood uric acid levels. Sodium urate crystals are deposited in joint causing it to become hot, swollen, and painful. Acute bouts of inflammatory arthritis
Describe the epidemiology of gout
Middle aged overweight males
Describe the aetiology of gout
Uric acid overproduction or excretion
Describe the risk factors for gout
High purine diet (meat, seafood, beer) increased cell turnover, CKD, diuretics
Describe the pathophysiology of gout
Purines oxidised to uric acid by xanthine oxidase. Uric acid is excreted by kidneys or converted to monosodium urate. Increased uric acid or CKD causing impaired excretion leads to more monosodium urate which forms crystals in joints.
Describe the key presentations of gout
Monoarticular (often big toe/DIPs/wrist/thumb) acute hot swollen painful joint
Describe the clinical manifestations of gout
Signs: Tophi – subcutaneous deposits of uric acid affecting small joints and connective tissue in DIPs, elbow, ears
Symptoms: Acute hot swollen painful inflamed joints.
What is the gold standard investigation for gout
Joint aspiration and polarised light microscopy (needle-like crystals, negative birefringent of polarised light, monosodium urate crystals)
Describe the first line investigations for gout
Joint aspiration, Increased serum uric acid
Other: Joint x-ray: maintained joint space, lytic lesions, punched out erosions with sclerotic borders or overhanging edges
What are the differential diagnosis for gout
Septic arthritis, pseudogout, trauma, rheumatoid arthritis, psoriatic arthritis
Describe the management for gout
Lifestyle changes (decreased purines, more diary – antigout)
Acute flare: NSAIDs, Colchicine, corticosteroids
Prevention: allopurinol (xanthine oxidase inhibitor > reduces uric acid)
Describe the complications for gout
Infection in tophi, joint destruction, nephrolithiasis, CKD
Define pseudogout
Type of crystal arthropathy caused by calcium pyrophosphate crystals deposited in joints.
Describe the epidemiology of pseudogout
Females over 70
Describe the aetiology of pseudogout
Calcium pyrophosphate crystals
Describe the risk factors for pseudogout
Females over 70, hyperthyroidism, hyperparathyroidism, excess iron or calcium, diabetes, metabolic diseases
Describe the pathophysiology of pseudogout
Damage to joint causes pathological formation of calcium pyrophosphate crystals.
Describe the key presentations for pseudogout
Often polyarticular with knee commonly involved. Hot swollen painful red joint. Other joints commonly affected: shoulder, wrist, hips
Describe the clinical manifestations for pseudogout
Signs: Recent injury to the joint in the history
Symptoms: Hot swollen tender joint, usually knees. Fever and malaise
What is the gold standard investigation for pseudogout
Joint aspiration and polarised light microscopy (rhomboid shaped crystals, positive birefringent of polarised light, calcium pyrophosphate crystals)
What are the differential diagnosis for pseudogout
Septic arthritis, osteoarthritis, gout, rheumatoid arthritis, psoriatic arthritis
Describe the management for pseudogout
1st line – NSAIDs, colchicine, corticosteroids/intra-articular steroid injection
What are the complications with pseudogout
Loss of joint function
Define osteoporosis
Reduction in the density of bones (by 2.5 standard deviations). Osteopenia is a less severe reduction in bone density.
Describe the epidemiology of osteoporosis
50+ postmenopausal Caucasian women
Describe the aetiology of osteoporosis
SHATTERED: steroids, hyper(para)thyroidism, alcohol, thin (low BMI), testosterone (low), early menopause, renal/liver failure, erosive/inflammatory bone disease, dietary low calcium
Describe the key presentations for osteoporosis
Fractures (proximal femur, colles wrist fracture, compression vertebral crush - kyphosis)
What is the gold standard investigation for osteoporosis
DEXA bone scan – dual energy x-ray absorptiometry yields T score (normal = T > -1, osteopenia = -2.5 < T < -1, osteoporosis = T < -2.5)
What are the differential diagnosis for osteoporosis
Osteomalacia, multiple myeloma, CKD bone-mineral disorder
Describe the first line investigations for osteoporosis
1st line: Bone mineral density with DEXA bone scan (normal = T > -1, osteopenia = -2.5 < T < -1, osteoporosis = T < -2.5) FRAX score (10-year probability of major osteoporotic fracture or hip fracture), Calcium, phosphate, ALP normal
Describe the management for osteoporosis
Lifestyle – exercise, weight, low alcohol and smoking. Vitamin D and calcium supplementation.
1st line –Bisphosphonates (reduce osteoclast activity), e.g., alendronate, risendronate, zoledronic acid.
2nd line – denosumab (monoclonal antibody which binds to RANK-ligand and blocks osteoclast)
Hormone replacement therapy, raloxifene (stimulates oestrogen bone receptor)
Describe the complications for osteoporosis
Fractures (hip, ribs, wrist), chronic pain
Define ankylosing spondylitis
Inflammatory condition mainly affecting sacroiliac joints and vertebral column and causing progressive stiffness and pain.
Spondyloarthropathies: chronic inflammatory disease that affect sacroiliac joints and axial skeleton. Seronegative (Rheumatoid Factor -ve) and associated with HLA B27.
