MSK Flashcards
What are spondyloarthropathies?
Group of overlapping conditions that all share certain clinical features
What are the similar features of spondyloarthropathies?
Axial inflammation - spine and sacroiliac joints
Asymmetrical peripheral arthritis
Absence of rheumatoid factor - seronegative
Strong associated with HLA-B27
What is HLA-B27?
Human leukocyte antigen
Class I surface antigen - present on all cells except RBCs
Encoded by MHC on chromosome 6
APCs
Plays role in immunity and self-recognition
Essentially a tissue type
Prevalence of it affects prevalence of ankylosing spondylitis
Molecular mimicry whereby an infection triggers an immune response and infectious agent has peptides very similar to HLA-B27 molecules so auto-immune response triggered
How do spondyloarthropathies present?
Sausage digit (dactylitis) Psoriasis Inflammatory back pain NSAID good response Enthesitis (particularly in heel) Arthritis Crohn's/colitis/elevated CRP HLA-B27 Eye (uveitis)
What is ankylosing spondylitis?
Chronic inflammatory disorder of spine, ribs and sacroiliac joints
What is ankylosis?
Abnormal stiffening and immobility of joint due to new bone formation
How common is ankylosing spondylitis?
More common and more severe in men
Usually presents at 16 -young adult < 30
88% HLA-B27 positive
Women present later and under-diagnosed
Low incidence in African and Japanese people
Native North American have high incidence
What can increase your risk of having ankylosing spondylitis?
HLA-B27 Environment - Klebsiella - Salmonella - Shigella
What is the pathology of ankylosing spondylitis?
Lymphocyte and plasma infiltration occurs with local erosion of bone at attachments of intervertebral and other ligamants (enthesitis - inflammation where tendons and ligaments insert into bone), which heals with new bone formation
Syndesmophyte - new bone formation and vertical growth from anterior vertebral corners
How does ankylosing spondylitis present?
Gradual onset of lower back pain, worse at night, spinal morning stiffness, relieved by exercise
Episodic inflammation of sacroiliac joints in late teen years or early 20s
Pain radiates from sacroiliac joints to hips/buttocks, usually improves towards end of day
Asymmetrical joint pain - oligoarthritis
Loss of lumbar lordosis
Increased kyphosis
Limitation of lumber spine mobility in both sagittal and frontal planes
Enthesistis
What are the non-articular features of ankylosing spondylitis?
Anterior uveitis Osteoporosis Aortic incompetence Cardiac conduction defects Apical lung fibrosis Amyloidosis IgA nephropathy
How is ankylosing spondylitis diagnosed?
Bloods - ESR/CRP raised, normocytic anaemia, HLA-B27 positive
X-ray - erosion and sclerosis of margins of sacroiliac joints which can proceed to ankylosis, blurring of upper and lower vertebral rims at throacolumbar junction caused by enthesitits, heals with new bone formation, fusion of sarcoiliac joints
MRI - shows sacrolitis before seen on x-rays
How is ankylosing spondylitis treated?
Treat quickly to prevent irreversible syndesmophyte formation and progressive calcification
Morning exercise to maintain posture and spinal mobility
NSAIDs
Methotrexate - helps with peripheral arthritis
TNF-alpha blocker - earlier you start the less syndesmophytes form
Local steroid injections for temporary relief
Surgery - hip replacement to improve pain and mobility
How common is psoriatic arthritis?
Can occur without psoriasis
10-40% with psoriasis
Can present before skin changes
What can increase your risk of getting psoriatic arthritis?
FHx of psoriasis
How does psoriatic arthritis present?
Asymmetrical oligoarthritis
Symmetrical seronegative polyarthritis
Spondylitis - unilater/bilateral sacrolitis and early cervical spine involvement
DIPJs involvement only
Adjacent nail dystrophy
Dactylitis
Arthritis mutilans - periarticular osteolysis and bone shortening
Hidden sites - behind/inside ear, scalp, pitting in nails/onokylisis, umbilicus, natal cleft, penile psoriasis
How is psoriatic arthritis diagnosed?
