Phase 2 - MSK Flashcards
Define Osteoarthritis
An AGE related, DYNAMIC REACTION PATTERN of a joint in response to INSULT and INJURY - also has a genetic component
(aka NON-INFLAM DEGENERATIVE MECHANINCAL SHEARING OF JOINTS, usually age related)
- All tissues of joint involved but esp ARTICULAR CARTILAGE
- Changes in underlying bone at joint margin
- Multifactorial in origin
Subtypes of osteoarthritis
- Nodal OA - strong genetic component- Inflammatory/erosive OA- Hip OA- Knee OA
OA Staging
1 = doubtful = ~10% cartilage loss2 - osteophyte development starts (looks like little bony outpouchings)3 - increased loss of joint space + osteophytes4 - severe
Epidemiology of OA
- Most common condition affecting synovial joints- Most important condition relating to disability as result of locomotor symptoms- 8.75 million people in the UK have sought treatment for OAImpact to UK economy ~1% GNP (2008):- Lost days of work- Incapacity benefit- Treatment strategies
Causes/risk factors of OA
- AGE (cumulative effect + decline in neuromuscular function) - esp >50 y/o- FEMALE (post menopause)- GENETIC predisposition - esp if POLYARTICULAR (COL2A1)- OBESITY - thought to be due to the low grade inflam state - release of IL1, TNF, ADIPOKINES (Leptin. adiponectin)- Occupation - manual labour - small hand joints - farming hips - football - kneesOthers:- Direct trauma- Inflam arthritis- Abnormal biomechanics (e.g. congenital hip dysplasia, hypermobility, NEUROPATHIC CONDITIONS)
Percentage of people over 65 with osteoarthritis
80-90% over 65 will have radiographic evidence of OA and 50% will have symptoms
Pathophysiology of osteoarthritis
Characterised by:- LOSS OF CARTILAGE due to shift in homeostatic balance of tissue (i.e. imbalance between the cartilage being worn down and the chondrocytes repairing so net loss) - Matrix metalloproteinases increase -> collagen degradation + cyst formation -> increased mechanical wear -> stiffness + pain - Nitric oxide further activates metalloproteinases- DISORDERED BONE REPAIR (attemt to overcome via T1 collagen -> formation of osteophytes)A METABOLICALLY ACTIVE + DYNAMIC PROCESS - mediated by CYTOKINES:- IL-1- TNFa- NOand DRIVEN BY MECHANICAL FORCES
SIgns + symptoms of OA
- PAIN (may not be present despite radiographic change)- Transient Morning stiffness <1 hr (some say < 30 mins) - stiffness gets worse over course of day/with more activity- FUNCTIONAL IMPAIRMENT: - Walking - Activities of daily living - Inability to do stuff -> muscle wasting -> make things worseSigns:- Altered GAIT- JOINT SWELLING (usually asymmetrical, hard + non-inflamed) - Bony enlargement - Heberden’s (DIP) and Bouchard’s (PIP) nodes + esp used joints 1st MCP, MTP, hip/knees(in nodal) - Effusion - Synovitis (if inflammatory component)- Limited range of motion- Crepitus (crackling noises - esp in patellar OA)- Tenderness- DeformitiesNo extra-articular presentation
Investigations for OA
X-RAY - remember findings as JOSSA (like bone fossa)- Joint space narrowing- Osteophyte formation- Sub-chondral sclerosis- Sub-chondral cysts- Abnormalities of bone contourBloods normal
Diff diagnosis OA
Rheumatoid or Reactive Arthritis
Non-medical management of OA
- Patient education/support- Activity/exercise- Weight loss (can be a pre-requisite for surgery)- Physiotherapy- Occupational therapyWeight bearing supports:- Footwear/orthoses (can get wedge to improve weight bearing)- Walking aids: stick, frame- Splints
Pharm treatments of OA
Pain killers/anti-inflamTopical- NSAIDs- Capsaicin creamOral- Paracetamol- NSAIDs (with caution - may be paired with PPIs)- Opioids (don’t work for chronic pain -> addiction)Transdermal patches- Buprenorphine (strong opiod)- Lignocaine (local anaesthetic + antiarrhythmic)Intra-articular steroid injections (not disease modifying and then get steroid side effects so not as commonly used if avoidable)DMARDs for inflam OA
Surgical treatment of OA
- Arthroscopy (only indicated for loose bodies) - camera into joint- Osteotomy (partial removal of bone)- Arthoplasty (complete replacement) - will eventually have to be replaced- Fusion of bones (if joint won’t tolerate replacement well e.g. ankle/foot) - stops pain but loss of mobility
Indications for Arthoplasty
- Significant/uncontrolled pain (esp at night)- Sig loss of functionIt may be discouraged in youger patients as they will inevitably need replacement
Complication of OA
- pain, loss of function etc.- Loose bodies (bone/cartilage fragment) can get stuck within joints and can cause the joint to ‘lock’ - esp in KNEE - only indication of ARTHROSCOPY in OA
Presentation of Nodal OA
- affects hands -> reduced function- Heberden’s (DIP) and Bouchard’s (PIP) nodes- MCP esp of thumb affected- Initial inflam phase- BONY SWELLINGS + CYSTS- Relapse/remit over a few years
Presentation of Knee OA
- Can affect 3 compartments (in isolation or a combination of these): - Medial (mc) - Lateral - Patellofemoral (request more views when imaging)- Slow evolution if no significant trauma- Oft stays stable for years once established (unless there is trauma)
Presentation of Hip OA
- Pain in groin - may persist at night and wake people up- Difficulty walking
Presentation of Erosive/Inflam OA
- Erosive element - can look like birds wings on scan- Inflammatory component- DMARD therapy oft used (ususally milder things like hydroxychloroquine)
When can a clinical diagnosis of OA be made without investigation
If patient is:- Over 45 - Has typical activity related joint pain - No morning stiffness or morning stiffness that lasts less than 30 minutes
Advice to give regarding a prescription of alendronate
- Take first thin in morning- On an empty stomach- Remain upright 30 mins after taking
Define fibromyalgia
A chronic pain syndrome diagnosed by presence of widespread MSK pain lasting >3 MONTHS with all other causes ruled out
DDx of Fibromyalgia
Polymyalgia Rheumatica also presents with widespread pain, more common in females- but presents almost exclusively OVER 50 Y/O- Also has raised ESR/CRP
Risk factors of Fibromyalgia
- FEMALE- Poor socieconomic status- Depression/stress- 20-50 Y/O
Pathophys of fibromyalgia
UnknownPossibly hyper excitability of pain fibre
Presentation of Fibromyalgia
- Increased sensitivity to pain- Fatigue- Sleep disturbance- Fibro-fog (problems with memory + conc)- Morning stiffness esp back + neck- Headaches- IBS
Investigations for Fibromyalgia
Clinically diagnosed:- Issues with widespread pain in combination with fatigue, memory, sleep difficulties - need to feel pain in 11+ out of 18 regions palpated all over bodyNo serological markers; NO raised ESR/CRP
Management of Fibromyalgia
- Educating patient on the condition - Exercise/physiotherapy- Relaxation- Analgesia (paracetamol, tramadol/codeine)- CBT, counselling, low dose tricyclic antidepressants - for SEVERE NEUROPATHIC PAIN
Complications of Fibromyalgia
- affects quality of life- anxiety, depression, insomina- opiate addiction
Define Antiphospholipid syndrome
An autoimmune disorder which causes a hypercoaguable state due to increasing the tendancy of blood to clot- characterised by thrombosis, recurrent miscarriages + aPL Abs
Can be primary or secondary to other AI e.g. SLE
Epidemiology of APS
Mostly in YOUNG FEMALES
RFx of APS
- FEMALE- DIABETES- HTN- OBESITY- Smoking- Oestrogen therapy (at menopause)- other AI e.g. SLE
Pathophys of APS
In APS abnormal antiphospholipid antibodies are produced and present in blood. These attack the phospholipids on the surface of blood constituent cells + vessel walls -> impaired blood flow. Can lead to arterial and venous clots.Particularly problematic in pregnancy with a risk of miscarriage.
Presentation of APS
Remember CLOTS:- Coagulopathy: - Thrombosis -> DVT, PE or Stroke/MI/Renal infarct (or antiphospholipid nephropathy)/Raynaud’s- Livedo reticularis- Obstetric issues - Recurrent miscarriages or early/severe pre-eclampsia- ThrombocytopeniaBalance problems, headaches, double vision etc.