SPINEACHE: sausage digits (dactylitis), psoriasis, inflammatory back pain, NSAIDs > good response, enthesitis (tendon/ligament insertion), arthritis, Crohn’s/colitis/CRP raised, HLA B27, eye (uveitis)
Describe the epidemiology of ankylosing spondylitis
Males 3x more common, young male/late teens, HLA B27 gene
Describe the aetiology of ankylosing spondylitis
HLA B27 gene
Describe the pathophysiology of ankylosing spondylitis
Inflammatory arthritis of spine and rib cage leads to formation of new bone and fusion of joints. Syndesmophytes replace spinal bone damaged by inflammation and make the spine less mobile
Describe the key presentations of ankylosing spondylitis
Progressively worse lower back pain and stiffness, worse with rest and improves with movement. Worse at morning and night. Sacroiliac pain. Flares of worsening symptoms.
Describe the clinical manifestations of ankylosing spondylitis
Signs: Anterior uveitis, dactylitis, enthesitis, lumbar pathology: decreased lumbar lordosis > more kyphosis, Schober test shows decreased lumbar flexion <20cm
Symptoms: Chronic pain, weight loss, fatigue, dyspnoea, sleep disturbance
What is the gold standard investigation for ankylosing spondylitis
X-ray of spine and sacrum:
* Bamboo spine (fusion of vertebral bodies)
* Sacroiliitis
* Squaring of vertebral bodies
* Subchondral sclerosis and erosions
* Syndesmophytes (bony outgrowths in spinal ligament)
* Ossification of ligaments, discs and joints
* Fusion of facet, sacroiliac and costovertebral joints
Describe the first line investigations for ankylosing spondylitis
Pelvic x-ray, CRP and ESR raised, HLA B27 genetic test, MRI spine (bone marrow oedema in early disease before x-ray changes)
What are the differential diagnosis for ankylosing spondylitis
Reactive arthritis, psoriatic arthritis, enteric/IBD arthritis
Describe the management for ankylosing spondylitis
1st line – NSAIDs (naproxen, indomethacin, ibuprofen)
Steroids during flares, anti-TNF drugs e.g., etanercept. Monoclonal antibodies against TNF (infliximab), physiotherapy and lifestyle advice, surgery for deformities
Describe the complications for ankylosing spondylitis
Vertebral fractures, osteoporosis, cardiac involvement, iritis
Define psoriatic arthritis
Inflammatory arthritis associated with psoriasis.
Spondyloarthropathies: chronic inflammatory disease that affect sacroiliac joints and axial skeleton. Seronegative (Rheumatoid Factor -ve) and associated with HLA B27.
SPINEACHE: sausage digits (dactylitis), psoriasis, inflammatory back pain, NSAIDs > good response, enthesitis (tendon/ligament insertion), arthritis, Crohn’s/colitis/CRP raised, HLA B27, eye (uveitis)
Describe the epidemiology of psoriatic arthritis
1 in 5 patients with psoriasis have psoriatic arthritis
Describe the aetiology of psoriatic arthritis
HLA B27, psoriasis
Describe the key presentations for psoriatic arthritis
Inflammatory joint pain, plaques of psoriasis (hidden – behind ears, under nails, scalp), onycholysis (separation of nail from nail bed), dactylitis (inflammation of finger), enthesitis (tendon/ligament insertion inflammation), nail pitting
Describe the clinical manifestations for psoriatic arthritis
Signs: Anterior uveitis, conjunctivitis, aortitis, amyloidosis
Symptoms: Joint pain and stiffness, reduced mobility
What is the gold standard investigation for psoriatic arthritis
Joint X-ray:
* erosion in distal interphalangeal joint and periarticular new bone formation.
* Osteolysis.
* Pencil-in-cup deformity (central erosions of bone beside the joints causing one to look hollow like a cup, and one to sit in the cup)
* Periostitis (periosteum inflammation causing thickened, irregular outline of bone)
* Ankylosis (joints fuse causing stiffness)
* Dactylitis (finger inflammation appears as soft tissue swelling)
Describe the first line investigations for psoriatic arthritis
CRP/ESR raised, joint x-ray, rheumatoid factor -ve, anti-CCG negative, joint aspiration negative for crystals or bacteria
What are the differential diagnosis for psoriatic arthritis
Reactive arthritis, rheumatoid arthritis, gout
Describe the management for psoriatic arthritis
1st line – NSAIDs for pain (naproxen, ibuprofen, indomethacin), intra-articular corticosteroid injection if severe
DMARDs (methotrexate, sulfasalazine, leflunomide), TNF inhibitor or monoclonal Ab (etanercept, adalimumab, infliximab), last resort – ustekinumab (Mab targeting IL 12 and 23)
Describe the complications for psoriatic arthritis
Arthritis mutilans (most severe psoriatic arthritis): occurs in phalanxes, osteolysis of bones around joints in digits > leads to progressive shortening > skin then folds as digit shortens > telescopic finger
Define reactive arthritis
Sterile inflammation of synovial membranes and tendons that occurs after exposure to certain GI or GU infections. Often monoarticular synovitis affecting single joint in lower limb (mc knee). Used to be called Reiter’s syndrome.
Spondyloarthropathies: chronic inflammatory disease that affect sacroiliac joints and axial skeleton. Seronegative (Rheumatoid Factor -ve) and associated with HLA B27.
SPINEACHE: sausage digits (dactylitis), psoriasis, inflammatory back pain, NSAIDs > good response, enthesitis (tendon/ligament insertion), arthritis, Crohn’s/colitis/CRP raised, HLA B27, eye (uveitis)
Describe the aetiology of reactive arthritis
Chlamydia trachomatis (most common), N. gonorrhoea
Gastroenteritis: campylobacter jejuni, salmonella enteritidis, shigella
Describe the risk factors of reactive arthritis
HLA B27 gene, male, preceding STI
Describe the pathophysiology of reactive arthritis
Immune-mediated syndrome triggered by recent infection
Describe the key presentations for reactive arthritis
1-4 weeks after infection. Asymmetrical oligoarthritis (joint swelling and stiffness in large joint e.g., knee). Painful swollen red and stiff joints. Dactylitis.
