MSK Flashcards

1
Q

Define Osteoarthritis

A

Osteoarthritis is characterised by progressive synovial joint damage resulting in structural changes, pain and reduced function. It is the ‘wear and tear’ of joints.

Usually primary, but can be secondary to joint disease or other conditions e.g. haemochromatosis, obesity, occupational.

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2
Q

Epidemiology of Osteoarthritis

A
  • The most common form of arthritis
  • It is estimated that 8.75 million people aged 45 or older in the UK have sought treatment for osteoarthritis.
  • F>M
  • More prevalent with increasing age
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3
Q

RF for Osteoarthritis

A
  • Age
  • Female sex
  • Raised BMI
  • Joint injury or trauma
  • Joint malalignment and congenital joint dysplasia
  • Genetic factors (COL2A1 collagen type 2 gene) and family history
  • Abnormal or excessive stress e.g. from exercise or particular occupations
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4
Q

Pathophysiology of Osteoarthritis

A

The pathology affects the whole unit of the synovial joint including the synovial fluid and adjacent bone.

Osteoarthritis is classes as a non-inflammatory arthritis, however inflammatory mediators and processes do play a key role in the pathogenesis. It appears inflammatory cytokines interrupt normal repair of cartilage damage.

As cartilage is lost, the joint space narrows, with areas of highest load affected the most. Bone on bone interaction may occur causing large amounts of stress and reactive changes with subchondral sclerosis (via a process called eburnation) seen on x-ray. Cystic degeneration may occur resulting in subchondral cysts.

Essentially, cartillage is lost and chondroblasts are unable to replace and repair the lost cartillage, this leads to abnormal bone repair.

Mechanisms:

  • Metalloproteinases secreted by chondrocytes degrade the collagen and proteoglycan
  • Interleukin 1 (IL-1) and tumour necrosis factor-alpha (TNF-alpha) stimulate metalloproteinase production and inhibit collagen production
  • Deficiency of growth factors such as insulin-like growth factor and transforming growth factor impairs matrix repair
  • Gene susceptibly (35-60% influence) from multiple genes rather than a single gene defect - mutations in the gene for type II collagen have been associated with early polyarticular OA

Most affected areas:

  • Knees
  • Hips
  • Sarco-ileac joints
  • Cervical spine
  • Wrist
  • Carpometacarpal (base of thumb)
  • Interphalangeal (finger joints)
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5
Q

Signs of Osteoarthritis

A
  • Heberden’s nodes: swelling in distal interphalangeal joint (top finger joint)
  • Bouchard’s nodes: swelling in proximal interphalangeal joint (middle finger joint)
  • Fixed flexion deformity of carpometacarpal (base of thumb)
  • Mucoid cysts: painful cyts found on dorsum of finger
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6
Q

Symptoms of Osteoarthritis

A
  • Joint pain which is worse with activity
  • Mechanical locking
  • Giving way
  • Joint tenderness
  • Joint effusion (fluid in or around joint)
  • Limited joint movement - stiffness
  • Crepitus - crunching sensation when moving joint
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7
Q

Diagnostic criteria for Osteoarthritis

A

Investigations not always needed if there is a typical presentation:

  • Over 45 years of age
  • Typical activity related pain
  • No morning stiffness (or morning stiffness <30 minutes)
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8
Q

1st line imaging for Osteoarthritis

A
  • X-ray can be used to check severity and confirm diagnosis (mnemonic LOSS)
    • Loss of joint space
    • Osteophytes (bits of bone sicking out - bony overgrowth)
    • Subarticular sclerosis (end of bone at point of articulation is thickened)
    • Subchondral cysts (cysts appearing around the articulation)
    Note: the x-ray findings are not directly related to the symptoms. Some patients may be asymptomatic and have these findings, and some patients may have severe symptoms and not have any of these findings on x-ray.
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9
Q

Other investigations for Osteoarthritis

A
  • MRI - good for knee imaging
  • CT
  • Ultrasound - can be used to exclude differentials or guide intervention e.g. steroid injections
  • Aspiration of synovial fluid if there is a painful effusion - this shows viscous fluid with few leucocytes
  • CRP may be slightly elevated
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10
Q

Differentials for Osteoarthritis

A
  • Rheumatoid arthritis
  • Chronic tophaceous gout
  • Psoriatic arthritis
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11
Q

Non-pharmacological management of Osteoarthritis

A
  • Patient education
  • Weight loss
  • Low impact exercise
  • Heat and cold packs at site of pain
  • Physiotherapy
  • Occupational therapy
  • Orthotics - helps with foot issues
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12
Q

Pharmacological management of Osteoarthritis

A
  • 1st line - oral paracetamol + topical NSAIDs + topical capsaicin
  • Oral NSAIDs + proton pump inhibitos (to protect the stomach from NSAID use)
  • Opiates (e.g. codeine, morphine) - do not work for chronic pain, have many side effects and other issues associated with dependence and withdrawal.
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13
Q

Other management for Osteoarthritis

A
  • Intra-articular steroid injection
  • Joint replacement (arthroplasty) e.g. hip and knee
  • Arthroscopy - only done if there are loose bodies causing knee lock
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14
Q

Prognosis for Osteoarthritis

A

OA is a chronic slowly progressive disease and is common with advancing age.

A combination of different modalities of treatment can provide adequate pain control and preserve function and quality of life for many patients. Despite treatment, most patients continue to have some degree of pain and functional limitation affecting their desired activities and quality of life.

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15
Q

Define Rheumatoid Arthritis

A

Rheumatoid arthritis (RA) is a chronic, systemic inflammatory disease. This leads to a deforming, symmetrical inflammatory arthritis of the small joints which progresses to involve larger joints and other organs of the body, e.g. skin and lungs.

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16
Q

Epidemiology of RA

A
  • The prevalence of RA is estimated to be 1% in the UK and it is the most common inflammatory arthritis.
  • Prevalence is high in smokers
  • Age: the peak age of onset is between 5th and 6th decade of life
  • Female gender: 2-4x more common in women
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17
Q

Aetiology of RA

A

Interplay between genetics and environment, leading to immune response against self-antigens, especially citrullinated peptides.

Genetics

  • HLA-DR1 and DR4are crucial in activating T-cells
  • A number of other genes have been implicated, such as PTPN22, which is involved in T-cell activation

Environment

  • Smoking
  • Other pathogens e.g. bacteria
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18
Q

RF for RA

A
  • Female gender
  • Smoking
  • Family history
  • Infections
  • Hormones: increased risk post-menopause, potentially due to a reduction in oestrogen levels
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19
Q

Pathophysiology of RA

A

Environmental triggers cause modification of self-antigens e.g. citrullination (arginine is converted to citrulline) of type II collagen and vimentin. Due to susceptibility genes (HLA-DR1 and -DR4) the immune cells cannot differentiate between self and non-self. Antigens are picked up by antigen presenting cells and carried to the lymph nodes, where T cells and B cells are activated. Autoantibodies are produced.

The T-cells and antibodies enter the circulation and reach the joints. Here, the T cells secrete cytokines (e.g. Interferon-gamma and IL-17) to recruit macrophages. Macrophages also produce cytokines (TNF, IL-1 and IL-6) which causes synovial cells to proliferate. This creates a pannus (thick synovial membrane made of fibroblasts, myofibroblasts and inflammatory cells). This can damage the cartilage, soft tissue and bones. Inflammatory cytokines also cause T-cells to express RANKL which can bind to osteoclasts, causing breakdown of bone.

Antibodies also enter the joint space:

  • Rhematoid factor - IgM antibody that targets altered IgG
  • Anti-CCP - targets cirtrullinated proteins. This forms an immune complex which can accumulate and activate complement system, promoting joint inflammation and injury. Chronic inflammation can also cause angiogensis, allowing more inflammatory cells to arrive.

Inflammatory cytokines can also escape the joint space and affect multiple organ systems e.g. causing fever in brain, rheumatoid nodules in skin, protein breakdown in muscle, inflamed blood vessels, fibroblasts and pleural effusion in lungs

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20
Q

Signs of RA

A

Can be articular or extra-articular (extra-articular outlined in complications section)

  • Signs
    • Symmetrical polyarthritis: (on both sides of body)
      • Swollen, warm and tender small joints of the hands and feet (MCP, PIP, MTP)
      • Progresses to larger joints (shoulder, elbow, knee, ankle)
    • Boutonniere deformity: PIP flexion and DIP hyperextension
    • Swan-neck deformity: PIP hyperextension and DIP flexion
    • Z-thumb deformity: hyperextension of the thumb IP joint with flexion of the MCP joint.
    • Ulnar deviation of the fingers
    • Popliteal cyst: synovial sac bulges posteriorly to the knee
    • Rheumatoid nodules - lumps that can appear under skin and other areas e.g. lungs, hearts, eye
    MCP: metacarpophalangeal; PIP: proximal interphalangeal; DIP: distal interphalangeal; MTP: metatarsophalangeal
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21
Q

Symptoms of RA

A
  • Morning stiffness: > 30 mins and improves throughout the day
  • Malaise
  • Myalgia
  • Low-grade fever
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22
Q

Primary investigations for RA

A
  • Primary investigations
    • ESR and CRP:raised markers of inflammation
    • Rheumatoid factor (RF):present in 70% of patients
      • RF is an IgM against the Fc portion of IgG
      • Low specificity and can be raised in other autoimmune diseases e.g. Sjogren’s disease
      • Absence of RF does not exclude RA
    • Anti-cyclic citrullinated peptide (anti-CCP):present in 80% of patients
      • May be detected 15 years prior to symptom onset
      • Similar sensitivity to RF but higher specificity (>90%)
      • Titres can predict therapeutic response to rituximab and anti-TNFα agents
    • Joint X-rays:X-rays of the affected joints can aid diagnosis
      • Soft-tissue swelling
      • Periarticular osteoporosis
      • Joint space narrowing
      • Bony erosions
      • Subluxation - incomplete or partial dislocation of a joint
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23
Q

Other investigations for RA

A

US and MRI - can help identify synovitis and have greater sensitivity in detecting bone erosions than x-ray

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24
Q

Differentials for RA

A
  • Psoriatic arthritis
  • Infectious arthritis
  • Gout
  • SLE
  • Osteoarthritis
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25
Q

Primary care management for RA

A
  • Primary care
    • NSAID: low dose NSAID (e.g. ibuprofen) to cover the period between symptom onset and rheumatology referral
    • Refer to specialist care
    • Physiotherapy and occupational therapy
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26
Q

Secondary care management for RA

A
  • Secondary care
    • 1st line - Disease modifying anti-rheumatic drug (DMARD) monotherapy
  • Subsequent therapy
    • Multiple DMARD’s
    • Biologics
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27
Q

Management of flares of RA

A
  • Management of flares
    • NSAIDs
    • Glucocorticoids: intra-articular therapy can be given in a localised flare. Alternatively, intramuscular steroids or oral prednisolone may be used if intra-articular therapy is not appropriate
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28
Q

Other management of RA

A
  • Surgery - may relieve pain, improve function and prevent deformity
  • Management of complication e.g. CVD risk
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29
Q

Monitoring for RA

A

Monitoring methotrexate:

FBC, LFTs and U&Es measured weekly until therapy stabilised, and 2-3 monthly thereafter

Monthly:

  • Measure CRP
  • Disease activity - using a composite score such as DAS-28. DAS-28 takes into account the overall health of the patient, the number of swollen joints, and the ESR count.

Annually:

  • Assess disease activity e.g. DAS-28 score
  • Measure impact on life and functional ability e.g. health assessment questionnaire (HAQ)
  • Check for comorbidities and complications
  • Assess need for surgery
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30
Q

Extra articular manifestations of RA

A

Skin

  • Rheumatoid nodules: inflammatory aggregates most prominent on extensor surfaces

Opthalmological

  • Keratoconjunctivitis sicca (most common)
  • Episcleritis
  • Scleritis
  • Corneal ulceration
  • Keratitis

Cardiovascular

  • Increased risk of ischaemic heart disease
  • Pericarditis

Respiratory

  • Pulmonary nodules
  • Pleurisy
  • Pleural effusion
  • Interstitial lung disease
  • Caplan’s syndrome: lung nodules with occupational coal exposure
  • Bronchiolitis obliterans
  • Bronchiectasis

Haematological

  • Anaemia of chronic disease

Musculoskeletal

  • Atlanto-axial subluxation
  • Tendon rupture
  • Carpal tunnel syndrome

Systemic

  • Secondary amyloidosis
  • Felty’s syndrome
    • Splenomegaly
    • Neutropaenia
    • Rheumatoid arthritis
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31
Q

Medication side effects for RA

A

Methotrexate - Myelosuppresion, Intersitial lung disease, Penumonitis, Heptotoxic, Mucositis
Sulfasalazine - Rash, Oligospermia, Interstitial lung disease, G6PD def anaemia
Leflunomide - Interstitial lung disease, Hepatotoxic, HTN
Hydroxychloroquine - Retinopathy, Corneal deposits
Prednisolone - Cushings
Anti-TNFa agents - Reactivation of tuberculosis, Demyelination
Rituximad - Infusion reactions

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32
Q

Prognosis for RA

A

Patients who aretreated earlyhave a good prognosis.

Leading cause of death is the accelerated artherosclerosis causing cardiovascular disease

Poor prognostic factors:

  • Functional disability
  • High disease activity
  • Antibody positive: anti-CCP and/or RF
  • Early presence of radiographic erosions
  • Extra-articular disease
  • High inflammatory markers
  • High swollen joint count
  • Failure of 2 or more DMARDs
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33
Q

Define Gout

A

Gout is an inflammatory arthritis caused by deposition of monosodium urate crystals within joints, most commonly the first metatarsophalangeal joint (MTP).