Bloods and ESR normal
X-ray
- Erosions central to joint
- Pencil cup deformity in intraphalangeal joints - bone erosions create pointed appearance and articulating bone concave
- Skin and nail disease can be mild and may develop after arthritis
How is psoriatic arthritis treated?
Similar to RA
NSAIDs and/or anagesics for pain - can worsen skin lesions
Local synovitis responds to intra-articular corticosteroid injections
Early intervention with DMARDs can help skin lesions eg methotrexate, sulfasalzine and leflunomide
Methotrexate and ciclosporin used for severe disease
Anti-TNF alpha agents such as stanercept and golimumab highly effective and safe for severe skin and joint disease - used when methrotrexate fails
What is reactive arthritis?
Sterile inflammation of synovial membrane (synovitis), tendons and fascia triggered by an infection at a distant site, usually gastro-intestinal or genital
Typically affects lower limb
How common is reactive arthritis?
In men who HLA-B27 positive 30-50 fold increased risk
Women less commonly affected
What can cause reactive arthritis?
GI infections - Salmonella - Shigella - Yersinia enterocolitica Sexually acquired - Urethritis from chlamydia trachomatis - Ureaplasma urealyticum
How does reactive arthritis occur?
Bacterial antigens or bacterial DNA found in inflammed synovium of affected joints - persistent antigenic material driving inflammatory response
How does reactive arthritis present?
Acute, asymmetrical lower limb arthritis Occurring a few days to couple weeks after infection Acute anterior uveitits Circinate balantis Enthesitis HLA-B27 pos - sacrolitis, spondylitis Sterile conjuncitivitis Skin lesions resembling psoriasis Keratoderma blennorrhagica Nail dystrophy
How is reactive arthritis diagnosed?
ESR and CRP raised Culture stool if diarrhoea Sexual health review Aspirated synovial fluid sterile with high neutrophil count X-ray shows enthesitis
How is reactive athritis treated?
Joint inflammation - NSAIDs and corticosteroid injections
Treat persisting infection with antibiotics
Screen sexual partners
Majority of individuals with reactive arthritis single attack that settles, few develop disabiling relapse and remitting arthritis
Relapse cases use methotrexate or sulfasalzine
Severe and persistent disease - TNF-alpha blockers such as etanercept and golimumab
What is osteoporosis?
Systemic skeletal disease characterised by low bone mass and a micro architectural deterioration of bone tissue, with a consequent increase in bone fragility and susceptibility to fracture
Bone mineral density more than 2.5 standard deviations below the young adult mean value
T score < 2.5
What is osteopenia?
Pre-cursor to osteoporosis characterised by low bone density
Defined as BMD between 1-2.5 SDs below young adult mean value -1 < T score < 2.5
What is osteomalacia?
Poor bone mineralisation leading to soft bone due to lack of calcium (adult form of Rickets)
How common is osteoporosis?
More common in women in the over 50s due to natural loss of trabeculae with age
In men, reduced bone formation but numbers of trabeculae more stable so lifetime fracture risk lower
Caucasians and Asians most at risk
Risk increases as we age
1/2 women will get a fracture due to osteoporossi
1/5 men
What increases your risk of getting osteoporosis?
Old age
Female
FHx of osteoporosis or fractures
Previous bone fractures
SHATTERED
Steroid use - prednisolone, heparin, ciclosporin, PPIs, anticonvulsants, GnHR analogues, SSRIs, androgen deprivation
Hyperthyroidism and hyperparathyroidism (increases bone turnover)
Alcohol and tobacco
Thin - BMI < 22 (reduced skeletal loading, increased bone resorption)
Testosterone decreases - increased bone turnover
Renal/liver failure
Erosive/inflammatory bone disease - cytokines increase bone turnover
Dietary calcium decrease/malabsorption, T1DM
What occurs in osteoporosis?