Diagnosis of APS
- Hx of thrombosis/pregnancy complications- FBC: may show THROMBOCYTOPENIA- Ab screen: - +VE ANTICARDIOLIPIN Ab (IgG/M) - +VE LUPUS ANTICOAG - +VE ANTI-BETA-2 GLYCOPROTEIN 1 Ab(not necessarily all together)Diagnose after 2 abnormal blood tests 12 weeks apart
Management of APS
- Low dose aspirin (or antiplatelets e.g. clopidogrel) if no history (prophylactic)- If history of clots + APS Ab: WARFERIN - contraindicated in pregnancy (birth defects + placenta bleeding)- Pregnant: LMWH + ASPIRIN- Lifestyle -> smoking cessation, reg exercise, healthy weight etc
Acronym to remember main parts of APS
CLOT:-Coag defect- Livedo reticularis- Obstetric complications- Thrombocytopenia (in some)
Red flags for Low Back Pain
TUNA FISH:- Trauma (suggests osteoporsis)- Unexplained weight loss (cancer)- Neurological symptoms (cauda equina syndrome)- Age >50 or <20 (secondary bone cancer, ank spond, herniated disk)- Fever (infection)- IV drug use (infection - esp pseudomonas aruginosa)- Steroid use (infection)- History of cancer (spine mets)
Diff diagnosis of mechanical lower back pain
- Lumbosacral muscle strains/sprains- Lumbar spondylosis- Herniated disk (oft involves L5/S1 nerve root)- Spondylolysis (minor stress fracture in lumbar vertebra)- Vertebral compression factor- Spondylolisthesis (a vertebra moves foward straining disk + connections to other vertebrae)Spinal stenosis
Most common primary bone cancers
- Chondrosarcoma- Osteosarcoma- Ewing sarcoma (mesenchymal stem cell in bone marrow) - v. rare (seen in teens - 15 y/o)(also Fibrosarcoma - but is not a bone cancer)Rarer; more common in childrenSecondary tumours and MYELOMAS are most common
RFx for primary bone cancer
- Previous RADIOTHERAPY- Previous CANCER- PAGET’S DISEASE- Benign bone LESIONSMore common in MALES
Presentation of Bone cancers
- Bone PAIN - WORSE at NIGHT (wake up at night) - Constant or intermittant (not associated with movement) - may increase in intensity - Resistant to analgesia- Atypical bony/soft tissue swelling/masses - Easy bruising (if affecting bone marrow) - may have path. fractures- Mobility issues (unexplained limp, joint stiffness, reduced range of motion) - esp of LONG BONE/VERTEBRAE- Inflammation/tenderness over bone- Systemic symptoms (fever, weight loss, fatigue)
Investigations for bone cancer
- 1st line: X-RAY - Gold: BIOPSY- Bloods: - FBC, - ESR/CRP, ALP, LDH, Ca all raised - U+E- CT chest/abdo/pelvis (staging)
Appearance of main bone cancers on X-ray
- Osteosarcoma: -looks fluffy (bone destruction), - sun burst, - Codman’s triangle (periosteum lifted off bone - can’t lay down new bone) - can have LUNG METS- Chondrosarcoma: - Popcorn calcification - Endosteal scalloping- Ewing sarcoma: - Onion skin change
Management for bone cancer
Chemo/Radiotherapy- Bisphosphonates if increased bone lysisSurgery -> limb sparing or amputation
Complications of bone cancers
Hypercalcemia, bone pain, metastases, pathological fractures
Most common primary bone cancer in children
Osteosarcoma - is the most common primary bone balignancy in general
Define osteomalacia
Poor bone mineralisation leading to soft bone, usually due to vit D deficiency (in adults) AFTER EPIPHYSIAL FUSIONRickets is specifically caused by inadequate mineralisation of bone and epiphyseal cartilage in a GROWING skeleton ie BEFORE EPIPHYSIAL FUSION (children)
Causes/Risk factors for Osteomalacia
- Inherited- Hyper PTH (could be due to low vit D)- Low vit D - Malabsorptive disorders (IBD) - low sunlight exposure/live in colder climate + spend most of time indoors - darker skin - CKD (kidneys convert vit D to 1,25-dihydroxyvitamin D (Calcitriol)) - Liver disease (decreased vit d hydroxylation - cholecalciferol -> 25-hydroxyvitamin D) - Anticonvulsant drugs (increased Cytochrome P450 metabolism of Vit D)
Pathophys of Osteomalacia
Poor bone mineralisation due to CALCIUM DEFICIENCY - usually due to vit D deficiency -> reduced Ca2+ and PO4^3- (forms hydroxyapitite - mineralises bones) -> soft bones
Presentation of Osteomalacia
- Fatigue- Bone pain + tenderness - dull ache which is worse on weight-bearing exercises - difficulty weight-bearing- Fractures (esp in neck of femur); abnormal fractures- PROXIMAL weakness/muscle aches- Waddling gait; difficulty with stairs
Presentation of Rickets
- Growth retardation- Hypotonia- Skeletal deformities: - Knock knees (valgus deformatiy) - Bow legs (varus deformity) - Wide epiphysis on imaging
Investigations for osetomalacia
- X- ray: loss of cortical bone due to defective mineralisation - Looser zones (transverse lucencies w/ sclerotic borders) - basically partial fractures - osteopenia - more radiolucent bones- DEXA -> low bone mineral density- Bloods: low serum calcium + phosphate, PTH will be raised if vit D def; ALP raised - Serum 25-hydroxyvitamin D - low- Bone biopsy - incomplete mineralisation - DIAGNOSTIC
Ranges for 25-hydroxyvitamin D (-cholecalciferol)
- < 25 nmol/L = vit D deficiency- 25-50 nmol/L = vit D insufficiency- >75 nmol/L = optimal
Management of Osteomalacia
- Vit D supplements (-> rapid mineralisation + reduce symptoms) - Colecalciferol (D3 tablets)/increase in diet e.g. eggs - for deficiency: - 50 000 IU 1/wk for 6wks - 20 000 IU 2/wk for 7wks - 4000 IU daily for 10wks - If dietary insufficiency/after initial treatment - 800 IU or more /day for life - If malabs - give IM calcitriol
Define Paget’s Disease
Focal disorder of excessive bone turnover/ remodelling that results in areas of sclerosis and lysis
Risk factors for Paget’s disease
- Age >50- MALE- European origin- FHx
Pathophysiology of Paget’s disease
- Excessive Osteoblast/clast activity (resorption + disorganised new bone formation) -> excessive bone turnover- Patchy areas of sclerosis in some places and lysis in others- Enlarged + misshapen bones -> risk of fracture- Particularly affects axial skeleton (skull, spine), pelvis + long bones of limbsHappens in 3 phases:- lytic phase- mixed phase- blastic phase
Investigations for Paget’s disease
X-ray:- Bone enlargement + deformity- Osteoporosis circumscripta (well defined lytic lesions) in some places (esp skull)- Cotton wool appearance in skull (poorly defined areas of sclerosis + lysis)- V-shaped defects in long bonesBloods: ALP RAISED, everything else normal
Management of Paget’s disease of bone
- Bisphosphonates- Calcium + vit D supplements (esp while on bisphosphonates)- NSAIDs for bone pain- Surgery to correct deformaties
Complications of Paget’s disease of bone
- OSTEOSARCOMA- Spinal stenosis (narrowing of spinal canal) -> cord compression -> potential neuro symps
Define polymyalgia rheumatica
Inflammatory condition that causes pain in shoulders, pelvic girdle and neck.