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34
Q

Epidemiology of gout

A
  • Prevalence = 1%
  • Incidence increases with age. Peak incidence between 40 and 60 years old.
  • M>F
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35
Q

Aetiology of gout

A

Uric acid overproduction

  • Increased cell turnover: such as haematological malignancies
  • Cytotoxic drugs: chemotherapeutic agents cause increased cell death
  • Purine rich diet: particularly meat, seafood and alcohol
  • Obesity: increased BMI and metabolic syndrome are associated with gout
  • Lesch-Nyhan syndrome:an**X-linked recessive deficiency of hypoxanthine-guanine phosphoribosyltransferase (HGPRTase) resulting in increased urate production. Other features include renal failure, kidney stones, learning difficulties and self-mutilation
  • Severe psoriasis

Decreased excretion of uric acid

  • Chronic kidney disease
  • Diuretics: thiazide and loop diuretics can increase the risk of gout
  • Pyrazinamide: causes an 80% reduction in renal clearance of uric acid
  • Lead toxicity
  • High fructose intake (sugary drinks, cakes, sweets and fruit sugars) - reduces uric acid excretion
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36
Q

RF for gout

A
  • Elderly
  • Men
  • Post-menopausal women
  • Family history of gout
  • Diet high in purines
  • Alcohol consumption
  • Diuretics
  • Impaired renal function
  • DM - high insulin levels lower urate excretion
  • Ischaemic heart disease and hypertension
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37
Q

Pathophysiology of gout

A

Urate is a metabolite of purine synthesis and the incidence of gout increases withhyperuricaemia(uric acid > 0.45 mmol/L). However, the disease can also occur at completely normal urate levels. Untreated gout can lead to chronic joint damage.

Uric acid is formed as a breakdown product of purines. The causes of gout can be broadly categorised into conditions that result in urateoverproductionorreduced excretionof urate.

Uric acid has limited solubility in the blood. When there is too much uric acid in the blood, it can become a urate ion and bind sodium, leading to the formation of monosodium urate crystals which deposit in areas with slow blood flow, including joints and kidney tubules.

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38
Q

Signs of gout

A

During a flare, symptoms usually last 7-10 days and are most severe within 12 hours. Patients can be asymptomatic between flares.

  • Signs
    • Joint inflammation: tenderness, erythema and swelling
    • Mainly monoarticular but can be oligoarticular (≤ 4 joints):
      • 1st MTPmost commonly affected in a first presentation (70%); previously known as podagra
      • The ankle, wrist, knee and small joints of the hand are also commonly affected
    • Gouty tophi: nodular masses of urate crystals form under the skin, usually as a late complication
      • Usually affect fingers, ears, and elbows
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39
Q

Symptoms of gout

A
  • Symptoms
    • Red, tender, hot, and swollen joint.
    • Joint stiffness
    • Rapid onset severe joint pain
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40
Q

Investigations for gout

A

Diagnosis can be made based on clinical presentation BUT have to exclude the diagnosis of septic arthritis

  • Primary investigations to confirm diagnosis
    • Joint aspiration:needle-shaped crystals with negative birefringence under polarised microscopy confirm the diagnosis. If there is bacterial growth, the patient is likely to have septic arthritis instead.
    • Serum urate:usually taken 4-6 weeksafterthe attack resolves as levels may be falsely low/normal during the attack as the urate is deposited within the joint. Hyperuricaemia doesnotconfirm gout, nor does a normal level exclude gout.
    • Joint X-ray:often normal, but may demonstrate some of the following features:
      • Earliest sign: joint effusion, with relatively preserved joint space
      • Well-defined ‘punched out’ erosions with sclerotic margins and overhanging edges in a juxta-articular distribution (rat-bite erosions)
      • Eccentric erosions and soft tissue tophi may be observed
      • An absenceof periarticular osteopenia (unlike rheumatoid arthritis)
      • Late sign: loss of joint space
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41
Q

Differentials for gout

A
  • Septic arthritis
  • Reactive arthritis
  • Haemarthrosis
  • Calcium pyrophosphate deposition
  • Rheumatoid arthritis
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42
Q

Acute gout flare management

A
  • Anti-inflammatory:
    • NSAIDs first line
    • Colchicine used first line when NSAIDs contraindicated or in renal insufficiency.
    • Continue until 24-48 hoursaftersymptoms have improved
    • Co-prescribe a proton pump inhibitor (PPI)
  • Corticosteroids:intra-articularsteroids may be used as a second-line agent, particularly for monoarticular disease. A short course oforalsteroids (usually 15 mg/day) is considered for oligoarticular disease (≤ 4 joints) or if NSAIDs/colchicine are contraindicated
  • If patients are already on allopurinol or febuxostat, it should becontinued during the acute flare
  • Rest and elevate joint
  • Ice packs
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43
Q

General management and prevention of gout flare

A
  • Lifestyle advice - food low in purine, lose weight, avoid alcohol
  • Xanthine oxidase inhibitors - reduces uric acid
    • Allopurinol - 1st line
    • Febuxostat - 2nd line

Note: when initiating these medications, they should be given at least 2 weeks after an acute attack. But if patient is already on these medications, they should be continued through the flare attack. When starting medication, cover with NSAIDs/ colchicine.

  • Uricosuric agent - e.g. sulfinpyrazone, probenecid, benzbromarone can be used if xanthine oxidase inhibitor not working. This increases the excretion of uric acid in the urine.
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44
Q

Other management for gout

A

Patients with gout often have cardiovascular comorbidities, such as hypertension, and should be optimised accordingly:

  • If hypertension is present,losartanmay be a good option as it has uricosuric action
  • Consider ceasingprecipitating drugs, such as thiazide diuretics
  • Patients on aspirin (75-150 mg) for cardiovascular prophylaxis shouldcontinuetheir medication
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45
Q

Complications of gout

A

Urate nephrolithiasis: there is an association between gout and urate renal stones due to hyperuricaemia

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46
Q

Prognosis of gout

A

The disease is typically self-limiting but in those who are not treated with urate-lowering therapy, there is an 83% risk of recurrence by the third year.

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47
Q

Define Pseudogout (Calcium Pyrophosphate deposition)

A

Pseudogout is a form of inflammatory arthritis caused by deposition of calcium pyrophosphate crystals in the synovium.

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48
Q

Epidemiology of Pseudogout

A

Most patients affected by acute pseudogout are over the age of 65

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49
Q

Rf for pseudogout

A

The deposition of calcium pyrophosphate crystals is thought to trigger synovitis, with the knee, shoulder, and wrist being most commonly affected.

Can be acute or chronic:

  • Acute - mainly affects larger joints in the elderly and is usually spontaneous but can be provoked by illness, surgery or trauma.
  • Chronic - inflammatory RA-like symmetrical polyarthritis and synovitis
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50
Q

Signs of pseudogout

A

Very similar to gout and usually indistinguishable until joint aspiration is performed.

  • Signs
    • Joint inflammation: pain, erythema and swelling
    • Signs can be monoarticular (1 joint) or polyarticular (several joints)
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51
Q

Symptoms of pseudogout

A
  • Symptoms
    • Rapid onset severe joint pain: knee, shoulder and wrist are most commonly affected
    • Joint stiffness
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52
Q

Primary investigations of pseudogout

A
  • Primary investigations
    • Joint aspiration:weakly-positively birefringent rhomboid-shaped crystals under polarised microscopy confirm the diagnosis. If any bacterial growth, then patient is likely to have septic arthritis
    • Joint X-ray:chondrocalcinosis (calcification of articular cartilage) is seen in 40% of casesand is highly suggestive of pseudogout but is not diagnostic; theabsenceof chondrocalcinosis doesnotexclude pseudogout
      • In the knee, this is seen as linear calcifications of the articular cartilage and meniscus
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53
Q

Investigating the underlying cause of pseudogout

A
  • Investigating the underlying causeUsually only done in young patients:
    • Serum bone profile and PTH: investigate for hyperparathyroidism and hypophosphataemia
    • Iron studies: investigate for haemochromatosis
    • Serum magnesium: investigate for hypomagnesaemia
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54
Q

Differentials for pseudogout

A
  • Gout
  • Septic arthritis
  • Rheumatoid arthritis
  • Osteoarthritis
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55
Q

Management of pseudogout (acute and chronic)

A

Acute

  • Anti-inflammatory:NSAIDs or colchicine, particularly in polyarticular disease
  • Corticosteroid:intra-articularsteroids can be used in monoarticular disease orsystemicsteroids in polyarticular disease
  • Cool packs and rest
  • Aspiration of the joints - relieves pain

Chronic

  • DMARDs: e.g. methotrexate and hydroxychloroquine may be considered in chronic pseudogout
  • Joint replacement: only indicated in chronic, recurrent cases with severe joint degeneration
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56
Q

Prognosis of pseudogout

A

Pseudogout is a self-limiting disease associated with rapid improvement in symptoms upon commencing treatment, with resolution usually occurring within a few days. However, a small proportion of patients may go on to develop chronic joint disease.

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57
Q

Define Osteoporosis

A

Osteoporosis is a complex skeletal disease characterised by low bone density and micro-architectural defects in bone tissue, resulting in increased bone fragility and susceptibility to fracture.

Osteopenia refers to a less severe reduction in bone density than osteoporosis.

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58
Q

Epidemiology of Osteoporosis

A
  • Osteoporosis affects over 3.2 million people in the UK.
  • Prevalence is higher in women and increases following menopause as oestrogen levels fall. Women also lose trabeculae with age.
  • An ageing population is contributing to a rise in fragility fractures
  • Caucasians and asians more at risk
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59
Q

Aetiology of Osteoporosis

A
  • Primary disease (e.g. with older age)
  • Secondary disease, may be due to:
    • Malignancy e.g. multiple myeloma
    • Endocrine conditions e.g. diabetes, Cushing syndrome, hyperparathyroidism, hyperthyroidism
    • Malabsorptive conditions e.g. IBD
    • Chronic liver disease
    • COPD
    • CKD
    • Other rheumatological conditions
    • Certain drugs - such as SSRIs, PPIs, anti-epileptics and anti-oestrogens
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60
Q

RF of Osteoporosis

A

Mnemonic SHATTERED

  • Steroid use (long term corticosteroids)
  • Hyperthyroidism, hyperparathyroidism, hypercalciuria
  • Alcohol and tobacco use
  • Thin - Low BMI (<18.5 kg/m2)
  • Testosterone decrease
  • Early menopause
  • Renal or liver failure
  • Erosive/ inflammatory bone disease e.g. myeloma or RA
  • Dietary (reduced Ca2+, malabsorption, diabetes)

Other

  • Older age
  • Female (especially post-menopausal, as oestrogen is protective)
  • Caucasian/ asian
  • Family history
  • Previous fragility fracture
  • Reduced mobility and activity
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61
Q

Pathophysiology of Osteoporosis

A

Osteoclast are primarily responsible for bone breakdown whilst osteoblasts are responsible for bone formation. As we age, the activity of osteoclasts increases and is not matched by osteoblasts.As such bone mass decreases.

The‘peak mass’ we reach as young adults is key, and a higher peak is somewhat protective. Genetics have a significant influence over the peak reached. Multiple genes are involved, including collagen type 1A1, vitamin D receptor and oestrogen receptor genes.

Nutritional factors, sex hormone status and physical activity also affect
peak bone mass. Oestrogen deficiency leads to an increased rate of bone loss. Oestrogen is key to the activity of bone cells with receptors found on osteoblasts, osteocytes, and osteoclasts. The mechanisms are still being understood, but it appears osteoclasts survive longer in the absence of oestrogen, and there is arrest of osteoblastic synthetic architecture.

Glucocorticoids cause increased turnover of boneand osteoporosis. Prolonged use can result in reduced turnover state - though even here synthesis is affected more leading to a loss of bone mass.

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62
Q

Clinical manifestations of Osteoporosis

A

Asymptomatic condition with the exception of fractures

Common fragility fractures include vertebral crush fracture and those of the distal wrist (Colles’ fracture) and proximal femur.

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63
Q

FRAX tool

A
  • FRAX tool
    • Predicts the risk of a fragility fracture over the next 10 years. Usually the first step of assessment and is done on patients at risk of osteoporosis
      • Women >65 years, men >75 years, younger patients with risk factors
    • It involves inputting information such as their age, BMI, co-morbidities, smoking, alcohol and family history +/- bone mineral density
    • It gives results as a percentage 10 year probability of a:
      • Major osteoporotic fracture
      • Hip fracture
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64
Q

DEXA SCAN

A
  • DEXA Scan (dual-energy xray absorptiometry)
    • Measures bone mineral density by measuring how much radiation is absorbed by the bones.
    • Can be measured anywhere on the skeleton but reading at the hip is KEY.
    • 2 scores are obtained:
      • Z score - represent the number of standard deviations the patients bone density falls below the mean for their age.
      • T score - represent the number of standard deviations below the mean for a healthy young adult their bone density is.
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65
Q

Other investigations of Osteoporosis

A
  • Vertebral fracture assessment: consider lateral lumbar and thoracic spine x-ray in patients with:
    • History of ≥4cm height loss
    • Kyphosis
    • Recent or current long-term oral corticosteroids
    • BMD T-score ≤-2.5
  • Consider other investigations if suspecting a secondary cause of osteoporosis
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66
Q

Management of Osteoporosis

A

Management based on NOGG guidelines, using the FRAX score

FRAX without bone mineral density

  • Low risk – reassure
  • Intermediate risk – offer DEXA scan and recalculate the risk with the results
  • High risk – offer treatment

FRAX with bone mineral density

  • Treat
  • Lifestyle advice and reassure
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67
Q

1st line management of Osteoporosis

A

Bisphosphonates

  • Interfere with osteoclasts and reducing their activity, preventing the reabsorption of bone.
  • Examples of bisphosphonates are:
    • Alendronate 70mg once weekly (oral)
    • Risedronate35mg once weekly (oral)
    • Zolendronic acid 5 mg once yearly (intravenous)
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68
Q

Other management for Osteoporosis

A

Lifestyle Changes:

  • Activity and exercise
  • Maintain a health weight
  • Adequate calcium intake
  • Adequate vitamin D
  • Avoiding falls
  • Stop smoking
  • Reduce alcohol consumption

Vitamin D and Calcium:

NICE recommendcalciumsupplementationwith vitamin Din patients at risk of fragility fractures with an inadequate intake of calcium.