Peak bone mass around 25
Results from increase bone breakdown by osteoclasts and decreased bone formation by osteoblasts, leading to loss of bone mass
Bone mass decreases with age, depends on peak mass attained in adult life and rate of loss
Genetic factors - multiple genes involved
Nutritional factors, sex hormone status and physical activity
Bone strength determined by bone mineral density, bone size and bone quality
What occurs in postmenopausal osteoporosis?
Oestrogen deficiency
Increased numbers of osteoclasts, permature arrest of osteoblastic synthetic activity and perforation of trabeculae with loss of resistance to fracture
High bone turnover
Predominantly cancellous bone loss
What changes in trabeculae occur with ageing?
Decrease in trabecular thickness - strain felt on bones head to tail, preferentially preserve vertical trabeculae and lose horizontal
Decrease in trabeculae thickness in connections between horizontal trabeculae resulting in decreased trabecular strength and increased susceptibility to fracture
How does osteoporosis present?
Fracture only cause of symptoms
Vertebral crush fracture
- Sudden onset severe pain of spin, radiating to front
- Thoracic vertebral fractures may lead to kyphosis
Colles’ fracture of wrist typically following falls
Fractures of proximal femur usually occur in older individuals falling on side or back
How is osteoporosis diagnosed?
T score - standard deviation score attained using DEXA scan, compared with gender-matched young adult average (peak bone mass)
X-ray for fractures
DEXA scan - low dose radiation, measures important fracture sites
Bloods - Ca, phosphate and alkaline phosphate all normal
How is osteoporosis treated?
Lifestyle measures - quit smoking and reduce alcohol consumption, weight bearing exercise may increase bone density, calcium and vitamin D deficient diet, balance exercises to reduce falls Anti-resportive - slow down osteoclasts and reduce bone turnover - Bisphosphonates - Strontium ranelate - Denosumab - HRT - Raloxifene - Testosterone
What is osteoarthritis?
Cartilage loss with accompanying periarticular bone response
Inflammation of articular and periarticular structure and alteration of cartilage structure
Non-inflammatory degenerative arthritis
Age-related, dynamic reaction pattern of a joint in response to insult or injury
All tissues of joint involved
Articular cartilage most affected
How common is osteoarthritis?
Most common condition affecting synovial joints
Majority primary with no obvious factor causing it
Secondary OA occurs in joint disease or other conditions
Prevalence increases with age - uncommon before age 50
Beyond 55 more common in women
What can increase your risk of osteoarthritis?
Joint hypermobility Insufficient joint repair Diabetes Increasing age - cummulative effect of traumatic insult, decline in neuromuscular function Gender - more common in women Genetic predisposition Obesity - pro-inflammatory state Occupation - manual labour (small joints of hand), farming (hips), football (knees) Local trauma Inflammatory arthritis
What occurs in osteoartritis?
Matrix of collagen fibres enclosing mixture of proteoglycans and water, smooth surface and shock absorbing
Normal balance between cartilage degradation and wear and production by chondrocytes lost - despite increased synthesis of extracellular matrix, cartilage becomes oedematous
Focal erosion of cartilage develops and chondrocytes die, repair attempted from adjacent cartilage but process disordered leading to failure of synthesis of extracellular matrix so surface becomes fibrillated and fissured
Exposes underlying bone to increased stress producing micro-fractures and cysts
Bone attempts repair producing abnormal sclerotic subchondral bone and overgrowths at joint margins which become calcified
Secondary inflammation
Exposed bone becomes sclerotic - increased vascularity and cyst formation
Metalloproteinases - secreted by chondrocytes degrade collagen and proteoglycan
Interleukin 1 and TNF-alpha - stimulate metalloproteinase production and inhibit collagen production
ILGF-1 and transforming growth factor impairs matrix repair
Gene susceptibility
What are the main pathological features of osteoarthritis?
Loss of cartilage
Disordered bone repair
How does osteoarthritis present?
