Rheumatology Flashcards

Question

Psoriatic arthritis

Answer 1

Psoriatic arthritis is an inflammatory arthritis associated with psoriasis. It can vary in severity from mild stiffening and soreness in the joints to complete joint destruction in arthritis mutilans. Psoriatic arthritis occurs in 10-20% of patients with psoriasis, usually within 10 years of developing the skin condition. Arthritis can occur before the skin changes. It is most common in middle age but can occur at any age. Psoriatic arthritis is part of the seronegative spondyloarthropathy group of conditions. It may be associated with extra-articular manifestations, particularly uveitis and inflammatory bowel disease.

Answer 2

There are 5 recognised patterns. Asymmetrical oligoarthritis and symmetrical polyarthritis are the most common. Asymmetrical oligoarthritis affects 1-4 joints at any given time, often on only one side of the body. Symmetrical polyarthritis presents similarly to rheumatoid arthritis. More than four joints are affected, such as the hands, wrists and ankles. Distal interphalangeal predominant pattern primarily affects the DIP joints. However, the DIP joints can be affected across all types of psoriatic arthritis. Spondylitis presents with back stiffness and pain. It involves the axial skeleton (spine and sacroiliac joints). Arthritis mutilans is the most severe form of psoriatic arthritis. It affects the phalanges (the bones of the fingers and toes). There is osteolysis (destruction) of the bones around the joints, leading to progressive shortening of the digits. The skin folds as the digit shortens, giving an appearance described as a telescoping digit. TOM TIP: Psoriatic arthritis tends to affect the distal interphalangeal (DIP) joints and axial skeleton, whereas rheumatoid arthritis tends not to affect these joints. This can help you distinguish them.

Answer 3

Plaques of psoriasis on the skin Nail pitting (tiny indents in the fingernails and toenails) Onycholysis (separation of the nail from the nail bed) Dactylitis (inflammation of the entire finger) Enthesitis (inflammation of the entheses, which are the points of insertion of tendons into bone)

Answer 4

The NICE guidelines on psoriasis (2017) suggest the Psoriasis Epidemiological Screening Tool (PEST) as a way of screening for psoriatic arthritis in patients with psoriasis. It involves questions about joint pain, swelling, a history of arthritis and nail pitting. A high score triggers a referral to a rheumatologist.

Answer 5

Characteristic x-ray changes in psoriatic arthritis include: Periostitis (inflammation of the periosteum, causing a thickened and irregular outline of the bone) Ankylosis (fixation or fusion of the bones at the joint) Osteolysis (destruction of bone) Dactylitis (inflammation of the whole digit, seen as soft tissue swelling) The classic x-ray finding in the digits is a “pencil-in-cup” appearance. There is erosion of the bones at the joint. There is central erosion on one side of the joint, giving a cup-like appearance. The other bone becomes pointed and looks like a pencil in the cup. This appearance is associated with arthritis mutilans.

Answer 6

There is a crossover between the systemic treatments used to treat the skin condition and psoriatic arthritis. Treatment is coordinated between dermatologists, rheumatologists and other multidisciplinary team members. Depending on the severity, treatment may involve: Non-steroidal anti-inflammatory drugs (NSAIDs) Steroids DMARDs (e.g., methotrexate, leflunomide or sulfasalazine) Anti-TNF medications (etanercept, infliximab or adalimumab) Ustekinumab is a monoclonal antibody that targets interleukin 12 and 23

Answer 7

Reactive arthritis involves synovitis in one or more joints in response to an infective trigger. Typically it causes acute monoarthritis, affecting a single joint (most often the knee), presenting with a warm, swollen and painful joint. A significant differential is septic arthritis, where an infection is inside the joint. Patients with reactive arthritis do not have an infection in the joint. The most common triggers of reactive arthritis are gastroenteritis or sexually transmitted infections. Chlamydia may cause reactive arthritis. Gonorrhoea typically causes septic arthritis rather than reactive arthritis. Reactive arthritis is a seronegative spondyloarthropathy. There is a link with the HLA B27 gene. It is more common in patients with HIV (HIV needs to be excluded in patients with reactive arthritis).

Answer 8

Bilateral conjunctivitis (non-infective) Anterior uveitis Urethritis (non-gonococcal) Circinate balanitis (dermatitis of the head of the penis) TOM TIP: The classic triad of conjunctivitis, urethritis and arthritis are remembered with the mnemonic, “can’t see, pee or climb a tree”.

Answer 9

Patients presenting with an acute warm, swollen, painful joint need to be treated according to the local hot joint policy. Septic arthritis needs to be excluded. Antibiotics may be given until septic arthritis is excluded. Joint aspiration is required. Synovial fluid is sent for microscopy, culture and sensitivity testing for infection, and crystal examination for gout and pseudogout. Management of reactive arthritis (after septic arthritis is excluded) involves: Treatment of the triggering infection (e.g., chlamydia) NSAIDs Steroid injection into the affected joints Systemic steroids may be required, particularly where multiple joints are affected Most cases resolve within 6 months and do not recur. Recurrent cases may require DMARDs or anti-TNF medications.

Answer 10

Ankylosing spondylitis (AS) is an inflammatory condition affecting the axial skeleton (mainly the spine and sacroiliac joints), causing progressive stiffness and pain. It is also known as axial spondyloarthritis. It is part of the seronegative spondyloarthropathy group of conditions, also including psoriatic arthritis and reactive arthritis. The main affected joints are the sacroiliac joints and the vertebral column joints. Inflammation causes pain and stiffness in these joints. It can progress to spine and sacroiliac joint fusion. There is a strong link with the HLA-B27 gene. Around 90% of AS patients have the HLA-B27 gene. It is thought that less than 10% of people with the gene will get AS. It is more common in men (but women can also be affected).

Answer 11

The typical presentation is a young adult male in their 20s. Symptoms develop gradually over at least three months. The main presenting features are Pain and stiffness in the lower back Sacroiliac pain (in the buttock region) The pain and stiffness is worse with rest and improves with movement. The pain worsens at night and in the morning and may wake them. The stiffness takes at least 30 minutes to improve in the morning. Symptoms improve with activity and worsen with rest. Additional symptoms and problems include: Chest pain related to the costovertebral and sternocostal joints Enthesitis (inflammation of the entheses, where tendons or ligaments insert into bone) Dactylitis (inflammation of the entire finger) Vertebral fractures (presenting with sudden-onset new neck or back pain) Shortness of breath relating to restricted chest wall movement)

Answer 12

There is a long list of associated conditions. The key ones can be remembered with the 5 As mnemonic: A – Anterior uveitis A – Aortic regurgitation A – Atrioventricular block (heart block) A – Apical lung fibrosis (fibrosis of the upper lobes of the lungs) A – Anaemia of chronic disease

Answer 13

Schober’s test assesses spinal mobility. With the patient standing straight, the L5 vertebra is located, and a point is marked 10cm above and 5cm below this level (15cm apart). Then the patient bends forward as far as possible, and the distance between the points is measured. A length of less than 20cm indicates a restriction in lumbar movement and helps support a diagnosis of ankylosing spondylitis.