Patients with an adequate calcium intake but lacking sun exposure should have vitamin D supplementation.

Other medical options (if bisphosphonates are contraindicated):

  • Denosumab: monoclonal antibody that blocks the activity of osteoclasts.
  • Strontium ranelate: stimulates osteoblasts and blocks osteoclasts (but increases the risk of DVT, PE and myocardial infarction).
  • Raloxifeneis used as secondary prevention only. It is a selective oestrogen receptor modulator that stimulates oestrogen receptors on bone but blocks them in the breasts and uterus.
  • Hormone replacement therapyshould be considered in women that go through the menopause early.
  • Teriparatide (recombinant PTH)- used in patients who have further fractures despite treatment
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69
Q

Monitoring for Osteoporosis

A

Low risk patients not being put on treatment should be given lifestyle advice and followed up within 5 years for a repeat assessment.

Patients on bisphosphonates should have a repeat FRAX and DEXA scan after 3-5 years and a treatment holiday should be considered if their BMD has improved and they have not suffered any fragility fractures. This involves a break from treatment of 18 months to 3 years before repeating the assessment.

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70
Q

Complications of Osteoporosis

A
  • Fractures
  • Side effects of bisphosphonates:
    • Refluxandoesophageal erosions. Oral bisphosphonates are taken on an empty stomach sitting upright for 30 minutes before moving or eating to prevent this.
    • Atypical fractures (e.g. atypical femoral fractures)
    • Osteonecrosis of the jaw
    • Osteonecrosis of the external auditory canal
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71
Q

Prognosis of Osteoporosis

A

With preventative treatment, fragility fractures of the hip, vertebrae, and wrist can be avoided.

Prognosis is good for people at risk of osteoporosis if steps are taken to prevent decline in bone density and strength.

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72
Q

Notes on bone strength

A

Determined by

  • BMD:
    • How much mineral in bone
    • Determine by the amount gained during growth and amount lost during ageing
  • Bone size:
    • Short and fat is stronger than long and thin
    • Distribution of cortical bone
  • Bone quality:
    • Bone turnover, the architecture of it and the mineralisation (if there is not enough mineralisation then bone break, if too much then bones are stiff and shatter)
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73
Q

What are the spondyloarthropathies

A

The spondyloarthropathies are a group of related chronic inflammatory conditions.

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74
Q

What clinical features are shared by all the spondyloarthropathies

A
  • Seronegativity (rheumatoid factor negative)
  • HLA-B27 association*
  • Axial arthritis - pathology in spine and sacroiliac joints
  • Asymmetrical large-joint oligoarthritis or monoarthritis
  • Enthesitis - inflammation at the site of insertion of a tendon or ligament into a bone
  • Dactylitis - infammation of entire digit e.g. sausage fingers
  • Extra-articular manifestations e.g. iritis (inflammation of eye), psoriaform rashes, oral ulcers, aortic valve incompetence, inflammatory bowel disease
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75
Q

What % of the UK are HLA-B27 positive and what proportion of this group are at risk of developing disease

A

Around 5% of the UK population is HLA-B27 positive but most do not have the disease. The chances of developing disease in this group of people is 1 in 4.

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76
Q

Name some common HLA-B27 diseases and the proportions of these groups who are HLA-B27+

A
  • Ankylosing spondylitis - 85-95% of people are HLA-B27+
  • Acute anterior uveitis - 50-60% of people are HLA-B27+
  • Reactive arthritis - 60-85% of people are HLA-B27+
  • Enteric arthropathy - 50-60% of people are HLA-B27+
  • Psoriatic arthritis - 60-70% of people are HLA-B27+
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77
Q

Theory of pathology for spondyloarthropathies

A

‘Molecular mimicry’ whereby an infection triggers an immune response and the infectious agent has peptides very similar to the HLA-B27 molecules so there is an auto-immune response triggered against HLA-B27.

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78
Q

When to suspect spondyloarthropathies

A

SPINEACHE:

  • Sausage digit (dactylitis)
  • Psoriasis
  • Inflammatory back pain
  • NSAID good response
  • Enthesitis (particularly in heel - plantar fasciitis)
  • Arthritis
  • Crohn’s/Colitis/elevated CRP (can be normal in AS)
  • HLA-B27
  • Eye (uveitis)
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79
Q

Define Ankylosing spondylitis

A

Ankylosing spondylitis (AS) is a chronic progressive inflammatory arthropathy. Mainly affects the spine and causes progressive stiffness and pain.

Ankylosis = abnormal stiffening and immobility of joint due to fusion of bones

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80
Q

Epidemiology of Ankylosing spondylitis

A
  • M>F
  • Most commonly presents in late teens/ twenties
  • Women present later and are under-diagnosed
  • 90% are HLA-B27 positive
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81
Q

Aetiology of ankylosing spondylitis

A

Unknown aetiology. Likely to be genetic and environmental interplay.

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82
Q

RF for ankylosing spondylitis

A
  • HLA-B27
  • Family history of ankylosing spondylitis
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83
Q

Pathophysiology and disease course of ankylosing spondylitis

A

Lymphocyte and plasma infiltration occurs with local erosion of bone at the attachments of the intervertebral and other ligaments (enthesitis - inflammation where tendons/ligaments insert into bone), which heals with new bone (syndesmophyte) formation.

The disease course is variable. Some progress to kyphosis (excessive outward curve of the spine), neck hyperextension and spino-cranial ankylosis

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84
Q

Key presentations of ankylosing spondylitis

A

Affects sacroiliac joint and joints of vertebral column. Asymmetrical joint pain - normally oligoarthritis (1 or 2 joints)

Symptoms present over 3 months. Symptoms will fluctuate with flares and periods of improvement.

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85
Q

Signs of ankylosing spondylitis

A
  • Enthesitis - inflammation at point of insertion of tendons and ligaments in bones
  • Dactylitis - inflammation of entire digit
  • Bamboo spine on x-ray due to fusion of the joints
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86
Q

Symptoms of ankylosing spondylitis

A
  • Pain and stiffness of joints
  • Lower back pain
  • Sacroiliac pain (buttock region)
  • Pain worst at night and in the morning (>30 minutes of stiffness in morning)
  • Pain worst with rest and improves with movement
  • Systemic symptoms e.g. weight loss and fatigue
  • Chest pain - related to costovertebral and costosternal joints
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87
Q

Investigations for Ankylosing spodnylitis

A
  • FBC - normocytic anaemia
  • CRP and ESR - elevated
  • Genetic testing - HLA-B27?
  • X-ray - of spine and sacrum
    • Bamboo spine - calcification of ligaments and fusion of the vertebral joints
    • Squaring of vertebral bodies
    • Subchondral sclerosis
    • Subchondral erosions
    • Syndesmophytes - areas of boney growth where the ligament normally inserts into the bone.
    • Ossification - structures such as ligaments turn into bone like tissue
    • Fusion - seen in facet joints, sacroiliac joints and costovertebral joints
  • MRI of spine if x-ray is normal - can show early changes which show up as bone marrow oedema as well as erosions, sclerosis and ankylosis
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88
Q

What is Schobers test

A

General examination of spine (especially lumbar spine) to assess mobility.

Patient stands straight. Find L5 vertebrae and mark a point 10cm above this and 5cm below. Ask patient to bend forward, and measure distance between two points.

If distance between the two points is less than 20cm, this indicates restriction in the lumbar movements.

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89
Q

Differentials for ankylosing spondylitis

A
  • Osteoarthritis
  • Psoriatic arthritis
  • Reactive arthritis
  • Vertebral fracture
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90
Q

Management of ankylosing spondylitis

A
  • NSAIDs e.g. ibuprofen or naproxen (2-4 weeks. If no improvement, switch to another NSAID)
  • Steroids - used during flares (oral, IM or directly into joints)
  • Anti-TNF e.g. etanercept or monoclonal antibodies against TNF e.g. infliximab, adalimumab
  • Monoclonal antibodies targeting IL-7 - e.g. secukinumab
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91
Q

Other management for ankylosing spondylitis

A
  • Physiotherapy - exercise and mobility encouragement
  • Avoid smoking
  • Bisphosphonates - used to treat osteoporosis if it occurs
  • Treatment for complications
  • Surgery - if vertebral fractures or deformities to spine or to other joints e.g. hip replacement or spinal osteotomy
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92
Q

Complications of Ankylosing spondylitis

A
  • Vertebral fractures
  • Osteoporosis
  • Anaemia
  • Anterior uveitis (eye inflammation)
  • Aortitis (inflammation of aorta)
  • Heart block - fibrosis of the heart conduction system
  • Restrictive lung disease - due to restrictive movement of chest wall
  • Pulmonary fibrosis - especially upper lobes of lungs
  • Inflammatory bowel disease
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93
Q

Prognosis of ankylosing spondylitis

A

There isn’t always a relationship between the activity of arthritis and the severity of the underlying inflammation.

Prognosis is worse if ESR >30, onset >16 years, early hip involvement or poor response to NSAIDs

Patients who do well are those who lead active lifestyles and maintain a disciplined exercise programme.

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94
Q

Define Psoriatic arthritis

A

Psoriatic arthritis is a chronic inflammatory joint disease associated with psoriasis, although it can occur without arthritis.

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95
Q

Epidemiology of PA

A
  • Psoriatic arthritis occurs in approximately 10% of patients with psoriasis
  • Usually occurs within 10 years of skin changes
  • Typically affects people in middle age
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96
Q

RF for PA

A
  • Psoriasis
  • Family history of psoriasis or psoriatic arthritis
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97
Q

Pathophysiology of PA

A

Psoriatic arthritis is anautoimmunechronic inflammatory joint diseasethat affects 10% of patients with psoriasis, which is an autoimmune skin condition associated with red, flaky, crusty patches of skin.

It falls under the category ofseronegative spondyloarthropathies. These conditions are allrheumatoid factor negative, associated withHLA-B27, and can affect theaxial skeleton.

Psoriatic arthritis has a strong genetic component and, although its pathogenesis is not fully understood, activation ofCD8+ T cellsis thought to play a critical role.

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98
Q

Signs of Psoriatic arthritis

A
  • Joint tenderness, warmth and reduced range of motion
    • Typically affects DIP joints, rather than MCP/PIP joints in rheumatoid arthritis
  • Dactylitis: swelling of an entire digit
  • Enthesitis: inflammation of the plantar fascia and Achilles’ tendon (back of foot)
  • Psoriasis: psoriatic lesions, scalp and nail symptoms (pitting of nails, onycholisis - separation of nail from nail bed)
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99
Q

Symptoms of psoriatic arthritis

A
  • Joint pain and stiffness:
    • Symptoms worse in the morning and improve on movement is typical of an inflammatory arthropathy
  • Swollen fingers or toes
  • Back pain if axial skeleton involved
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100
Q

Outline the typical presentation of psoriatic arthritis

A

Presentations vary from mild stiffness to arthritis mutilans. Most patients will have skin manifestations before arthritic manifestations. But some patients wont have a diagnosis of psoriasis before psoriatic arthritis.

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101
Q

Types of Psoriatic arhtritis

A
  • Symmetric polyarthritis (rheumatoid-like)
    • Affects ≥ 5 joints
    • Affects hands, wrists, ankles, DIP joints
    • Symmetrical distribution
    • More common in women
    • Resembles rheumatoid arthritis
  • Asymmetric oligoarthritis
    • Affects ≤ 4 joints
    • Asymmetrical distribution
    • Typically affects the hands and feet
  • Distal arthritis (DIP joint disease)
    • Affects distal interphalangeal joints of hands and/or feet
    • Usually occurs alongside other types
  • Spondyloarthritis (sacroiliitis)
    • Primarily involves spine, sacroiliac joints and atlanto-axial joint
    • More common in men
  • Arthritis mutilans
    • Most severe and least common form
    • Deforming and destructive subtype
    • Occurs in the digits
    • Osteolysis around the phalynxes
    • Skin around the bones, folds in on itself as the bones get shorter (telescopic finger)
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102
Q

CASPAR Criteria for Diagnosing PA

A

History of psoriasis - 2 points
Psoriatic nail changes - 1 point
Rheumatoid factor negative - 1 point
History of dactylitis - 1 point
Radiological evidence (Juxta-articular periostitis)

They need to score 3 or above for diagnosis

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103
Q

What is PEST

A

Psoriasis epidemiological screening tool should be used to assess everyone with psoriasis.

Asking about:

  • Joint pain
  • Swelling
  • Arthritis
  • Nail pitting
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104
Q

X-Ray changes for PA

A

X-ray changes include:

  • Periostitis - inflammation of the periosteum
  • Ankylosis - bones fuse together
  • Osteolysis - bone loss
  • Dactylitis - inflammation of the entire digit
  • Pencil-in-cup appearance - central erosions of bone which causes the appearance of one bone being hollow and looking like a cup, and the other bone looking narrow and pencil-like.
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105
Q

Differentials for PA

A
  • Rheumatoid arthritis
  • Gout
  • Reactive arthritis
  • Erosive osteoarthritis
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106
Q

Management of PA

A

Management is similar to RA.

