MSK

Question 1

Define Osteoarthritis

Answer 1

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.

Question 2

Epidemiology of Osteoarthritis

Answer 2

• 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

Question 3

RF for Osteoarthritis

Answer 3

• 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

Question 4

Pathophysiology of Osteoarthritis

Answer 4

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)

Question 5

Signs of Osteoarthritis

Answer 5

• 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

Question 6

Symptoms of Osteoarthritis

Answer 6

• 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

Question 7

Diagnostic criteria for Osteoarthritis

Answer 7

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)

Question 8

1st line imaging for Osteoarthritis

Answer 8

• 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.

Question 9

Other investigations for Osteoarthritis

Answer 9

• 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

Question 10

Differentials for Osteoarthritis

Answer 10

• Rheumatoid arthritis
• Chronic tophaceous gout
• Psoriatic arthritis

Question 11

Non-pharmacological management of Osteoarthritis

Answer 11

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

Question 12

Pharmacological management of Osteoarthritis

Answer 12

• 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.

Question 13

Other management for Osteoarthritis

Answer 13

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

Question 14

Prognosis for Osteoarthritis

Answer 14

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.

Question 15

Define Rheumatoid Arthritis

Answer 15

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.

Question 16

Epidemiology of RA

Answer 16

• 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

Question 17

Aetiology of RA

Answer 17

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

Question 18

RF for RA

Answer 18

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

Question 19

Pathophysiology of RA

Answer 19

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

Question 20

Signs of RA

Answer 20

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

Question 21

Symptoms of RA

Answer 21

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

Question 22

Primary investigations for RA

Answer 22

• 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

Question 23

Other investigations for RA

Answer 23

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

Question 24

Differentials for RA

Answer 24

• Psoriatic arthritis
• Infectious arthritis
• Gout
• SLE
• Osteoarthritis

Question 25

Primary care management for RA

Answer 25

• 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

Question 26

Secondary care management for RA

Answer 26

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

Question 27

Management of flares of RA

Answer 27

• 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

Question 28

Other management of RA

Answer 28

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

Question 29

Monitoring for RA

Answer 29

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

Question 30

Extra articular manifestations of RA

Answer 30

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

Question 31

Medication side effects for RA

Answer 31

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

Question 32

Prognosis for RA

Answer 32

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

Question 33

Define Gout

Answer 33

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

Question 34

Epidemiology of gout

Answer 34

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

Question 35

Aetiology of gout

Answer 35

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

Question 36

RF for gout

Answer 36

• 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

Question 37

Pathophysiology of gout

Answer 37

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.

Question 38

Signs of gout

Answer 38

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

Question 39

Symptoms of gout

Answer 39

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

Question 40

Investigations for gout

Answer 40

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

Question 41

Differentials for gout

Answer 41

• Septic arthritis
• Reactive arthritis
• Haemarthrosis
• Calcium pyrophosphate deposition
• Rheumatoid arthritis

Question 42

Acute gout flare management

Answer 42

• 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

Question 43

General management and prevention of gout flare

Answer 43

• 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.

Question 44

Other management for gout

Answer 44

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

Question 45

Complications of gout

Answer 45

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

Question 46

Prognosis of gout

Answer 46

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.

Question 47

Define Pseudogout (Calcium Pyrophosphate deposition)

Answer 47

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

Question 48

Epidemiology of Pseudogout

Answer 48

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

Question 49

Rf for pseudogout

Answer 49

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

Question 50

Signs of pseudogout

Answer 50

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)

Question 51

Symptoms of pseudogout

Answer 51

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

Question 52

Primary investigations of pseudogout

Answer 52

• 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

Question 53

Investigating the underlying cause of pseudogout

Answer 53

• 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

Question 54

Differentials for pseudogout

Answer 54

• Gout
• Septic arthritis
• Rheumatoid arthritis
• Osteoarthritis

Question 55

Management of pseudogout (acute and chronic)

Answer 55

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

Question 56

Prognosis of pseudogout

Answer 56

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.

Question 57

Define Osteoporosis

Answer 57

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.

Question 58

Epidemiology of Osteoporosis

Answer 58

• 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

Question 59

Aetiology of Osteoporosis

Answer 59

• 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

Question 60

RF of Osteoporosis

Answer 60

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

Question 61

Pathophysiology of Osteoporosis

Answer 61

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.