Classic triad: conjunctivitis, urethritis/balanitis (dermatitis of head of penis), arthritis (can’t see, can’t pee, can’t climb a tree)
Describe the clinical manifestations for reactive arthritis
Circinate balanitis (head of penis dermatitis), keratoderma blennorrhagicum (brown rash on foot)
What is the gold standard investigation for reactive arthritis
No GS. Joint aspiration MC+S to rule out organism in synovial fluid. Polarised light microscopy rules out crystal arthropathy
Describe the first line investigations for reactive arthritis
ESR and CRP raised, antinuclear antibodies negative, rheumatoid factor negative, x-ray (sacroiliitis or enthesopathy), joint aspiration negative (exclude septic arthritis and gout), stool cultures, urine dipstick
What are the differential diagnosis for reactive arthritis
Septic arthritis (painful red hot swollen joint + signs/Hx of infection), gout, ankylosing spondylitis, psoriatic arthritis
Describe the management for reactive arthritis
1st line – antibiotics and joint aspiration until septic arthritis is ruled out.
NSAIDs (naproxen, ibuprofen, indometacin), intra-articular corticosteroid injection, DMARDs (sulfasalazine) or TNF inhibitors in chronic arthritis
What are the complications for reactive arthritis
Secondary osteoarthritis, iritis/uveitis, keratoderma blennorrhagicum
Define septic arthritis
Infection of 1 or more joints caused by pathogenic inoculation of microbes – via direct inoculation or haematogenous spread. Medical emergency
Describe the aetiology of septic arthritis
Staphylococci (most common), streptococci, N. Gonorrhoea, E. coli/pseudomonas (IVDU)
Describe the risk factors for septic arthritis
Pre-existing joint disease (OA/RA), IVDU, joint prosthesis, immunosuppression, alcohol misuse, diabetes, intra-articular corticosteroid injection, recent joint surgery
Describe the pathophysiology of septic arthritis
Organism spreads to the joint via blood or through direct entry to the joint. Synovium has little defence against infection. Inflammation of the joint increases pressure and reduces blood flow within the joint, damaging the joint.
Describe the key presentations for septic arthritis
Acutely hot, swollen, painful, restricted joint. Onset < 2 weeks. Fever. Knee most common joint. Stiffness and reduced range of motion
Describe the clinical manifestations for septic arthritis
Fever, lethargy, sepsis (tachycardia, hypotension, cold, clammy, shaking)
What is the gold standard investigation for septic arthritis
Joint aspiration MC+S (ID organism)
What are the differential diagnosis for septic arthritis
Reactive arthritis (sterile, crystal free joint), gout (sterile, -ve birefringent needle crystals), pseudogout (+ve birefringent rhomboid crystals)
Describe the management for septic arthritis
Aspirate joint (drainage) then empirical antibiotic.
Pathogen-directed Abx e.g., flucloxacillin (gram -ve; E.coli/pseudomonas), vancomycin (MRSA, s. aureus), IM ceftriaxone + azithromycin (N. gonorrhoea).
NSAIDs for analgesia. If on steroids, double dose while infected
Describe the complications for septic arthritis
Osteomyelitis, joint destruction
Define systemic lupus erythmatosus
SLE is an inflammatory autoimmune connective tissue disorder, affecting multiple organs
Describe the epidemiology of SLE
Young Afro-Caribbean women
Describe the risk factors for SLE
Female, drugs (isoniazid), HLA link
Describe the pathophysiology for SLE
Anti-nuclear antibodies are antibodies which attack proteins in the person’s cell nucleus. This generates an inflammatory response and damage.
Describe the key presentations for SLE
Photosensitive red malar butterfly rash, glomerulonephritis (nephritic), arthralgia, fatigue, fever, hair loss, mouth ulcers, lymphadenopathy
Describe the clinical manifestations for SLE
Signs: Butterfly rash, ulnar deviation, mouth ulcers, anaemia, Raynaud’s, lymphadenopathy and splenomegaly, pleuritic chest pain, hair loss, seizures and psychosis
Symptoms: Weight loss, fever, fever, joint pain, myalgia, shortness of breath
What is the gold standard investigation for SLE
Antinuclear antibodies (ANA)and clinical diagnosis
Describe the first line investigations for SLE
FBC (anaemia, leukopenia, thrombocytopenia), Normal CRP, raised ESR, raised urea and creatinine, urine protein:creatinine (proteinuria)
urine dipstick (haematuria, proteinuria)
anti-nuclear (ANA) and anti-double-stranded DNA (aDsDNA) antibodies present
Other: Renal USS (for nephritis)
What are the differential diagnosis for SLE
Rheumatoid arthritis, antiphospholipid syndrome, HIV, glomerulonephritis
Describe the management for SLE
1st line – Hydroxychloroquine (anti-malarials)
Consider: NSAIDs, corticosteroid, immunosuppressant (methotrexate), biologics (rituximab)
What are the complications for SLE
Cardiovascular disease, infection, pericarditis, pleuritis, interstitial lung disease, anaemia
Define primary bone tumours
Sarcomas are cancers originating in muscle, bone, and other connective tissues. The main bone cancers are: osteosarcoma, chondrosarcoma, Ewing sarcoma
Describe the epidemiology of primary bone tumours
Osteosarcoma most common primary tumour (10-20yo), commonly long bones
Describe the aetiology of primary bone tumours
Mutation. Primary – osteosarcoma, chondrosarcoma (cartilage), Ewing sarcoma (bone and soft tissue), fibrosarcoma
Secondary (most common) – prostate, thyroid, lung, breast, kidney
Describe the risk factors for primary bone tumours
Previous radiotherapy, previous cancer, Paget’s disease, benign bone lesions
Describe the pathophysiology of primary bone tumours
Tumours which metastasise to bone: PROSTATE, THYROID, LUNG, BREAST, KIDNEY
KPBLT
Describe the key presentations for primary bone tumours
Bone pain: worse at night, constant or intermittent, resistant to analgesia, may increase in intensity.
