MSK Flashcards

Question

Primary care management for RA

Answer 1

- 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**

Answer 2

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

Answer 3

- 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

Answer 4

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

Answer 5

**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

Answer 6

**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

Answer 7

**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

Answer 8

Patients who are **treated early** have 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

Answer 9

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

Answer 10

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

Answer 11

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

Answer 12

- 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

Answer 13

Urate is a metabolite of purine synthesis and the incidence of gout increases with **hyperuricaemia** (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 urate **overproduction** or **reduced excretion** of 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.

Answer 14

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 MTP** most 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

Answer 15

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

Answer 16

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 weeks **after** the attack resolves as levels may be falsely low/normal during the attack as the urate is deposited within the joint. Hyperuricaemia does **not** confirm 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 absence** of periarticular osteopenia (unlike rheumatoid arthritis) - **Late sign**: loss of joint space

Answer 17

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

Answer 18

- **Anti-inflammatory:** - NSAIDs first line - Colchicine used first line when NSAIDs contraindicated or in renal insufficiency. - Continue until 24-48 hours **after** symptoms have improved - Co-prescribe a proton pump inhibitor (PPI) - **Corticosteroids:** **intra-articular** steroids may be used as a second-line agent, particularly for monoarticular disease. A short course of **oral** steroids (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 be **continued** during the acute flare - **Rest and elevate joint** - **Ice packs**

Answer 19

- **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.

Answer 20

Patients with gout often have cardiovascular comorbidities, such as hypertension, and should be optimised accordingly: - If hypertension is present, **losartan** may be a good option as it has uricosuric action - Consider ceasing **precipitating drugs**, such as thiazide diuretics - Patients on aspirin (75-150 mg) for cardiovascular prophylaxis should **continue** their medication

Answer 21

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

Answer 22

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.

Answer 23

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

Answer 24

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

Answer 25

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

Answer 26

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)

Answer 27

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

Answer 28

- 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 cases and is highly suggestive of pseudogout but is not diagnostic; the **absence** of chondrocalcinosis does **not** exclude pseudogout - In the knee, this is seen as linear calcifications of the articular cartilage and meniscus

Answer 29

- Investigating the underlying cause Usually 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

Answer 30

- Gout - Septic arthritis - Rheumatoid arthritis - Osteoarthritis

Answer 31

Acute - **Anti-inflammatory:** NSAIDs or colchicine, particularly in polyarticular disease - **Corticosteroid:** **intra-articular** steroids can be used in monoarticular disease or **systemic** steroids 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

Answer 32

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.

Answer 33

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.

Answer 34

- 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

Answer 35

- 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

Answer 36

**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

Answer 37

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

Answer 38

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.

Answer 39

- **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

Answer 40

- **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.

Answer 41

- **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

Answer 42

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**

Answer 43

**Bisphosphonates** - Interfere with osteoclasts and reducing their activity, preventing the reabsorption of bone. - Examples of bisphosphonates are: - Alendronate 70mg once weekly (oral) - Risedronate 35 mg once weekly (oral) - Zolendronic acid 5 mg once yearly (intravenous)

Answer 44

**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 recommend **calcium** supplementation **with vitamin D** in 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). - **Raloxifene** is 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 therapy** should be considered in women that go through the menopause early. - **Teriparatide** (recombinant PTH)- used in patients who have further fractures despite treatment

Answer 45

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.

Answer 46

- **Fractures** - **Side effects of bisphosphonates:** - Reflux and oesophageal 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

Answer 47

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.

Answer 48

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)

Answer 49

The spondyloarthropathies are a group of related chronic inflammatory conditions.

Answer 50

- 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

Answer 51

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.

Answer 52

- **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+**

Answer 53

‘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.

Answer 54

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)

Answer 55

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

Answer 56

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

Answer 57

Unknown aetiology. Likely to be genetic and environmental interplay.

Answer 58

- HLA-B27 - Family history of ankylosing spondylitis

Answer 59

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

Answer 60

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.

Answer 61

- 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

Answer 62

- 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

Answer 63

- **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

Answer 64

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.

Answer 65

- Osteoarthritis - Psoriatic arthritis - Reactive arthritis - Vertebral fracture

Answer 66

- **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

Answer 67

- **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

Answer 68

- **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**

Answer 69

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.

Answer 70

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

Answer 71

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

Answer 72

- Psoriasis - Family history of psoriasis or psoriatic arthritis

Answer 73

Psoriatic arthritis is an **autoimmune** **chronic inflammatory joint disease** that 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 of **seronegative spondyloarthropathies.** These conditions are all **rheumatoid factor negative**, associated with **HLA-B27**, and can affect the **axial skeleton**. Psoriatic arthritis has a strong genetic component and, although its pathogenesis is not fully understood, activation of **CD8+ T cells** is thought to play a critical role.