Affects many joints, mechanical pain with movement and/or loss of function
Gradual onset and progressive
Joint pain - made worse after movement and relieved by rest
Joint stiffness after rest
Only transient stiffness - less than 30 mins morning stiffness
DIPJs (Heberden’s nodes)
1st carpometacarpal joints
1st metatarsalphalangeal joints
Weight bearing joints
Limited joint movement
Muscle wasting of surrounding muscle groups
Crepitus - crunching sensation when moving joint
Joint effusions
Bouchard’s node (PIPJ)
What could be a differential diagnosis for osteoarthritis?
RA - differentiated by pattern of joint involvement and absence of systemic features and marked early morning stiffness
Chronic tophaceous gout and psoriatic arthritis affecting DIPJs
How is osteoarthritis diagnosed?
Deformity and bony enlargement on exam
CRP elevated
Rheumatoid factor and anti-nuclear antibodies negative
X-rays LOSS
- Loss of joint space
- Osteophytes
- Subarticular sclerosis
- Abnormalities of bone contour
MRI - early cartilage injury and subchondral bone marrow changes
Aspiration of synovial fluid if painful effusion - viscous fluid with few leucocytes
How is osteoarthritis treated?
Non-medical
- Exercise - muscle strength, mobility of weight bearing joints, fitness
- Weight loss if obese
- Local heat/ice packs
- Bracing devices, joint supports, insoles for stability, footwear with shock absorbing properties
- Acupuncture, physio, occupational therapy
Paracetamol before NSAIDs
Weak opioids with paracetamol
Intra-articular corticosteroid injections produce short-term improvement when painful joint effusion
Surgery
- Arthroscopy
- Arthroplasty - joint replacements for uncontrolled pain, or significant limitation of function
- Osteotomy - cut bone to change shape/length
- Fusion - usually of ankle and foot to prevent painful grinding of bones
What is rheumatoid arthritis?
Chronic systemic autoimmune disease causing symmetrical polyarthritis
Disease of synovial joints
Inflammatory autoimmune arthritis
How common is rheumatoid arthritis?
Affects 1% of population worldwide with peak prevalence between 30-50 years
Increased prevalence in smokers
Not seen as much in elderly in contrast to OA
More common in women
What can cause RA?
Suggested role of female sex hormones Immune system - Triggering antigen unknown - T cells - interferon, IL-2, IL-4 - Macrophages - IL-1, IL-8, TNF-alpha - Mast cells - histamine and TNF-alpha Fibroblasts - IL-6 - Local production of rheumatoid factor by B cells and formation of immune complexes with complement activation also maintains chronic inflammation
What are the factors that can increase your risk of RA?
Female - before menopause women affected 3x more than men, equal incidence post-menopause
Genetics - HLA-DR4 and HLA-DRB1 confer susceptibility and associated with development of more severe erosive disease
Smoking
Immune system
What is the pathology of RA?
Predominantly synovial disease and synovitis occurs when chemoattractants produced in joint recruit circulating inflammatory cells
Over-production of TNF-alpha leads to synovitis and joint destruction - interaction of macrophages, T and B lymphocytes drives overproduction
Synovium becomes greatly thickened and becomes infiltrated with inflammatory cells
Generation of new synovial blood vessels induced by angiogenic cytokines and activated endothelial cells produce adhesion molecules forcing leukocytes into synovium where trigger inflammation
Synovium proliferates and grows out over surface of cartilage, producing tumour-like mass called pannus
Pannus of inflammed synovium damages underlying cartilage by blocking normal route for nutrition and by direct effects of cytokines on chondrocytes
Cartilage thins and underlying bone exposed
Pannus destroys articular cartilage and subchondral bone resulting in bony erosions
How does RA present?
Slowly progressive, symmetrical swollen, painful stiff MCP, PIP DIPs normally spared Metatarsophalangeal of feet Wrists, elbows, shoulders, knees, ankles Warm and tender Symptoms worse in mornings Morning stiffness lasting more than 30 mins Symmetrical peripheral polyarthritis Movement limitation, muscle wasting Hand deformities - ulnar deviation, swan neck thumb, boutonniere deformity Fatigue, sleep disturbed Synovitis and effusions in knees Tenosynovitis - inflammation of tendons
What are the extra-articular manifestations of RA?
