Musculoskeletal Medicine E-book

Question 1

Hyperuricaemia and Gout

Answer 1

Gout is a disease from history that lives on in the early 21st century. Hippocrates himself noted that gout only presented in men after puberty and in women following the menopause. Van Leeuwenhoek (1632-1723) described the appearance of microscopic crystals in a tophus, and in 1847 Garrod discovered that gout was associated with hyperuricaemia.

Question 2

Symptoms

Gout

Answer 2

Gout is one of the most painful conditions known to man. A classical presentation of acute gout would involve a middle aged man presenting with sudden onset extreme pain in the great toe at night, although any joint can be affected. The joint will be swollen and inflamed; sometimes patients will not even be able to stand the bed sheet touching the joint. Normally only one joint is affected and an attack will last around 7-14 days without treatment. Following the initial attack patients may suffer a similar event within the next 12 months. Other symptoms of gout include renal colic and gouty nephropathy

Question 3

Causes - gout

Answer 3

In the past gout was considered to be a disease of the
rich. Both alcohol and a high consumption of red meat
do contribute to the development of gout, however one of the main risk factors for the development of the disease is hyperuricaemia (increased levels of uric acid in the blood). Hyperuricaemia is caused by a disorder of purine metabolism. When the levels of uric acid reach a critical concentration in the blood, it tends to precipitate. Specifically this occurs in the joints, causing uric acid crystals to be deposited. These lead to the classic symptoms of pain and inflammation. After an extended period of hyperuricaemia, tophi may develop, these are hard aggregates of uric acid crystals which tend to form in the ears or joints.

Question 4

Summary of factors contributing to hyperuricaemia

Answer 4

Overproduction

• Myeloproliferative disorders
• Chemotherapy
• Trauma

Diet

• Alcohol (especially beer)
• Red meat

Under excretion

• Thiazide diuretics
• Alcohol
• Renal impairment
• Genetic factors e.g. male Maori

Question 5

Gout can be classified according to four phases:

Answer 5

asymptomatic hyperuricaemia, acute gout, interval or intercritical gout and chronic tophaceous gout.

Question 6

Diagnosis and Treatment - gout

Answer 6

Any patient presenting with severe pain, swelling and inflammation in one joint with a history of alcohol consumption should be considered for a diagnosis of gout. A careful history should be taken as previous injuries to the affected joint and a systemic temperature
could suggest septic arthritis. There are diagnostic criteria that can be used. The definitive diagnostic test will show uric acid crystals in the fluid that has been aspirated from the affected joint. Serum uric acid levels can also be measured. Treatment involves two main approaches: reduction of uric acid levels, by diet or pharmacological means, and pain relief.

Question 7

Summary of lifestyle changes recommended for a patient with acute gout

Answer 7

• Optimise weight - Slow weight loss
• Reduce alcohol intake
• Modify diet - avoid high purine foods
• Adequate fluid intake
• Withdraw drugs that may precipitate an attack e.g. thiazide diuretics

Question 8

Medicines used in an acute attack of gout

Answer 8

NSAIDs provide the cornerstone of pain relief. A patient should also be prescribed a gastroprotective agent as per relevant guidance. Aspirin is not indicated in gout as it can reduce uric acid excretion. Colchicine can be given but toxicity can develop at higher doses e.g. vomiting, diarrhoea and abdominal pain. Dose adjustments may be necessary due to drug interactions. There is a maximum dose of 6mg per course and the course should not be repeated within 3 days. Canakinumab and oral, parenteral or intra-articular corticosteroids can also be used.

Question 9

Long-term treatment of gout

Answer 9

Allopurinol is widely used for the long-term (interval) treatment of gout. It inhibits the enzyme xanthine-oxidase which catalyses purine metabolism. The starting dose is
dependent on the severity of the condition and doses can be adjusted according to uric acid concentrations. If renal impairment is present then dose reductions may be necessary. Side effects include skin rashes and hypersensitivity. Febuxostat is also a xanthine-oxidase
inhibitor, it is only recommended by NICE for patients who have contra-indications to or are intolerant of allopurinol. It can cause serious hypersensitivity reactions.

Sulfinpyrazone is a uricosuric drug that can also be used. Allopurinol, febuxostat and sulfinpyrazone should never be started during an acute attack; they are usually started 1–2 weeks after the attack has settled. They can precipitate an acute attack, therefore an anti-inflammatory analgesic or colchicine should be used prophylactically for at least one month after the hyperuricaemia has been corrected. Other drugs used for the long term control of gout include colchicine and benzbromarone.