Answer 14

Key investigations include: Inflammatory markers (e.g., CRP and ESR) may rise with disease activity HLA B27 genetic testing X-ray of the spine and sacrum MRI of the spine can show bone marrow oedema early in the disease before there are any xray changes

Answer 15

A “bamboo spine” is the typical x-ray finding in the later stages of ankylosing spondylitis, where there is fusion of the sacroiliac and spinal joints. X-rays in ankylosing spondylitis can show: Squaring of the vertebral bodies Subchondral sclerosis and erosions Syndesmophytes (areas of bone growth where the ligaments insert into the bone) Ossification of the ligaments, discs and joints (these structures start turning into bone) Fusion of the facet, sacroiliac and costovertebral joints

Answer 16

The rheumatology multidisciplinary team will manage patients. Treatment aims to control symptoms and preserve function. Medical management may involve: Non-steroidal anti-inflammatory drugs (NSAIDs) are first-line Anti-TNF medications are second-line (e.g., adalimumab, etanercept or infliximab) Secukinumab or ixekizumab are third-line (monoclonal antibodies against interleukin-17) Upadacitinib is another third-line option (JAK inhibitor) Intra-articular steroid injections may be considered for specific joints. Additional management: Physiotherapy Exercise and mobilisation Avoiding smoking Bisphosphonates for osteoporosis Surgery is occasionally required for severe joint deformity

Answer 17

Systemic lupus erythematosus (SLE) is an inflammatory autoimmune connective tissue disorder. It is “systemic” because it affects multiple organs and systems. “Erythematosus” refers to the typical red malar rash across the face. SLE can affect anyone but occurs more commonly in: Women Asian, African, Caribbean and Hispanic ethnicity Young to middle-aged adults SLE typically takes a relapsing-remitting course, with flares of worse symptoms and periods where symptoms settle. The result of chronic inflammation means SLE can shorten life expectancy (although this is mitigated with effective management). Cardiovascular disease and infection are significant complications.

Answer 18

SLE is characterised by anti-nuclear antibodies (ANA). These are autoantibodies against proteins within the cell nucleus. These antibodies generate a chronic inflammatory response, leading to the condition’s features.

Answer 19

SLE presents with many non-specific symptoms: Fatigue Weight loss Arthralgia (joint pain) Non-erosive arthritis Myalgia (muscle pain) Fever Photosensitive malar rash Lymphadenopathy Splenomegaly Shortness of breath Pleuritic chest pain Mouth ulcers Hair loss Raynaud’s phenomenon Oedema (due to nephritis) The typical malar rash is “butterfly” shaped across the nose and cheeks. It is triggered or worsened by sunlight.

Answer 20

Abnormal investigation findings in SLE include: Autoantibodies (more information below) Full blood count may show anaemia of chronic disease, low white cell count and low platelets CRP and ESR may be raised with active inflammation C3 and C4 levels may be decreased in active disease Urinalysis and urine protein:creatinine ratio shows proteinuria in lupus nephritis Renal biopsy may be used to investigate for lupus nephritis

Answer 21

Around 85% of patients with SLE will be positive for anti-nuclear antibodies (ANA). These can be positive in healthy individuals and those with other autoimmune conditions (e.g., autoimmune hepatitis). A positive result needs to be interpreted in the context of their symptoms. Anti-double stranded DNA (anti-dsDNA) antibodies are highly specific to SLE, meaning a positive result suggests SLE rather than other causes. Around half of patients with SLE have anti-dsDNA antibodies. The levels vary with disease activity, making them helpful in monitoring disease activity and response to treatment. An extractable nuclear antigen panel looks for antibodies to specific proteins in the cell nucleus and helps diagnose and distinguish between specific connective tissue disorders: Anti-Sm (highly specific to SLE but not very sensitive) Anti-centromere antibodies (most associated with limited cutaneous systemic sclerosis) Anti-Ro and anti-La (most associated with Sjögren’s syndrome) Anti-Scl-70 (most associated with systemic sclerosis) Anti-Jo-1 (most associated with dermatomyositis) Antiphospholipid antibodies and antiphospholipid syndrome can occur secondary to SLE in up to 40% of patients. These antibodies are associated with an increased risk of venous thromboembolism.

Answer 22

The European League Against Rheumatism (EULAR) / American College of Rheumatology (ACR) criteria (2019) can be used for diagnosis. This takes into account the clinical features and autoantibodies suggestive of SLE.

Answer 23

Cardiovascular disease is a leading cause of death. Chronic inflammation in blood vessels leads to hypertension and coronary artery disease. Infection is more common, both from the disease process and secondary to immunosuppressant drugs. Anaemia in SLE can be due to anaemia of chronic disease, autoimmune haemolytic anaemia, bone marrow suppression by medications or kidney disease. It can also cause leucopenia (low white cells), neutropenia (low neutrophils) and thrombocytopenia (low platelets). Pericarditis (inflammation of the pericardial sac surrounding the heart) causes sharp chest pain that gets worse on lying flat. Pleuritis (inflammation of the lining of the lungs) causes sharp chest pain on inspiration. Interstitial lung disease can be caused by inflammation in the lung tissue, leading to pulmonary fibrosis. Lupus nephritis (inflammation in the kidney) can progress to end-stage renal failure. Investigations include a urine protein:creatinine ratio and renal biopsy. The renal biopsy is often repeated to assess the response to treatment. Neuropsychiatric SLE is caused by inflammation in the central nervous system. It can present with optic neuritis (inflammation of the optic nerve), transverse myelitis (inflammation of the spinal cord) or psychosis. Recurrent miscarriage is more common in SLE. There is also an increased risk of intrauterine growth restriction, pre-eclampsia and pre-term labour. Venous thromboembolism may be associated with antiphospholipid syndrome occurring secondary to SLE.