Risk factors/associations of Polymyalgia rheumatica
Strong association with GCV - oft occur together- Age > 50- FEMALE- Caucasian
Pathophys of Polymyalgia rheumatica
Cause unknown but believed to be multifactorial.Inflammation of muscles in shoulder, neck + pelvic girdle -> pain + stiffness
Presentation of Polymyalgia rheumatica
Symps must have been present for 2 weeks to be diagnosed- Bilateral shoulder pain (may radiate to elbow)- Bilateral pelvic girdle pain- Worse in morning (>30min)/with inactivity- Interferes with sleep- RESPONDS WELL TO STEROIDS (like GCV)Systemic: weight loss, fatigue, low grade fever, low mood- upper arm tenderness- carpel tunnel syndrome- pitting oedema
DDx for Polymyalgia rheumatica
- SLE- myositis- hyper/hypo thyroid- Osteomalacia- Osteoarthritis- Rheumatoid arthritis- Cervical spondylosis- Adhesive capsulitis- Fibromyalgia
Investigations for polymyalgia rheumatica
Diagnosis mainly based on clinical presentation + response to steroids- Bloods: Raised inflam markers- NORMAL CREATINE KINASE (diff from myositis - no muscle damage) and creatinine (rhabdomyolysis)For diffs - check before starting steroids:- FBC, U+E, urin dipstick, LFTs, Ca, TSH, CK, RF (-ve)- Serum protein electrophoresis (for myeloma/other protein abnormalities)
Management of polymyalgia rheumatica
Initially: 15mg PREDNISOLONE per DAY - rapid improvementIf poor response to steroids after 1 week - probs not PMR - stop steroids + consider alt diagnosisAfter 3 weeks:- would expect 70% improvement in symps + normal inflam markers to diagnose PMR-> reducing regime (15mg till fully controlled, 12.5mg for 3 wks, 10mg for 4-6wks, reduce by 1mg every 4-8 wks)
Things to consider when on long term steroids
Pt needs to be aware they will become steroid dependant after ~3 weeks and must not stop steroids as - risk of ADRENAL CRISIS
think STOP:
- Sick day rules - if sick, increase dose
- Treatment card - to inform others they are steroid dependant if they become unresponsive
- Ostoporosis prevention (consider prophylactic bisphosphonates + calcium/vit d supplements)
- PPIs (consider for gastric protection)
Define Rheumatoid arthritis
Autoimmune inflammation (and subsequent destruction) of joints (typically starting with small joints leading onto big joint inflammation) in a symmetrical pattern of involvement. No spinal involvement
Epidemiology of RA
- 1-2% population- 2-3x more common in females- Middle age (but any age)- Increase risk of mortality esp CVD- Increasing damage + disability if left untreated (infalmmation treatable. Damage irreversible)
Risk factors for RA
- Women 30-50 - 3x more likely than in men pre-menopause - equalises with men after menopause- FHx - HLA DRA/HLA DRB1 genetic link (same group as DM)- Smoking
Pathophys of RA
- ARGININE -> CITRULINE mutation in T2 COLLAGEN - anti-CCP (cyclic citrulinated peptide) formation- Increased T cell mediated w/ neutrophil + monocyte involvement inflammation - releases cytokines -> SYNOVIAL LINING HYPERPLASIA -> PANNUS (inflam cells + cytokines) - Pannus releases metalloproteinase + grows past joint margins -> Erode into cartilage and then bone- After cartilage breakdown - bones rub against each other + degenerate
Which cytokines particularly linked to RA
IL-1 + TNFa
presentation of RA
- Pain, hot swelling of: - Symmetrical, typically small joints: hands, wrists, - forefeet - DIP sparing- Hand deformaties: - Boutonniere (like pushing button) - Swan neck - Z thumb - Ulnar finger deviation- Prolonged early MORNING STIFFNESS (>1 hour) - improves as day progresses - Sudden change in function- Big joints involved later, bad prognostic sign if involved at presentation - BAKER’S CYST - popliteal synovial sac bulgeCan get Intermittent, Migratory or Additive involvement- No spinal involvementExtra-articular involvement
What are the Extra articular complications of RA
- Lungs = pulm fibrosis- Heart = increased IHD risk- eyes = episcleritis, keratoconjunctivitis siccs (dry eyes)- Kidney = CKD- RHEUMATOID SKIN NODULES (most common - esp at elbows)- increased risk of vasculitis and Sjogren’s
Diagnosis of RA
- Physical Exam- Bloods: - CRP (+/-ESR) - can be raised up to 100 in a flare - RF (70% with RA are RF +ve but non-specific) - Anti-CCP (cyclic citrullinated peptide) - 70-80% with RA are +ve (specific) - Selective for patients with most AGGRESSIVE disease (likelihood of damage, multisystem features - tells us additional treatment needed)- XR esp Hands + feet - DIAGNOSTIC + prognostic
Findings of physical exam of RA
- Decreased grip strength / difficulty in fist formation- Often subtle synovitis – MCPs, PIPs, MTPs, ankles- DIPs are spared- Usually symmetrical- Deformity unusual at presentation
Findings of XR for RA
LESS- LOSS OF JOINT SPACE (narrowing)- EROSION OF BONE- Soft tissue swelling- Soft bone from PERIARTICULAR OSTEOPENIA (imbalanced remodelling)
Treatment of RA
- DMARDs - need to give quickly as 65-75% efficacy raised to 90% if started within 3 months - METHOTREXATE (Gold - contraindicated in preg - inhibits folate) - 10-25mg per week - Also Sulfasalazine, Leflunomide, Hydroxychloroquine (sulfasalzine + hydroxychloroquine ok in preg)- Physio, Ortho, Podiatry -> support + educate- Escalate to BIOLOGICS if RESISTANT (v expensive) - Anti- TNF = INFLIXIMAB (1ST LINE biologic - alongside MTX), ADALIMUMAB - Rituximab (anti CD20 - ie anti B cell) - 2nd line - Tocilizumab (IL-6 inhib) - Abatacept (anti-T cell) - JAK INHIBITORS (Baricitinib/Filgotonib)- NSAIDs- STEROIDS injections if v painful (can give oral too)- Ice- Splints/rest
Define gout
Acute joint pain + swelling caused by inflammatory response to deposition of monosodium urate crystals intra-articularly
Epidemiology of gout
Gout 6x more common in MEN (7.3% >75 y/o) + ELDERLY - esp OVERWEIGHT- Overall male : female ratio 5:1- Uncommon in females under 50 due to hormone
RFx for gout
HyperuricaemiaIntake:- ALCOHOL (beer, lager, stout) - rich in GUANOSINE- Diet – red meat, shellfish, offal- Sweetened soft drinks (fructose shares renal uric acid transporter so promotes uric acid pathway -> don’t get rid of uric acid -> hyperuricemia)Output:- CKD (more common in elderly) -> lactic acid + ketones- Drugs - esp DIURETICS, aspirin, cyclosporin, TB drugs- Genetics- Fructose shares renal uric acid transporterUric acid also a product of DNA/RNA metabolism - high cell turnover -> increased urate
What food is anti-gout
DAIRY
Pathophys of gout
HYPERURICAEMIA (plasma supersaturated at 360mmol/L -> MONOSODIUM URATE crystal formation- deposit in joints -> affects synovial cells- immunological reaction initiated to try and remove them, leads to acute pain and swelling
Presentation of gout
- Acute episodes (will recover spontaneously within 7-10) - recurrent - typically predictable = MONOARTICULAR esp MTP big toe joint - also Mid-foot, ankle, knee, wrist, elbow, hand - esp at NIGHT - Swelling, Erythema, Shiny overlying skin - possible periarticular involvement - E.g. Olecranon bursitis - bursa fills with extra fluid due to irritation/inflam -> swollen - activates inate immune so sometimes get systemic - can’t put weight on it - Chronic = has Tophi (pathognomonic)