Question 10

Main Clinical Features - Rheumatoid arthritis

Answer 10

Systemic involvement, MCPs, PIPs

Question 11

Main Clinical Features - Systemic Lupus Erythematous

Answer 11

Malar Rash, psychological symptoms, renal involvement

Question 12

Main Clinical Features - Reactive arthritis

Answer 12

Often follows infection

Question 13

Main Clinical Features - Enteropathic arthritis

Answer 13

Associated with Crohn’s and Ulcerative Colitis

Question 14

Main Clinical Features - Ankylosing spondylitis

Answer 14

“Bamboo spine” tends to affect men < 40 years old

Question 15

Main Clinical Features - Psoriatic arthritis

Answer 15

DIP involvement, nail changes

Question 16

Main Clinical Features - Juvenile idiopathic arthritis

Answer 16

Patient <16 years old

Question 17

Rheumatoid Arthritis (RA)

Answer 17

Rheumatoid Arthritis (RA) is an inflammatory autoimmune disease which primarily affects the synovial joints. It is characterised by joint swelling, tenderness and eventually
destruction of the synovial joint. It typically affects the small joints of the hands and feet especially the metacarpophalangeal (MCP) and proximal interphalangeal (PIP) joints of the hand and the metatarsophalangeal (MTP) joints of the feet. It is a systemic disease so other tissues such as the heart, eyes and lungs can also be affected.

Rheumatoid arthritis patients have a reduced life expectancy and have an increased risk of heart disease, osteoporosis and opportunistic infections.

Question 18

Aetiology

Rheumatoid Arthritis

Answer 18

Rheumatoid Arthritis affects approximately 400,000 adults aged 16 and over in the UK. As with many autoimmune diseases, the specific reason why the body starts to attack itself is unknown. The HLA-DR1, 4 and 10 alleles are associated with the disease, pregnancy
alleviates symptoms and smoking slightly increases the risk of developing RA.

Question 19

Physical Symptoms

RA

Answer 19

RA is a systemic progressive polyarthritis. Classical symptoms include inflammation of the small joints of the hands and feet, causing pain and stiffness. Larger joints can also be affected and the pattern of joint involvement tends to follow a symmetrical course. The stiffness in RA tends to be worse in the morning and is termed ‘early morning stiffness’, this can confine patients to their beds for hours.

Other signs include raised inflammatory markers such as ESR and CRP, and raised autoantibodies such as anti-CCP and Rheumatoid Factor. In later disease, the characteristic changes of joint destruction can be seen with ulnar deviation of the fingers and boutonnière and swan neck deformities.

Question 20

Diagnosis

RA

Answer 20

RA is becoming more difficult to diagnose as healthcare professionals have become more aware of the destructive nature of the disease. In fact, some medics now believe that it will be a disease of the past in 15-20 years as cytokines and autoantibodies can be detected in
the bloodstream before any joint damage occurs. Referral from primary care for a specialist opinion is indicated for any adult with suspected persistent synovitis of undetermined cause and urgent referral if the small joints of the hands or feet are affected, more than one joint
is affected or there has been a delay of 3 months or longer between onset of symptoms and seeking medical advice

Question 21

Classical symptoms of RA

Answer 21

• Symmetrical polyarthropathy
• Early morning stiffness (may last for hours)
• Tender and swollen joints
• Arthritis of MCP, PIP joints
• Increased CRP and ESR
• Fatigue, weight loss and myalgia
• May have a positive rheumatoid factor
• May have positive anti-cyclic citrullinated peptide (anti-CCP) years before diagnosis
• Joint damage visible on X-ray

Question 22

Treatment for RA

Answer 22

Treatment for RA has greatly improved over the last 20 years as our understanding of the disease has progressed. It is now widely recognised that aggressive treatment is required in early disease to prevent the progression to joint destruction.

Question 23

Summary of treatments available for RA

Answer 23

• Non-steroidal anti-inflammatory drugs (NSAIDs) - Anti-inflammatory, pain relief
• Analgesics (Not NSAIDs) - Symptomatic pain relief
• Corticosteroids (oral, intra-muscular or intra-articular) -
  Anti-inflammatory
• Disease Modifying Anti-Rheumatic Drugs (DMARDs) -
  Prevention/attenuation of disease progression
• Biological agents e.g. anti-TNFs - Prevention/attenuation of disease progression

Question 24

DMARDs

Answer 24

Previously DMARDs were reserved only for patients in the later stages of RA who had joint deformity, now newly diagnosed patients will ideally be commenced on a conventional DMARD (cDMARD) of oral once weekly methotrexate, leflunomide or sulfasalazine. Hydroxychloroquine can be considered in some cases. cDMARDs can cause bone marrow suppression and thus require regular blood test monitoring. Specific tests are also required for some e.g. patients treated with hydroxychloroquine should be tested for visual acuity at specific intervals.
DMARDs are not pain killers and only slow down the
progression of the disease. It may take some months
before any benefit is seen with treatment, it is therefore important that patients with RA receive adequate relief from pain and inflammation

Question 25

Methotrexate

Answer 25

Methotrexate is a widely used anti-neoplastic drug. However because of its ‘side-effects’ of bone marrow depression and leucopaenia, it is also used in a large number of autoimmune diseases. In these diseases
patients should always be given a once WEEKLY dose, patients have died from prescribing errors involving daily doses.