Answer 24

Treatment aims to control symptoms and reduce complications with the least medications and side effects. Suncream and sun avoidance are essential measures in managing the photosensitive malar rash. First-line options include: Hydroxychloroquine NSAIDs Steroids (e.g., prednisolone) Treatment options for resistant or more severe SLE include: DMARDs (e.g., methotrexate, mycophenolate mofetil or cyclophosphamide) Biologic therapies Biological therapies include: Rituximab (a monoclonal antibody that targets the CD20 protein on the surface of B cells) Belimumab (a monoclonal antibody that targets B-cell activating factor)

Answer 25

Discoid lupus erythematosus (DLE) is an autoimmune chronic skin condition. It is more common in women and typically presents between the ages of 20-50. It is more common in darker-skinned patients and smokers. Discoid lupus is associated with an increased risk of developing systemic lupus erythematosus. However, this risk is below 5%. Rarely the lesions can progress to squamous cell carcinoma (SCC) of the skin.

Answer 26

The lesions typically occur on the face, scalp and ears. They are photosensitive, meaning they are made worse by exposure to sunlight. They are associated with scarring alopecia (with scarring and hair loss in affected areas) and hyperpigmentation or hypopigmentation. The appearance of the lesions or plaques are: Inflamed Dry Erythematous (red) Scaling

Answer 27

A skin biopsy can be used to confirm the diagnosis. Treatment is with Sun protection Topical steroids Intralesional steroid injections Hydroxychloroquine

Answer 28

Systemic sclerosis is an autoimmune connective tissue disease involving inflammation and fibrosis (hardening or scarring) of the connective tissues, skin and internal organs. The cause is unclear. Scleroderma translates directly to the hardening of the skin. The terms systemic sclerosis and scleroderma are often used interchangeably. Most patients with scleroderma have systemic sclerosis. However, a localised version of scleroderma only affects the skin. There are two main patterns of disease in systemic sclerosis: Limited cutaneous systemic sclerosis Diffuse cutaneous systemic sclerosis

Answer 29

Limited cutaneous systemic sclerosis is the more limited version of systemic sclerosis. It used to be called CREST syndrome. CREST forms a mnemonic for remembering the features of limited cutaneous systemic sclerosis: C – Calcinosis R – Raynaud’s phenomenon E – oEsophageal dysmotility S – Sclerodactyly T – Telangiectasia

Answer 30

Diffuse cutaneous systemic sclerosis includes the CREST features and also affects internal organs, causing: Cardiovascular problems (e.g., hypertension and coronary artery disease) Lung problems (e.g., pulmonary hypertension and pulmonary fibrosis) Kidney problems (e.g., glomerulonephritis and scleroderma renal crisis)

Answer 31

Scleroderma refers to the hardening of the skin, giving the appearance of shiny, tight skin without the normal skin folds. These changes are most notable on the hands and face. Sclerodactyly describes the skin changes in the hands. Skin tightening around the joints restricts the range of motion and reduces function. The fat pads on the fingers are lost. The skin can break and ulcerate. Telangiectasia refers to dilated blood vessels in the skin measuring less than 1mm in diameter. Calcinosis refers to calcium deposits under the skin, most commonly found on the fingertips. Oesophageal dysmotility is caused by atrophy and dysfunction of the smooth muscle, as well as fibrosis of the oesophagus. It causes swallowing difficulties, chest pain, acid reflux and oesophagitis. Systemic and pulmonary hypertension is caused by connective tissue dysfunction in the systemic and pulmonary arterial systems. Systemic hypertension can be worsened by renal impairment. Pulmonary fibrosis occurs in severe systemic sclerosis, with a gradual onset of dry cough and shortness of breath. Scleroderma renal crisis is a medical emergency with severe hypertension and renal failure.

Answer 32

Raynaud’s phenomenon is where the fingertips change colour in response to even mildly cold triggers (e.g., opening the fridge). It is caused by vasoconstriction of the vessels supplying the fingers. The typical pattern is: First white, due to vasoconstriction Then blue, due to cyanosis Then red, due to reperfusion and hyperaemia Raynaud’s disease is where Raynaud’s phenomenon occurs without an associated systemic disease. It is idiopathic and makes up 80-90% of patients with Raynaud’s phenomenon. Systemic sclerosis is the most important secondary cause. It is less commonly associated with SLE. Nailfold capillaroscopy is a technique to magnify and examine the peripheral capillaries where the skin meets the base of the fingernail (the nail fold). Abnormal capillaries, avascular areas and micro-haemorrhages suggest systemic sclerosis. Patients with Raynaud’s disease (without systemic sclerosis) have normal nailfold capillaries. Treatment options for Raynaud’s include: Keeping the hands warm (e.g., gloves and hand warmers) Calcium channel blockers (e.g., nifedipine) Other specialist drugs include losartan, ACE inhibitors, sildenafil and fluoxetine Beta blockers can worsen the symptoms of Raynaud’s.

Answer 33

Antinuclear antibodies (ANA) are positive in most patients with systemic sclerosis. They are non-specific. Anti-centromere antibodies are most associated with limited cutaneous systemic sclerosis. Anti-Scl-70 antibodies are most associated with diffuse cutaneous systemic sclerosis and more severe disease.

Answer 34

The American College of Rheumatology / European League Against Rheumatism (ACR/EULAR) classification criteria from 2013 can be used to make the diagnosis. This takes into account the clinical features, antibodies and nailfold capillaroscopy.

Answer 35

DMARDs (e.g., methotrexate) and biologic therapies (e.g., rituximab) are options in diffuse disease. Steroids may be considered but are associated with an increased risk of scleroderma renal crisis. Non-medical management involves: Avoiding smoking Gentle skin stretching to maintain the range of motion Regular emollients Avoiding cold triggers for Raynaud’s Physiotherapy to help maintain healthy joints Occupational therapy for adaptations to daily living to cope with limitations Medical management focuses on treating symptoms and complications: Nifedipine is usually first-line for Raynaud’s phenomenon Proton pump inhibitors (e.g., omeprazole or lansoprazole) for acid reflux Prokinetic medications (e.g., metoclopramide) for gastrointestinal symptoms Analgesia for joint pain Antibiotics for skin infections Antihypertensives (e.g., ACE inhibitors) to treat hypertension and scleroderma renal crisis Endothelin receptor antagonists (e.g., bosentan) may be used for pulmonary hypertension and digital ulcers Sildenafil may be used for pulmonary hypertension and digital ulcers associated with Raynaud’s Intravenous iloprost may be used for digital ulcers Oxygen where required for pulmonary fibrosis Stem cell transplantation may be considered in rapidly progressing severe disease but carries significant risks

Answer 36

Polymyalgia rheumatica (PMR) is an inflammatory condition that causes pain and stiffness in the shoulders, pelvic girdle and neck. There is a strong association with giant cell arteritis, and the two conditions often occur together. The cause is not fully understood. There are no relevant antibodies. It is more common in older white patients.