DDx of inflamed joint
Septic arthritisTraumaGoutCalcium Pyrophosphate Arthritis (pseudogout)Rheumatoid Arthritis(Osteoarthritis!) - also oft commonly involves toe
Clinical phases of untreated gout
🡪 asymptomatic hyperuricemia, 🡪 acute/recurrent gout,🡪 intercritical gout (recurrent flares - intercritical = time between flare, typically occurs within 2 years) - more + more frequent🡪 chronic tophaceous gout (typically after 10yrs or more of recurrent polyarticular/poorly controlled gout - Tophi can form in soft tissue, osseous tissues, ligaments and different organs and either in presence or absence of gouty arthritis) - tophi is just the name of the stone like monosodium urate deposits - esp undersurrounding skin
Diagnosis of gout
Gold = JOINT ASPIRATION + POLARISED LIGHT MICROSCOPY - STRONGLY NEGATIVELY BIREFRINGENT NEEDLE SHAPED crystals - not seen in normal healthAlso:- FBC (raised WCC)- U+E (checking kidney function - affects treatment)- LFT if concern re alcohol- Serum Uric Acid (often normal during acute attack as uric acid is in joint so less in blood)- CRP- Only use Xray if recurrent episodes or concern re sepsis - Punched out/Rat bite EROSIONS (joint space preserved but erosion away from/below articular border) - extensive in late disease
Tx of acute gout
- Rest, ice, hydrate, continue urate lowering therapy- NSAID (short course) but CONTRAINDICATED if: - Renal failure - Peptic Ulcer Disease - Some pts with asthma- COX-2 inhibitors (NSAID alt) - Elderly don’t tolerate NSAIDs well- Colchicine (alt to NSAIDs) - anti-mitotic - disrupts multiple inflam pathways - SE = Diarrhoea- Corticosteroids - Intra-articular injections - Oral - low dose (5-10mg short course)Other analgesics don’t work! - they don’t deal with inflammationEDUCATE PATIENT - explain the disease -Advice about lifestyle, Alcohol, Diet, Weight loss - reduce purines, increase dairy - Adequate fluid intake (increased incidence in summer due to dehydration)
Tx of long tem gout
URIC ACID LOWERING THERAPY:Xanthine Oxidase Inhibitors: - 1. Allopurinol (1st line)- 2. Febuxostat (if allopurinol not tolerated/doesn’t work - e.g. CKD) – more potent Xanthine Oxidase InhibitorIncreases urate excretion- 3. Benzbromarone / Probenecid – if allergic / intollerant- LosartanGive Colchicine 500microg OD for 6 months alongside this as there is an increased risk of CV morbidity (lots of uric acid being moved around body)
Indications for uric acid lowering therapy
- Recurrent attacks2. Evidence of tophi or chronic gouty arthritis3. Associated renal disease4. Normal serum Uric acid cannot be achieved by life-style modifications
Aim of uric acid lowering therapy
REDUCE URIC ACID BELOW <300 umol/l
complications of gout
Disability and miseryTophiRenal disease:- Calculi 10 -15%- Chronic urate nephropathy- Acute urate nephropathy (cytotoxics)
Pathophys of pseudogout
Deposition of CALCIUM PYROPHOSPHATE crystals along joint capsule
Epidemiology of pseudogout
3x more common in WOMEN - esp ELDERLY- Typically on background for OA
RFx of pseudogout
- Diabetes- metabolic disease- OA
Sx of pseudogout
- oft POLYARTICULAR w/ KNEE commonly involved (also wrists, hands)- SWOLLEN, HOT, RED joint
Diagnosis of pseudogout
JOINT ASPIRATION + POLARISED LIGHT MICROSCOPY - slightly positive birefringent rhomboid shaped crystals - can sometimes be found in normal healthAlso:- FBC (raised WCC)- CRP- X RAY - CHONDROCALCINOSIS - May see subcondral cysts
Tx of pseudogout
Only acute treatment- NSAIDs- then Colchicine- then Steroid injections
Define osteoporosis
A systemic skeletal disease characterised by low bone mass and microarchitectural deterioration of bone tissue, with a consequent increase in bone fragility and susceptibility to fracture
Epidemiology of osteoporosis
% of people who will get an osteoporotic fracture:- 50% of females over 50 (POST MENOPAUSAL CAUCASIAN WOMEN)- 20% of males over 50
RFx for osteoporosis
SHATTERED- Steroids or RAISED CORTISOL (Cushings) - increase resorption + induce osteoblast apoptosis- Hyperthyroid/Hyper PTH- Alcohol + smoking (poisons osteoblasts)- Thin (low BMI)/reduced skeletal loading- Testosterone LOW - EARLY MENOPAUSE (low oestrogen)- Renal/Liver failure- Erosive/Inflam disease - cytokines increase resorption- DMT1 or MalabsorptionOlder age, any type of hypogonadism, previous fractures- FAMILY HISTORY (50% bone structure inherited)Drugs: Depo-provera (in young women)Aromatose inhibitors (breast cancer)GnRH analoguesAndrogen deprivation
Pathophys of osteoporosis
Fractures triggered by some sort of force greater than strength of boneBone strength affected by:- Bone mineral density (standard measure of osteoporosis)- Bone size- Bone quality (depends on Turnover, Architecture + Mineralisation)Oestrogen keeps bone turnover damped down - Post menopausal -> loss of restraining effectsIncreased bone turnover (more and more left in partially resorped state) → net loss of boneTrabecular architecture becomes poorer with age:-> loss of cross connecter trabeculae which prevent buckling -> ~16x weaker boneRemodelling unit activation frequency increases with age - damage more likely so remodelling needed more
Sx of osteoporosis
FRACTURES- Wrist (Colles) - fall on outstreatched wrist - more common in 50-60 y/o- Hip/Proximal femur - older ppl fall + can’t catch themselves- Compression vertebral crush (may cause kyphosis)
Dx of osteoporosis
Bone densitometry - DEXA scan - Duel energy XR absorptionometry but low radiation dose- For risk assessment + diagnosis - Sites: - LUMBAR SPINE - PROXIMAL FEMUR - DISTAL RADIUS- Gives a T-SCORE - a standard deviation score: - Number used for DIAGNOSIS - Compares with a GENDER-MATCHED YOUNG ADULT meanAlso FRAX score (Fracture Risk Assesment Tool)- assess 10y fracture risk in osteoporotic patients
Diagnostic criteria for osteoporosis + osteopenia
T-score- Osteoporosis = < -2.5- Osteopenia = -1 - -2.5severe osteoporosis os <-2.5 + a fracture
Tx for osteoporosis
Anti-resorptive:- BISPHOSPHONATES - inhibit osteoclasts by inhibiting RANK-L signelling - Oral: ALENDRONATE (daily/weekly), Risedronate, Ibadronate - IV: Ibadronate, Zolendronate (once yearly)- Denosumab - rapid acting RANK-RANKL inhibitor (potential rebound turnover increase if stopped)Anabolic: Teriparatide (PTH analogue) - expensiveAlso:- HRT- oestrogen receptor modulator - raloxifere
Define septic arthritis
Direct bacterial infection of a joint- direct access or haematogenou spread
Epidemiology of septic arthritis
45% > 65 y/oProsthetic joint infection > native- Risk of infections in prosthetic joints increasing- Septic revision = X2 cost of non-septic and >3x cost of primary replacementM = F
Presentation of septic arthritis
- V Painful, red, swollen, hot joint w/ joint in previously fit person - Children may just not use it so you may not notice at first- 90% monoarthritis (don’t rule out if polyarticular)- KNEE > Hip > shoulderMEDICLA EMERGENCY - can destroy knee in 24hrs or less!