Treatment is coordinated between dermatologists and rheumatologists

  • Mild disease
    • NSAIDs and physiotherapy: first-line options to reduce inflammation, improve range of motion and strengthen muscles
    • Intra-articular steroids - for intra-articular synovitis
  • Progressive disease
    • Disease-modifying antirheumatic drugs (DMARDs): used in addition to the above for patients with polyarthritis or joint erosions.Methotrexateis first-line, whilstsulfasalazineis used in patients who are intolerant to methotrexate
    • Biologic agents: TNF-α inhibitors, such as etanercept or infliximab, should be considered in patients with oligoarthritis or polyarthritis following the failure of 2 DMARDs
    • Ustekinumab - used to treat psoriasis - monoclonal antibody that targets IL-12 and IL-23 to dampen down inflammation
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107
Q

Complications of PA

A
  • Cardiovascular: patients with psoriatic arthritis have an increased risk of ischaemic heart disease and hypertension. All patients must have a baseline lipid profile and fasting blood glucose.
  • Aortitis - inflammation of aorta
  • Amyloidosis
  • Eye disease
    • Conjunctivitis
    • Anterior uveitis
  • Methotrexate hepatotoxicity
  • Treatment related malignancy
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108
Q

Prognosis for PA

A

Earlier studies prior to the use of DMARDs demonstrated a 20% risk of progressing to disabling arthritis, as well as reduced survival. This has improved with the advent of earlier intervention with more appropriate therapies, with approximately 7% of patients experiencing progressive disease requiring joint surgery.

Due to the risk of cardiovascular disease, all patients require optimisation of their cardiovascular co-morbidities. Psoriatic arthritis is associated with a better prognosis than rheumatoid arthritis.

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109
Q

Define reactive arthritis

A

Reactive arthritis refers to synovitis occurring due to a recent infective trigger. This is an autoimmune response to infection elsewhere in the body. This usually presents as acute monoarthritis.

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110
Q

Epidemiology of Reactive arthritis

A
  • Males who are HLA-B27 positive have an 30-50 fold increased risk
  • Women less commonly affected
  • Mainly occurs in adults
  • The prevalence is thought to be 30 to 40 cases per 100,000 adults
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111
Q

Aetiology of Reactive arthritis

A

Infective triggers include:

  • Gastroenteritis
    • Salmonella
    • Shigella
    • Yersinia enterocolitica
  • Sexually transmitted infections
    • Chlamydia
    • Ureaplasma urealyticum
    • Gonorrhea (may also cause gonococcal septic arthritis, so this must be considered)
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112
Q

RF for Reactive arthritis

A
  • HLA-B27 gene
  • Male sex
  • Preceding chlamydial or gastrointestinal infection
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113
Q

Pathophysiology of Reactive arthritis

A

Reactive arthritis is one of the seronegative spondyloarthropathies, and is linked to the HLA-B27 gene.

The immune system is responding to the recent infection. This response also results in antibodies or inflammation that also affect the joints.

In reactive arthritis, there are no actual joint infections (as seen in septic arthritis). The infection is at another site!

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114
Q

Key presentations of reactive arthritis

A

Acute, asymmetrical monoarthritis, typically in the lower leg.

Patients may present with triad of - urethritis, arthritis and conjunctivitis ‘Can’t see, pee or climb a tree’

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115
Q

Signs of Reactive arthritis

A
  • Warm and swollen joint
  • Iritis - swelling and irritation of eye
  • Keratoderma blenorrhagica - painless, red, raised plaques and pustules
  • Circinate balanitis - dermatitis of the head of the penis
  • Enthesitis - inflammation of the site where tendons and ligaments insert into the bone
  • Nail dystrophy
116
Q

Symptoms of Reactive arthritis

A
  • Warm, swollen, painful joint
  • Mouth ulcers
117
Q

Investigations for reactive arhtritis

A
  • ESR and CRP - elevated
  • Infectious serology
  • If diarrhoea - culture stool
  • Aspirate joint - MCS and crystal examination - to rule out septic arthritis and crytalopathies
  • Sexual health review
  • X-ray - may show enthesitis with periosteal reaction
118
Q

Differentials for reactive arthtritis

A
  • Septic arthritis
  • Gout
  • Pseudogout
  • Ankylosing spondylitis
  • Psoriatic arthritis
119
Q

Management for reactive arthritis

A
  • If patient presents with acute, warm, swollen and painful joint
    • Hot joint policy - presume patient has septic arthritis until its excluded
      • Antibiotics
      • Aspirate joint - MCS & crystal examination
    • After excluding septic arthritis
      • NSAIDs
      • Steroid injections
      • Systemic steroids, if needed (multiple joints may be affected)
  • Other
    • Splint affected joints
    • Screen sexual partners
  • Recurrent/ persistent reactive arthritis
    • DMARDs e.g. methotrexate or sulfasalazine
    • Anti-TNF
120
Q

Complications of Reactive arthritis

A
  • Eyes
    • Bilateral conjuctivitis (non-infective)
    • Anterior uveitis
  • Genital tract
    • Circinate balanitis (dermatitis of the head of the penis)
  • Keratoderma blennorrhagica
121
Q

Prognosis for Reactive arthritis

A

Most cases of reactive arthritis resolve within 6 months and don’t reoccur.

122
Q

Define Septic Arthritis

A

Septic arthritis is defined as the infection of 1 or more joints caused by pathogenic inoculation of microbes. It occurs either by direct inoculation or via haematogenous spread. It is a medical emergency!

123
Q

Epidemiology of SA

A
  • Septic arthritis is a rare but potentially devastating condition, affecting 5 per 100,000 people each year in the developed world
  • Increases with age - 45% over 65 yrs
124
Q

Aetiology of SA

A
  • Staphylococcus aureus - the most common cause in all age groups
  • Staphylococcus epidermidis - prosthetic joints
  • Streptococcus pyogenes - children under 5 years old
  • Neisseria gonorrhoeae - young, sexually-active adults
  • Pseudomonas aeruginosa - immunosuppressed, eldery and IV drug abuse
  • Escherichia coli - immunosuppressed, eldery and IV drug abuse
125
Q

RF for SA

A
  • Underlying joint disease:10-fold increased risk; conditions such as rheumatoid arthritis, osteoarthritis and gout
  • Intravenous drug use:transfer of pathogenic organisms into the bloodstream
  • Immunocompromised:elderly, diabetes, HIV
  • Prosthetic joint
  • Recent joint surgery
126
Q

Pathophysiology of SA

A

Septic arthritis must be considered amedicalemergencydue to the risk of permanent joint destruction, osteomyelitis and sepsis. It is most commonly caused by a bacterial infection, with the microbes either invading the joint directly or via the bloodstream from other sites of infection.

Up to 90% of cases are caused bystaphylococci or streptococci, often as a complication of other pathologies such as cellulitis, chronic osteomyelitis, or drug abuse. Fungal and viral causes are rare.

127
Q

Key presentations of SA

A

Septic arthitis mainly affects one joint and so should be suspected in all monoarthritic cases. The knee is most commonly affected, but hip, shoulder, wrist and elbow joints are also affected.

128
Q

Signs of SA

A
  • Hot, tender, erythematous, swollen joint
    • In the elderly and immunosuppressed and in RA the articular signs may be muted
  • Very limited range of movement
129
Q

Symptoms of SA

A
  • Difficulty weight bearing
  • Fever
130
Q

1st line investigations for SA

A
  • FBC: leukocytosis
  • CRP and ESR: elevated due to inflammation and used for monitoring response to treatment
  • Blood cultures: should be performed onallpatients before commencing antibiotics
  • Joint aspiration (arthrocentesis): definitive investigation ideally prior to commencing antibiotics; synovial fluid should be sent to the lab for microscopy and culture
    • Plain X-ray: not diagnostic but recommended as a baseline investigation to assess underlying joint disease. Early septic arthritis may show evidence of joint effusion
131
Q

Gold standard investigation for SA

A

Joint aspiration - MSC

132
Q

Other investigations for SA

A

Ultrasound or MRI: further imaging may reveal evidence of infection, e.g. effusion, but synovial fluid analysis is definitive. MRI may be useful if suspecting spread to the surrounding bone causing osteomyelitis

133
Q

Scoring criteria for SA

A

Kocher criteria has been used in the diagnosis of septic arthritis. A score of 2 suggests a 40% probability and a score of 3 suggests a 93% probability.

Non-weight bearing - 1
Temp <38.5 - 1
ESR >40mm/hr - 1
WCC > 12x10^9/L - 1

134
Q

Differentials for SA

A

Crystal arthropathies - gout and pseudogout

135
Q

Management of SA

A
  • IV antibiotics for 2 weeks followed by oral antibiotics for 4 weeks. Broad spectrum antibiotics should be given urgently and then tailored once the causative agent has been identified.
    • Empirical therapy: flucloxacillin is first-line
    • Penicillin allergy: clindamycin
    • Suspected or confirmed MRSA: vancomycin
    • Gonococcal arthritis or gram-negative infection: cefotaxime or ceftriaxone
  • Joint drainage
    • Aspiration
    • Arthroscopic drainage
    • Open drainage
136
Q

Monitoring for SA

A

After resolution of the acute illness, the patient should be followed up on at least one occasion to confirm complete recovery and to check for the presence of joint damage.

137
Q

Complications of SA

A
  • Osteomyelitis: the spread of infection from the joint to the surrounding bone
  • Permanent joint destruction
  • Sepsis
138
Q

Prognosis of SA

A

Mortality from septic arthritis ranges from 10 to 20% with treatment, and up to 66% without treatment.

With prompt antibiotic treatment, joint function is restored in 50% of patients. Delayed treatment is associated with permanent joint destruction and osteomyelitis. In general, gonococcal septic arthritis is not associated with long term impairment.

139
Q

Define and overview of Osteomyelitis

A

Osteomyelitis is an inflammatory condition of bone/ bone marrrow caused by an infecting organism, most commonly Staphylococcus aureus.

Severity can be staged depending on the aetiology of the infection, its pathogenesis, extent of bone involvement, duration, and host factors particular to the individual patient.

All forms of acute osteomyelitis may evolve and become chronic, sharing a final common pathophysiology, with compromised soft-tissue surrounding dead, infected, and reactive new bone.

140
Q

Epidemiology of Osteomyelitis

A
  • Osteomyelitis predominantly occurs in children
  • Majority of haematogenous acute osteomyelitis occurs in children
  • Adolescents and adults tend to get osteomyelitis due to infection secondary
    to direct trauma
  • In developed countries, the reported incidence of peripheral bone infection is about 2% per year
  • The annual incidence is higher for men than for women and increases with age.
141
Q

Aetiology of Osteomyelitis

A

Causative agents:

  • Staphylococcus aureus:A gram-positive cocci. Includes MRSA (Methicillin Resistant Staphylococcus Aureus) a penicillin resistant organism. MOST COMMON!
  • Pseudomonas aeruginosa:A gram-negative rod. More commonly seen in IV drug users.
  • Salmonellaspp.:Gram-negative rods. Most commonly seen in patients with sickle cell anaemia.
  • Neisseria gonorrhoeae:A gram-negative diplococci. Seen in the sexually active where rarely it may cause a disseminated infection.
  • Mycobacterium tuberculosis:Acid fast bacilli. May cause osteomyelitis - characteristically in Pott’s disease (TB affecting the spine).
  • Polymicrobial:More commonly seen in those with ulcers secondary to vascular disease, neuropathy and diabetes.

There are many other causative pathogens that may be isolated or suspected. Relatively rarely fungal species can cause osteomyelitis.

142
Q

RF for Osteomyelitis

A
  • Diabetes
  • Old age
  • Peripheral vascular disease
  • Immunocompromise
  • Malnutrition
  • Trauma/ injury

Patients with peripheral vascular disease, neuropathy, diabetes, reduced mobility or nutritional deficiency are at greater risk of developing skin ulcers and having poor healing following surgery.

143
Q

Pathophysiology of Osteomyelitis

A

Osteomyelitis may be caused by the haematogenous spread or non-haematogenous spread of pathogens to bone.

  • Non-haematogenous spread - occurs due to breakdown or removal of the normal protective barriers of skin and soft tissue or contiguous spread (e.g. local skin infection like cellulitis spreading to the bone).
    • Open fractures
    • Skin ulcers
    • Surgery
    • Prosthesis
    • Trauma
    • Animal/ insect bites
  • Haematogenous spread - refers to the spread of a pathogen via the blood. Most commonly affects the axial skeleton, primarily the vertebral bones. After the vertebral bones the next most frequently affected sites are other axial bones like the sternum and pelvis. In children, long-bone osteomyelitis is seen - which when affecting the metaphysis may lead to septic arthritis.
    • Indwelling intravascular catheter(e.g. Hickman line)
    • Haemodialysis
    • Endocarditis
    • IV drug use
  • Acute and chronic osteomyelitis
    • Once the bacteria reach the bone they start to proliferate. This alerts nearby immune cells - specifically dendritic cells and macrophages - that try to fight off the infection. This represents the acute phase of the disease and occurs over a course of weeks. The immune cells release chemicals and enzymes that break down bone and cause local destruction. Usually acute osteomyelitis comes to a resolution - the immune systemdestroys all of the invading bacteria.
    • If the lesion is not that extensive, and there’s viable bone the osteoblasts and the osteoclasts begin to repair the damage over a period of weeks. However, in some cases, the process turns into a chronic osteomyelitis - lasting months to years.
    • In that situation, the affected bone sometimes becomes necrotic and separates from the healthy part of the bone - and that’s called a sequestrum. At the same time, the osteoblasts that originate from the periosteum may form new bone that wraps the sequestrum in place, this is called an involucrum.
    • Cloaca may also form - an opening in an involucrum that allows the internal necrotic bone and pusto discharge out.
    • Occasionally, in both acute and chronic osteomyelitis the inflammation may involve the periosteum. The periosteum is loosely attached to the compact bone, so the two layers can separate and allow an abscess to form between them. The abscesstracks along the periosteum, lifting it up - away from the compact bone.
    • The infection can also spread further to involve a nearby joint - particularly the knee or hip joint in young children, as well as overlying muscle, skin, and even get into blood vessels.
144
Q

Signs of Osteomyelitis

A
  • Erythema
  • Swelling
  • Evidence of previous surgery or trauma
  • Tenderness
  • Discharging sinus
  • Ulcers / skin breaks
145
Q

Symptoms of Osteomyelitis

A
  • Symptoms
    • Fever
    • Pain
    • Overlying redness
    • Swelling
    • Malaise
146
Q