Answer 37

Patients may have a relatively rapid onset of symptoms over days to weeks. Symptoms should be present for two weeks before a diagnosis is considered. The core symptoms are pain and stiffness of the: Shoulders, potentially radiating to the upper arm and elbow Pelvic girdle (around the hips), potentially radiating to the thighs Neck The characteristic features of the pain and stiffness are: Worse in the morning Worse after rest or inactivity Interfere with sleep Take at least 45 minutes to ease in the morning Somewhat improve with activity Associated features include: Systemic symptoms (e.g., weight loss, fatigue and low-grade fever) Muscle tenderness Carpel tunnel syndrome Peripheral oedema

Answer 38

The presenting symptoms are not specific to PMR, and there is a long list of differentials, including: Osteoarthritis Rheumatoid arthritis Systemic lupus erythematosus Statin-induced myopathy Myositis (e.g., polymyositis) Cervical spondylosis Adhesive capsulitis (frozen shoulder) Hyperthyroidism or hypothyroidism Osteomalacia Fibromyalgia Lymphoma or leukaemia Myeloma

Answer 39

Diagnosis is based on clinical presentation, response to steroids and excluding differentials. Inflammatory markers (e.g., ESR and CRP) are usually raised (but may be normal). The NICE clinical knowledge summaries (updated January 2023) advise investigations before initiating steroids: Full blood count Renal profile (U&E) Liver function tests Calcium (abnormal in hyperparathyroidism, cancer and osteomalacia) Serum protein electrophoresis for myeloma Thyroid-stimulating hormone for thyroid function Creatine kinase for myositis Rheumatoid factor for rheumatoid arthritis Urine dipstick Additional investigations to consider: Anti-nuclear antibodies (ANA) for systemic lupus erythematosus Anti-cyclic citrullinated peptide (anti-CCP) for rheumatoid arthritis Urine Bence Jones protein for myeloma Chest x-ray for lung and mediastinal abnormalities (e.g., lung cancer or lymphoma)

Answer 40

Treatment of PMR is with steroids. The NICE clinical knowledge summaries (updated January 2023) recommend: 15mg prednisolone daily initially Follow up after 1 week Patients with PMR have a dramatic improvement in symptoms (at least 70%) within one week. Inflammatory markers return to normal within one month. A poor response to steroids suggests an alternative diagnosis. Treatment with steroids typically lasts 1-2 years. NICE suggest the following reducing regime of prednisolone: 15mg until the symptoms are fully controlled, then 12.5mg for 3 weeks, then 10mg for 4-6 weeks, then Reducing by 1mg every 4-8 weeks The reducing regime can go faster or slower depending on the individual and their symptom control. Additional management for patients on long-term steroids can be remembered with the “Don’t STOP” mnemonic: Don’t – steroid dependence occurs after 3 weeks of treatment, and abruptly stopping risks adrenal crisis S – Sick day rules (steroid doses may need to be increased if the patient becomes unwell) T – Treatment card – patients should carry a steroid treatment card to alert others that they are steroid-dependent O – Osteoporosis prevention may be required (e.g., bisphosphonates and calcium and vitamin D) P – Proton pump inhibitors are considered for gastro-protection (e.g., omeprazole)

Answer 41

Giant cell arteritis (GCA) is also known as temporal arteritis. It is a type of systemic vasculitis affecting the medium and large arteries. There is a strong link with polymyalgia rheumatica. It is more common in older white patients. The key complication of giant cell arteritis is vision loss, which is often irreversible.

Answer 42

Unilateral headache is the primary presenting feature, typically severe and around the temple and forehead. It may be associated with: Scalp tenderness (e.g., noticed when brushing the hair) Jaw claudication Blurred or double vision Loss of vision if untreated The temporal artery may be tender and thickened to palpation, with reduced or absent pulsation. Associated features include: Symptoms of polymyalgia rheumatica (e.g., shoulder and pelvic girdle pain and stiffness) Systemic symptoms (e.g., weight loss, fatigue and low-grade fever) Muscle tenderness Carpel tunnel syndrome Peripheral oedema

Answer 43

The diagnosis is based on: Clinical presentation Raised inflammatory markers, particularly ESR (usually more than 50 mm/hour) Temporal artery biopsy (showing multinucleated giant cells) Duplex ultrasound (showing the hypoechoic “halo” sign and stenosis of the temporal artery)

Answer 44

Steroids are the mainstay of treatment. They are started immediately, before confirming the diagnosis, to reduce the risk of vision loss. There is usually a rapid and significant response to steroid treatment. Initial treatment is: 40-60mg prednisolone daily with no visual symptoms or jaw claudication 500mg-1000mg methylprednisolone daily with visual symptoms or jaw claudication Once the diagnosis is confirmed and the condition is controlled, the steroid dose is slowly weaned over 1-2 years. Other medications include: Aspirin 75mg daily decreases vision loss and strokes Proton pump inhibitor (e.g., omeprazole) for gastroprotection while on steroids Bisphosphonates and calcium and vitamin D for bone protection while on steroids A combination of specialties manages patients with GCA: Rheumatology for specialist diagnosis and management Vascular surgeons for a temporal artery biopsy Ophthalmology review for visual symptoms

Answer 45

Steroid-related complications (e.g., weight gain, diabetes and osteoporosis) Visual loss Cerebrovascular accident (stroke)

Answer 46

Polymyositis and dermatomyositis are autoimmune disorders causing muscle inflammation (myositis). Both present with proximal muscle weakness. Dermatomyositis also involves characteristic skin changes, specifically Gottron papules affecting the backs of the hands and heliotrope rash affecting the eyelids. Polymyositis or dermatomyositis can be caused by an underlying cancer, making them paraneoplastic syndromes. A viral infection may be the trigger (e.g., Coxsackie virus or HIV). Certain HLA genes are risk factors.

Answer 47

The typical presenting symptom is gradual-onset, symmetrical, proximal muscle weakness, causing difficulties standing from a chair, climbing stairs or lifting overhead. There may be muscle pain (myalgia), but not always. Polymyositis occurs without any skin features. Potential skin changes in dermatomyositis include: Gottron lesions (scaly erythematous patches) on the knuckles, elbows and knees Heliotrope rash (a purple rash on the face and eyelids) Periorbital oedema (swelling around the eyes) Photosensitive erythematous rash on the back, shoulders and neck

Answer 48

The critical test for myositis is a creatine kinase blood test. Creatine kinase is an enzyme found inside muscle cells. Inflammation in the muscle cells (myositis) releases creatine kinase. Creatine kinase is usually less than about 300 IU/L. With myositis, the result is often in the multiples of thousands. Other causes of a raised creatine kinase include: Rhabdomyolysis Acute kidney injury Myocardial infarction Statins Strenuous exercise

Answer 49

The diagnosis is made by a rheumatology specialist, based on: Clinical features Elevated creatine kinase Autoantibodies Electromyography (EMG) Magnetic resonance imaging (MRI) Muscle biopsy There are many myositis-specific antibodies with varying associations. The most common one to remember is anti-Jo-1 antibodies associated with polymyositis.