Question 26

glucocorticoids

Answer 26

A short-term course of glucocorticoids can be considered as bridging treatment. Symptom control can be achieved with pain relief which may include traditional NSAIDs and COX II selective inhibitors. Choice of symptom control is dependent on a patient’s co-morbidities, parameters, possible allergies and intolerances, and their medication history.

Question 27

Biological agents used in the treatment of RA in the UK

Answer 27

• Anti-TNF alpha: Infliximab, Etanercept, Adalimumab, Certolizumab, Golimumab
• IL-1 antagonist: Anakinra (not currently recommended by NG100)
• T cell antagonist: Abatacept
• IL-6 antagonist: Tocilizumab, Sarilumab
• Targeted synthetic DMARD: Baricitinib, Tofacitinib
• B cell depletor: Rituximab

Question 28

Systemic Lupus Erythematosus (SLE)

Answer 28

Systemic lupus erythematosus or lupus as it is more commonly known is a complex autoimmune disease that attacks a variety of organs.

Possible causes and contributory factors
• Genetic and environmental factors
• UV light
• Vitamin D deficiency
• Female sex hormones particularly oestrogen
• Drug induced e.g. hydralazine, procainamide

Question 29

Symptoms and disease progression - SLE

Answer 29

Clinical manifestations can be varied and non-specific and range from mild to severe. The ‘classical’ presentation involves a woman of child bearing age presenting with a butterfly facial rash, mouth ulcers and alopecia.
Other symptoms of lupus include photosensitive (discoid) skin rashes, pleuritis, headaches,
depression, anxiety and Raynaud’s phenomenon.
SLE disease activity can be variable and it can relapse and remit, although remission can be difficult to classify. In mild SLE, skin and joint involvement is common. Moderate to severe SLE may involve many internal organs ranging from the lungs (pleuritis), the heart (pericarditis), kidneys (lupus nephritis) as well as the central nervous system (anxiety, depression, demyelination). Joint involvement is normally milder than in conditions such as rheumatoid arthritis, joint deformity or destruction resulting from SLE is very rare. Two conditions known as Sjögren’s syndrome and antiphospholipid syndrome are also closely associated with lupus. Sjögren’s syndrome involves the lacrimal ducts which are attacked via an autoimmune mechanism, resulting in a condition involving dry eyes and dry mouth.
Antiphospholipid syndrome significantly increases the risk of patients having a thrombotic event e.g. DVT or PE. Young women with a history of recurrent miscarriage may have antiphospholipid syndrome.

Question 30

Diagnosis of SLE

Answer 30

A diagnosis of SLE is often difficult as patients often present with non-specific symptoms. It involves looking at the clinical presentation of the patient and then combining these findings with accurate blood test results. The main feature of SLE is the wide variety of autoantibodies that are produced which attack various sites of the body.

Question 31

Pharmacological management - SLE

Answer 31

There is no known cure for lupus and as you would expect, the treatment options for SLE depend on the extent and the severity of the disease.

There are two main categories to this treatment:
• Induction – medicines used during a flare to induce remission.
• Maintenance – medicines used to consolidate remission and reduce the risk of further flares.

Question 32

three major complications associated with SLE

Answer 32

Sjögren’s Syndrome
- The treatment for SLE itself tends to reduce the symptoms of Sjögren’s. However symptomatic treatments such as hypromellose eye drops for dry eyes, and artificial saliva pastilles for dry mouth are beneficial. More severe cases of Sjögren’s can be treated with pilocarpine tablets.

Antiphospholipid Syndrome
- This is probably one of the more severe complications associated with SLE, it increases the risk of thrombosis in both arteries and veins. Around 30% of women with SLE will develop antiphospholipid syndrome. Avoidance of exogenous oestrogens is extremely important.
Treatment is individualised for each patient with extra consideration needed during pregnancy

Raynaud’s Phenomenon
- This is caused by spasm of the peripheral arterioles, symptoms include cold hands and feet which may turn blue in cold weather. When blood returns to the extremities it can be extremely painful. Treatment involves keeping the extremities warm and wearing gloves. In more severe cases nifedipine may be used for its peripheral vasodilatory properties.

Question 33

SLE and pregnancy

Answer 33

Pregnant women who have SLE, have an increased risk of disease flares, miscarriage, thrombosis, pre-eclampsia and preterm delivery. Careful discussion between female patients with SLE (regardless of whether they have antiphospholipid syndrome) and a specialist clinician should take place ideally, before conception.

Question 34

Extra-articular features of RA include

Answer 34

episcleritis and scleritis; pericarditis and vasculitis, spinal cord compression, exhaustion, weight loss, and anaemia of chronic disease