Histopathology of Osteomyelitis

A
  • HistopathologyAcute changes:
    • Inflammatory cells
    • Oedema
    • Vascular congestion
    • Small vessel thrombosis
    Chronic changes:
    • Necrotic bone ‘sequestra’
    • New bone formation - involucrum
    • Neutrophil exudates
    • Lymphocytes & histiocytes (tissue macrophages)
147
Q

Investigations for Osteomyelitis

A

Bloods

  • FBC - elevated WCC
  • CRP and ESR - elevated
  • U&Es
  • LFTs
  • HbA1c - patients who don’t have known diabetes, should be screened

Microbiology

  • Urine MSU
  • Blood cultures
  • Wound swabs
  • Bone biopsy and culture

Imaging

  • X-ray of suspected area
    • Local osteopenia
    • Areas of bone lysis
    • Cortical loss
    • Periosteal reaction
    • Sequestrum and involucrum may be seen in advanced disease
  • MRI
    • Good visualisation of bone and surrounding soft tissue
    • Bone marrow oedema can be seen early on
    • Can identify abscesses
  • CT
    • Good for defining bone and small sequestrum and involucrum
    • Can be used to aid surgical planning
148
Q

Gold standard investigation for Osteomyelitis

A

MRI - imaging modality of choice

149
Q

Other management for Osteomyelitis

A
  • Further investigations based on suspected aetiology e.g. echocardiogram for suspected infective endocarditis
  • Other imaging techniques - if diagnostic uncertainty remains. These include FDG-PET and Technetium-99m bone scintigraphy.
150
Q

Management of Osteomyelitis

A
  • Multidisciplinary management!
  • Antibiotics
    • Antibiotic courses tend to be a minimum of 4-6 weeks and are guided by microbiology (usually given after blood culture results obtained)
    • Empiric regimens may be given e.g. ceftriaxone and vancomycin for good coverage against S. aureus and MRSA. This can then be updated when positive cultures are obtained.
    • Length of course varies (normally a minimum of 4-6 weeks). Patients should be monitored with repeat blood tests and imaging to decide.
  • Surgical debridement
    • Most commonly used in non-haematogenous spread. Indications for surgery:
      • Failure to respond to antibiotic therapy
      • Formation of discrete abscess
      • Neurological deficit(vertebral osteomyelitis)
      • If surgical metalwork is present, its removal must be considered.
151
Q

Complications of Osteomyelitis

A
  • Septic arthritis - if infection spreads to joints
  • Growth disturbance in children and adolescents
  • Amputations
152
Q

Prognosis for Osteomyelitis

A

Most patients with acute osteomyelitis recover with no long-term complications if osteomyelitis is diagnosed promptly and treated adequately.

Recurrence of infection may occur early or late. Early relapse is usually seen shortly after stopping antibiotics and can be treated by repeated surgery. Most patients who relapse have symptoms within the first 2 years after surgery. Although recurrence becomes less likely with the passage of time, a few patients can relapse many years later.

153
Q

Define Systemic Lupus Erythematosus (SLE)

A

Systemic lupus erythematosus (SLE) is a chronic systemic autoimmune condition caused by a type 3 hypersensitivity reaction due to a complex interplay between genetic and environmental factors.

154
Q

Epidemiology of SLE

A
  • Most commonly affects women in their reproductive years
  • North America has the highest estimated incidence and prevalence of SLE
  • Most common in African-Caribbean and Asians
  • Peak age of onset is between 15 and 45 years old
155
Q

Aetiology of SLE

A
  • Genetics
  • Environmental triggers e.g.
    • UV light
    • Smoking
    • Medications e.g. procainamide, hydralazine, isoniazid
    • Sex hormones e.g. oestrogen
    • EBV
156
Q

RF for SLE

A
  • Middle-aged: peak age of onset is between 15 and 45 years old
  • Female gender: SLE is 12 times more common in females
  • African and Afro-Caribbean: SLE is more common and more severe in these patients; incidence amongst black Americans ishigherthan black Africans for unknown reasons
  • Family history
  • Drugs: procainamide, isoniazid, hydralazine may cause drug-induced Lupus
  • HLA associations: HLA-B8, -DR2, -DR3
157
Q

Pathophysiology of SLE

A
  • Environmental triggers e.g. UV light cause cell death. This creates apoptotic bodies. Due to specific genes, there is reduced clearance or these apoptotic bodies and cellular debris (e.g. nuclear antigens). Genetics play a further role as the immune system of these patients don’t recognise the cellular debris as self and so attack the cell material, forming nuclear antigen-antibody complexes. These complexes can deposit in different tissues and activate complement causing inflammation and damage. This is known as a type III hypersensitivity reactionThis deposition can occur anywere so multiple organs are affected e.g. skin, joints, kidneys, heart and brain.
  • Many patients also develop antibodies targeting other cells like red and white blood cells, and molecules like various phospholipids, which can mark them for phagocytosis and destruction, leading to additional symptoms. This is considered a type II hypersensitivity reaction.
158
Q

Classic presentation of SLE

A

Malar ‘butterfly’ rash (across cheeks but not nose), fatigue and widespread musculoskeletal pain in a middle-aged, African female.

The disease follows a relapsing and remitting course.

159
Q

General presentations of SLE

A
  • Fatigue
  • Fever
  • Lymphadenopathy
  • Weight loss
160
Q

Dermatological S/S of SLE

A
  • Malar ‘butterfly’ rash: on cheeks but spares nasolabial folds
  • Discoid rash: scaly, well-demarcated plaques in sun-exposed areas (pigmented → hyperkeratotic → atrophic)
  • Photosensitivity
  • Livedo reticularis: ‘lace-like’ skin discolouration
  • Non-scarring alopecia
  • Raynaud’s phenomenon: decreased blood flow to fingers
161
Q

MSK S/S of SLE

A
  • Arthralgia
  • Non-erosive arthritis
162
Q

Pulmonary S/S of SLE

A
  • Pleurisy
  • Interstitial lung disease
  • Pulmonary embolism
163
Q

CVS S/S of SLE

A
  • Pericarditis and myocarditis: pericarditis is the most common cardiac manifestation
  • Libman-Sacks endocarditis (non-infective)
  • Neonatal heart block: anti-Ro antibodies cross the placenta
164
Q

GI S/S of SLE

A
  • Lupus peritonitis
  • Mesenteric artery occlusion
165
Q

Renal S/S of SLE

A

Lupus nephritis: most commonly diffuse proliferative glomerulonephritis

166
Q

Neuropsychiatric S/S of SLE

A
  • Psychosis
  • Seizures
  • Depression and anxiety
167
Q

Opthalmological S/S of SLE

A
  • Keratoconjunctivitis sicca
  • Sjögren’s syndrome
168
Q

Haematological S/S of SLE

A
  • Autoimmune haemolytic anaemia
  • Thrombocytopaenia
  • Leukopenia
  • Antiphospholipid syndrome
169
Q

Other S/S of SLE

A

Affects the mucosa - mouth and nose ulcers

170
Q

1st line investigations of SLE

A

Blood tests:

  • FBC:anaemia, thrombocytopaenia and leukopaenia may be present
  • U&E:lupus nephritis can cause chronic kidney disease, urea and creatinine raised
  • ESR and CRP:ESR is raised in active disease, whilst CRP is actually usually normal; raised CRP may suggest underlying infection
  • Clotting screen:prolonged APTT will be present in antiphospholipid syndrome
  • Complement (C3 and C4):low in active disease as complement is consumed in the process of complex formation

Antibodies

  • ANA (anti-nuclear antibodies):most sensitive test and present in 99% of patients
  • Anti-dsDNA:high specificity (99%) but less sensitive (70%); may be used in disease monitoring
  • Anti-Smith antibodies: targets ribonucleoproteins. Most specific (> 99%), low sensitivity (30%)
  • Anti-Roandanti-La: associated with Sjögren’s syndrome and neonatal lupus
  • Anti-histone: found in 80-90% of patients withdrug-induced lupus
  • Rheumatoid factor:20% are positive
  • Anti-U1 RNP
  • Antiphospholipid antibodies: targets proteins bound to phospholipid e.g. anticardiolipin, lupus anticoagulant, and anti-B2 glycoprotein 1. Consider in patients with recurrent miscarriages or thromboses
171
Q

Other investigations to consider for SLE

A
  • Urinalysis: lupus nephritis may cause proteinuria and haematuria
  • Skin or renal biopsy
  • Imaging:consider joint X-rays in the presence of arthralgia or a chest X-ray if respiratory symptoms are present
172
Q

Diagnostic Criteria for SLE

A

Biopsy proven lupus nephritis with positive ANA or anti-DNA OR >4 (at least 1 lab and 1 clinical) of the following features:

Clinical criteria

  • Malar rash
  • Discoid rash
  • Non-scarring alopecia
  • Oral and nasal ulcers
  • Synovitis
  • Serositis
  • Urinalysis (presence of proteinuria or haematuria)
  • Neurological features
  • Haemolytic anaemia
  • Leucopenia
  • Thrombocytopenia

Lab criteria

  • +ve ANA
  • Anti-dsDNA
  • Anti-smith antibodies
  • Antiphospholipid antibodies
  • Low complement
  • +ve direct Coombs test - detects antibodies that are stuck to the surface of RBCs
173
Q

Differentials for SLE

A
  • Scleroderma
  • Rheumatoid arthritis
  • Antiphospholipid syndrome
  • Mixed connective tissue diseases (CTDs)
  • Raynaud’s syndrome
  • Sjögren’s syndrome
174
Q

Management of SLE

A
  • Lifestyle changes - avoidance of sun and use of sunscreen
  • Acute management
    • Acute flares may be mild, moderate or severe.
    Mild: Prednisolone (corticosteroid) + hydroxychloroquine + NSAIDsModerate and severe: Prednisolone and hydroxychloroquine and an immunosuppressant
    • Immunosuppressents commonly used: Methotrexate, Mycophenolate mofetil, Azathioprine, Tacrolimus, Leflunomide, Ciclosporin
    Refractory cases - biologics such as belimumab or rituximab may be considered
  • Maintenance therapy
    • Initially, use the flare-up medication at a reduced dose
    • Then switch to therapy with just hydroxychloroquine
175
Q

Prognosis for SLE

A

The mortality associated with SLE is improving and fortunately, the majority of people with lupus can expect a normal or near-normal life expectancy.

However, patients do have an overall increased risk of premature death compared to the general population. Early mortality is predominantly due to renal and central nervous system involvement, thrombosis and infection. Later mortality is due to infection and premature atherosclerotic vascular disease.

~80% survival at 15 years

176
Q

Pathophysiology and overview of Bone tumours

A

Bone tumours form when a bone cell divides uncontrollably and forms a mass or tumour.

If the tumour remains confined and doesn’t spread into surrounding tissues, then it’s considered benign. But if the tumour invades into surrounding tissues and metastasises or spreads through blood or lymph, then it’s considered malignant.

Malignant tumours can either be primary which is when they arise from the bone cells, or secondary, which is when a tumour developed somewhere else in the body, metastasised, and spread to the bones.

Bone pain may also be due to:

  • Multiple myeloma
  • Lymphoma
177
Q

Explain Osteochondroma (Pri, benign)

A
  • Thought to arise from mutations in the Exostosin 1 (EXT1) and Exostosin 2 (EXT2) genes, which encode the Exostosin 1 and 2 proteins.
    • These proteins help to synthesize heparin sulfate, which is a protein that regulates the growth of the growth plate.
  • Tumour arises from the growth plate, and it typically results in a lateral bony projection (exostosis) that has a cap, made mostly of hyaline cartilage.
  • Tumours typically develop in the metaphysis of long bones, most usually the distal femur and the proximal tibia, around the knee joint, but they can also occur in flat bones like the ilium, one of the hip bones, as well as the scapula.
  • Commonly affects men under 25 years of age
178
Q

Explain Giant cell tumour (Pri, benign)

A
  • Risk factor: bony trauma e.g. fracture or radiation exposure
  • The tumor cells arises from osteoclasts cells, that develop into cells that have numerous nuclei - typically over 50 nuclei.
  • Tumour typically arises in the epiphysis of the long bones, like the distal femur and the proximal tibia.
  • On rare occasions, this tumor can become malignant, especially in elderly individuals.
179
Q

Explain Osteoblastoma (Pri, Benign)

A
  • Arise from osteoblasts
  • Tumours form a nidus – a disorganized mix of small blood vessels, tiny rods of bone called trabeculae, and unmineralized bony tissue called osteoid.
    • Nidus are large with a diameter of over 1.5 cm.
  • Tend to affect the bones of the axial skeleton, usually the mandible, and erode the surrounding bone.
180
Q

Explain Osteoid Osteomas (Pri, Benign)

A
  • Arise from osteoblasts
  • Tumours form a nidus – a disorganized mix of small blood vessels, tiny rods of bone called trabeculae, and unmineralized bony tissue called osteoid.
    • Nidus are smaller than 1.5cm in diameter and surrounded by a ring of sclerotic bone tissue. Sclerotic tissue often produces prostaglandins which trigger the sensation of pain.
  • Typically affect the diaphysis of long bones like the tibia, and don’t usually erode the surrounding bone.
181
Q

Explain Osteosarcoma

A

Pri, Malignant

  • Arise from osteoblasts of different sizes - pleomorphic - and they produce too much osteoid tissue.
  • Often form in the metaphysis where there’s a lot of cell division occurring. Common sites are around knee and proximal humerus.
  • Associated mutations include:
    • Mutations in the pRB protein, also seen in familial retinoblastoma
    • Mutations in the p53 protein, also seen in Li-Fraumeni syndrome, a condition in which there are a variety of cancers throughout the body.
  • They most commonly affect adolescents.
  • Tumours destroy bone and and spread into surrounding tissue.
  • Rapidly metastasise to the lungs
182
Q

Explain Ewing sarcoma

A

Pri, Malignant

  • Thought to arise from neuroectodermal cells
  • Associated with chromosomal mutations, specifically a translocation between the EWSR1 gene on chromosome 22 and FLI1 gene on chromosome 11.
  • The EWSR1/FLI1 fusion results in the expression of an abnormal protein called the ESWR1/FL1 fusion protein or the Ewing sarcoma protein.
    • This protein causes defects in the differentiation process of human mesenchymal stem cell and neuroectodermal cells, resulting in Ewing sarcoma tumour cells.
  • Affect a number of different bones (arms, legs, chest), but most commonly affects the femur and the sacrum.
  • Look like small, round, blue cells on microscopy.
  • Common in adolescents, typically between the age of 10 to 20 years.
183
Q

Explain chrondrosarcoma

A

Pri, Malignant

  • Arises from the chondrocytes which are cartilage-producing cells.
  • Mainly affects bones of the pelvis and scapula but can also affect long bones like the proximal femur and proximal humerus.
  • On imaging, the mass is typically within the medullary cavity.
184
Q

What are the most common sources of Secondary bone tumours

A

breast, prostate, the lungs, the thyroid, and the kidneys.