RFx for septic arthritis
- Any cause for bacteraemia- Direct/penetrating TRAUMA- Local skin BREAKS/ULCERS- DAMAGED joints - PROSTHETIC JOINTS- IMMUNOSUPPRESSION (including just steroids)- ELDERLY (>65 Y/O)- RA or other immune diseases- DIABETES
Common pathogens affecting adult native joints
- Staph Aureus (esp consider if have RA/DM) - mc- Strep - Group A (pyogenes) - b haemolytic - Group B - Strep pneumoniae- Neisseria gonorrhoea (consider in young, sexually active, MSM)- Gram -ve bacilli (consider in extremes of age, if systemically unwell or IVDU) - E coli - Pseudomonas Aeruginosa- Anaerobes (diabetes) - Clostridium - Bacterioides- Mycobacterium - typically TB (immunocomp)- Fungi (immunocomp)
Most common pathogens affecting native joints in children
<2 y/o:- S AUREUS- Strep esp Gp A- Gram -ve bacilli (e.g. Kingella Kingae - a oropharyngeal commensal) - Historically most common were HAEMOPHILUS INFLUENZA, s aureus and strep (Gp A) but H influenza is no longer a common infection due to the vaccination program>2 y/o:- S AUREUS- Strep- Gram -ve bacilli -Historically H influenza was more common than gram -ve
Common pathogens affecting prosthetic joints
- STAPH AUREUS (most common)- Enterococci- MRSA- Enterobacter- Pseudomonas- Diphtheriodes- Haemolytic strep- Anaerobes
Dx of septic native joint
- FBC: high WCC (neutrophilia)- CRP raised (esp if over 100 - up to 100 could indicate a RA flare) - ESR can be normal- Blood cultures (sepsis)- sexual health review to check for gonorrhoea- Joint aspirate (usually seeded by bacteraemia) - GOLD, always do - Turbid fluid (ie more opaque/cloudy/thick+gloopy) - Leukocyte positive - Gram stain for microbes - polarised light microscopy to rule out gout/pseudogout
Dx of prosthetic joint
- History - Oft present with just pain (not hot/swollen) - Local: wound healed slowly; always been sore (means infection was always there since prosthesis put in - presents faster) - Haematogenous: became painful after recent infection/dental work- Examination- X-rays- FBC (usually unfelpful - high WCC uncommon as usually chronic)- ESR, CRP - Single CRP >10 and ESR >30 = 50% chance of infection (if normal 90% chance not infected) - Multiple raised = 80% chance of infection (if multiple normal = 95% chance not infected)If other tests inconclusive: Alpha defensin (antimicrobial peptide secreted by neutrophils) - sensitivity/specificity ~95% but v expensiveASPIRATION -> Microbio culture (aerobic + anaerobic)- Patient needs to be off antibiotics for at least 2 weeks
Tx of native septic joint
- Stop immunosuppression - If on long term steroids - DOUBLE DOSE as they may be unable to naturally increase steroid levels- Analgesia (NSAIDs)- JOINT ASPIRATION (repeatedly if needed) + washout until no recurrent effusion- empirical ANTIBIOTICS - long course: 6 WEEKS MIN - flucloxacillin for g-ve, - vancomycin for MRSA, - ceftriaxone + azithromycin (gonorrhoea)- Splinting/rest/off-load with crutches/physio
Tx of prosthetic septic joint
- Analgesia- Stop immunosuppression, increase steroids etcPotential options:- after determining specific bacteria -> ANTIBIOTIC SUPPRESSION - will not eliminate sepsis but used if unfit for surgery/if they have multiple prosthetic infections- DEBRIDEMENT + retention of prosthetic - NOT FOR CHRONIC, retains infection - only if prosthesis not loose- EXCISION ARTHOPLASTY (remove only infected section, let it fill in with scar tissue) - if HIGH RISK- One stage arthroplasty - RADICAL DEBRIDEMENT - avoid bone graft - will reinfect - 85% success- Two stage arthroplasty - radical debridement - can put in local antibiotic spacer/give systemic Abx in waiting period - 90-95% success- Amputation
Characteristic presentation of gonococcal arthritis
Occurs from disseminated gonococcal infection- Fever (potentially), arthritis, tenosynovitis (inflammation of tendon sheath/synovial membrane around tendons - harder to aspirate) - Polyarticular - multiple joint, small + large- Maculopapular (grey base - pustular lesions) - Esp in Peripheries (palms, soles) - Painful before it is visible - Usually >5 lesions
Define osteomyelitis
Acute inflamed infected BM
Epidemiology of Osteomyelitis
Increasing incidence of chronic osteomyelitis - increased prevalence of predisposing conditions such as diabetes mellitus and peripheral vascular disease.- Ageing population**Bimodal age distribution **- Children 80% of acute, haematogenous osteomyelitis- Adults >50 y/o - Adolescents and adults get contiguous osteomyelitis/direct inoculation (often associated with direct trauma) - Older patients: oft contigous linked to Diabetes mellitus/Peripheral Vascular disease/Arthroplasties
Causes/RFx for osteomyelitis
- Behavioural factors -Ie risk of trauma - e.g. if they enjoy extreme sports etc- Vascular supply (poor) - Arterial disease - DM - Sickle cell disease- Pre-existing bone/joint problem - Inflammatory arthritis - Prosthetic material including arthroplasty- Immune deficiency - Immunosuppressive drugs - Primary immunodeficiency- Similar RFx to IE - IVDU - Central lines; on dialysis - Catheter- UTI/other infection
Common pathogens associated with osteomyelitis
Common microbes:- STAPH AUREUS (mc)- coagulase-negative staphylococci, - aerobic gram-negative bacilli (30%)Others:- Streptococci (skin, oral) - Enterococci (bladder, bowel) - Anaerobes (bowel)- Fungi, (immunocomp)- Mycobacterium tuberculosis (immunocomp)In SCD:- SALMONELLAIn IVDU:- PSEUDOMONAS AERUGINOSA- Serratia marcescens
Routes of how pathogens can cause osteomyelitis
- Direct innoculation - trauma/surgery (poly/monomicrobial)- Contigous spread - from adjacent soft tissue/joints (poly/monomicrobial)- Haematogenous seeding (monomicrobial)
Haematogenous seeding osteomyelitis - which bones commonly affected + pathophys
Children = LONG BONES- High but slow blood flow to metaphysis of growing long bones (high metabolic activity)- Endothelial basement membranes absent (easier to get into bone)- Capillaries lack/have inactive phagocytic lining cells (less immune defence)- Predisposes to infectionAdults = VERTEBRAE + clavicle/pelvis- Vertebrae become more vascular with AGE- Bacterial seeding of vertebral endplate more likely- Also: lumbar vertebral veins communicate with pelvic veins with valveless anastemoses. Can get infection via retrograde flow from lower GU infectionsIV Drug Users = CLAVICLE + PELVIS (oft younger so vertebrae less vascular)
Pathophys of osteomyelitis
Microbial surface components adhere to matrix molecules- Acutely -> inflammation + bone oedema- Chronic -> SEQUESTRUM INVOLUCRUM - Infalm exudate in marrow - Causes increased intramedullary pressue - Causing extension of exudate into bone cortex - It ruptures through periosteum - Interrupts periosteal blood supply -> NECROSIS - Leaves separated pieces of dead bone - NEW BONE forms - necrotic bone embedded in pus + thick sclerotic bone placed around sequestra to compensate + support abnormal
Presentation of osteomyelitis
- Onset over SEVERAL DAYS- DULL BONY PAIN + HOT + SWOLLEN + ERYTHEMA- May be aggravated by MOVEMENT- Systemic: FEVER, RIGORS, sweats, malaiseIf Vertebral OM: lumbar most common- May extend posteriorly -> epidural/subdural abscess or meningitis- Anterior/lateral extension -> abscesses in surrounding structures e.g. retroperitoneum, psoas If chronic: typical signs + any of below- DEEP ULCERS (sequestrae) that fail to heal despite several weeks of treatment- Non-healing fractures- Draining sinus tractCan also occur close to joint and pus can discharge into joint when infection breaks through cortex (more common in infants)
DDx for osteomyelitis
- Soft tissue infection (Cellulitis (deep dermis + subcut) and erysipelas (dermis +/- superficial cutaneous lympatics))- Bursitis (swelling of joint soft tissue)- CHARCOT JOINT - Progressive degeneration of weight bearing joint + bony destruction due to sensory nerve damage e.g. in DIABETIC NEUROPATHY - Oft affects foot -> presents w/ Diabetic feet- Gout- Avascular necrosis of bone (from steroids, radiation, bisphosphonates)- Fracture- Malig