Atypical bony or soft tissue swelling/masses, pathological fractures, mobility issues (unexplained limp, joint stiffness, reduced motion), inflammation and tenderness over bone
Describe the clinical manifestations for primary bone tumours
Cancer symptoms: weight loss, fever, fatigue, easy bruising, malaise
What is the gold standard investigation for primary bone tumours
Bone biopsy
Describe the first line investigations for primary bone tumours
1st line X-ray (osteosarcoma – sunburst appearance), bloods – FBC, raised ESR, ALP, lactate dehydrogenase, Ca, U&E.
Other: CT chest/abdomen/pelvis
What are the differential diagnosis for primary bone tumours
Secondary bone tumours
Describe the management for primary bone tumours
1st line – chemo, radiotherapy, surgery (limb sparing or amputation). Bisphosphonates
Define fibromyalgia
Chronic pain syndrome characterised by widespread pain in body for 3+ months in addition to tenderness in 11 of 18 designated sites.
Describe the risk factors for fibromyalgia
Women, low socioeconomic status, 20-50 yo, stress, depressed
Describe the pathophysiology of fibromyalgia
Abnormal pain processing and signalling
Describe the key presentations for fibromyalgia
Widespread chronic body pain and tenderness, insomnia, morning stiffness (back and neck)
Describe the clinical manifestations for fibromyalgia
Fatigue, confusion, pain, morning stiffness
Describe the first line investigations for fibromyalgia
1st line Clinical diagnosis: 11 tender points in 18 sites (9 pairs R+L).
No serology or inflammatory markers
Describe the differential diagnosis for fibromyalgia
Polymyalgia rheumatica (chronic pain syndrome, Dx = raised CRP/ESR), osteoarthritis, rheumatoid arthritis
Describe the management for fibromyalgia
1st line – tricyclic antidepressants, e.g., amitriptyline. Serotonin-noradrenaline reuptake inhibitors SNRIs, e.g., duloxetine. Gabapentinoids, e.g., pregabalin
Non-pharmacological: exercise, relaxation, CBT
Analgesia (naproxen, tramadol)
Describe the complications for fibromyalgia
Poor quality of life, anxiety, depression, insomnia, opiate addiction
Describe mechanical lower back pain and vertebral disc degeneration
Discogenic low back pain is a multi-factorial condition characterised by lower back pain and degenerative intervertebral disc disease. Mechanical back pain means it isn’t caused by a specific disease. Lumbar spondylosis is degeneration of intervertebral disc
Describe the aetiology of mechanical lower back pain and vertebral disc degeneration
Trauma/work, muscle/ligament sprain, myeloma (elderly), spinal cord decompression (neuropathic pain), intervertebral disc degeneration (lumbar spondylosis), arthritis
Describe the pathophysiology of mechanical lower back pain and vertebral disc degeneration
Vertebral disc degeneration: loses its compliance and thins over time. Usually L5/S1 or L4/L5
Describe the key presentations for mechanical lower back pain and vertebral disc degeneration
Chronic lower back pain, movement restriction, neurological deficit (leg weakness, sensory loss, bladder and bowel symptoms)
Describe the first line investigations for mechanical lower back pain and vertebral disc degeneration
SOCRATES, clinical examination, x-ray if serious pathology suspected, e.g., myeloma, neuropathic pain. MRI
Describe the management for mechanical lower back pain and vertebral disc degeneration
Analgesia (1st line NSAIDs), education, exercise, physiotherapy
Define osteomalacia
Poor bone mineralisation leading to soft bone due to lack of Ca2+. In adults
Rickets: inadequate mineralisation of the bone and epiphyseal cartilage in the growing skeleton of children
Describe the aetiology of osteomalacia
Hyperparathyroidism – increased Ca2+ release from bone so less for mineralisation due to low Vit D
Vitamin D deficiency – malabsorption/reduced intake/poor sunlight.
CKD/renal failure – decreased active vitamin D production (25-hydroxyvit D > 1,25-dihydroxyvit D)
Liver failure – decreased reaction in vitamin D pathway (cholecalciferol > 25-hydroxyvitamin D)
Anticonvulsant drugs – increased CYP450 metabolism of vitamin D
Describe the pathophysiology of osteomalacia
Calcium deficiency due to lack of vitamin D. vitamin D increased Ca2+ absorption from gut and reabsorption from kidney PCT
7-dehydrocholesterol converted by UVB to cholecalciferol (vitamin D3). > 25-hydroxyvitamin D in the liver. > 1,25-dihydroxyvitamin D in kidneys (active vitamin D) > bone, GIT, PCT kidney
Describe the key presentations for osteomalacia
Osteomalacia: bone pain and tenderness. Dull ache, worse on weight-bearing exercises. Fractures (esp neck of femur), muscle weakness (waddling gait, difficulty with stairs)
Rickets: growth retardation, hypotonia, knock-kneed, bow-legged
Describe the clinical manifestations for osteomalacia
Fatigue, bone pain, muscle weakness and aches
What is the gold standard investigation for osteomalacia
bone biopsy (incomplete mineralisation)
Describe the first line investigations for osteomalacia
X-ray (loss of cortical bone – defective mineralisation, looser zone), U&E (low calcium and phosphate), raised PTH, low serum 25-hydroxyvitamin D (<25 nmol/L = deficiency)
Describe the management for osteomalacia
1st line - Vitamin D supplements (cholecalciferol)
Calcium supplements
Define Paget’s disease of bone
Disorder of bone turnover. Areas of patchy bone due to excessive osteoclast and osteoblast activity. Leads to areas of sclerosis and lysis.