Question 62

Clinical manifestations of Osteoporosis

Answer 62

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.

Question 63

FRAX tool

Answer 63

• 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

Question 64

DEXA SCAN

Answer 64

• 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.

Question 65

Other investigations of Osteoporosis

Answer 65

• 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

Question 66

Management of Osteoporosis

Answer 66

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

Question 67

1st line management of Osteoporosis

Answer 67

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)

Question 68

Other management for Osteoporosis

Answer 68

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

Question 69

Monitoring for Osteoporosis

Answer 69

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.

Question 70

Complications of Osteoporosis

Answer 70

• 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

Question 71

Prognosis of Osteoporosis

Answer 71

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.

Question 72

Notes on bone strength

Answer 72

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)

Question 73

What are the spondyloarthropathies

Answer 73

The spondyloarthropathies are a group of related chronic inflammatory conditions.

Question 74

What clinical features are shared by all the spondyloarthropathies

Answer 74

• 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

Question 75

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

Answer 75

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.

Question 76

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

Answer 76

• 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+

Question 77

Theory of pathology for spondyloarthropathies

Answer 77

‘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.

Question 78

When to suspect spondyloarthropathies

Answer 78

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)

Question 79

Define Ankylosing spondylitis

Answer 79

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

Question 80

Epidemiology of Ankylosing spondylitis

Answer 80

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

Question 81

Aetiology of ankylosing spondylitis

Answer 81

Unknown aetiology. Likely to be genetic and environmental interplay.

Question 82

RF for ankylosing spondylitis

Answer 82

• HLA-B27
• Family history of ankylosing spondylitis

Question 83

Pathophysiology and disease course of ankylosing spondylitis

Answer 83

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

Question 84

Key presentations of ankylosing spondylitis

Answer 84

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.

Question 85

Signs of ankylosing spondylitis

Answer 85

• 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

Question 86

Symptoms of ankylosing spondylitis

Answer 86

• 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

Question 87

Investigations for Ankylosing spodnylitis

Answer 87

• 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

Question 88

What is Schobers test

Answer 88

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.

Question 89

Differentials for ankylosing spondylitis

Answer 89

• Osteoarthritis
• Psoriatic arthritis
• Reactive arthritis
• Vertebral fracture

Question 90

Management of ankylosing spondylitis

Answer 90

• 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

Question 91

Other management for ankylosing spondylitis

Answer 91

• 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

Question 92

Complications of Ankylosing spondylitis

Answer 92

• 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

Question 93

Prognosis of ankylosing spondylitis

Answer 93

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.

Question 94

Define Psoriatic arthritis

Answer 94

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

Question 95

Epidemiology of PA

Answer 95

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

Question 96

RF for PA

Answer 96

• Psoriasis
• Family history of psoriasis or psoriatic arthritis

Question 97

Pathophysiology of PA

Answer 97

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.

Question 98

Signs of Psoriatic arthritis

Answer 98

• 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)

Question 99

Symptoms of psoriatic arthritis

Answer 99

• 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

Question 100

Outline the typical presentation of psoriatic arthritis

Answer 100

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.

Question 101

Types of Psoriatic arhtritis

Answer 101

• 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)

Question 102

CASPAR Criteria for Diagnosing PA

Answer 102

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

Question 103

What is PEST

Answer 103

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

Asking about:

• Joint pain
• Swelling
• Arthritis
• Nail pitting

Question 104

X-Ray changes for PA

Answer 104

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.

Question 105

Differentials for PA

Answer 105

• Rheumatoid arthritis
• Gout
• Reactive arthritis
• Erosive osteoarthritis

Question 106

Management of PA

Answer 106

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

Question 107

Complications of PA

Answer 107

• 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

Question 108

Prognosis for PA

Answer 108

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.

Question 109

Define reactive arthritis

Answer 109

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.

Question 110

Epidemiology of Reactive arthritis

Answer 110

• 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

Question 111

Aetiology of Reactive arthritis

Answer 111

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)

Question 112

RF for Reactive arthritis

Answer 112

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

Question 113

Pathophysiology of Reactive arthritis

Answer 113

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!