Answer 50

A rheumatologist guides management. New cases are assessed for possible underlying cancer. They may benefit from physiotherapy and occupational therapy to help with muscle strength and function. Corticosteroids are the first-line treatment of both conditions. Other medical options where the response to steroids is inadequate: Immunosuppressants (e.g., methotrexate or azathioprine) IV immunoglobulins Biological therapy (e.g., infliximab or etanercept)

Answer 51

Antiphospholipid syndrome is an autoimmune disorder caused by antiphospholipid antibodies. These antibodies target the proteins that bind to the phospholipids on the cell surface, causing inflammation and increasing the risk of thrombosis (blood clots). It can occur in isolation or associated with another autoimmune condition, particularly systemic lupus erythematosus.

Answer 52

The specific antiphospholipid antibodies are: Lupus anticoagulant Anticardiolipin antibodies Anti-beta-2 glycoprotein I antibodies

Answer 53

The key complications of antiphospholipid syndrome are: Venous thromboembolism (e.g., deep vein thrombosis and pulmonary embolism) Arterial thrombosis (e.g., stroke, myocardial infarction and renal thrombosis) Pregnancy-related complications (e.g., recurrent miscarriage, stillbirth and pre-eclampsia) Catastrophic antiphospholipid syndrome is a rare complication with rapid thrombosis in multiple organs within a few days. This has a high mortality rate. TOM TIP: In your exams, look out for the patient with thrombosis (e.g., deep vein thrombosis or stroke) and a history of recurrent miscarriage. The diagnosis is likely antiphospholipid syndrome.

Answer 54

Livedo reticularis is a purple lace-like (reticular) rash that gives a mottled appearance to the skin. A more permanent version of this rash, called livedo racemosa, is associated with antiphospholipid syndrome. Libmann-Sacks endocarditis is a non-bacterial endocarditis with growths (vegetations) on the heart valves (most often the mitral and aortic valves). It is associated with SLE and antiphospholipid syndrome. Thrombocytopenia (low platelets) is common in antiphospholipid syndrome.

Answer 55

Diagnosis is based on clinical features and persistent antiphospholipid antibodies. Long-term warfarin with a target INR of 2-3 is used to prevent thrombosis. Low molecular weight heparin (e.g., enoxaparin) and aspirin are used in pregnancy to reduce the risks. Warfarin is contraindicated in pregnancy.

Answer 56

Sjögren’s syndrome is an autoimmune condition affecting the exocrine glands, notably the lacrimal and salivary glands, causing symptoms of dry mouth, eyes and vagina. Dry eyes and dry mouth can be called sicca symptoms. It can also cause dry skin, joint pain and stiffness. It is more common in women and typically presents in middle age. Primary Sjögren’s is where the condition occurs in isolation. Secondary Sjögren’s is where it occurs due to other diseases such as systemic lupus erythematosus and rheumatoid arthritis. Antibodies associated with Sjögren’s are: Anti-SS-A antibodies (also called anti-Ro) Anti-SS-B antibodies (also called anti-La)

Answer 57

The Schirmer test involves inserting folded filter paper under the lower eyelid with the end hanging out. Moisture from the eye will travel by diffusion along the filter paper. After 5 minutes, the distance that the moisture travels along the filter paper is measured. In a healthy young adult, 15mm is expected. Less than 10mm is significant.

Answer 58

The diagnosis is typically made based on the clinical features and presence of antibodies. Salivary gland biopsy may be used to confirm the diagnosis but is not usually necessary. Management involves rheumatology and ophthalmology. Treatment options include: Artificial tears (e.g., polyvinyl alcohol eye drops during the day and carbomer gel at night) Artificial saliva Vaginal lubricants Pilocarpine (oral) can be used to stimulate tear and saliva production Hydroxychloroquine may be considered, mainly in patients with associated joint pain Pilocarpine stimulates muscarinic receptors, stimulating the parasympathetic nerves and promoting salivary and lacrimal gland secretion.

Answer 59

Complications related to exocrine gland dysfunction include: Eye problems, such as keratoconjunctivitis sicca and corneal ulcers Oral problems, such as dental cavities and candida infections Vaginal problems, such as candida infection and sexual dysfunction Sjögren’s can rarely affect other organs, causing complications such as: Pneumonia Bronchiectasis Non-Hodgkins lymphoma Peripheral neuropathy Vasculitis Renal impairment

Answer 60

Vasculitis is the name for inflammation of the blood vessels. There are many different types of vasculitis that affect different sizes of blood vessel. They are categorised based on whether they affect small vessels, medium sized vessels or large vessels. They each have some unique features that will help you spot them in exams.

Answer 61

Henoch-Schonlein purpura Eosinophilic Granulomatosis with Polyangiitis (Churg-Strauss syndrome) Microscopic polyangiitis Granulomatosis with polyangiitis

Answer 62

Polyarteritis nodosa Eosinophilic Granulomatosis with Polyangiitis (Churg-Strauss syndrome) Kawasaki Disease

Answer 63

Giant cell arteritis Takayasu’s arteritis

Answer 64

There are some generic features that apply to most types of vasculitis. These are things that should make you think about a possible vasculitis: Purpura. These are purple-coloured non-blanching spots caused by blood leaking from the vessels under the skin. Joint and muscle pain Peripheral neuropathy Renal impairment Gastrointestinal disturbance (diarrhoea, abdominal pain and bleeding) Anterior uveitis and scleritis Hypertension They are also associated with systemic manifestations of: Fatigue Fever Weight loss Anorexia (loss of appetite) Anaemia

Answer 65

Inflammatory markers (CRP and ESR) are usually raised in vasculitis. Anti neutrophil cytoplasmic antibodies (ANCA) is the blood test to remember for vasculitis. If you remember this alone you will be able to answer many questions on vasculitis. There are two type of ANCA blood tests: p-ANCA and c-ANCA. P-ANCA are also called anti-MPO antibodies. C-ANCA are also called anti-PR3 antibodies. These different ANCA tests are associated with different types of vasculitis: p-ANCA (MPO antibodies): Microscopic polyangiitis and Churg-Strauss syndrome c-ANCA (PR3 antibodies): Granulomatosis with polyangiitis