Describe the aetiology of Paget’s disease
Idiopathic
Describe the risk factors for Paget’s disease
Females 40+
Describe the pathophysiology of Paget’s disease
Excessive bone turnover (formation and reabsorption) due to excessive activity of osteoclasts and osteoblasts. The excessive turnover is not coordinated, leading to patchy areas of high density (sclerosis) and low density (lysis). This results in enlarged and misshapen bones with structural problems that increase the change of pathological fractures.
Describe the key presentations of Paget’s disease
Bone pain, bone deformity (bowed tibia and skull), fractures, hearing loss (if bones of ear are affected)
What is the gold standard investigation for Paget’s disease
X-ray of bones
Describe the first line investigations for Paget’s disease
x-ray (bone enlargement + deformity, osteoporosis circumscripta – well defined osteolytic lesions, cotton wool appearance of skull – poorly defined areas of sclerosis and lysis, V-shaped defects in long bones)
urinary hydroxyproline (protein constituent of collagen)
bloods: raised ALP, normal calcium and phosphate
Describe the management for Paget’s disease
1st line – Bisphosphonates
NSAIDs for pain, calcium + vit D supplements
Describe the complications for Paget’s disease
Osteosarcoma, spinal stenosis and cord compression, deafness (CN8 nerve compression), hydrocephalus (sylvian aqueduct blockage)
Define Marfan’s syndrome
Connective tissue disorder. Autosomal dominant condition affecting the gene responsible for fibrillin production, an important component of connective tissue.
Describe the aetiology of Marfan syndrome
Autosomal dominant condition
Describe the risk factors for Marfan syndrome
Family history
Describe the key presentations for Marfan syndrome
Tall stature, long limbs, long fingers (arachnodactyly), hypermobility, pectus carinatum (breastbone juts out of chest)/pectus excavatum (breastbone sunken in chest), high arch palate, heart murmur/aortic complications
What is the gold standard investigation for Marfan syndrome
Genetic testing
Describe the first line investigations for Marfan syndrome
Physical exam, Echocardiogram, MRI, eye exam. Ghent criteria:
MAJOR: enlarged aorta, lens dislocation, FHx, at least 4 skeletal problems
MINOR: myopia (near-sighted), loose joints, high arched palate
Describe the differential diagnosis for Marfan syndrome
Aortic dissection, bicuspid aortic valve, Ehlers-Danlos syndrome
Describe the management for Marfan syndrome
Lifestyle - avoid intense exercise, avoid caffeine
Medication – beta blockers, angiotensin receptor blockers
Surgery: aortic dissection, lens correction, bone problems.
Yearly echocardiogram, ophthalmologist
Describe the complications for Marfan syndrome
Mitral/aortic valve prolapse with regurgitation, aortic aneurysms, aortic dissection, lens dislocation, GORD, pneumothorax, scoliosis
Define Ehlers-Danlos syndrome
Group of inherited connective tissue disorders causing defects in collagen, resulting in hypermobility of joints and abnormalities in connective tissue
Describe the aetiology of Ehlers-Danlos syndrome
Autosomal dominant mutation
Describe the risk factors for Ehler-Danlos syndrome
Family history
Describe the pathophysiology of Ehlers-Danlos syndrome
Hypermobile EDS (most common) > joint hypermobility, soft, stretchy skin
Classical EDS > stretchy skin (smooth, velvety to touch), joint hypermobility, joint pain, abnormal wound healing
Vascular EDS > vascular abnormalities, prone to rupture
Describe the key presentations for Ehlers-Danlos syndrome
Joint hypermobility, easily stretched skin (hyperextensibility), easy bruising, chronic joint pain, re-occurring dislocations, cardiovascular complications (mitral regurg, AAA, dissection)
What is the gold standard investigation for Ehlers-Danlos syndrome
Physical exam, Beighton score to assess hypermobility (touch ground with straight legs, elbows/knees/little finger hyperextend, thumb bend to touch forearm), collagen mutations
Describe the differential diagnosis for Ehlers-Danlos syndrome
Marfan syndrome
Describe the management for Ehlers-Danlos syndrome
No cure, focus on maintaining healthy joints: physiotherapy, occupational therapy, psychological support (chronic pain)
Describe the complications for Ehlers-Danlos syndrome
Classical EDS: hernias, prolapse, valve/aortic problems (regurgitation, AAA, dissection), joint pain, abnormal wound healing
Vascular EDS: skin, internal organs, blood vessels prone to rupture
Define antiphospholipid syndrome
Disorder associated with antiphospholipid antibodies where blood becomes prone to clotting = hypercoagulable state. Main associations are thrombosis and miscarriage
Describe the aetiology of antiphospholipid syndrome
Primary – idiopathic. Secondary – autoimmune condition e.g., SLE
Describe the risk factors for antiphospholipid syndrome
Young female, diabetes, hypertension, obesity, autoimmune condition, smoking, oestrogen therapy
Describe the pathophysiology of antiphospholipid syndrome
Autoimmune condition where abnormal proteins, antiphospholipid antibodies are made in the blood, making it prone to clotting. This causes abnormal flow and clotting in veins and arteries which leads to thrombosis and pregnancy complications – miscarriage.