Question 114

Key presentations of reactive arthritis

Answer 114

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’

Question 115

Signs of Reactive arthritis

Answer 115

• 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

Question 116

Symptoms of Reactive arthritis

Answer 116

• Warm, swollen, painful joint
• Mouth ulcers

Question 117

Investigations for reactive arhtritis

Answer 117

• 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

Question 118

Differentials for reactive arthtritis

Answer 118

• Septic arthritis
• Gout
• Pseudogout
• Ankylosing spondylitis
• Psoriatic arthritis

Question 119

Management for reactive arthritis

Answer 119

• 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

Question 120

Complications of Reactive arthritis

Answer 120

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

Question 121

Prognosis for Reactive arthritis

Answer 121

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

Question 122

Define Septic Arthritis

Answer 122

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!

Question 123

Epidemiology of SA

Answer 123

• 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

Question 124

Aetiology of SA

Answer 124

• 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

Question 125

RF for SA

Answer 125

• 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

Question 126

Pathophysiology of SA

Answer 126

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.

Question 127

Key presentations of SA

Answer 127

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.

Question 128

Signs of SA

Answer 128

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

Question 129

Symptoms of SA

Answer 129

• Difficulty weight bearing
• Fever

Question 130

1st line investigations for SA

Answer 130

• 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

Question 131

Gold standard investigation for SA

Answer 131

Joint aspiration - MSC

Question 132

Other investigations for SA

Answer 132

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

Question 133

Scoring criteria for SA

Answer 133

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

Question 134

Differentials for SA

Answer 134

Crystal arthropathies - gout and pseudogout

Question 135

Management of SA

Answer 135

• 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

Question 136

Monitoring for SA

Answer 136

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.

Question 137

Complications of SA

Answer 137

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

Question 138

Prognosis of SA

Answer 138

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.

Question 139

Define and overview of Osteomyelitis

Answer 139

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.

Question 140

Epidemiology of Osteomyelitis

Answer 140

• 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.

Question 141

Aetiology of Osteomyelitis

Answer 141

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.

Question 142

RF for Osteomyelitis

Answer 142

• 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.

Question 143

Pathophysiology of Osteomyelitis

Answer 143

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.

Question 144

Signs of Osteomyelitis

Answer 144

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

Question 145

Symptoms of Osteomyelitis

Answer 145

• Symptoms
  
  • Fever
  • Pain
  • Overlying redness
  • Swelling
  • Malaise

Question 146

Histopathology of Osteomyelitis

Answer 146

• 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)

Question 147

Investigations for Osteomyelitis

Answer 147

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

Question 148

Gold standard investigation for Osteomyelitis

Answer 148

MRI - imaging modality of choice

Question 149

Other management for Osteomyelitis

Answer 149

• 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.

Question 150

Management of Osteomyelitis

Answer 150

• 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.

Question 151

Complications of Osteomyelitis

Answer 151

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

Question 152

Prognosis for Osteomyelitis

Answer 152

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.

Question 153

Define Systemic Lupus Erythematosus (SLE)

Answer 153

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.

Question 154

Epidemiology of SLE

Answer 154

• 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

Question 155

Aetiology of SLE

Answer 155

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

Question 156

RF for SLE

Answer 156

• 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

Question 157

Pathophysiology of SLE

Answer 157

• 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.

Question 158

Classic presentation of SLE

Answer 158

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.

Question 159

General presentations of SLE

Answer 159

• Fatigue
• Fever
• Lymphadenopathy
• Weight loss

Question 160

Dermatological S/S of SLE

Answer 160

• 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

Question 161

MSK S/S of SLE

Answer 161

• Arthralgia
• Non-erosive arthritis

Question 162

Pulmonary S/S of SLE

Answer 162

• Pleurisy
• Interstitial lung disease
• Pulmonary embolism

Question 163

CVS S/S of SLE

Answer 163

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

Question 164

GI S/S of SLE

Answer 164

• Lupus peritonitis
• Mesenteric artery occlusion

Question 165

Renal S/S of SLE

Answer 165

Lupus nephritis: most commonly diffuse proliferative glomerulonephritis

Question 166

Neuropsychiatric S/S of SLE

Answer 166

• Psychosis
• Seizures
• Depression and anxiety

Question 167

Opthalmological S/S of SLE

Answer 167

• Keratoconjunctivitis sicca
• Sjögren’s syndrome

Question 168

Haematological S/S of SLE

Answer 168

• Autoimmune haemolytic anaemia
• Thrombocytopaenia
• Leukopenia
• Antiphospholipid syndrome

