Rheumatology Flashcards

Question

Hydroxychloroquine -what is the adverse effect? -What is recommended for screening?

Answer 1

Hydroxychloroquine is used in the management of rheumatoid arthritis and systemic/discoid lupus erythematosus. It is pharmacologically very similar to chloroquine which is used to treat certain types of malaria. Adverse effects -bull's eye retinopathy - may result in severe and permanent visual loss -recent data suggest that retinopathy caused by hydroxychloroquine is more common than previously thought and the most recent RCOphth guidelines (March 2018) suggest colour retinal photography and spectral domain optical coherence tomography scanning of the macula baseline ophthalmological examination and annual screening is generally recommened

Answer 2

A contrast to many drugs used in rheumatology, hydroxychloroquine may be used if needed in pregnant women. Monitoring the BNF advises: 'Ask patient about visual symptoms and monitor visual acuity annually using the standard reading chart'

Answer 3

Leflunomide is a disease modifying anti-rheumatic drug (DMARD) mainly used in the management of rheumatoid arthritis. It has a very long half-life which should be remembered considering it's teratogenic potential. Contraindications pregnancy - the BNF advises: 'Effective contraception essential during treatment and for at least 2 years after treatment in women and at least 3 months after treatment in men (plasma concentration monitoring required' caution should also be exercised with pre-existing lung and liver disease

Answer 4

Adverse effects -gastrointestinal, especially diarrhoea -hypertension -weight loss/anorexia -peripheral neuropathy -myelosuppression -pneumonitis

Answer 5

Monitoring FBC/LFT and blood pressure Stopping leflunomide has a very long wash-out period of up to a year which requires co-administration of cholestyramine

Answer 6

Methotrexate is an antimetabolite that inhibits dihydrofolate reductase, an enzyme essential for the synthesis of purines and pyrimidines. It is considered an 'important' drug as whilst it can be very effective in controlling disease the side-effects may be potentially life-threatening - careful prescribing and close monitoring is essential. Indications inflammatory arthritis, especially rheumatoid arthritis psoriasis some chemotherapy acute lymphoblastic leukaemia

Answer 7

Adverse effects -mucositis -myelosuppression pneumonitis -the most common pulmonary manifestation similar disease pattern to hypersensitivity pneumonitis secondary to inhaled organic antigens -typically develops within a year of starting treatment, either acutely or subacutely -presents with non-productive cough, dyspnoea, malaise, fever -pulmonary fibrosis -liver fibrosis

Answer 8

Pregnancy women should avoid pregnancy for at least 6 months after treatment has stopped the BNF also advises that men using methotrexate need to use effective contraception for at least 6 months after treatment

Answer 9

Prescribing methotrexate -methotrexate is a drug with a high potential for patient harm. It is therefore important that you are familiar with guidelines relating to its use -methotrexate is taken weekly, rather than daily -FBC, U&E and LFTs need to be regularly monitored. The Committee on Safety of Medicines recommend 'FBC and renal and LFTs before starting treatment and repeated weekly until therapy stabilised, thereafter patients should be monitored every 2-3 months' -folic acid 5mg once weekly should be co-prescribed, taken more than 24 hours after methotrexate dose -the starting dose of methotrexate is 7.5 mg weekly (source: BNF) -only one strength of methotrexate tablet should be prescribed (usually 2.5 mg)

Answer 10

Interactions -avoid prescribing trimethoprim or co-trimoxazole concurrently - increases risk of marrow aplasia -high-dose aspirin increases the risk of methotrexate toxicity secondary to reduced excretion Methotrexate toxicity the treatment of choice is folinic acid

Answer 11

Reactive arthritis is one of the HLA-B27 associated seronegative spondyloarthropathies. It encompasses what was formerly called Reiter's syndrome, a term which described a classic triad of urethritis, conjunctivitis and arthritis following a dysenteric illness during the Second World War. Later studies identified patients who developed symptoms following a sexually transmitted infection (post-STI, now sometimes referred to as sexually acquired reactive arthritis, SARA). Reactive arthritis is defined as an arthritis that develops following an infection where the organism cannot be recovered from the joint.

Answer 12

Features time course typically develops within 4 weeks of initial infection - symptoms generally last around 4-6 months around 25% of patients have recurrent episodes whilst 10% of patients develop chronic disease arthritis is typically an asymmetrical oligoarthritis of lower limbs dactylitis symptoms of urethritis eye conjunctivitis (seen in 10-30%) anterior uveitis skin circinate balanitis (painless vesicles on the coronal margin of the prepuce) keratoderma blenorrhagica (waxy yellow/brown papules on palms and soles)

Answer 13

Psoriatic arthropathy is an inflammatory arthritis associated with psoriasis and is classed as one of the seronegative spondyloarthropathies. It correlates poorly with cutaneous psoriasis and often precedes the development of skin lesions. Around 10-20% of patients with skin lesions develop an arthropathy with males and females being equally affected.