Investigations for osteomyelitis
- History (symptoms)- Examination (signs)- Lab tests: CRP + WCC (FBC) - Acute - HIGH WCC - Chronic - can have NORMAL WCC - CRP raised but can be normal- Imaging: - PLAIN XR - Poor sensitivity/specificty esp in EARLY OM - Only osteopenia initially - >1-2 weeks before bone changes - MRI (more senstitive) - marrow oedema from 3-5 days - Delineates cortical, bone marrow and soft tissue inflammation - CT (alternative to MRI) - Nuclear Bone scan if metalwork makes CT/MRI impossible- BLOOD CULTURES (can be diagnostic) - may not need invasive diagnostic testing if organism isolated from blood is a pathogen likely to cause osteomyelitis. - +ve in 50% of Acute OM- BIOPSY (diagnostic) - Open bx»_space;> needle bx - 2 specimens better than 1 - Culture - 16sRNA PCR may be necessary (to get enough to culture)- Histology showing inflammation and osteonecrosis
What are the XR changes seen in chronic osteomyelitis
- cortical erosion, - periosteal reaction, (edge raised) - mixed lucency, - Sclerosis - sequestra - soft tissue swelling
Tx of osteomyelitis
- Immobilise- ANTIMICROBIAL THERAPY - 6 weeks IV minimum - first broad spectrum empirical then tailor to specific - Vanc/Teicoplanin (MRSA + s aureus) - Fusidic acid (s aureus) - Flucoxacillin (salmonella) - poor penetration to bone if vascular disease - stop based on CRP response - failure to respond -> re-image (but bone changes may persist even with infection resolution) - faster resolution if TOTAL SURGICAL DEBRIDEMENT
Why may Teicoplanin be prefered over vancomycin in osteomyelitis and what are its SE
it’s longer lasting- GI upset- Pruritis
Complicated osteomyelitis
TB OM- May be slower onset- Systemic symptoms- Epidemiology different from pyogenic OM- Blood Culture less useful- Biopsy essential - prolonged mycobacterial culture - Caseating Granolumata on histology - Induced sputum may help (sometimes occult pulmonary TB)- Longer treatment 6 months
Define Seronegative spondyloarthropathies + epidemiology
- Asymmetrical inflammation of BIG joints with SPINAL involvement (excluding psoriatic arthritis which can be Symmetrical)- Seronegative = RF negative- More common in MEN- ASSOCIATED w/ HLA B27 (MHC-1) - link to IBD
General features of Spondylathropathies
SPINE ACHE- Sausage digits (dactylitis)- Psoritis- Inflam back pain- NSAID GOOD RESPONSE- Enthesitis (inflam of enthesis - site where ligaments insert into bone - esp heel)- Arthritis- Crohn’s/Colitis/raised CRP (can have normal CRP in AnkSpond)- HLA B27- Eye (anterior uveitis)
Pathophys Ankylosing Spondylitis
Abnormal stiffening of joints - primarily sacrioiliac + axial skeleton - due to new bony formation- Prolonged Inflam/oedema -> fatty change -> calcium deposists along tendon - SYNDESMOPHYTES (vertical abnormal growth) esp at corners of vertebrae - make spine less mobile
RFx for Ank Spond
- HLA-B27 ASSOCIATED - class 1 so in all cells (possible to have without HLA-B27 tho) - Molecular mimicry (e.g. if pathogenic molecule has compound similar to HLA-B27 -> ) - Misfolding theory (sets of inflam due to diff shape) - IL23, IL17, 16, TNFa - KEY - Heavy chain homodimer hypothesis- MALE - usually <40 y/o- Smokers
Presentation of Ank Spond + 1 key complication
- Progressively worsening (in flares) LOWER BACK PAIN + STIFFNESS - Worse in morning/after inactivity; better with movement - alternating nagging sacroileac/BUTTOCK pain- EMPHASITIS (esp achiles tendon) - swollen, thick, increased blood flow- Anterior uvitis - photophobia, possible vision blurring, iris scarring if recurrent- Psorisis (elbows + knees - extensor surfaces) - red base, white scale, itchy- clear synovial fluid accumulation- End-stage: fusion of spine + SI joint - Severe kyphosis (question mark posture)- can get costovertebral + costosternal inflammation -> potenitally eventual restrictive lung diseaseComplication: vertebral fractures
Classic presentation of inflam spine disease
- Youngish patient (teens/20s)- Gradual onset over >3 months- Can go to sleep fine but wake up in middle of night due to (usually thoracic) back pain - Improves with movement- Significant morning stiffness (>30 mins)- Alternating, nagging buttock pain - radiating down back of thigh (sacroileac joint pain)
Diagnosis of Ank Spond
- CRP + ESR - raised (1st LINE)- HLA B27 genetic test - oft positive- MRI spine - Subchondral periarticular bone marrow oedema (early changes) breaking out of cortical bone - over time heals with fatty change- XR spine/pelvis (takes 8-10 years to show up usually) - bamboo spine (END STAGE) due to ossification of ligaments, discs + joints (calcium has grown along ligaments, fused spine together) -> radiographic stage (ankylosing spondilitis) - Syndesmophytes (bony growth originating from spinal ligament - like stalactites) - more common in men; more likely if elevated CRP - Squaring of vertebral bodies - Subchondral sclerosis + erosions - Can get ribcage involvement (fusion of facet + costovertebral joints) - Sacroiliitis (sacrum + hips) - have fused together - stops being painful but reduced mobility
Test to check lumbar flexion ability
SCHOBER TEST- they make marks 10cm above and 5cm below the ileac crest or L5 (around 15 cm apart)- When they bend over with the legs fully extended (and feet 30 cm apart) - the marked area should extend by around 5cm or more (at least ~20cm)- <5cm increased length on flexion = indicative of ank spond- <2 = severe
Treatment of ank spond
- Exercise, Physiotherapy, lifestyle advice (smoking ceaseation)- NSAIDs - Biologics (disease modifying) - Anti-TNF, - etanercept (not an Ab), infliximab, adalimumab - Anti-IL17 - Secukinumab - JAK inhib (good for whole spectrum) - works inside cellsSULFAZALASINE DOESN’T WORK on SPINAL INFLAM
Epidemiology of psoritic arthritis
- 10-40% w/ psorisis develop within 10 y- 1 in 5 with psoriasis have psoriatic artheritis- 40-60% have HLA B27
Presentation of psoritic arthritis
- Symmetrical or Asym - INVOLVES DIPs - ATLANTA-AXIAL joint involvement - ENTHESITIS - Achiles tendon, plantar fascia- DACTYLITIS- NAIL PITTING (>5-10 pits across both hands = indicative) - ONYCHOLYSIS - lifiting of nail from nail bed- End-stage = bone fusion
V severe presentation of psoritic arthritis
ARTHRITIS MUTILANS (v rare)- Occurs in phalanxes- Osteolysis of bones around joints in digits → progressive shortening - Skin then folds as digit shortens → telescopic fingerPENCIL IN CUP DEFORMITY
Investigation of psoritic arthritis
- Bloods: ESR + CRP - normal or raised; RF -ve; ant-CCP -ve- HLA-B27 genetic test - may be positive- X RAY: - DIP EROSION - Periarticular NEW BONE formation (looks DARKER) - Osteolysis (destruction) - Dactylitis (diffuse inflam appears as soft tissue swelling - may be more visible on MRI) - Pencil-in-cup deformity (in MUTILANS)
Treatment of psoariatic arthritis
- NSAIDs for symps - steroid injection if severe- Physio- DMARDS esp METHOTREXATE - try avoid sulfasalazine - CVD issues- if fails then ANTI-TNF (INFLUXIMAB, ETANERCEPT, adalimumab)- if that fails: IL12/23 BLOCKERS - USTEKINUMAB - works best for peripheries- IL17 blockers
Define reactive arthritis
Sterile inflammation of synovial membranes + tendons triggered by infection at DISTANT site- usually GI or genital/STI
Common triggering pathogens of reactive arthritis
- C trachomatis- Campy jejuni- Salm enteritidis- ShigellaAlso:- yersinia- ureaplasma urealyticum
Presentation of Reactive arthritis
Usually 2 days - 2 weeks post infection- Asymmetrical Oligoarthritis (affects 4 or less joints) - esp knees, ankles, feet - hot, swollen, painful, red + stiff joint- Dactylitis- REITER’S TRIAD: can’t see, can’t pee, can’t climb a tree - Conjunctivitis (discharge, burning, photophobia) - typically bilateral - may have anterior uveitis - Urethritis/Circinate balanitis (inflam of penile head with lesions) - Reactive arthritis + Enthesistis- Keratoderma blennorrhagica - palmo-plantar browny pustular rash