Lungs - pleural effusions, fibrosing alveolitis, pneuoconiosis, interstitial lung disease, bronchiectasis
Heart - pericarditis, pericardial rub, Raynauds, pericardial effusion
Eyes - dry eyes, episcleritis, scleritis
Neurological - peripheral sensory neuropathies, compression/entrapment neuropathies, cord compression
Kidneys - amyloidosis, nephrotic syndrome, CKD
Skin - subcutaneous nodules
How is RA diagnosed?
Bloods - normochromic, normocytic anaemia, ESR/CRP raised in proportion to activity of inflammatory process, positive rheumatoid factor, positive anti-cyclic citrullinated peptide (presents early)
X-ray
- Soft tissue swelling in early disease
- Joint space narrowing in late disease
- Peri-articular erosions
MRI and USS - erosions at joint margins and bones
If effusions present then aspiration of joint
How is RA treated?
No cure
Smoking cessation - reduces risk of CVS disease
Reduce weight
Exercise
Surgery - synovectomy to reduce bulk of inflammed tissue and prevent damage
Pain management - NSAIDs relieving joint pain and stiffness, paracetamol w/w/o opioid
Corticosteroids - suppress disease activity but risk of long-term toxicity
DMARDs - methotrexate, sulfalazine, leflunomide
Biological therapy
- TNF-alpha blockers
- B cell inhibitors
- Interleukin blockers
- T cell activation blockers
What is gout?
An inflammatory arthritis that is associated with hyperuricaemia and intra-articular monosodium urate crystals
How common is gout?
Prevalence increasing especially in developing countries
More common in men
Rarely occurs before young adulthood
Most common inflammatory arthritis in UK
What can cause gout?
High alcohol intake (highest risk for beer then wine)
Purine rich foods (red meats)
High fructose intakes - reduces uric acid excretion
High saturated fat diet
Drugs - low dose aspirin
IHD
Renal causes - defective gene for URAT1 transporter in kidney
- High insulin levels reduces urate excretion
- Diuretics impair uric acid excretion
Increased production of uric acid
- Increased purine turnover
- Myeloproliferative
- Lymphoproliferative disorders
- Carcinoma and psoriasis - increased cell turnover
- Cell damage - surgery
- Cell death - chemotherapy
FHx
What is the pathology of gout?
Purines need to be excreted
Last 2 steps of purine metabolism = hypoxanthine converted to xanthine and xanthine converted to uric acid under enzyme xanthine oxidase
Uric acid excreted via kidneys - if some hyperuricaemia converted to monosodium urate crystals - causes symptomatic gout and pain
Serum uric acid levels higher in men than women
Hyperuricaemia defined as serum acid level greater than 420 micromol/L (M) or 360 micromol/L (F)
Need to have hyperuricaemia to develop gout but doesn’t guarantee gout - just increases risk
Serum uric acid levels increase with age, obesity, DM, IHD, hypertension
Monosodium urate crystals tend to form in joints that have had previous trauma and form at lower temps so form in more peripheral joints
Monosodium urate crystals can trigger intracellular inflammation resulting in more pain
How does hyperuricaemia present?
Can be asymptomatic or may cause acute/chronic gout or tophaceous gout
What is acute gout?
Occurs when monosodium urate crystals form
Typically in middle aged men
Sudden onset agonising pain, swelling and redness of 1st MTP joint
Usually just on joint affected but can be polyarthritis
Attack may be precipitated by excess food, alcohol, dehydration or diuretic therapy, cold, trauma, sepsis
What is chronic gout?
Rare
Except in elderly on long term diuretics in renal failure or have been started on allopourinol too soon
What is tophaceous gout?
In people with perisitent hyperuricaemia - monosodium urate crystals form smooth, white deposits (tophi) in skin and around joints, on ear, fingers/achilles tendon
Tophi onion like aggregates of monosodium urate crystals with inflammatory cells
Tophi release local proteolytic enzyme hence erosions to bone - form circular punch like holes
Associated with renal impairment and/or long-term used of diuretics
What can gout increase the risk of ?