Question 169

Other S/S of SLE

Answer 169

Affects the mucosa - mouth and nose ulcers

Question 170

1st line investigations of SLE

Answer 170

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

Question 171

Other investigations to consider for SLE

Answer 171

• 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

Question 172

Diagnostic Criteria for SLE

Answer 172

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

Question 173

Differentials for SLE

Answer 173

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

Question 174

Management of SLE

Answer 174

• 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

Question 175

Prognosis for SLE

Answer 175

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

Question 176

Pathophysiology and overview of Bone tumours

Answer 176

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

Question 177

Explain Osteochondroma (Pri, benign)

Answer 177

• 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

Question 178

Explain Giant cell tumour (Pri, benign)

Answer 178

• 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.

Question 179

Explain Osteoblastoma (Pri, Benign)

Answer 179

• 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.

Question 180

Explain Osteoid Osteomas (Pri, Benign)

Answer 180

• 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.

Question 181

Explain Osteosarcoma

Answer 181

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

Question 182

Explain Ewing sarcoma

Answer 182

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.

Question 183

Explain chrondrosarcoma

Answer 183

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.

Question 184

What are the most common sources of Secondary bone tumours

Answer 184

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

Question 185

Clinical manifestations of Bone tumours

Answer 185

• 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.

Question 186

Investigations for bone cancer

Answer 186

• 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

Question 187

X ray findings for suspected bone cancer

Answer 187

• 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

Question 188

Management of Bone cancer

Answer 188

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.

Question 189

Define Fibromyalgia

Answer 189

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

Question 190

Epidemiology of Fibromyalgia

Answer 190

• 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.

Question 191

RF for Fibromyalgia

Answer 191

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

Question 192

Pathophysiology of Fibromyalgia

Answer 192

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.

Question 193

Key presentations of Fibromyalgia

Answer 193

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

Question 194

Symptoms of Fibromyalgia

Answer 194

• 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

Question 195

Investigations for Fibromyalgia

Answer 195

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

Question 196

Investigations to exclude other conditions for Fibromyalgia

Answer 196

• 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)

Question 197

Differentials for Fibromyalgia

Answer 197

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

Question 198

Management for Fibromyalgia

Answer 198

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.

Question 199

Prognosis for Fibromyalgia

Answer 199

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.

Question 200

Overview of Mechanical lower back pain

Answer 200

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

Question 201

Epidemiology of MLBP

Answer 201

Common in young people: 20-55 yrs

Question 202

Aetiology of MLBP

Answer 202

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

Question 203

RF for MLBP

Answer 203

• 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

Question 204

Pathophysiology of MLBP

Answer 204

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.

Question 205

Explain Lumbar spondylosis

Answer 205

• 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

Question 206

Explain facet joint syndrome

Answer 206

• 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

Question 207

Explain Fibrositic nodulosis

Answer 207

• 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

Question 208

Explain postural back pain and ‘swayback’ of pregnancy

Answer 208

• 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

Question 209

Clinical manifestations of MLBP

Answer 209

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

Question 210

Investigations for MLBP

Answer 210

• 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

Question 211

Red flags for serious pathology when investigating MLBP

Answer 211

• 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)

Question 212

Differentials for MLBP

Answer 212

• 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.

Question 213

Management for MLBP

Answer 213

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.

Question 214

Define Osteomalacia

Answer 214

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.

Question 215

Epidemiology of Osteomalacia

Answer 215

• 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.

Question 216

Aetiology of Osteomalacia

Answer 216

Deficiency or impaired metabolism of:

• Vitamin D
• Calcium
• Phosphate

Question 217

RF for Osteomalacia

Answer 217

• 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

Question 218

Pathophysiology of Osteomalacia

Answer 218

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.

Question 219

S/S of Osteomalacia

Answer 219

• 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

Question 220

Primary investigations for Osteomalacia

Answer 220

• 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

Question 221

Gold standard investigation for Osteomalacia

Answer 221

Iliac bone biopsy with double tetracycline labelling

Question 222

Other investigations to consider for Osteomalacia

Answer 222

• 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.