Diagnosis of reactive arthritis
- Bloods: ESR + CRP raised- HLA B27 may be +ve- ANA - negative- RF - negative- X-RAY - Sacroiliitis (pain in SI joints) - Enthesitis- Joint aspirate (MC+S) - negative (to exclude septic) - Can confirm not gout if sent for crystal examinationSexual health review + stool culture
Treatment of reactive arthritis
- NSAIDs- Steroid injections (systemic steroids if polyarticular)- Prophylactic Abx till septic excluded>6 consequtively = CHRONIC- DMARDs (MTX) then anti-TNF if MTX doesn’t work
What is enteric arthritis
Inflam arthritis that flares up alongside IBD. Oft has inflam pain without overt arthritis. Oft involves SACROILIITIS.Peripheral arthritis that subsides with remission of IBD.- same extra-articular manifestations as IBD
Define/Pathophys of Systemic Lupus Erythamatosus
Autoimmune systemic inflammation caused by a Type 3 hypersensitivity reaction (antigen-antibody complex deposition)Impaired apoptotic debris is pressented to TH2 cells -> B cell activation -> immune complex formation + deposition -> inflammation + tissue damage
Epidemiology of SLE
Most common in FEMALES- more common in Afro-Caribbean premenopausal women (20-40)
RFx for SLE
- FEMALE (12x higher risk) (16-64 - of child bearing age)- HLA B8/ DR2/DR3 - Low C4 (due to null allele)- Drugs (e.g. isoniazid - anti-TB)Strong association with Antiphospholipid syndrome + thrombosis
Presentation of SLE
Specific skin changes:- Acute: - Malar (butterfly) rash (photosensitive) - sparing of nasolabial folds (crease from nose to mouth) - Generalised erythema - Bullous LE (blistering)- Subacute - Annular (ring around lesions) - Psoriasiform- Chronic - Discoid (scarring) - Scarring alopecia (no hair regrowth) - Lupus profundus (tender, deep, subcutaneous nodules/plaques - localised on esp lateral aspects of arms/shoulders, breast, trunk, buttocks; also scalp, face, proximal extremities)Non-specific skin changes:- Panniculitis (inflammation of subcut fat - red + tender)- Urticarial lesions (raised, v itchy rash e.g. hives/welts)- Vasculitis- Livedo reticularis (mottled appearance)- Oral lesions- Non-scarring alopeciaJoints:- Symmetrical + non-errosive- Deformaties can be corrected- Less proliferative than RACan affect any system:- GLOMERULONEPHRITIS (nephrItic)- Seizures + Psychosis- Serositis (pleural/peritoneal/pericardial inflam) - Pleural effusion- ANAEMIA (AHA - Coombs pos)- RAYNAUD’S- Potential Pyrexia- Recurrent miscarriages - Antiphospholipid syndrome
Dx of SLE
- FBC - CYTOPENIAS (Hb, WCC, plts) - RAISED ESR - CRP may be NORMAL - Creatinine raised- Urine dipstick - haematuria + proteinuria (Nephritic syndrome)- Serology: - 99% ANA +VE (sensitive) - Anti-dsDNA Ab (specific - monitor progression) - Anti-Ro, La, SM (smooth muscle) - may have ribonucleoprotein Ab- LOW C3 + C4- CXR - potential PLEURAL EFFUSION
Tx of SLE
No treatment if mild:- Educate + support (avoid triggers esp sunlight)- Assess any major organ damage- IF ANTIPHOSPHOLIPID AB +VE - AFFECTS TREATMENT DURING PREG- Control atherosclerosis risk factors- Topical - Sunscreen - Corticosteroids- Oral/IV steroids if evidence of active disease (not long term)- Topical/oral Cytotoxic if SEVERE (careful in pregnancy) - Azathioprine, Mycophenolate, Ciclosporin, Methotrexate, Cyclophosphamide (most powerful)- NSAIDs (for joints)- Hydroxychloroquine if DMARD needed- Anticoags- Biologics - Rituximab (if severe) - Belinumab - Autologous stem cell transplant (last resort)
Raynaud’s phenomenon
- Pale + cyanotic changes esp in peripheries- Can be precipitated by drugs- Can get vascular damage e.g. Atherosclerosis, frostbite, secondary to vibrating toolsPrimary:- Fairly benign- No digital ulcersSecondary - related to connective tissue diseases esp Systemic sclerosis, SLE and mixed- Can develop later in life- Can get digital ulcers
Define Sjogren’s syndrome
Multisystem autoimmune EXOCRINE DYSFUNCTIONCan be primary or secondary (Associated with other AI conditions)
Presentation of Sjogren’s
Dry, dry, dry- Dry eyes (keratoconjunctivitis sicca)- Dry mouth (xerostomia) - Parotid swelling- Dry vaginaAlso:- Arthritis- Rash- Vasculitis- Neurological- Interstitial lung disease- Association with pericarditis- Renal tubular acidosis (type 1)
Investigations for Sjogren’s
- Serology: - Anti-Ro + Anti La (for PRIMARY sjogren’s) - ANA oft +ve; RF may be +ve- SCHIRMER TEST - induce tears + place filter paper in/under eyes - <10mm significant (healthy should travel at least 15mm)- US - abnormal salivary glandsUncommonly a lip biopsy may be done -> Sialadenitis (salivary gland infection)
Tx of Sjogren’s
- Tear + saliva replacement- Vaginal lubrication- Hydroxychloroquine - if history of fatigue, mayalgia, arthralgia or rashes - can stop progression- Corticosteroids (if organ-threatening involvement)- Immunosuppression if lung/kidney involvement
Complications of Sjogrens’s
Risk of RENAL TUBULAR ACIDOSIS - type 1:- Syndrome characterised by hyperchloremic metabolic acidosis (ie acidosis caused by bicarb loss) with a normal anion gap- (type 1 = problem at distal part of tubules; type 2 = problem at proximal part of tubules, type 3 = carbonic anhydrase 2 def + carbonic anhydrase inhib block metabolism of bicarbonate + carbonic acid (rare); type 4 = hyperkaelemic distal)- Treat with alkali therapyDirectly confers Increased risk of LYMPHOMA- Eye infections (conjunctivitis, corneal ulcers)- Oral problems (dental cavities, candida infections)- Vaginal problems (candidiasis, sexual dysfunction)
Define Systemic sclerosis + types
A vasculopathy related to excessive collagen deposition. There is inflammation and often autoantibodies are produced.- Most common type is LIMITED CUTANEOUS SCLERODERMA- Diffuse cutaneous- Sine scleroderma (no skin changes)- Mixed connective tissue disease
Presentation of Limited cutaneous scleroderma
CREST- Calcinosis (deposits subcutaneously) - can feel chalky if they break through skin-> RENAL FAILURE- Raynaud’s (long history) -> digital ulcers- Esophageat dysmotility/STRICTURES (swallowing difficulty)- SCLERODACTYLY (local skin thickening/tightening on digits) -> restricted movement (similar skin tightening can occur on the face -> small mouth)- Telangiectasia (spider veins - skin/mucous membranes - sometimes just look like erythamatous points) - whiten when pressed -> risk of pulm HTN at late stageCan get iron deficiency anaemia - can see ‘watermelon stomach’ on endoscopy
Presentation of diffuse scleroderma
- Proximal scleroderma (skin tightening) with trunk involvement- Shorter history of raynaud’s- Increased risk of renal crisis, - Increased risk of cardiac involvement, (e.g. myocarditis, pericarditis)- Increased risk of interstitial lung fibrosis
Dx of scleroderma
Limited:- ANTI CENTROMERE Ab - 70%Diffuse = Scl-70 (topoisomerase) Ab- Oft ANA +VE- may be RNA polymerase Ab pos
Tx for scleroderma
No cure - treat sympsRaynauds:- Physical protection e.g. gloves- Vasodilators - issue if hypotensive - Nifedipine, Iloprost (IV for digital ulcers), Sildenafil, Bosentan - Fluoxitine (SSRI) - Sympathectomy (strip away adventitia from affected vessels)- Gastro-oesophageal reflux = PPIs for life- Prevent renal crisis -> ACE-IEarly detection of pulm arterial HTN:- Annual echos + pulm function testsTreat pulm fibrosis - Cyclophosphamide- NintedanibTreat skin oedema:- No treatment (mild)- Mycophenolate (more severe)- Autologous stem cell transplantation (widespread + severe)
Define Dermatomyositis/Polymyositis
Included in a group of autoimmune conditions characterised by progressive muscle weakness, aching or pain. Causes inflam + necrossi of skeletal muscle- Dermatomyositis also affects skinCan be caused as part of paraneoplastic syndrome
Epidemiology of Dermato/Polymyositis
POLYMYOSITIS: more common in WOMEN; esp 30-60 Y/ODERMATOMYOSITIS: more common in WOMEN; can also affect CHILDREN (juvenile dermatomyositis)HLA B8/DR3 genetic link