Urate renal stone formation
Gout also increases risk of hypertension, renal disease, CVS disease, T2DM and osteoarthritic damage to joints
Recurrent gout attacks can lead to renal impairement
What could be a differential diagnosis of gout?
Septic arthritis in any acute monoarthropathy
How is gout diagnosed?
Joint aspiration and microscopy
- Diagnostic
- Shows long needle shaped crystals that are negatively bifringent under polarised light
Raised serum uric acid
Serum urea and creatinine and eGFR - monitoring for signs of renal impairment
How is gout treated?
Aim to decrease uric acid level to below normal so crystals reverse Lose weight Less alcohol Avoid purine rich foods Dairy Acute - High dose NSAIDs - If NSAID not tolerated - colchicine (v toxic in overdose) IM, oral, intra-articular corticosteroid
What are the side effects of colchicine?
Diarrhoea
Abdominal pain
How is gout prevented?
Stop diuretics and switch to angiotensin receptor blocker
Allopurinol
Febuxostat - non-purine xanthine oxidase inhibitor, use if allopurinol CI or due to side effects
What is pseudogout?
Deposition of calcium pyrophosphate crystals on joint surface
Who is most affected by pseudogout?
Elderly women
What can increase your risk of pseudogout?
Old age Diabetes Osteoarthritis Joint trauma/injury Metabolic disease - hyperparathyroidism, haemochromatosis
What occurs in pseudogout?
Deposition of calcium pyrophosphate in articular cartilage and periarticular tissue producing radiological appearance of chonedrocalcinosis
How does pseudogout present?
Shedding of crystals into joint produces acute synovitis that resembles acute gout but is more common in elderly women and usually affects knee/wrist
Painful attacks
Acute hot swollen wrist/knee
Can be mistake for septic arithtis
How is pseudogout diagnosed?
Joint aspiration and microscopy
- Small rhomboid crystals under microscopy
- Positively bifringent crystals under polarised light
- Joint fluid looks purulent so sent for culture to exclude septic arthritis
X-ray
- Shows chonedrocalcinosis - linear calcifcation parallel to articular surfaces
Bloods
- Raised WCC
How is pseudogout treated?
High dose NSAIDs eg naproxen/ibuprofen
Colchicine if NSAID not tolerated
IM/oral/intra-articular corticosteroid
Aspiration of joint reduces pain dramatically
What is septic arthritis?
Medical emergency
Acutely inflammed joint which can destroy a joint in under 24 hours
Knee affected in more than 50% cases
Joints become infected by direct injury or by blood-borne infection from an infected skin lesion or other site
In which age group is septic arthritis most common?
Incidence increases with age 45% over 65
What pathogens cause septic arthritis?
Staph aureus - most common
Streptococci
Neisseria gonorrhoea
Haemophilius influenzae in children (rare due to immunisations)
Gram-negative bacteria eg E coli/P aeruginosa in eldery/v young/systemically unwell/IVDU
What can increase your risk of getting septic arthritis?
Pre-existing joint disease DM Immunosuppression Chronic renal failure Recent joint surgery Prosthetic joints IV drug abuse Those over 80 and infants Recent intra-articular steroid injection Direct/penetrating trauma
How does septic arthritis present?
Agonisingly painful, red, hot, swollen joint
In elderly and immunocompromised and RA articular signs may be muted
In children - might not use joint, limping/protecting joint
Fever
Monoarthritis
Most common in knee, hip, shoulder, can occur in any joint
Early infection - wound inflammation/discharge, joint effusion, loss of function and pain
Late disease - presents with pain/mechanical dysfunction
What could be a differential diagnosis for septic arthritis?
Gout
Pseudogout
How is septic arthritis diagnosed?
Urgent joint aspiration - urgent gram stain and culture
- Purulent/opaque/thick/pussy fluid due to high WCC
- Normal fluid clear, yellow, thin
- Always aspirate before antibiotics
Polarised light microscopy for crystals - exclude gout
ESR, CRP, WCC raised
X-ray
- No value in septic arthritis
- Loosening/bone loss around a previously well-fixed implant suggests infection
Skin wound swab, sputum and throat swab or urine if gonococcal infection possibility
How is septic arthrits treated?