Question 223

Differentials for Osteomalacia

Answer 223

• Osteoporosis
• Paget’s disease

Question 224

Management for Osteomalacia

Answer 224

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

Question 225

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

Answer 225

• 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

Question 226

Monitoring for Osteomalacia

Answer 226

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

Question 227

Complications of Osteomalacia

Answer 227

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

Question 228

Prognosis for Osteomalacia

Answer 228

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

Question 229

Notes on rickets

Answer 229

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

Question 230

Differences between Osteomalacia, Osteoporosis and Osteoarthritis

Answer 230

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

Question 231

Overview of vertebral disc degeneration

Answer 231

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.

Question 232

Define acute disc disease

Answer 232

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

Question 233

Epidemiology of acute disc disease

Answer 233

• 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

Question 234

Aetiology of acute disc disease

Answer 234

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

Question 235

Rf for acute disc disease

Answer 235

• Genetic predisposition
• Advanced age
• Menopause
• Repeated spinal trauma

Question 236

Pathophysiology of acute disc disease

Answer 236

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

Question 237

Clinical manifestations of acute disc disease

Answer 237

• 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

Question 238

Investigations for acute disc disease

Answer 238

• 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

Question 239

Management of acute disc disease

Answer 239

• 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

Question 240

Complications of acute disc disease

Answer 240

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

Question 241

Define chronic disc disease

Answer 241

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

Question 242

Clinical manifestations of chronic disc disease

Answer 242

• 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

Question 243

Management of chronic disc disease

Answer 243

• 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

Question 244

Define Cervical spondylosis

Answer 244

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

Question 245

Pathophysiology of Cervical spondylosis

Answer 245

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.

Question 246

Signs of cervical spondylosis

Answer 246

• 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

Question 247

Symptoms of Cervical spondylosis

Answer 247

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

Question 248

Investigations for Cervical spondylosis

Answer 248

MRI

Question 249

Management of Cervical spondylosis

Answer 249

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

Question 250

Bone remodelling notes

Answer 250

• 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

Question 251

Define Pagets disease

Answer 251

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.

Question 252

Epidemiology of Pagets

Answer 252

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

Question 253

Aetiology of Pagets

Answer 253

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

Question 254

RF for Pagets

Answer 254

• Family history
• Age >50 years
• Infection

Question 255

Pathophysiology of Pagets

Answer 255

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’

Question 256

Clinical manifestations of Pagets

Answer 256

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

Question 257

Investigations of Pagets

Answer 257

• 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

Question 258

Management of Pagets

Answer 258

• 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

Question 259

Monitoring of Pagets

Answer 259

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

Question 260

Complications of Pagets

Answer 260

• 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

Question 261

Prognosis of Pagets

Answer 261

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.

Question 262

Microfibril and fibrillin notes

Answer 262

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.

Question 263

Define Marfans

Answer 263

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

Question 264

Epidemiology of Marfans

Answer 264

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

Question 265

Pathophysiology of Marfans

Answer 265

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

Question 266

Clinical manifestations of Marfans

Answer 266

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

Question 267

Investigations and Diagnosis for Marfans

Answer 267

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

Question 268

Differentials for Marfans

Answer 268

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

Question 269

Management for Marfans

Answer 269

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.

Question 270

Monitoring for Marfans

Answer 270

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

Question 271

Complications of Marfans

Answer 271

• 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

Question 272

Prognosis of Marfans

Answer 272

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.

Question 273

Define Ehlers-Danlos syndrome (EDS)

Answer 273

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.

Question 274

Epidemiology of EDS

Answer 274

Hypermobile EDS is the most common subtype

Question 275

RF for EDS

Answer 275

• Family history (most common subtypes are autosomal dominant)

Question 276

Pathophysiology of EDS

Answer 276

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

Question 277

Clinical manifestations of EDS

Answer 277

Musculoskeletal

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

Skin

• Hyperelasticity
• Easy bruising
• Atrophic skin

Question 278

Investigations for EDS

Answer 278

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

Question 279

Management for EDS

Answer 279

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

Question 280

Complications of EDS

Answer 280

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

Question 281

Prognosis of EDS

Answer 281

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.

Question 282

Define Antiphospholipid syndrome (APS)

Answer 282

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.

Question 283

Epidemiology of APS

Answer 283

• 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.

Question 284

Pathophysiology of APS

Answer 284

• 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)

Question 285

Clinical manifestations of APS

Answer 285

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

Question 286

Investigations of APS

Answer 286

• 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

Question 287

Management of APS

Answer 287

• 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)