Describe the key presentations for antiphospholipid syndrome
Thrombosis, recurrent miscarriages, livedo reticularis (purple discolouration of skin), thrombocytopenia
What is the gold standard investigation for antiphospholipid syndrome
Hx of thrombosis/pregnancy complications + serology:
Anticardiolipin antibodies
Lupus anticoagulant
Anti-beta-2 glycoprotein 1 antibodies
Describe the management for antiphospholipid syndrome
Long term warfarin (INR range 2-3)
Pregnant: LMWH (enoxaparin) + aspirin
Describe the complications for antiphospholipid syndrome
Venous thromboembolisms (DVT, PE), arterial thromboembolism (stroke, MI, renal thrombosis), pregnancy complications (miscarriage, pre-eclampsia)
Define dermatomyositis/polymyositis
Autoimmune disorders causing inflammation of muscles. Polymyositis = chronic inflammation of muscles. Dermatomyositis = connective tissue disorder with inflammation of muscles and skin
Describe the aetiology of dermatomyositis/polymyositis
Autoimmune. Also caused by malignancy – lung, breast, ovarian, gastric (paraneoplastic syndromes)
Describe the risk factors for dermatomyositis/polymyositis
Females, genetic link
Describe the key presentations for dermatomyositis/polymyositis
Symmetrical wasting of muscles of shoulder and pelvic girdle.
Dermatomyositis = gottron lesions (scaly erythematous patches) on knuckles, elbows, and knees. Purple rash on face and eyelids. Photosensitive erythematous rash on back, shoulders and neck. Periorbital oedema. Subcutaneous calcinosis
Describe the clinical manifestations for dermatomyositis/polymyositis
Muscle pain, fatigue, weakness. Hard to stand from sitting, to squat, to put hand on top of head
What is the gold standard investigation for dermatomyositis/polymyositis
Muscle fibre biopsy – inflammation, necrosis
Describe the first line investigations for dermatomyositis/polymyositis
Lactate dehydrogenase raised, AST and ALT raised, myoglobin raised, creatinine kinase raised (>1000 U/L. Normal = <300.)
Serology: anti-Jo-1 (polymyositis), anti Mi2 (dermatomyositis), anti-nuclear antibodies (dermatomyositis). Electromyograph
Describe the differential diagnosis for dermatomyositis/polymyositis
Rhabdomyolysis, myasthenia gravis, muscular dystrophy
Describe the management for dermatomyositis/polymyositis
1st line – prednisolone. Also, IV immunoglobulin
2nd line – immunosuppressant (methotrexate, azathioprine)
3rd line – rituximab or cyclophosphamide
Describe the complications for dermatomyositis/polymyositis
Corticosteroid complications
Define enteropathic arthritis/ IBD associated arthritis
Spondylarthritis and peripheral arthritis due to inflammatory bowel disease – ulcerative colitis, Crohn’s
Describe the aetiology of enteropathic arthritis
HLA B27, ulcerative colitis, Crohn’s disease
Describe the pathophysiology of enteropathic arthritis
Mainly affects peripheral joints, especially lower limbs
Describe the key presentations of enteropathic arthritis
Abdominal pain, diarrhoea, blood in stool, weight loss.
Bony deformity, painful red hot swollen joints. Stiffness and reduced motion. SPINEACHE
What is the gold standard investigation for enteropathic arthritis
Clinical diagnosis + symptoms + medical history
Describe the first line investigations for enteropathic arthritis
Joint aspiration, stool culture, colonoscopy and biopsy, faecal-calprotectin raised, FBC (anaemia – malabsorption, raised WCC), CRP/ESR raised, joint x-ray
Describe the differential diagnosis for enteropathic arthritis
Ulcerative colitis, Crohn’s, ankylosing spondylitis, reactive arthritis, psoriatic arthritis
Describe the management for enteropathic arthritis
DMARDs (methotrexate, leflunomide, sulfasalazine), NSAIDs (naproxen, ibuprofen, indomethacin), TNF inhibitors (etanercept, infliximab)
Treat ulcerative colitis/Crohn’s disease
Define giant cell arteritis
Vasculitis is a group of diseases causing inflammation of blood vessels. Giant cell arteritis affects large blood vessels
Describe the aetiology of giant cell arteritis
Autoimmune attacking of blood vessels
Describe the risk factors for giant cell arteritis
Over 50 y.o, northern European, females, Hx of polymyalgia rheumatica
Describe the pathophysiology of giant cell arteritis
Affects aorta and/or its major branches (carotid and vertebral arteries). Temporal artery often involved > temporal arteritis
Describe the key presentations of giant cell arteritis
Headache (new onset, unilateral over temporal area), scalp tenderness (hurts to brush hair), jaw claudication, visual disturbances (blurred, diplopia, amaurosis fugax – transient vision loss, blindness), thickened temporal arteries and weak pulses
Describe the clinical manifestations for giant cell arteritis
Malaise, fatigue, weight loss, fever, aching and stiffness
What is the gold standard investigation for giant cell arteritis
Temporal artery biopsy (shows giant cells, granulomatous inflammation – patchy lesions therefore take big sample)
Describe the first line investigations for giant cell arteritis
Raised CRP, Raised ESR >50mm/hr. FBC (anaemia), LFT/RFT may be abnormal
Halo sign (wall thickening) on vascular ultrasonography of temporal and axillary artery
Describe the differential diagnosis for giant cell arteritis
Large vessel vasculitis: Takayasu’s arteritis (Asian women, mainly affects aortic arch, Px: pulseless disease, arm claudication, syncope. GS = CT angiography)
Polymyalgia rheumatica, rheumatic arthritis
Describe the management for giant cell arteritis
1st line – high dose corticosteroid (e.g., prednisolone 40-60mg)
Consider: tocilizumab, methotrexate. Amaurosis fugax – high dose IV methylprednisolone.