Stop immunosuppressants
Double prednisolone dose if on long term prednisolone
Joint immobilised early followed by early physio to prevent stiffness and muscle wasting
If in doubt - start antibioitics after joint aspiration IV for 2 wks
Joint drainage repeatedly until no recurrent effusion can help relieve pain
NSAIDs for pain
What is flucloxacillin used for?
Most gram -ves
What is erythromycin/clindamycin used for?
If allergic to penicillin
Most gram -ves
What is cefotaxime used for?
Gram negatives/gonococcal
What is vancomycin used for?
MRSA
What antibiotics do you give if patient immunocompromised?
Flucloxacillin and gentamycin
What is osteomyelitis?
Bone marrow inflammation
Infection localised to bone
Either due to metastatic haematogenous spread or due to local infection
How common is osteomyelitis?
Predominantly occurs in children
Increasing incidence of chronic osteomyelitis
Majority of haematogenous acute osteomyelitis occurs in children
Adolescents and adults tend to get osteomyelitis due to infection secondary to direct trauma
Elderly get it due to risk factors
What pathogens cause osteomyelitis?
S aureus - most common
Coagulase negative staphylococcus
Haemophilius influenzae
Salmonella - complication of sickle cell anaemia
Pseudomonas aeruginosa and serratia marcesans in IVDU
What can increase your risk of getting septic arthritis?
DM PVD Malnutrition Inflammatory arthritis Debilitating disease Decreased immunity Sickle cell disease Prosthetic material Immunosuppressive drugs Trauma
What can increase your risk of haematogenous seeding osteomyeltits?
Central line Dialysis Sickle cell disease Urethral catheterisation UTI
What are the different ways pathogens can get into bone?
Direct inoculation of infection into bone either via trauma or surgery (easy)
Contiguous spread of infection to bone - w/o breaking skin, infection of adjacent soft tissue spreading into bone, seen in elderly who tend to have DM, chronic ulcers, vascular disease, joint replacements and prostheses
Haematogenous seeding
What is haematogenous seeding?
Infection spreading from skin to blood then bone
In children more likely to go to long bones at metaphysis
- Blood flow slower, endothelial basement membrane absent and capillaries lack or have inactive phagocytic lining cells - predisposed to bacteria migrating from blood into bone and growth of bacteria in bone
In adults more likely to go to vertebrae
- Vertebrae become more vascular with age, making bacterial seeding more likely
Occurs mainly in children and adults over 50
Risk in IVDU
What is the pathology of osteomyelitis?
Inflammatory exudate in marrow leads to increased intramedullary pressuew with extension of exudate into bone cortex
Causes rupture through periosteum and interruption of periosteal blood supply resulting in necrosis
Leaves pieces of separated dead bone called sequestra
New bone forms called involucrum
What is the histopathology of osteomyelitis?
Acute changes - inflammatory cells, oedema, vascular congestion, small vessel thrombosis
Chronic changes - necrotic bone sequestra, new bone formation - involucrum, neutrophil exudates, lymphocytes, histocytes
How does osteomyelitis present?
Onset over several days
Dull pain at site aggravated by movement
Fever, sweats, rigors, malaise
Acute - tenderness, warmth, erythema, swelling
Chronic - tenderness, warmth, erythema, swelling, deep large ulcers failing to heal despite treatment
Can also present as septic arthritis
- infection breaks through cortex resulting in discharge of pus into joint, more common in infants due to patent transphyseal blood vessels and immature growth plates
What could be a differential diagnosis of osteomyelitis?
Charcot joint - damage due to sensory nerves affected by diabetes
Soft tissue infection - cellulitis and erysipelas
Avascular necrosis of bone causes - steroids, radiation, bisphosphonate use
Gout
Fractures
Malignancy
How is osteomyelitis diagnosed?