Presentation of Poly/Dermatomyositis
- Symmetrical wasting of muscles of shoulder + pelvic girdle -> stiffness worse in morning, improves with activity - oft complains: trouble raising arms/raising from chairs or squatting- may involve resp muscles - linked to INTERSTITIAL LUNG DISEASEDerm:- GOTTRON’S PAPULES - rashes on backs of knuckles (DIPs, PIPs)- HELIOTROPE eyelid rash- Photosensitive shawl sign- may get Malar rash- may get calcinosis cutis
Dx of Myositis
- Bloods: LDH + Creatine Kinase RAISED- Serology: Anti Jo1 - Dermatomyositis only = Anti Mi2- Electromyography (EMG) - muscle inflam- MUSCLE FIBRE/skin BIOPSY -> Inflam/NECROSIS (DIAGNOSTIC)- CXR, pulm function tests, high res CT - check lungsScreen for malig (PET-CT)
Tx of Myositis
- 1st line = steroids: PREDNISOLONE - 1 m then titre down dose- If inadequate response -> Immunosuppression - MYCOPHENOLATE, AZATHIOPRINE - IV Rituximab if needed
Define vasculitis + sub types
Heterogenous, multisystem inflammation of blood vesselsLarge vessel:- Giant cell arteritis- Takayatsu (same as GCA but specifically affects aortic arch of east asian, mainly women)Medium vessel:- POLYARTERITIS NODOSA- Buerger’s disease (male smokers 20-40, peripheral skin necrosis)- Kawaski disease (Coronary artery aneurysm in KIDS)Small vessel:- pANCA ASSOCIATED (Eosiniophilic granulomatosis w/ polyangitis)- cANCA ASSOCIATED - GRANULOMATOSIS w/ POLYANGITIS (GPA)- Henloch Schonlen Purpura/IgA vasculitis (Immune complex mediated)
Types of classification of vasculitis
- Vessel size- Chappel Hill Consensus classification - Hybrid of vessel size, pathophys + underlying
Pathophys of GCA
Affects branches of EXTERNAL CAROTIDHistologically:- Activated immune cell (lymphocytes/macrophages) infiltration of vessel wall -> DIRECT damage + stimulates smooth muscle cell remodelling- Blurred margin between media and adventitia- Intima proliferated into lumen -> narrowed- Vessel wall infiltration, proliferation + damage -> weakening + occlusion of vessel -> Ischaemia, infarction + ANEURYSM -> clinical manifestation Temporal = headachesOpthalmological = visionFacial = jaw claudication
Epidemiology of GCA
- UK prevalence - 0.41% - most common vasculitis- Peak incidence 70-80 y/o; rare below 50 y/o- Most common in white esp Scandinavian
RFx for GCA
- Associated with polymyalgia rheumatica and ANCA associated vasculitis- Associated with CANCER- More common in FEMALE
Presentation of GCA
Cranial GCA:- Temporal artery - NEW ABRUPT LOCALISED (oft TEMPORAL) HEADACHE - Changes to temporal artery: Tenderness, Thickening, REDUCED/ABSENT PULSATION - Granulomatous -> Skip lesions - SCALP TENDERNESS (classic - pain when brushing hair)- Lingual or facial artery - Tongue/JAW CLAUDICATION (less common) - builds up with chewing- Vision affected: - BLURRING - Amaurosis fugax (like veil over vision) - Diplopia (double vision) - Photopsia (flashing lights) - Visual lossExtra cranial - e.g. Aortitis- May mimic infection/cancer-CONSTITUTIONAL SYMPTOMS/B SYMPTOMS: - Weight loss, low-grade fever, Anaemia, Malasise- POLYMYALGIA- Limb CLAUDICATION
Important negative features differentiating GCA from serious headache
GCA has no:- Vomiting (related to raised intracranial pressure - NOT GCA)- Acute localising clinical signs (can indicate Acute intercranial bleeding, Encephalitis, Meningitis)- Fever (indicates infection - unusual in acute ischaemic cranial headache but may sometimes get fever in large vessel vasculitis if many extra-cranial vessels inflamed)
Dx of GCA
- 1st line = FBC -> RAISED ESR +/- CRP - anaemia of chronic disease - Thrombocytosis- Diagnostic: - TEMPORAL ARTERY US (colour doppler) -> HALO SIGN (non-compressable) - TEMPORAL ARTERY BIOPSY (large samples - granulomatous inflam of media + intima in skip lesions)- PET-CT + Axillary US - check extra-cranial (+ check for cancer)- If vision loss -> ophthalmology review - Pal optic disc
US vs biopsy
US:- Non invasive- Can check multiple sites/vessels (including extracranial) in one visit- Better sensitivity than TA biopsyBUT- Must be done quickly + OPERATOR DEPENDANT (variability in reliability based on experience)Biopsy:- Invasive- Only check 1 area at a time- 100% specific but 39% sensitive
Tx of GCA
- 40-60mg ORAL PREDNISOLONE (higher up to 60mg if Hx of ischaemic symptoms e.g. visual loss, limb/jaw claudication) - responds V. WELL- IV METYLPREDNISOLONE if EVOLVING visual loss- Reduce to zero over 12-18 months provided no return in symptomsFor Relapse:- METHOTREXATE +/- TOCILIZUMAB (IL6 inhib - can be a steroid weaning measure)
Complications of high dose steroids + counter measures
- Steroid induced diabetes/worsens pre-existing DIABETES- OSTEOPOROSIS (assess to prevent fractures; give calcium + vitD (Adcal-D3)/bisphosphonates (Alendronic acid - 70mg))- INFECTION- GI TOXICITY (peptic ulcers)Can give PPIs + BISPHOSPHONATES
Complications of GCA
- Strokes if untreated (1%)- SUDDEN PAINLESS VISION LOSS (can be bilateral) - temporary Amaurosis Fugax (seen in TIA) - if not treated asap -> PERMENANT -> HIGH DOSE IV METHYLPREDNISOLONE
Epidemiology/RFx of Polyarteritis nodosa
- MALES > 50 Y/O- Associated with HEP B (hep C + HIV)- more common in developing countries
Pathophys of Polyarteritis Nodosa (PN)
Affects muscles, skin, GI, kidneys + heart, nervous system (systemic)- particularly affects branching points
Presentation of PN
- Unilateral orchitis (characteristic)- Peripheral neuropathy -> mononeuritis multiplex (damage to at least 2 diff areas of PNS)- GI - Abdo pain - Malabsorption- Skin involvement: - Livedo reticularis - mottled, purpleish, lace like appearance - Ulcers - Cutaneous/subcutaneous nodules (hallmark) - Gangrene- Kidneys: - PRE RENAL AKI/CKD -> HTN- Heart: - HF, Coronary A obs
Diagnosis of PN
- CRP/ESR raised - HBsAg may be present- CT angiogram -> beads-on-string appearance (microaneurysms)- BIOPSY (in e.g. kidney): transmural fibrinoid necrosis/NECROTISING VASCULITIS due to HTN
Tx of PN
- CORTICOSTEROIDS (+ cyclophosphamide if needed)- Control HTN -> ACE-I- If Hep B +ve = +antiviral + plasma exchange if needed
Complications of Polyarteritis Nodosa
GI perforation + haemorrhagesArthritisRenal infarctsStrokesMI
Epidemiology of granulomatosis w/ polyangitis (GPA)
Late teens/early adulthood- most commonly seen in caucasians but could be any ethnicityStaph aureus nasal carriage - associated with relapse in established disease
Presentation of GPA
Triad of ENT, lung and kidney signs.- SADDLE SHAPED NOSE (due to perforated nasal septum)- Epistaxis- Crusty nasal/ear secretions - otorrhoea -> HEARING LOSS- Sinusitis- Cough, wheeze - Haemoptysis (may mistake for pneumonia on CXR)- GLOMERULONEPHRITIS (more advanced)+ constitutional symps (fatigue, fever, malaise, night sweats, weight loss etc.)May also have:- ocular, rashes/ulcers, myalgia/arthralgia, neuropathy (esp mononeuritis multiplex) + thromboembolism (esp during active disease - but usually asymp)
Dx of GPA
- FBC: Anaemia (Eosniophilia??) - CRP +/- ESR elevated - CT chest (lung involvement oft present but asymp) - nodules; infiltrates - may do pulm function test -> elevated diffusion capacity = haemorrhage- Immunoassay - (proteinase 3) PR3-ANCA +ve - if -ve but still suspecious -> Immunoflouresence = c-ANCA POSITIVE (not p-ANCA) - If still -ve -> Renal/skin biopsy: GRANULOMAS, necrosis, vasculitis- Urinealysis + microscopy - check renal involvement - elevated creatinine shows up after haematuria etc.
Tx of GPA
- Nasal corticosteroid- Cyclophosphamide
Epidemiology of mechanical lower backpain
- v common, oft self limiting- May be normal esp in ppl 20-55 - Trauma/work related
Signs of serious pathology in lower back pain
- ELDERLY (may be myeloma)- NEuropathic pain (spinal cord compression)
Lumbar spondylosis
Degeneration of IV disc -> loss of compliance + thins over time- seen in ELDERLYInitialy asymp -> progressive- MC = L4/L5 or L5/S1Give analgesia + physio if simple mechanical painIf serious pathology suspected -> XR + MRI