Describe the complications for giant cell arteritis
Blindness (permanent if not given high dose IV methylprednisolone), irreversible neuropathy, large vessel stenosis
Define osteomyelitis
Inflammatory condition of bone and bone marrow caused by an infectious organism, most commonly staph aureus. Spread via haematogenous spread or direct contamination of joint.
Describe the epidemiology of osteomyelitis
Mainly children. Children = haematogenous spread most common. Adults = direct infection
Describe the aetiology of osteomyelitis
Staphylococci aureus, salmonella in sickle cell patients
Describe the risk factors for osteomyelitis
Previous osteomyelitis, penetrating injury, IVDU, diabetes (diabetic foot ulcers), HIV, recent surgery, infection, sickle cell, rheumatoid arthritis, chronic kidney disease, children (upper respiratory tract or varicella infection)
Describe the pathophysiology for osteomyelitis
Direct inoculation/local spread/haematogenous > acute bone diagnosis = inflammation and bone oedema. Chronic bone diagnosis (complication) = sequestra (necrotic bone embedded in pus), involucrum (thick sclerotic bone placed around sequestra to compensate for support)
Describe the key presentations for osteomyelitis
Acute = Limp or reluctance to weight-bear (children), hot, erythema and swollen joint, dull non-specific pain at site of infection, bone oedema
Chronic = sequestra (deep ulcers - necrotic bone embedded in pus)
Describe the clinical manifestations for osteomyelitis
low grade fever, malaise, fatigue, muscle aches
What is the gold standard investigation for osteomyelitis
Bone marrow biopsy and culture (identify organism)
Describe the first line investigations for osteomyelitis
FBC – raised WCC, raised CRP/ESR, blood culture MC+S, x-ray (osteopenia - thinning, periosteal reaction – changes to bone surface, destruction of bone), MRI (bone marrow oedema)
Describe the differential diagnosis for osteomyelitis
Charcot joint (damage to sensory nerves due to diabetic neuropathy, causes progressive degeneration of weight-bearing joint)
Tuberculosis osteomyelitis (bone marrow biopsy – caseating granuloma +ve), septic arthritis, reactive arthritis
Describe the management for osteomyelitis
1st line – immobilise and antibiotics: vancomycin (MRSA, S. aureus), fusidic acid (S. aureus), flucloxacillin (salmonella)
Supportive therapy and surgical removal of necrotic bone
Describe the complications for osteomyelitis
Chronic osteomyelitis, fracture, amputation
Define polyarteritis nodosa
Vasculitis is inflammation of blood vessels. Polyarteritis nodosa affects medium blood vessels.
Describe the epidemiology of polyarteritis nodosa
Associated with Hep B, developing countries
Describe the aetiology of polyarteritis nodosa
Autoimmune
Describe the pathophysiology of polyarteritis nodosa
Affects skins, kidney, GI tract and heart
Describe the key presentations for polyarteritis nodosa
Peripheral neuropathy (mononeuritis multiplex – ischaemia of vasa nervorum), cutaneous/SC nodules, abdominal pain, unilateral orchitis (testicle inflammation), livedo reticularis (mottled, purple lace rash), AKI/CKD, hypertension
Describe the clinical manifestations for polyarteritis nodosa
Malaise, fatigue, weight loss and fever
What is the gold standard investigation for polyarteritis nodosa
Biopsy e.g. kidney (transmural fibrinoid necrosis)
Describe the first line investigations for polyarteritis nodosa
Raised ESR, raised CRP, HBsAg (Hep B antigen), CT angiogram (beaded appearance – aneurysms)
Describe the differential diagnosis for polyarteritis nodosa
Medium vessel vasculitis: Kawasaki disease (children, strawberry tongue, causes coronary artery aneurysm), eosinophilic granulomatosis with polyangiitis (Churg-Strauss – pANCA positive)
Describe the management for polyarteritis nodosa
Hep B negative: corticosteroids and cyclophosphamide (DMARDs)
Hep B positive: antiviral agent, plasma exchange and corticosteroids
Describe the complications for polyarteritis nodosa
GI perforation and haemorrhages, arthritis, renal infarcts, stroke, MI
Define polymyalgia rheumatica
Inflammatory condition causing pain and stiffness in shoulders, pelvic girdle, and neck. Large cell vasculitis presenting as chronic pain syndrome. Affects joints and muscles
Describe the epidemiology for polymyalgia rheumatica
Females, always 50+, associated with giant cell arteritis
Describe the key presentations for polymyalgia rheumatica
Shoulder pain radiating to elbow, pelvic girdle pain, worse with movement, insomnia, morning stiffness >45 mins, rapid response to corticosteroids
What is the gold standard investigation for polymyalgia rheumatica
Clinical presentation, Raised ESR and CRP, and response to steroids
What are the further investigations for polymyalgia rheumatica
Temporal artery biopsy may show giant cell arteritis, FBC (anaemia of chronic disease)
Describe the differential diagnosis for polymyalgia rheumatica
Fibromyalgia, giant cell arteritis, osteoarthritis, rheumatoid arthritis
Describe the management for polymyalgia rheumatica
1st line – oral prednisolone
Define scleroderma
Systemic sclerosis in which normal tissue is replaced with thick dense connective tissue. It affects skin, blood vessels and internal organs. 2 types: limited cutaneous systemic sclerosis (CREST syndrome) and diffuse cutaneous systemic sclerosis.