185
Q

Clinical manifestations of Bone tumours

A
  • Commonly cause local bone pain, swelling, and fractures.
  • Pain ofosteoid osteoma typically gets worse at night
  • Chondrosarcoma associated with dull, deep pain and affected area is swollen & tender
  • Ewing sarcoma can present with painful swelling, redness in the area surrounding the tumour, malaise, anorexia, weight loss, fever, paralysis and/or incontinence if affecting
    the spine, numbness in affected limb
  • Osteochondromas and Osteoblastomas sometimes press against spinal nerves, causing numbness and limb weakness.
  • Can cause avascular necrosis of certain regions within the bone, if the tumour impinges on a major blood vessels.
  • Malignant tumors typically cause a chronic inflammatory response which leads to fever, malaise, night sweats, and weight loss.
  • Bony tumours often metastasise to the lungs, so can cause pulmonary symptoms like coughing and shortness of breath.
186
Q

Investigations for bone cancer

A
  • Testing for serum tumour markers
  • ALP (from bone elevated)
  • Hypercalcaemia
  • PSA (prostate specific antigen) raised in presence of prostatic metastases
  • Skeletal isotope scan - show bony metastases as ‘hot’ areas before radiological changes
  • Medical imaging e.g. X-rays, CT-scans, and MRI
187
Q

X ray findings for suspected bone cancer

A
  • X-ray findings
    • Osteochondroma - can see exostoses
    • Giant cell tumour - can see multicystic bone lesions that look like soap bubbles.
    • Osteosarcoma - can see lytic bone lesions, referred to as a sunburst appearance, because the radiating tumour streaks look like sun rays. Can also cause the periosteum to lift and that’s commonly called Codman’s triangle.
    • Ewing sarcoma - can see lytic bone lesions referred to as onion skin appearance, because the periosteum looks like a sliced onion bulb.
    • Chondrosarcoma - can see patchy lytic lesions that make the bone look like a “moth-eaten” piece of cloth.
    • Osteosclerotic (increased bone density) metastases are characteristic
      of prostatic carcinoma
188
Q

Management of Bone cancer

A

Depends on whether tumour is malignant or benign.

  • General symptomatic management: analgesics and anti-inflammatory drugs. Biphosphonates may help.
  • Benign tumours: can be surgically removed to reduce pain and the risk of fractures.
  • Malignant tumours: radiotherapy, chemotherapy, hormone-therapy and surgery depending on the type and spread of the tumour.
189
Q

Define Fibromyalgia

A

Fibromyalgia is a chronic pain syndrome characterised by the presence of widespread body pain.

190
Q

Epidemiology of Fibromyalgia

A
  • 0.5-4% prevalence
  • F>M
  • Affects people mainly in middle age
  • Can be associated with other somatic syndromes e.g. chronic fatigue syndrome, IBS, chronic headaches syndromes, RA, AS and SLE.
191
Q

RF for Fibromyalgia

A
  • Female sex
  • Middle age
  • Genetic association
  • Environmental e.g. child abuse, low household income, divorced, low educational status, emotional problems, social withdrawal
192
Q

Pathophysiology of Fibromyalgia

A

In fibromyalgia, the underlying mechanism isn’t well understood, but there seems to be a problem with how the brain receives pain signals.

Generally speaking, individuals have low levels of serotonin, which is involved in inhibiting pain signals, and elevated levels of substance P, and nerve growth factor, which are involved in propagating pain signals.

Together, these are thought to play a role in the hypersensitivity to pain, which hints that fibromyalgiamight be a condition of central sensitization. In other words, they would perceive more pain compared to other people. In addition, central sensitization means that a person might have a wide range of sensitivities- affecting everything from how they sleep to how they feel to how they think. If the person has negative emotions like depression, anxiety, and psychological factors like negative beliefs and attributions it can also amplify this sensitivity to pain.

193
Q

Key presentations of Fibromyalgia

A
  • Allodynia - pain in response to non-painful stimulus
  • Hyperaesthesia - exaggerated perception of pain to mildly painful stimulus
194
Q

Symptoms of Fibromyalgia

A
  • Widespread pain
    • Aggravated by stress, cold and activity
  • Extreme tenderness
  • Sleep disturbance
  • Fatigue - extreme and present after minimal exertion
  • Morning stiffness
  • Paraesthesiae - abnormal sensation in skin
  • Headaches
  • Poor concentration
  • Low mood
195
Q

Investigations for Fibromyalgia

A

Investigations are all normal!

Diagnosis of fibromyalgiais based on clinical features:

  • Chronic pain that has been present for at least 3 months
  • Widespread pain - involved left and right sides, above and below waist, and the axial skeleton.
  • Palpate tender point sites - severe pain in 3 to 6 different areas of your body, or you have milder pain in 7 or more different areas
  • No other reason for symptoms has been found
196
Q

Investigations to exclude other conditions for Fibromyalgia

A
  • Thyroid function test (to exclude hypothyroidism)
  • ANA’s and DsDNA (to exclude SLE)
  • ESR & CRP (to exclude PMR)
  • Ca2+ and electrolytes (to exclude high calcium)
  • Vit D (to exclude low vitamin D)
  • Examine patient and CRP (to exclude inflammatory arthritis)
197
Q

Differentials for Fibromyalgia

A
  • Rheumatoid arthritis
  • Chronic fatigue syndrome
  • Hypothyroidism
  • SLE
  • Polymyalgia rheumatica (PMR)
  • High calcium
  • Low vitamin D
  • Inflammatory arthritis
198
Q

Management for Fibromyalgia

A

Treatment of fibromyalgiarequires a holistic approach:

Non-pharmacological:

  • Regular exercise like cardiovascular fitness training which includes fast walking, biking, swimming, or water aerobics can help by reducing pain and fatigue. Grading of exercise is important to avoid over-exertion and fatigue.
  • Relaxation techniques and good sleep hygiene can also help.
  • Physiotherapy and rehabilitation
  • CBT

Pharmacological:

  • Amitriptyline - tricyclic antidepressant
  • Serotonin-norepinephrinereuptake inhibitors (SNRIs) e.g. duloxetine

Help by elevating serotonin and norepinephrine levels.

  • Anticonvulsants like pregabalin and gabapentinwhich slow nerve impulses can help with sleep problems.
199
Q

Prognosis for Fibromyalgia

A

With good adherence to exercise, sleep, and behavioural therapy, most patients will improve over time.

The goal of treatment is to decrease physical and mental symptoms and to increase functioning, not to cure.

200
Q

Overview of Mechanical lower back pain

A
  • Mechanical means that the source of the pain may be in your spinal joints, discs, vertebrae, or soft tissues.
201
Q

Epidemiology of MLBP

A

Common in young people: 20-55 yrs

202
Q

Aetiology of MLBP

A

Many causes, including

  • Strain
  • Heavy manual handling
  • Stooping and twisting whilst lifting
  • Pregnancy
  • Trauma
  • Lumbar disc prolapse
  • Spondylolisthesis (one vertebrae slips out of place causing back pain)
  • Osteoarthritis
  • Fractures
  • Exposure to whole body vibration
203
Q

RF for MLBP

A
  • Female
  • Increasing age
  • Pre-existing chronic widespread pain - fibromyalgia
  • Psychosocial factors e.g. high levels of psychological distress, poor self-rated health, smoking and dissatisfaction with work
204
Q

Pathophysiology of MLBP

A

Spinal movement occurs at the disc and the posterior facet joints - stability is normally achieved by a complex mechanism of spinal ligaments and muscles. Any of these structures may be a source of pain.

205
Q

Explain Lumbar spondylosis

A
  • Lumbar spondylosis
    • Main lesion occurs in an intervertebral disc - a fibrous structure whose tough capsule inserts into the the rime of the adjacent vertebra. This capsule encloses a fibrous outer zone and a gel-like inner zone
    • The disc allows rotation and bending
    • Changes in the discs occasionally start in teenage years or early twenties and often increase with age
    • The gel changes chemically, breaks up, shrinks and loses its compliance
    • The surrounding fibrous zone develop circumferential or radial issues
    • In the majority - this is initially asymptomatic, but visible on MRI as decreased hydration
    • Later - the discs become thinner and less compliant
    • These changes cause circumferential bulging of the intervertebral ligaments
    • Reactive changes develop in adjacent vertebrae; the bone becomes sclerotic and osteophytes form around the rim of the vertebra
    • The most common site for lumbar spondylosis is L5/S1 & L4/L5
    • In young people, disc prolapse may occur through an adjacent vertebral end-plate, producing a Schmorl’s node (herniations) on X-ray - this process is painless but may accelerate disc degeneration
    • Spondylosis may be symptomless but can cause:
      • Episodic spinal pain
      • Progressive spinal stiffening
      • Facet joint pain
      • Acute disc prolapse, with or without nerve irritation
      • Spinal stenosis
206
Q

Explain facet joint syndrome

A
  • Lumbar spondylosis causes secondary osteoarthritis of the misaligned facet joints
  • Pain is typically worse on bending backwards and when straightening from flexion - it is lumbar in site, unilateral or bilateral and radiates to the buttock
  • Facet joints are well seen on MRI and may show osteoarthritis, an effusion or a ganglion cyst
    • Treatment consists of direct corticosteroid injections under imaging
    • Physiotherapy and help to reduce weight may also be offered
207
Q

Explain Fibrositic nodulosis

A
  • There are tender nodules in the upper buttock and along the iliac crest
  • This condition causes unilateral or bilateral lower back and buttock pain
    • Local intralesional corticosteroid injections may help
208
Q

Explain postural back pain and ‘swayback’ of pregnancy

A
  • Low back pain is common in pregnancy and reflects altered spinal posture and increased ligamentous laxity (looseness)
    • Weight control and pre- and postnatal exercises are helpful, and the pain usually settles after delivery
    • Analgesics and NSAIDs are best avoided during pregnancy and breastfeeding
  • Poor posture causes a similar syndrome in the non-pregnant, owing to obesity or muscular weakness
  • Poor sitting posture at work is a frequent cause of chronic low back pain
209
Q

Clinical manifestations of MLBP

A

Variety of presentations depending on pathology:

  • Back is stiff
  • Scoliosis (spine twists and curves to a side) may be present when patient is standing
  • Muscular spasm is visible and palpable and causes local pain and tenderness - lessens when sitting or lying
  • Pain is often unilateral (but can be bilateral) and helped by rest
  • Pain usually worse in the evening
  • Exercise aggravates pain
  • Morning stiffness is absent
  • Sudden onset
  • Episodes are generally short-lived and self-limiting - but high chance of recurrence once individual has experienced one episode
210
Q

Investigations for MLBP

A
  • MRI - imagine modality of choice. Can see disc prolapse, cord compression, cancer, infection or inflammation.
  • Bone scans
  • Examine patient to exclude pathologies e.g. nerve root lesions affecting reflexes
  • Spinal X-rays - ONLY done if there are red flags for serious pathology.
  • Arrange specific test if pathology suspected e.g. myeloma, infection, tumour, Paget’s
    • e.g. FBC, ESR, CRP, U&E, ALP, serum/urine electrophoresis
211
Q

Red flags for serious pathology when investigating MLBP

A
  • Age of onset <20 or >55 yrs
  • Acute onset in elderly people
  • Constant or progressive pain
  • Nocturnal pain
  • Worse pain on being supine
  • Fever, night sweats, weight loss
  • History of malignancy
  • Abdominal mass
  • Thoracic back pain
  • Morning stiffness
  • Bilateral or alternating leg pain (points to cauda equina compression, can lead to bladder and bowel incontinence- a surgical emergency!)
  • Neurological disturbance e.g. sciatica
  • Sphincter disturbance (may signify acute cord compression!)
  • Current or recent infection
  • Immunosuppression e.g. steroids or HIV
  • Leg claudication or exercise-related leg weakness/ numbness (spinal stenosis)
  • Violent trauma e.g. fall from height or road traffic accident (RTA)
212
Q

Differentials for MLBP

A
  • Polymyalgia rheumatica (PMR): in elderly, ESR and CRP will distinguish this from mechanical back pain
  • Sinister causes of back pain e.g. malignancy, infection or inflammatory causes. Must be excluded with spinal x-ray.
213
Q

Management for MLBP

A

Usually self-limiting

Supportive care:

  • Analgesia e.g. paracetamol, NSAIDs, codeine
    • Consider low dose amitriptyline or duloxetine if these fail.
  • Combined with physiotherapy and exercise programmes, if no improvement seen.
  • Acupuncture may be considered
  • Patient should avoid excessive rest
  • Address psychosocial issues
  • Re-education in lifting and exercises to prevent further attacks of pain
  • Comfortable sleeping position using a mattress of medium (not hard) firmness

Other:

  • Refer to pain clinic or surgical options for any intractable symptoms
  • Urgent referral if any neurosurgical emergencies identified e.g. acute cord compression or acute cauda equina compression
    • Treatment may involve laminectomy, radiotherapy, decompression.
214
Q

Define Osteomalacia

A

Osteomalacia is a metabolic bone disease characterised by incomplete mineralisation of the underlying mature organic bone matrix (osteoid) following growth plate closure in adults.