Answer 74

- **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)

Answer 75

- **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

Answer 76

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.

Answer 77

- **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)

Answer 78

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

Answer 79

Psoriasis epidemiological screening tool should be used to assess everyone with psoriasis. Asking about: - Joint pain - Swelling - Arthritis - Nail pitting

Answer 80

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.

Answer 81

- Rheumatoid arthritis - Gout - Reactive arthritis - Erosive osteoarthritis

Answer 82

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. **Methotrexate** is first-line, whilst **sulfasalazine** is 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

Answer 83

- 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

Answer 84

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.

Answer 85

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.

Answer 86

- 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

Answer 87

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)

Answer 88

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

Answer 89

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!

Answer 90

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'**

Answer 91

- **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**

Answer 92

- **Warm, swollen, painful joint** - **Mouth ulcers**

Answer 93

- **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

Answer 94

- Septic arthritis - Gout - Pseudogout - Ankylosing spondylitis - Psoriatic arthritis

Answer 95

- 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

Answer 96

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

Answer 97

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

Answer 98

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!

Answer 99

- 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

Answer 100

- **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

Answer 101

- **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**

Answer 102

Septic arthritis must be considered a **medical** **emergency** due 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 by **staphylococci or streptococci**, often as a complication of other pathologies such as cellulitis, chronic osteomyelitis, or drug abuse. Fungal and viral causes are rare.

Answer 103

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.

Answer 104

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

Answer 105

- Difficulty weight bearing - Fever

Answer 106

- **FBC**: leukocytosis - **CRP and ESR**: elevated due to inflammation and used for monitoring response to treatment - **Blood cultures**: should be performed on **all** patients 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

Answer 107

**Joint aspiration - MSC**

Answer 108

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

Answer 109

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

Answer 110

Crystal arthropathies - gout and pseudogout

Answer 111

- 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

Answer 112

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.

Answer 113

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

Answer 114

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.

Answer 115

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.

Answer 116

- 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.

Answer 117

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. - ***Salmonella* spp.:** 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.

Answer 118

- 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.

Answer 119

**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 system destroys 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 pus to 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 abscess tracks 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.

Answer 120

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

Answer 121

- Symptoms - **Fever** - **Pain** - **Overlying redness** - **Swelling** - **Malaise**

Answer 122

- Histopathology Acute changes: - **Inflammatory cells** - **Oedema** - **Vascular congestion** - **Small vessel thrombosis** Chronic changes: - **Necrotic bone ‘sequestra’** - **New bone formation - involucrum** - **Neutrophil exudates** - **Lymphocytes & histiocytes (tissue macrophages)**

Answer 123

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

Answer 124

MRI - imaging modality of choice

Answer 125

- 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.

Answer 126

- 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.

Answer 127

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

Answer 128

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.

Answer 129

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.

Answer 130

- 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

Answer 131

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

Answer 132

- **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 is **higher** than black Africans for unknown reasons - **Family history** - **Drugs**: procainamide, isoniazid, hydralazine may cause drug-induced Lupus - **HLA associations**: HLA-B8, -DR2, -DR3

Answer 133

- 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 reaction This 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.

Answer 134

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.

Answer 135

- **Fatigue** - **Fever** - **Lymphadenopathy** - **Weight loss**

Answer 136

- **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

Answer 137

- **Arthralgia** - **Non-erosive arthritis**

Answer 138

- **Pleurisy** - **Interstitial lung disease** - **Pulmonary embolism**

Answer 139

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

Answer 140

- **Lupus peritonitis** - **Mesenteric artery occlusion**

Answer 141

Lupus nephritis: most commonly diffuse proliferative glomerulonephritis

Answer 142

- **Psychosis** - **Seizures** - **Depression and anxiety**

Answer 143

- **Keratoconjunctivitis sicca** - **Sjögren's syndrome**

Answer 144

- **Autoimmune haemolytic anaemia** - **Thrombocytopaenia** - **Leukopenia** - **Antiphospholipid syndrome**

Answer 145

Affects the mucosa - mouth and nose ulcers

Answer 146

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-Ro** and **anti-La**: associated with Sjögren's syndrome and neonatal lupus - **Anti-histone**: found in 80-90% of patients with **drug-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