Answer 66

Henoch-Schonlein Purpura (HSP) is an IgA vasculitis that commonly presents with a purpuric rash affecting the lower limbs or buttocks in children. Inflammation occurs due to immunoglobulin A deposits in the blood vessels of affected organs such as the skin, kidneys and gastro-intestinal tract. The condition is often triggered by an upper airway infection (e.g. tonsillitis) or a gastroenteritis. It is most common in children under the age of 10 years. The rash is caused by inflammation and leaking of blood from small blood vessels under the skin, forming purpura. The four classic features are purpura (100%), joint pain (75%), abdominal pain (50%) and renal involvement (50%). HSP affects the kidneys in about 50% of patients, causing an IgA nephritis. Management is typically supportive, such as simple analgesia, rest and proper hydration. The benefits of steroids are unclear. The abdominal pain usually settles within a few days. Patients without kidney involvement can expect to fully recover within 4-6 weeks. A third of patients have a recurrence of the disease within 6 months. 1% of patients will go on to develop end stage renal failure.

Answer 67

Eosinophilic granulomatosis with polyangiitis used to be called Churg-Strauss syndrome and is still often referred to by this name. It is a small and medium vessel vasculitis. It is most associated with lung and skin problems, but can affect other organs such as kidneys. It often presents with severe asthma in late teenage years or adulthood. A characteristic finding is elevated eosinophil levels on the full blood count.

Answer 68

Microscopic polyangiitis is a small vessel vasculitis. The main feature of microscopic polyangiitis is renal failure. It can also affect the lungs causing shortness of breath and haemoptysis.

Answer 69

Granulomatosis with polyangiitis is a small vessel vasculitis. It was previously known as Wegener’s granulomatosis. It affects the respiratory tract and kidneys. In the upper respiratory tract, it commonly affects the nose causing nose bleeds (epistaxis) and crusty nasal secretions, ears causing hearing loss and sinuses causing sinusitis. A classic sign in exams is the saddle-shaped nose due to a perforated nasal septum. This causes a dip halfway down the nose. In the lungs, it causes a cough, wheeze and haemoptysis. A chest x-ray may show consolidation, and it may be misdiagnosed as pneumonia. In the kidneys, it can cause rapidly progressing glomerulonephritis.

Answer 70

Polyarteritis nodosa (PAN) is a medium vessel vasculitis. It is most associated with hepatitis B but can also occur without a clear cause or with hepatitis C and HIV. It affects the medium sized vessels in locations such as the skin, gastrointestinal tract, kidneys and heart. This can cause renal impairment, strokes and myocardial infarction. It is associated with a rash called livedo reticularis. This is a mottled, purplish, lace like rash.

Answer 71

Kawasaki disease is a medium vessel vasculitis. It affects young children, typically under 5 years of age. There is no clear cause. Clinical features are: Persistent high fever > 5 days Erythematous rash Bilateral conjunctivitis Erythema and desquamation (skin peeling) of palms and soles “Strawberry tongue” (red tongue with prominent papillae) A key complication is coronary artery aneurysms. Treatment is with aspirin and IV immunoglobulins.

Answer 72

Takayasu’s arteritis is a form of large vessel vasculitis. It mainly affects the aorta and it’s branches. It also affect the pulmonary arteries. These large vessels and their branches can swell and form aneurysms or become narrowed and blocked. This leads to it’s other name of “pulseless disease”. It usually presents before the age of 40 years with non-specific systemic symptoms, such as fever, malaise and muscle aches, or with more specific symptoms of arm claudication or syncope. It is diagnosed using CT or MRI angiography. Doppler ultrasound of the carotids can be useful in detecting carotid disease.

Answer 73

Behçet’s disease is a complex inflammatory condition. It characteristically presents with recurrent oral and genital ulcers. It can also cause inflammation in a number of other areas such as the skin, gastrointestinal tract, lungs, blood vessels, musculoskeletal system and central nervous system. The presentation can vary a lot between patients, with some patients mildly affected and others affected dramatically. There is a link with the HLA B51 gene. This is a prognostic indicator of severe disease.

Answer 74

Mouth ulcers are very common. There is a long list of differentials to mouth ulcers: Simple aphthous ulcers are very common Inflammatory bowel disease (particularly Crohn’s disease) Coeliac disease Vitamin deficiency (B12, folate or iron) Herpes simplex ulcers Hand, foot and mouth disease (coxsackie A virus) Squamous cell carcinoma

Answer 75

Mouth Ulcers Patients with Behçet’s disease are expected to get at least 3 episodes of oral ulcers per year. They are painful, sharply circumscribed erosions with a red halo. They occur on the oral mucosa and heals over 2-4 weeks. Genital Ulcers Genital ulcers are similar in appearance to the oral ulcers. “Kissing ulcers” are where an ulcer develops on two opposing surfaces so that they are facing each other. Skin The skin is very easily inflamed in Behçet’s disease. Particular skin findings in Behçet’s disease are: Erythema nodosum Papules and pustules (similar to acne) Vasculitic type rashes Eyes Eye manifestations need emergency review by ophthalmology as they can be sight treating. Anterior or posterior uveitis Retinal vasculitis Retinal haemorrhage Musculoskeletal System Morning stiffness Arthralgia Oligoarthritis often affecting the knee or ankle. This causes swelling without joint destruction. Gastrointestinal System Inflammation and ulceration can occur through the gastrointestinal tract. This tends to affect the: Ileum Caecum Ascending colon Central Nervous System Memory impairment Headaches and migraines Aseptic meningitis Meningoencephalitis Veins In Behçet’s disease the veins can become inflamed and this can lead to vein thrombosis. Examples of this are: Budd Chiari syndrome Deep vein thrombosis Thrombus in pulmonary veins Cerebral venous sinus thrombosis These thrombosis tend to stay in place and don’t embolism as they are related to inflammation in the vessel wall. Lungs Pulmonary artery aneurysms can develop. If they rupture this can be fatal.

Answer 76

Behçet’s disease is a clinical diagnosis based on the features of the condition. The only particular investigation to be aware of is the pathergy test. The pathergy test involves using a sterile needle to create a subcutaneous abrasion on the forearm. This is then reviewed 24 – 48 hours later to look for a weal 5mm or more in size. It tests for non-specific hypersensitive in the skin. It is positive in Behçet’s disease, Sweet’s syndrome and pyoderma gangrenosum.