This results in softening of the bones.

The faulty process of bone mineralisation results in rickets in children and osteomalacia in adults.

215
Q

Epidemiology of Osteomalacia

A
  • In the developed world, it is estimated that 40% of individuals over the age of 50 years are vitamin D deficient; this is the most common cause of osteomalacia.
  • Fortification of foods with vitamin D and the use of vitamin supplements has greatly reduced the incidence of osteomalacia in the Western world.
216
Q

Aetiology of Osteomalacia

A

Deficiency or impaired metabolism of:

  • Vitamin D
  • Calcium
  • Phosphate
217
Q

RF for Osteomalacia

A
  • Limited exposure to sunlight
  • Dark skin
  • Dietary vitamin D deficiency: fish, cheese, eggs
  • Chronic kidney disease: reduced activation of vitamin D (1-alpha-hydroxylation)
  • Liver dysfunction:reduced activation of vitamin D (25-hydroxylation)
  • Malabsorption: such as inflammatory bowel disease
  • Anticonvulsant use: phenytoin, carbamazepine and phenobarbital all increase cytochrome P450 metabolism of vitamin D
  • Tumour induced: tumour production of FGF-23 which causes hyperphosphaturia (low phosphate)
  • Vitamin D resistance: some inherited conditions
218
Q

Pathophysiology of Osteomalacia

A

Physiology:

Vitamin D requires activation by the liver (25-hydroxylation) and then by the kidney (1-alpha-hydroxylation/ calcitriol). Active vitamin D raises serum calcium and phosphate by increasing intestinal absorption, as well as resorption from the bone and kidney. These electrolytes then contribute to bone mineralisation.

Parathyroid hormone - stimulates resorption of Ca2+ and phosphate from bone, increases Ca2+ reabsorbtion and phosphate excretion from kidneys and also boosts 1-alpha-hydroxylase activity causing increased levels of vit D.

Pathophysiology:

Osteomalacia is primarily caused byvitamin D deficiencywhich can be due to reduced sunlight exposure, poor nutrition, malabsorption, liver failure, and renal failure. Occasionally osteomalacia can be caused by hypophosphataemia due to inborn errors in metabolism.

219
Q

S/S of Osteomalacia

A
  • Signs
    • Skeletal deformities
    • Waddling gait: a late sign
    • Signs of hypocalcaemia: such as Chvostek sign (contraction of facial muscles provoked by lightly tapping over the facial nerve)
  • Symptoms
    • Generalised bone pain: rib, hip, pelvis, thigh and foot pain are typical
    • Proximal muscle weakness
    • Difficulty walking upstairs
    • Muscle spasms and numbness due to hypocalcaemia
    • Fracture: often secondary to mild trauma, most commonly affecting the long bones
220
Q

Primary investigations for Osteomalacia

A
  • Serum calcium and phosphate: assess for hypocalcaemia and hypophosphataemia caused by vitamin D deficiency
  • Serum 25-hydroxyvitamin D
    • <25 nmol/L: vitamin D deficiency
    • 25–50 nmol/L: vitamin D insufficiency
    • > 50 nmol/L: adequate vitamin D levels
  • Parathyroid hormone (PTH) level: hypocalcaemia due to low vitamin D causes secondary hyperparathyroidism
  • Serum ALP: raised in 80% of patients with osteomalacia
  • Renal and liver function: assess for chronic kidney or liver disease as an underlying cause
221
Q

Gold standard investigation for Osteomalacia

A

Iliac bone biopsy with double tetracycline labelling

222
Q

Other investigations to consider for Osteomalacia

A
  • X-ray: not required for adults if the diagnosis is clear. Characteristic findings include:
    • Pseudofractures: ‘Looser’s zones’ are linear areas of low-density bone surrounded by sclerotic borders; a pathognomonic finding in osteomalacia
    • Osteopenia
    • Coarsened trabeculae
    • In children: cupped, ragged metaphyseal surfaces
  • DEXA scan: it is difficult to distinguish between osteoporosis and osteomalacia on DEXA scan as both show low bone density
  • Iliac bone biopsy with double tetracycline labelling: the gold standard for diagnosis but rarely performed due to invasiveness. Shows incomplete mineralisation.
223
Q

Differentials for Osteomalacia

A
  • Osteoporosis
  • Paget’s disease
224
Q

Management for Osteomalacia

A

Treat underlying cause!

Generally, Calcium D3 given if dietary insufficiency. If malabsorption or hepatic disease, then give vitamin D2 (ergocalciferol) or IM calcitriol. If renal disease of vitamin D resistance, then give alfacalcidol or calcitriol

225
Q

Treatment for Osteomalacia for Vit D Deficiency, Vit D insufficiency and Adequate Vit D levels

A
  • Vit D deficiency
    • Loading regime: typically a total of 300 000 IU. Common regimens are 50,000 IU once a week for 6 weeksor20,000 IU twice a week for 7 weeks (280,000 IU in total)
    • Lifelong maintenance: after the loading regimen, patients receive 800 IU a day. Some may receive up to 4000 IU, such as those with malabsorption disorders
    • Increasing dietary calcium:onlyoffer supplementation if the patient is unable or unwilling to increase their dietary intake
  • Vit D insufficiency
    • Only treat if the patient has concomitant risk factors e.g. dark skin, previous fragility fracture, or malabsorption
    • Lifelong maintenance:same regime as above, but patients are not offered a loading regime
    • Increasing dietary calcium:onlyoffer supplementation if the patient is unable or unwilling to increase their dietary intake
  • Adequate Vit D levels
    • Supplementation: all adults in the UK should take 400 IU vitamin D throughout the year, and offer dietary advice regarding calcium
226
Q

Monitoring for Osteomalacia

A

Monitor plasma Ca2+, initially weekly, and nausea and vomiting.

227
Q

Complications of Osteomalacia

A
  • Insufficiency fracture
  • Complications of treatment:hypercalcaemia, hyperphosphataemia
  • Secondary hyperparathyroidism
228
Q

Prognosis for Osteomalacia

A

The prognosis of patients with osteomalacia is generally very good but is dependent on the underlying cause.

Rickets and osteomalacia normally respond rapidly to vitamin D replacement, which manifests as increased mobility and muscle strength

229
Q

Notes on rickets

A

Ricketsresults from the same underlying process but occurs inchildren and adolescentsbefore the closure of the epiphyseal growth plates. This causes growth retardation and skeletal deformities.

Presents with

  • Knock-knees
  • Genu varum - bow legs
  • Craniotabes - thin, soft skull bones
  • Delayed closure of fontanelles
  • Prominent frontal bone
  • Protruding abdomen in severe disease
  • Fractures
  • Features of hypocalcaemia
  • Rachitic rosary - little bumps across the chest due to widening of junction between ribs and costal cartilage in front of the ribcage.

X-ray findings

  • Metaphyseal cupping and flaring - edges of metaphysis widen laterally (flares) and drops inwards (looks like a cup)
  • Metaphyseal fraying
  • Bowing of legs
230
Q

Differences between Osteomalacia, Osteoporosis and Osteoarthritis

A

Definition
Osteomalacia - Normal bony tissue but decreased mineral content
Osteoporosis - Decreased bone density
Osteoarthritis - Progressive cartilage and bone degradation or ‘wear and tear’

Bone Composition
Osteomalacia - soft and weak, because or poor mineralisation
Osteoporosis - bone is thin and porous with reduced mass although it is properly mineralised
Osteoarthritis - Joint space narrowing, osteophytes, subchondral sclerosis

Commonest cause
Osteomalacia - Vit D def
Osteoporosis - Increasing age and menopause
Osteoarthritis - Joint overuse or trauma

Presentation
Osteomalacia - Generalised bone pain and weakness, as well as fragility fractures
Osteoporosis - Fragility fracture
Osteoarthritis - Joint pain and stiffness, most commonly hips, knees and fingers

231
Q

Overview of vertebral disc degeneration

A

Intervertebral disc disease is a common condition characterised by the breakdown (degeneration) of one or more of the discs that separate the bones of the spine (vertebrae), causing pain in the back or neck and frequently in the legs and arms.

Discs in the lower lumbar spine are most commonly affected.

232
Q

Define acute disc disease

A

Progressive intervertebral disc breakdown leading to prolapse of the intervertebral disc resulting in acute back pain (lumbago)

233
Q

Epidemiology of acute disc disease

A
  • Disease of younger people (20-40 yrs) - the disc degenerates with age
    and in the elderly it is no longer able to prolapse
    • In older patients, sciatica is more likely to result (as opposed to prolapse) - due to compression of the nerve root by osteophytes in the lateral recess of
      the spinal canal
234
Q

Aetiology of acute disc disease

A
  • Accumulation of natural stress, minor injury throughout life
  • Genetic predisposition
235
Q

Rf for acute disc disease

A
  • Genetic predisposition
  • Advanced age
  • Menopause
  • Repeated spinal trauma
236
Q

Pathophysiology of acute disc disease

A

Intervertebral disc’s nucleus pulposus (mostly water) dehydration → decreased proteoglycan and collagen → decreased padding between vertebrae → unable to absorb shock → disc collapse → annular tears, herniation of disc contents into spinal canal → nerve impingement → pain

237
Q

Clinical manifestations of acute disc disease

A
  • Sudden onset of severe back pain - often following a strenuous activity
  • Decreased range of motion
  • Tingling, paresthesia and numbness
  • Muscle weakness and atrophy
  • Muscle spasm leads to a sideways tilt when standing
  • Decreased tendon reflexes
  • The radiation of the pain and the clinical findings depend on the disc
    affected - the lower three disks are more commonly affected
    Headache, dizziness and vertigo

Root lesion
S1 - Pain in buttock down the back of thigh to ankle/foot, loss of ankle jerk reflex and diminished straight leg raising
L5 - Buttock to lateral aspect of leg and top of foot, no loss of reflex
L4 - Pain in lateral aspect of thigh to medial side of calf, loss of knee jerk reflex, Positive femoral stretch test

238
Q

Investigations for acute disc disease

A
  • X-rays are often normal - can detect fracture
  • MRI
    • Evaluates spinal canal
    • Detects annular tears
    • Increased signal may indicate disc dehydration
    • If surgery is being considered
239
Q

Management of acute disc disease

A
  • Acute stage -
    • Bed rest on a firm mattress, analgesia (NSAIDs) and local/epidural corticosteroid injection (severe disease)
  • Surgery only for severe or increasing neurological impairment e.g. foot drop
    or bladder symptoms
    • Corpectomy - vertebral portion removed to enlarge intervertebral space
    • Discectomy - herniated disc portion removed
    • Nerve root injection
    • Intervertebral disc arthroplasty - replacement with artificial discs
    • Laminotomy - lamina removal to relieve nerve root pressure
  • Recovery phase -
    • Physiotherapy to help correct posture and restore movement
240
Q

Complications of acute disc disease

A
  • Spine collapse
  • Disc herniation
  • Compression fracture
  • Bony spur growth
  • Neurological deficit
  • Myelopathy
  • Vertebral artery compression
241
Q

Define chronic disc disease

A

Associated with degenerative changes in the lower lumbar discs and facet joints (joining the vertebral bones together)

242
Q

Clinical manifestations of chronic disc disease

A
  • Pain is usually of the mechanical type i.e. aggravated by movement
  • Sciatic radiation may occur with pain in the buttocks radiating into the posterior
    thigh
  • Usually the pain is long-standing and there is no cure
243
Q

Management of chronic disc disease

A
  • NSAIDs, physiotherapy and weight reduction can be useful
  • Surgery can be done when pain arises from a single identifiable level -
    fusion at this level with decompression of the affected nerve roots
244
Q

Define Cervical spondylosis

A

Osteoarthritis of the spine, which includes the spontaneous degeneration of either disc or facet joints.

245
Q

Pathophysiology of Cervical spondylosis

A

Degeneration of annulus fibrosus (the tough outer coating of the intervertebral discs), combined with osteophyte formation on the adjacent vertebra leads to narrowing of the spinal canal and intervertebral foramina.

As the neck flexes and extends, the cord is dragged over these osteophytes and is indented by the thickened ligamentum flavum posteriorly.

246
Q

Signs of cervical spondylosis

A
  • Limited neck movement
  • Neck flexion may produce tingling down spine (Lhermitte’s sign) - does not differentiate between a cord or root issue.
  • Root compression presents with:
    • Pain in arms or fingers at the level of compression, with numbness and dull reflexes
    • Lower motor neuron weakness and wasting of muscles innervated by the affected root
    • Weak clumsy hands
    • Gait disturbance
247
Q

Symptoms of Cervical spondylosis

A
  • Neck stiffness
  • Crepitis (crunching) on moving neck
  • Stabbing or dull arm pain
  • Forearm/ wrist pain
248
Q

Investigations for Cervical spondylosis

A

MRI

249
Q

Management of Cervical spondylosis

A
  • Analgesia
  • Encourage gentle activity
  • Cervical collars for brief painful episodes
  • If no improvement consider:
    • Epidural
    • Surgical decompression
250
Q

Bone remodelling notes

A
  • Osteoblasts release RANKL which binds to osteoclasts and activates them.
  • Osteoclasts then resorb the bone by secreting lysosomal enzymes e.g. collagenase and HCl. This digests the collagen and dissolve the minerals in the bone matrix.
  • Osteoblasts then secrete osteoprotegerin, which stops the activity of osteoclasts by binding to RANKL.
  • Osteoblasts then release osteoid seam (mainly collagen), which builds a scaffold upon which calcium and phosphate can get deposited upon.
  • New bone is then formed
251
Q

Define Pagets disease

A

A chronic bone disorder that is characterised by focal areas of increased bone remodelling, resulting in overgrowth of poorly organised bone.