Answer 147

- **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

Answer 148

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

Answer 149

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

Answer 150

- Lifestyle changes - avoidance of sun and use of sunscreen - Acute management - Acute flares may be mild, moderate or severe. ![https://s3-us-west-2.amazonaws.com/secure.notion-static.com/8de01821-110f-414f-94ec-38618ed4ab75/Screenshot_2021-02-16_at_15.14.49.png](https://s3-us-west-2.amazonaws.com/secure.notion-static.com/8de01821-110f-414f-94ec-38618ed4ab75/Screenshot_2021-02-16_at_15.14.49.png) **Mild:** Prednisolone (corticosteroid) + hydroxychloroquine + NSAIDs **Moderate 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

Answer 151

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

Answer 152

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

Answer 153

- 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

Answer 154

- 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.

Answer 155

- 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.

Answer 156

- 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.

Answer 157

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

Answer 158

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.

Answer 159

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.

Answer 160

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

Answer 161

- Commonly cause **local bone pain, swelling, and fractures.** - Pain of osteoid 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.**

Answer 162

- 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**

Answer 163

- 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

Answer 164

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.

Answer 165

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

Answer 166

- 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.

Answer 167

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

Answer 168

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 fibromyalgia might 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.

Answer 169

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

Answer 170

- 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

Answer 171

Investigations are all normal! **Diagnosis of fibromyalgia is 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

Answer 172

- 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)

Answer 173

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

Answer 174

Treatment of fibromyalgia requires 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-norepinephrine reuptake inhibitors (SNRIs)** e.g. duloxetine Help by elevating serotonin and norepinephrine levels. - **Anticonvulsants** like pregabalin and gabapentin which slow nerve impulses can help with sleep problems.

Answer 175

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.

Answer 176

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

Answer 177

Common in young people: 20-55 yrs

Answer 178

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

Answer 179

- 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

Answer 180

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.

Answer 181

- 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

Answer 182

- 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

Answer 183

- 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

Answer 184

- 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

Answer 185

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

Answer 186

- 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

Answer 187

- 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)

Answer 188

- 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.

Answer 189

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.

Answer 190

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.

Answer 191

- 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.

Answer 192

Deficiency or impaired metabolism of: - **Vitamin D** - **Calcium** - **Phosphate**

Answer 193

- **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

Answer 194

**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 by **vitamin D deficiency** which 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.

Answer 195

- 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

Answer 196

- **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

Answer 197

Iliac bone biopsy with double tetracycline labelling

Answer 198

- **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.

Answer 199

- Osteoporosis - Paget's disease

Answer 200

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

Answer 201

- Vit D deficiency - **Loading regime**: typically a total of 300 000 IU. Common regimens are 50,000 IU once a week for 6 weeks **or** 20,000 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**: **only** offer 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**: **only** offer 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

Answer 202

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

Answer 203

- **Insufficiency fracture** - **Complications of treatment:** hypercalcaemia, hyperphosphataemia - **Secondary hyperparathyroidism**

Answer 204

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

Answer 205

**Rickets** results from the same underlying process but occurs in **children and adolescents** before 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

Answer 206

**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

Answer 207

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.

Answer 208

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

Answer 209

- 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*

Answer 210

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

Answer 211

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

Answer 212

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

Answer 213

- 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

Answer 214

- 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

Answer 215

- 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

Answer 216

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

Answer 217

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

Answer 218

- 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

Answer 219

- 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

Answer 220

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

Answer 221

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.

Answer 222

- 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

Answer 223

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

Answer 224

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

Answer 225

- 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

Answer 226

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.

Answer 227

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

Answer 228

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

Answer 229

- Family history - Age >50 years - Infection

Answer 230

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'

Answer 231

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

Answer 232

- 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

Answer 233

- 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

Answer 234

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

Answer 235

- **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

Answer 236

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.

Answer 237

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.

Answer 238

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

Answer 239

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

Answer 240

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

Answer 241

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

Answer 242

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

Answer 243

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

Answer 244

**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.

Answer 245

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

Answer 246

- 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

Answer 247

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.

Answer 248

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.

Answer 249

Hypermobile EDS is the most common subtype

Answer 250

- Family history (most common subtypes are autosomal dominant)

Answer 251

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

Answer 252

**Musculoskeletal** - Joint hypermobility and pain - Recurrent dislocation - Scoliosis and spinal pain **Skin** - Hyperelasticity - Easy bruising - Atrophic skin

Answer 253

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

Answer 254

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

Answer 255

**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

Answer 256

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.

Answer 257

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.

Answer 258

- 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.

Answer 259

- 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)

Answer 260

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

Answer 261

- 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

Answer 262

- 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)

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