Answer 77

Management is coordinated by a specialist, usually a rheumatologist. Other specialities may be involved depending on the affected areas, for example dermatology, ophthalmology and neurology. Management involves a combination of: Topical steroids to mouth ulcers (e.g. soluble betamethasone tablets) Systemic steroids (i.e. oral prednisolone) Colchicine is usually effective as an anti-inflammatory to treat symptoms Topical anaesthetics for genital ulcers (e.g. lidocaine ointment) Immunosuppressants such as azathioprine Biologic therapy such as infliximab

Answer 78

Behçet’s disease is a relapsing remitting condition. Patients generally have a normal life expectancy and the condition may go in to complete remission. There is an increased mortality with haemoptysis, neurological involvement and other major complications.

Answer 79

Gout is a type of crystal arthropathy associated with chronically high blood uric acid levels. Urate crystals are deposited in the joint causing it to become hot, swollen and painful. Gouty tophi are subcutaneous deposits of uric acid typically affecting the small joints and connective tissues of the hands, elbows and ears. The DIP joints are most affected in the hands. It typically presents with a single acute hot, swollen and painful joint. The obvious and extremely important differential diagnosis is septic arthritis.

Answer 80

Male Obesity High purine diet (e.g. meat and seafood) Alcohol Diuretics Existing cardiovascular or kidney disease Family history

Answer 81

Base of the big toe (metatarsophalangeal joint) Wrists Base of thumb (carpometacarpal joints) Gout can also affects large joints like the knee and ankle.

Answer 82

Gout is diagnosed clinically or by aspiration of fluid from the joint. Excluding septic arthritis is essential as this is a potential joint and life-threatening diagnosis. Aspirated fluid will show: No bacterial growth Needle shaped crystals Negatively birefringent of polarised light Monosodium urate crystals Joint xray: Typically the space between the joint is maintained Lytic lesions in the bone Punched out erosions Erosions can have sclerotic borders with overhanging edges

Answer 83

During the acute flare: NSAIDs (e.g. ibuprofen) are first-line Colchicine second-line Steroids can be considered third-line Colchicine is used in patients that are inappropriate for NSAIDs, such as those with renal impairment or significant heart disease. A notable side effect is gastrointestinal upset. Diarrhoea is a very common side effect. This is dose-dependent meaning lower doses cause less upset than higher doses.

Answer 84

Allopurinol is a xanthine oxidase inhibitor used for the prophylaxis of gout. It reduces the uric acid level. Lifestyle changes can reduce the risk of developing gout. This involves losing weight, staying hydrated and minimising the consumption of alcohol and purine-based food (such as meat and seafood). TOM TIP: Do not initiate allopurinol prophylaxis until after the acute attack is settled. Once treatment of allopurinol has been started then it can be continued during an acute attack.

Answer 85

Pseudogout is a crystal arthropathy caused by calcium pyrophosphate crystals. Calcium pyrophosphate crystals are deposited in the joint causing joint problems. It is also known as chondrocalcinosis.

Answer 86

A typical presentation of pseudogout is an older adult with a hot, swollen, stiff, painful knee. Other joints that are commonly affected are the shoulders, wrists and hips. It can be a chronic condition and affect multiple joints. It can also be asymptomatic and picked up incidentally on an xray of the joint.

Answer 87

In any patient presenting with a hot, painful and swollen joint, septic arthritis needs to be excluded as it is a medical emergency that is joint and life threatening. It tends the be milder in presentation compared with gout and septic arthritis. To establish a definitive diagnosis the joint needs to be aspirated for synovial fluid. Aspirated fluid will show: No bacterial growth Calcium pyrophosphate crystals Rhomboid shaped crystals Positive birefringent of polarised light Chondrocalcinosis is the classic xray change in pseudogout. It appears as a thin white line in the middle of the joint space caused by the calcium deposition. This is pathognomonic (diagnostic) of pseudogout. Other joint xray changes are similar to osteoarthritis. Remember the mnemonic LOSS: L – Loss of joint space O – Osteophytes S – Subarticular sclerosis S – Subchondral cysts

Answer 88

Chronic asymptomatic changes found on an xray do not require any action. Symptoms usually resolve spontaneously over several weeks. Symptomatic management involves: NSAIDs Colchicine Joint aspiration Steroid injections Oral steroids Joint washout (arthrocentesis) is an option in severe cases.

Answer 89

Osteoporosis is a condition where there is a reduction in the density of the bones. Osteopenia refers to a less severe reduction in bone density than osteoporosis. Reduced bone density makes bone less strong and more prone to fractures.

Answer 90

Older age Female Reduced mobility and activity Low BMI (<18.5 kg/m2) Rheumatoid arthritis Alcohol and smoking Long term corticosteroids. NICE suggest the risk increases significantly with the equivalent of more than 7.5mg of prednisolone per day for more than 3 months) Other medications such as SSRIs, PPIs, anti-epileptics and anti-oestrogens Post-menopausal women are a key group where osteoporosis should be considered. Oestrogen is protective against osteoporosis. Unless they are on HRT postmenopausal women have less oestrogen. They also tend to be are older and often have other risk factors for osteoporosis.

Answer 91

The FRAX tool gives a prediction of the risk of a fragility fracture over the next 10 years. This is usually the first step in assessing someone’s risk of osteoporosis. It involves inputting information such as their age, BMI, co-morbidities, smoking, alcohol and family history. You can enter a result for bone mineral density (from a DEXA scan) for a more accurate result but it can also be performed without the bone mineral density. It gives results as a percentage 10-year probability of a: Major osteoporotic fracture Hip fracture

Answer 92

Bone mineral density (BMD) is measured using a DEXA scan, which stands for dual-energy xray absorptiometry. DEXA scans are brief xray scans that measure how much radiation is absorbed by the bones, indicating how dense the bone is. The bone mineral density (BMD) can be measured at any location on the skeleton, but the reading at the hip is key for the classification and management of osteoporosis. Bone density can be represented as a Z score or T score. Z scores represent the number of standard deviations the patients bone density falls below the mean for their age. T scores represent the number of standard deviations below the mean for a healthy young adult their bone density is. The most clinically important outcome is the T score at the persons hip. This forms the basis for the WHO classification of their level of osteoporosis. DEXA scans can be used to confirm osteoporosis and monitor treatment.