Describe the aetiology of scleroderma
Autoimmune antibodies attacking connective tissue
Describe the risk factors for scleroderma
Women 30-50yo, family history, exposure to environmental substances and toxins (silica dust, solvents)
Describe the pathophysiology of scleroderma
Autoimmune response involving endothelial damage, inflammation and fibrosis
Describe the key presentations for scleroma
CREST:
Calcinosis (calcified nodules under skin),
Raynaud’s phenomenon,
Esophageal dysmotility (strictures, food gets stuck on swallowing),
Sclerodactyly (tightening and thickening of skin over fingers distal to MCP joint),
Telangiectasia (prominent dilated capillaries, especially on cheeks)
Describe the clinical manifestations for scleroderma
Signs: Coronary artery disease, pulmonary hypertension, pulmonary fibrosis, GORD, kidney failure
Symptoms: Swelling of hands and feet, finger pits/ulcers, fatigue, skin thickening and stiffening, myalgia, fatigue
What is the gold standard investigation for scleroderma
Anti centromere antibodies (limited/CREST), Anti-SCL70 (diffuse)
What are the first line investigations for scleroderma
Antinuclear antibodies maybe present - Anti-centromere antibodies present, anti-SCL70.
Other FBC, U&E, CRP normal. pulmonary function tests
Describe the management for scleroderma
No treatment. Immunosuppressants to slow progression.
Treat symptoms: analgesia, CCB for Raynaud’s, PPI for oesophageal reflux, topical emollient, ACEi for kidneys
Describe the complications for scleroderma
Malabsorption, pulmonary artery hypertension, hypothyroidism, kidney failure
Define Sjogren’s syndrome
Autoimmune condition affecting exocrine glands causing dry mucous membranes
Describe the aetiology for Sjogren’s syndrome
Autoimmune.
Primary – exists by itself. Secondary – complication of SLE with rheumatoid arthritis
Describe the risk factors for Sjogren’s syndrome
Family history, female, 40+ yo
Describe the key presentations for Sjogren’s syndrome
Dry mucous membranes – dry mouth (xerostomia), dry eyes (keratoconjunctivitis sicca), dry vagina
What is the gold standard investigation for Sjogren’s syndrome
Anti-Ro and anti-La antibodies
Describe the first line investigations for Sjogren’s syndrome
Anti-Ro and anti-La antibodies. Schirmer test – tears travelling <10mm (>15mm is normal)
Describe the differential diagnosis for Sjogren’s syndrome
Systemic lupus erythematosus, systemic sclerosis, rheumatoid arthritis
Describe the management for Sjogren’s syndrome
1st line – artificial tears, artificial saliva, vaginal lubricant.
Hydroxychloroquine used to halt progression
Describe the complications for Sjogren’s syndrome
Eye infections (conjunctivitis, corneal ulcers), oral problems (candida infection, dental cavities), vaginal problems (candidiasis, sexual dysfunction). Lymphomas
Define Wegener’s granulomatosis (granulomatosis with polyangitis)
Vasculitis is inflammation of blood vessels. Wegener’s granulomatosis affects small blood vessels.
Describe the aetiology for Wegener’s granulomatosis
Autoimmune
Describe the risk factors for Wegener’s granulomatosis
Young adult
Describe the pathophysiology for Wegener’s granulomatosis
Small vessel vasculitis affecting ENT, lungs and kidneys
Describe the key presentations for Wegener’s granulomatosis
ENT: Saddle shaped nose due to perforated nasal septum, epistaxis, crusty nasal/ear secretions > hearing loss, sinusitis,
Lungs: Cough, wheeze, haemoptysis, dyspnoea
Kidneys: glomerulonephritis > haematuria
Describe the clinical manifestations for Wegener’s granulomatosis
Malaise, fatigue, weight loss, fever, night sweats
What is the gold standard investigation for Wegener’s granulomatosis
cANCA positive and symptoms
Describe the first line investigations for Wegener’s granulomatosis
FBC: raised eosinophils, raised CRP/ESR, tissue biopsy shows granulomas, CT chest shows lung nodules, urinalysis (haematuria), ANCA positive
Describe the differential diagnosis for Wegener’s granulomatosis
Small vessel vasculitis: Henoch-Schoenlein purpura (IgA deposits, purpura, joint pain, abdo pain, renal involvement), microscopic polyangiitis (pANCA +ve), eosinophilic granulomatosis with polyangiitis (Churg-Strauss – asthma, pANCA positive, raised eosinophils)
Describe the management for Wegener’s granulomatosis
Corticosteroids (methylprednisolone and prednisolone) and immunosuppression (rituximab, cyclophosphamide). Plasmapheresis, IV immunoglobulin.
Describe the complications for Wegener’s granulomatosis
Glomerulonephritis, deafness, chronic renal failure