Imaging - plain x-ray showing osteopenia - MRI show marrow oedema 3-5 days (after x-ray) - Bone scans Bloods - Blood culture to determine aetiology - ESR and CRP raised - Acute - raised WCC - Chronic - can have normal WCC Bone biopsy and culture to determine cause
How is osteomyelitis treated?
Immobilisation
Antimicrobial therapy
- Tailored to culture and sensitivity findings
- IV teicoplanin S/E rash, pruritus, GI upset
- IV flucloxacillin
- Oral fusidic acid
- Stop treatment guided by ESR/CRP
What is TB osteomyelitis?
Usually due to haematogenous seeding spread from reactivated focus in lungs/GI tract
May be slower onset with systemic symptoms eg malaise, fever, night sweats
Local pain and swelling if pus collected
Biopsy essential
Longer treatment - 12 months with same treatment as for pulmonary TB
What is systemic sclerosis?
Multisystem disease with involvement of skin and Raynaud’s phenomenon
Distinct from localised scleroderma such as morphea, do not involve internal organ disease and are rarely associated with vasospasm (Raynaud’s phenomenon)
How common is systemic sclerosis?
Highest case-specific mortality compared to any other autoimmune rheumatic disease Occurs worldwide More common in women Peak incidence between 30-50 Rare in children
What can increase your risk of systemic sclerosis?
Exposure to vinyl chloride, silica dust, adulterate rapeseed oil and tricholoethylene
Drugs such as bleomycin
Genetics
What is that pathology of systemic sclerosis?
Widespread vascular damage involving small arteries, arterioles and capillaries early features
Initial endothelial cell damage with release of cytokines, including endothelin-1, causes vasoconstriction
Continued vascular damage and increased vascular permeability and activation of endothelial cells leads to upregulation of adhesion molecules, cell adhesion, migration of cells through leaky endothelium and into extracellular space
Stimulates produciton of cytokines and growth factors which mediate proliferation and activation of vascular and connective tissue cells - particularly fibroblasts
Fibroblasts increase quantities of collagen type 1 and 2 producing fibrosis in lower dermis of skin and internal organs
Uncontrolled and irreverible proliferation of connective tissue and thickening of vascular walls with narrowing of lumen
Damage to small blood vessels also produces widespread obliterative arterial lesions leading to chronic ischaemia
How does limited cutaneous scleroderma present?
Begins with Raynaud’s phenomenon, skin involvement limited to hands, face, feet and forearms
- Skin tight over fingers, flexion deformities
- Beak-like nose, small mouth
- Painful digital ulcers and telangiectasia
- GI tract involvement
- CREST - calcinosis, Raynauds, esophageal dysmotility/strictures, sclerodactylyl, telenagiectasia
How does diffuse cutaneous scleroderma present?
Skin changes develop more rapidly and more widespread than limited cutaneous scleroderma
Early involvement of other organs
- GI - dilation and atony (loss of strength) - heartburn, malabsorption
- Renal - AKI and CKD
- Lung disease - fibrosis, pulmonary vascular disease
- Myocardial fibrosis - arryhthmias and conduction disturbances
What is Raynaud’s phenomenon?
Spasm of arteries causes reduced blood flow
Blanched areas of hands
How is systemic sclerosis diagnosed?
Bloods - Normochromic, normocytic anaemia - Microangiopathic haemolytic anaemia - Urea and creatinine raised in AKI - Autoantibodies - Rheumatoid factor Urinalysis - If proteinuria - albumin/creatinine ratio Imaging - CXR - exclude other pathology - Hand x-ray - deposits of calcium - Barium swallow - oesophageal motility - High resolution CT - confirms fibrotic lung involvement
How is systemic sclerosis treated?
No cure
Raynauds - hand warmers, oral vasodilators (CCBs)
Nutritional supplementation for malabsorption
Prevention of renal crisis (ACEi)
Early detection of pulmonary hypertension with annual ECHO and pulmonary function tests
Pulmonary fibrosis - immunosuppressant, oral prednisolone