Answer 93

T Score at the Hip Bone Mineral Density More than -1 Normal -1 to -2.5 Osteopenia Less than -2.5 Osteoporosis Less than -2.5 plus a fracture Severe Osteoporosis

Answer 94

The first step is to perform a FRAX assessment on patients at risk of osteoporosis: Women aged > 65 Men > 75 Younger patients with risk factors such as a previous fragility fracture, history of falls, low BMI, long term steroids, endocrine disorders and rheumatoid arthritis. The NOGG Guidelines from 2017 suggest the next step in management based on the probability of a major osteoporotic fracture from the FRAX score: FRAX outcome without a BMD result will suggest one of three outcomes: Low risk – reassure Intermediate risk – offer DEXA scan and recalculate the risk with the results High risk – offer treatment FRAX outcome with a BMD result will suggest one of two outcomes: Treat Lifestyle advice and reassure

Answer 95

Lifestyle Changes: Activity and exercise Maintain a healthy 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. An example of this would be Calcichew-D3, which contains 1000mg of calcium and 800 units of vitamin D (colecalciferol). Patients with an adequate calcium intake but lacking sun exposure should have vitamin D supplementation. Bisphosphonates: Bisphosphonates are the first-line treatment for osteoporosis. They work by interfering with osteoclasts and reducing their activity, preventing the reabsorption of bone. There are a few key side effects to remember: 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 Examples of bisphosphonates are: Alendronate 70mg once weekly (oral) Risedronate 35 mg once weekly (oral) Zoledronic acid 5 mg once yearly (intravenous) Other Medical Options: Other options if bisphosphonates are contraindicated, not tolerated or not effective: Denosumab is a monoclonal antibody that works by blocking the activity of osteoclasts. Strontium ranelate is a similar element to calcium that 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 menopause early.

Answer 96

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 97

Osteomalacia is a condition where defective bone mineralisation causes “soft” bones. Osteo– means bone, and –malacia means soft. It results from insufficient vitamin D. The same process in children causes rickets.

Answer 98

Vitamin D is a hormone the skin creates in response to sunlight. It is also obtained in limited amounts from food. It is vital in regulating bone mineralisation, hormone secretion and immune function. Low vitamin D is very common. Vitamin D is created from cholesterol by the skin in response to UV radiation. Patients with darker skin require more prolonged sun exposure to generate the same vitamin D. It is also obtained from food as a fat-soluble vitamin. A regular diet does not contain enough vitamin D to compensate for reduced sun exposure. Patients with malabsorption disorders (e.g., inflammatory bowel disease) are at higher risk of vitamin D deficiency. Patients with chronic kidney disease are also at higher risk of vitamin D deficiency as the kidneys help convert vitamin D into its active form. Vitamin D is essential in calcium and phosphate absorption in the intestines and reabsorption in the kidneys. It is also responsible for regulating bone turnover and promoting bone reabsorption to increase the serum calcium level. Inadequate vitamin D leads to low serum calcium and phosphate. Since calcium and phosphate are required for the construction of bone, low levels result in defective bone mineralisation and osteomalacia. Low calcium leads to increased parathyroid hormone (PTH) secretion by the parathyroid glands (secondary hyperparathyroidism). Increased parathyroid hormone promotes calcium reabsorption from the bones, further impairing bone mineralisation. TOM TIP: Most guidelines recommend against testing asymptomatic patients with risk factors for deficiency for their vitamin D level. They should be advised to take maintenance vitamin D without needing a test.

Answer 99

Patients with vitamin D deficiency and osteomalacia may not have any symptoms. Typical symptoms include: Fatigue Bone pain Muscle weakness Muscle aches Pathological or abnormal fractures Looser zones are fragility fractures that go partially through the bone. TOM TIP: Consider vitamin D deficiency risk factors in your exams and clinical practice. Patients with osteomalacia are likely to have risk factors such as darker skin, low exposure to sunlight, living in colder climates and spending most of their time indoors.

Answer 100

Serum 25-hydroxyvitamin D is the laboratory investigation for vitamin D: Less than 25 nmol/L – vitamin D deficiency 25 to 50 nmol/L – vitamin D insufficiency Other laboratory investigation results include: Low serum calcium Low serum phosphate High serum alkaline phosphatase High parathyroid hormone (secondary hyperparathyroidism) Imaging investigations include: X-rays may show osteopenia (more radiolucent bones) DEXA scan shows low bone mineral density

Answer 101

Treatment is with colecalciferol (vitamin D₃). There are various loading regimes (e.g., for patients with symptoms) suggested by the NICE clinical knowledge summaries (2022), for example: 50,000 IU once weekly for 6 weeks 4000 IU daily for 10 weeks A maintenance dose of 800-2000 IU per day is continued following the loading regime (or as the initial treatment in patients that do not require rapid treatment. NICE CKS (2022) recommend checking the serum calcium within a month of the loading regime. It may be: Low in calcium deficiency High in primary hyperparathyroidism (previously masked by the vitamin D deficiency) High in other conditions that cause hypercalcaemia, such as cancer, sarcoidosis or tuberculosis

Answer 102

Paget’s disease of bone involves excessive bone turnover (reabsorption and formation) due to increased osteoclast and osteoblast activity. The excessive turnover is not coordinated, leading to patchy areas of high density (sclerosis) and low density (lysis). The result is enlarged and misshapen bones, structural problems and an increased risk of pathological fractures. It particularly affects the axial skeleton (the bones of the head and spine). The cause is unknown. It typically affects older adults.

Answer 103

Patients may be asymptomatic (diagnosed incidentally on an x-ray), or present with: Bone pain Bone deformity Fractures Hearing loss

Answer 104

X-ray findings include: Bone enlargement and deformity Osteoporosis circumscripta (well-defined osteolytic lesions that appear less dense compared with normal bone) Cotton wool appearance of the skull (poorly defined patchy areas of increased and decreased density) V-shaped osteolytic defects in the long bones Blood tests include: Raised alkaline phosphatase Normal calcium Normal phosphate

Answer 105

Bisphosphonates are the main treatment. They are generally very effective. They interfere with osteoclast activity and restore normal bone metabolism. They improve symptoms and prevent further abnormal bone changes. Other measures include: Calcitonin is a treatment option where bisphosphonates are unsuitable Analgesia (e.g., NSAIDs) for bone pain Calcium and vitamin D supplementation, if necessary Surgery is rarely required to treat fractures, severe deformities and arthritis Monitoring involves checking the serum alkaline phosphatase (ALP) and reviewing symptoms. Effective treatment should normalise the ALP and eliminate symptoms.

Answer 106

The key complications to remember are: Hearing loss (if it affects the bones of the ear) Heart failure (due to hypervascularity of the abnormal bone) Osteosarcoma Spinal stenosis and spinal cord compression Osteosarcoma is a type of bone cancer with a poor prognosis. It is rare complication of Paget’s. It presents with focal bone pain, bone swelling or pathological fractures. Spinal stenosis may occur where deformity in the spine leads to spinal canal narrowing. Pressure on the spinal nerves can cause neurological signs and symptoms. Spinal stenosis is diagnosed with an MRI scan. It may be treated effectively with bisphosphonates. Surgical intervention may be necessary.