Also known as osteitis deformans.

252
Q

Epidemiology of Pagets

A
  • Typically affects older people (rare in under-40s)
  • Commoner in temperate climates and anglo-saxons
  • UK has highest prevalence in the world
253
Q

Aetiology of Pagets

A
  • Can be triggered by infections e.g. measles virus
  • Linked to genetic mutations e.g. SQSTM1
254
Q

RF for Pagets

A
  • Family history
  • Age >50 years
  • Infection
255
Q

Pathophysiology of Pagets

A

3 phases of the disease:

  • Phase 1 - lytic phase
    • Osteoclasts which have up to 100 nuclei aggressively demineralise the bone (x20 more than normal).
  • Phase 2 - mixed phase (lytic and blastic)
    • Blastic phase - rapid, disorganised proliferation of new bone tissue by a large number of osteoblasts. Collagen deposited in a haphazard way.
  • Phase 3 - sclerotic phase
    • New bone formation exceeds bone resorption. The bone is structurally disorganised and weak.
  • Osteoblastic activity slows down leading to dormant phase - ‘burned out state’
256
Q

Clinical manifestations of Pagets

A

Can affect single bone or whole skeletal system. Commonly affects skull, lumbar vertebrae, pelvis and femur.

Early on - asymptomatic

With time -

  • Pain - due to bone impinging on nerves
  • Growth of bones in skull can cause:
    • Leontiasis - lion like face
    • Hearing loss - narrow auditory foramen and impinge on auditor nerve
    • Vision loss - bony overgrowth impinges on optic nerve
  • Kyphosis - curved spine
  • Lower limb muscle weakness - due to compression of spinal cord
  • Pelvic asymmetry
  • Bone enlargement - particularly pelvis, lumbar spine, skull, femur and tibia
  • Bowlegs - if tibia and femur becomes too weak to support weight
257
Q

Investigations of Pagets

A
  • Biochemisty - ALP elevated, calcium and phosphate normal
  • X-ray -
    • Bone enlargement and deformity
    • Osteoporosis circumscripta - lytic lesions during the lytic phase
    • Cotton wool appearance of the skull - poorly defined patchy areas of increased density (sclerosis) and decreased density (lysis)
    • V-shaped defects in the long bones - osteolytic bone lesions within the healthy bone
    • Thickened bone cortices in advanced cases
  • Bone biopsy - to exclude malignancies that may mimic findings of Paget’s disease
258
Q

Management of Pagets

A
  • Pain relief
    • NSAIDs
  • Anti-resorptive medication - Biphosphonates e.g. alendronic acid
    • Along with calcium and vit D supplementation
  • Surgery -
    • Correct bone deformities
    • Decompress impinged nerve
    • Decrease fracture risk
259
Q

Monitoring of Pagets

A

Check the serum alkaline phosphatase (ALP) and review symptoms. Effective treatment should normalise the ALP and eliminate symptoms.

260
Q

Complications of Pagets

A
  • Paget’s sarcoma (osteosarcoma) - bony overgrowth can cause genetic mutations leading to sarcoma
  • Spinal stenosis and spinal cord compression - deformity in the spine leads to spinal canal narrowing. If this presses on the spinal nerves it causes neurological signs and symptoms.
  • Fractures
  • Vision loss
  • Hearing loss
  • Arthritis - if any joint involvement
  • High-output cardiac failure and myocardial hypertrophy - due to increased bone blood flow
261
Q

Prognosis of Pagets

A

The outlook for patients with Paget’s disease is usually good, although it varies between people. The outlook is improved if treatment is provided before any significant complications have developed. Treatment can control Paget’s disease and may induce remission for a period of time but it is not a cure and the disease may become active again. The prognosis is significantly worse if an osteosarcoma develops but fortunately this is a rare complication.

262
Q

Microfibril and fibrillin notes

A

Normally the interstitial space of body tissue is full of microfibril (rope like structure that forms connective tissue). The main component of microfibrils is a microprotein called fibrillin.

In some structure microfibrils form a scaffold for additional proteins like elastin. Elastin fibres are highly cross-linked, which allows the tissue to stretch and spring back to their shape. These tissues include - arteries, skin and lungs.

Tissues that have microfibrils but no underlying elastin include tendons and ciliary zonules which hold the eye lens in place. These tissues aren’t as stretchy but still have tensile strength.

Fibrillin also regulates tissue growth. It sequesters TGF-beta which is responsible for stimulating tissue growth.

263
Q

Define Marfans

A

A genetic disorder that results in defective connective tissue. This can affect the skeleton, heart, blood vessels, eyes and lungs.

264
Q

Epidemiology of Marfans

A

The incidence in the European population is estimated to be 3 in 10,000.

265
Q

Pathophysiology of Marfans

A

Marfan syndrome is caused by mutations in a gene called FBN1 (fibrillin 1) on chromosome 15. This is autosomal dominant.

FBN1 gene encodes fibrillin 1 protein. In Marfan syndrome, fibrillin 1 is either dysfunctional or less abundant, which results in fewer functional microfibrils. This also means there is less tissue integrity and elasticity.

Additionally, TGF-beta doesnt get successfully sequestered so TGF-beta signalling is excessive in these tissues = more growth

266
Q

Clinical manifestations of Marfans

A

Features may not always be present and will vary in severity. Symptoms show with age, but there may sometimes be symptoms present at birth (early onset).

  • Tall stature, long arms and long legs due to excessive long bone growth
  • Arachnodactyly - long fingers and toes
  • Pectus excavatum (chest sinks in) or pectus carinatum (chest points out)
  • Scoliosis
  • Inability to extend elbows to 180 degrees
  • Flexible joints (hypermobility)
  • Downward slant of the eyes
  • Narrow high-arch palate - crowds teeth
  • Stretch marks
267
Q

Investigations and Diagnosis for Marfans

A

Diagnosis is based on clinical features (diagnose if >2 features)

  • Lens dislocation
  • Aortic dissection/ dilation
  • Dural ectasia - widening of the dural sac
  • Skeletal features e.g. long arms, arachnodactyly
  • Pectus deformity
  • Scoliosis
  • Pes planus - flat feet

MRI for dural ectasia

268
Q

Differentials for Marfans

A
  • Ehlers-Danlos syndrome
  • Erdheim’s deformity - presents with dilation of aortic root
  • Homocystinuria - body cannot process amino acids properly. Presents similar to Marfan syndrome
269
Q

Management for Marfans

A

General

  • Physiotherapy can be helpful in strengthening joints and reducing symptoms arising from hypermobility.
  • Genetic counselling is important in considering the implications of having children that may be affected by the condition

Eye-related

  • Replacement of dislocated lens with artificial lens

Cardiovascular-related

  • Lifestyle changes, such as avoiding intense exercise and avoiding caffeine and other stimulants - minimise stress to help cardiac complications
  • Beta blockers can also be used to stop aortic dilation
  • Angiotensin receptor blocker e.g. losartan - decreases tgf-beta signalling and can also decrease aortic dilation
  • Surgical repair of wide aorta.
270
Q

Monitoring for Marfans

A

Patients are also regularly followed up and monitored for complications. This often involves yearly echocardiograms and review by an ophthalmologist.

271
Q

Complications of Marfans

A
  • Retinal detachment and lens dislocation
  • Joint dislocations and pain due to hypermobility
  • Bulla formation on lungs - leading to pneumothorax
  • Cardiovascular:
    • Aortic dilation causing aortic valve insufficiency
    • Cystic medial necrosis (tunica media of aortic wall degenerates)
    • Increased risk of aortic dissection, aneurysm and rupture
    • Mitral valve prolapse
    • Aortic valve prolapse
272
Q

Prognosis of Marfans

A

The average life expectancy used to be only 32 years but, due to early surgery, it is now approaching that of the general population.

Long-term survival is excellent with beta-blocker control and surgery when indicated. Once aortic dissection occurs, survival is considerably reduced to between 50% and 70% at 5 years.

273
Q

Define Ehlers-Danlos syndrome (EDS)

A

Ehlers-Danlos syndrome (EDS) is a group of connective tissue disorders caused by mutations of connective tissue proteins, with collagen being the most commonly affected.

274
Q

Epidemiology of EDS

A

Hypermobile EDS is the most common subtype

275
Q

RF for EDS

A
  • Family history (most common subtypes are autosomal dominant)
276
Q

Pathophysiology of EDS

A

Various (13) different types of Ehlers-Danlos syndrome caused by mutations which lead to weakened connective tissue in the skin, bones, blood vessels, and organs, which accounts for the numerous features of the disorder.

Mutations in collagen encoding genes:

  • Classical Ehlers-Danlos syndrome
    • Caused by mutation in COL5A1 and COL5A2 genes
    • Passed on by autosomal dominant inheritance
  • Vascular Ehlers-Danlos syndrome
    • Mutation in COL3A1
    • Decrease in type III collagen weakens blood vessels
    • Most dangerous due to risk of aneurysms and aortic and organ rupture

Mutations in other genes e.g. genes that assist in collagen synthesis: (autosomal recessive)

  • Classical-like Ehlers-Danlos Syndrome
    • Mutation in gene that encodes TNXB (causes defect in protein called tenascin X)
      • Tenascin-X provides flexibility and also plays a role in regulating production and assembly of certain types of collagen
  • Kyphoscoliotic Ehlers-Danlos syndrome
    • Insufficient lysyl hydroxylase
  • Musculocontractural Ehlers-Danlos syndrome
    • Defect in collagen peptidase

Other:

  • Hypermobile Ehlers-Danlos syndrome
    • No genetic mutation has been identified
    • Most common subtype
277
Q

Clinical manifestations of EDS

A

Musculoskeletal

  • Joint hypermobility and pain
  • Recurrent dislocation
  • Scoliosis and spinal pain

Skin

  • Hyperelasticity
  • Easy bruising
  • Atrophic skin
278
Q

Investigations for EDS

A

A clinical diagnosis based on generalised joint hypermobility alongside other features such as a positive family history and musculoskeletal complications.

  • Investigations to consider
    • Examine joints and skin
    • Genetic testing to identify mutation
    • Echocardiogram:assess for mitral valve prolapse and aortic root dilatation
    • Spine X-ray:evidence of scoliosis or spondylolisthesis (vertebral misalignment); usually required in patients with spinal pain or scoliosis on examination
279
Q

Management for EDS

A

Supportive care:

  • Physiotherapy
  • Orthopaedic instrument e.g. bracing, wheelchair and casting
  • Lifestyle advice: avoid contact sports and heavy labour to reduce the risk of tissue damage and joint dislocation
  • Analgesia
  • Psychological input: due to chronic pain and the impact on quality of life, patients may develop mental illness
280
Q

Complications of EDS

A

Cardiovascular

Mitral valve prolapse: mid-systolic click and late-systolic murmur

Aortic dissection

Abdominal aortic aneurysms

Organ rupture

Other

Subarachnoid haemorrhage

Angioid retinal streaks

Abdominal hernia

Gastro-oesophageal reflux disease

Degenerative arthritis due to recurrent joint dislocation

Depression and anxiety

281
Q

Prognosis of EDS

A

Only vascular EDS is associated with a shortened life expectancy, with a median age of survival of 48 years old due to arterial or organ rupture.

Management is predominantly supportive in order to ensure minimal impact on the patient’s quality of life, whilst also assisting with chronic pain and psychological needs.

282
Q

Define Antiphospholipid syndrome (APS)

A

Antiphospholipid syndrome is the association of antiphospholipid antibodies (lupus anticoagulant, anticardiolipin antibody, and/or anti-beta2-glycoprotein I) with a variety of clinical features characterised by thromboses (arterial and venous) and pregnancy-related morbidity.

283
Q

Epidemiology of APS

A
  • Associated with SLE in 20-30% of cases
  • Often occurs as a primary disease (no underlying autoimmune disease)
  • More common in females than males
  • APS has been reported to have a prevalence of between 1.0% and 5.6% in normal healthy populations and may increase with age.
284
Q

Pathophysiology of APS

A
  • Antiphospholipid antibodies (aPL) play a role in thrombosis by binding to phospholipid on the surface of cells such as endothelial cells, platelets and monocytes
  • Once bound, it alters the functioning of those cells leading to thrombosis and/or miscarriage.
  • Thrombotic tendency affects cerebral, renal and other vessels
  • Antiphospholipid antibodies (aPL) cause CLOTs:
    • Coagulation defect
    • Livedo reticularis - lace-like purplish discolouration of skin
    • Obstetric issues i.e. miscarriage
    • Thrombocytopenia (low platelets)
285
Q

Clinical manifestations of APS

A
  • Thrombosis
  • Miscarriage
  • Livedo-reticularis
  • Thrombocytopenia
  • Ischaemic stroke, TIA, MI - arteries
  • Deep vein thrombosis, Budd-chiari syndrome - veins
  • Valvular heart disease, migraines, epilepsy
286
Q

Investigations of APS

A
  • Anticardiolipin test:
    • Detects IgG or IgM antibodies that bind the negatively charged phospholipid - cardiolipin
  • Lupus anticoagulant test:
    • Detects changes in the ability of the blood to clot
  • Anti-B2-glycoprotein I test:
    • Detects antibodies that bind B2-glycoprotein I, a molecule that interacts closely with phospholipids
  • A persistently positive test (positive on at least two occasions more than 12 weeks apart) in one or more of these tests, along with clinical features is needed to diagnose APS
287
Q

Management of APS

A
  • Long term warfarin to minimise thrombosis
  • Pregnant women:
    • Oral aspirin and SC heparin early on in pregnancy
    • Reduces chance of miscarriage but pre-eclampsia and poor fetal growth remain common
  • Prophylaxis:
    • Aspirin or Clopidogrel for people with aPL, especially those with a high IgG aPL (antiphospholipid antibody)