Answer 14

Patterns symmetric polyarthritis -very similar to rheumatoid arthritis -30-40% of cases, most common type asymmetrical oligoarthritis: typically affects hands and feet (20-30%) -until recently it was thought asymmetrical oligoarthritis was the most common type, based on data from the original 1973 Moll and Wright paper. Please see the link for a comparison of more recent studies sacroiliitis DIP joint disease (10%) arthritis mutilans (severe deformity fingers/hand, 'telescoping fingers')

Answer 15

Other signs psoriatic skin lesions periarticular disease - tenosynovitis and soft tissue inflammation resulting in: -enthesitis: inflammation at the site of tendon and ligament insertion e.g. Achilles tendonitis, plantar fascitis -tenosynovitis: typically of the flexor tendons of the hands -dactylitis: diffuse swelling of a finger or toe nail changes pitting onycholysis

Answer 16

Dactylitis describes the inflammation of a digit (finger or toe). Causes include: spondyloarthritis: e.g. Psoriatic and reactive arthritis sickle-cell disease other rare causes include tuberculosis, sarcoidosis and syphilis

Answer 17

X-ray often have the unusual combination of coexistence of erosive changes and new bone formation periostitis 'pencil-in-cup' appearance

Answer 18

Management should be managed by a rheumatologist treatment is similar to that of rheumatoid arthritis (RA). However, the following differences are noted: -mild peripheral arthritis/mild axial disease may be treated with 'just' an NSAID, rather than all patients being on disease-modifying therapy as with RA -if more moderate/severe disease then methotrexate is typically used as in RA -use of monoclonal antibodies such as ustekinumab (targets both IL-12 and IL-23) and secukinumab (targets IL-17) -apremilast: phosphodiesterase type-4 (PDE4) inhibitor → suppression of pro-inflammatory mediator synthesis and promotion of anti-inflammatory mediators -has a better prognosis than RA

Answer 19

Ankylosing spondylitis is a HLA-B27 associated spondyloarthropathy. It typically presents in males (sex ratio 3:1) aged 20-30 years old. Features -typically a young man who presents with lower back pain and stiffness of insidious onset -stiffness is usually worse in the morning and improves with exercise -the patient may experience pain at night which improves on getting up

Answer 20

Clinical examination -reduced lateral flexion -reduced forward flexion - Schober's test - a line is drawn 10 cm above and 5 cm below the back dimples (dimples of Venus). The distance between the two lines should increase by more than 5 cm when the patient bends as far forward as possible -reduced chest expansion

Answer 21

Other features - the 'A's -Apical fibrosis -Anterior uveitis -Aortic regurgitation -Achilles tendonitis -AV node block -Amyloidosis and cauda equina syndrome peripheral arthritis (25%, more common if female)

Answer 22

Inflammatory markers (ESR, CRP) are typically raised although normal levels do not exclude ankylosing spondylitis. HLA-B27 is of little use in making the diagnosis as it is positive in: 90% of patients with ankylosing spondylitis 10% of normal patients

Answer 23

Plain x-ray of the sacroiliac joints is the most useful investigation in establishing the diagnosis. Radiographs may be normal early in disease, later changes include: -sacroiliitis: subchondral erosions, sclerosis squaring of lumbar vertebrae -'bamboo spine' (late & uncommon) -syndesmophytes: due to ossification of outer fibers of annulus fibrosus -chest x-ray: apical fibrosis

Answer 24

If the x-ray is negative for sacroiliac joint involvement in ankylosing spondylitis but suspicion for AS remains high, the next step in the evaluation should be obtaining an MRI. Signs of early inflammation involving sacroiliac joints (bone marrow oedema) confirm the diagnosis of AS and prompt further treatment. Spirometry may show a restrictive defect due to a combination of pulmonary fibrosis, kyphosis and ankylosis of the costovertebral joints.

Answer 25

Systemic lupus erythematosus (SLE) is a multisystem, autoimmune disorder. It typically presents in early adulthood and is more common in women and people of Afro-Caribbean origin. General features fatigue fever mouth ulcers lymphadenopathy

Answer 26

Skin -malar (butterfly) rash: spares nasolabial folds -discoid rash: scaly, erythematous, well demarcated rash in sun-exposed areas. Lesions may progress to become pigmented and hyperkeratotic before becoming atrophic -photosensitivity -Raynaud's phenomenon -livedo reticularis -non-scarring alopecia

Answer 27

Musculoskeletal arthralgia non-erosive arthritis

Answer 28

Cardiovascular pericarditis: the most common cardiac manifestation myocarditis Respiratory pleurisy fibrosing alveolitis

Answer 29

Renal proteinuria glomerulonephritis (diffuse proliferative glomerulonephritis is the most common type) Neuropsychiatric anxiety and depression psychosis seizures

Answer 30

Antibodies 99% are ANA positive this high sensitivity makes it a useful rule out test, but it has low specificity 20% are rheumatoid factor positive anti-dsDNA: highly specific (> 99%), but less sensitive (70%) anti-Smith: highly specific (> 99%), sensitivity (30%) also: anti-U1 RNP, SS-A (anti-Ro) and SS-B (anti-La)

Answer 31

Monitoring inflammatory markers -ESR is generally used -during active disease the CRP may be normal - a raised CRP may indicate underlying infection complement levels (C3, C4) are low during active disease (formation of complexes leads to consumption of complement) anti-dsDNA titres can be used for disease monitoring (but note not present in all patients)

Answer 32

Discoid lupus erythematosus is a benign disorder generally seen in younger females. It very rarely progresses to systemic lupus erythematosus (in less than 5% of cases). Discoid lupus erythematosus is characterised by follicular keratin plugs and is thought to be autoimmune in aetiology

Answer 33

Features -erythematous, raised rash, sometimes scaly -may be photosensitive -more common on face, neck, ears and scalp -lesions heal with atrophy, scarring (may cause scarring alopecia), and pigmentation

Answer 34

Management -topical steroid cream -oral antimalarials may be used second-line e.g. hydroxychloroquine -avoid sun exposure

Answer 35

In drug-induced lupus not all the typical features of systemic lupus erythematosus are seen, with renal and nervous system involvement being unusual. It usually resolves on stopping the drug.

Answer 36

Features -arthralgia -myalgia -skin (e.g. malar rash) and pulmonary involvement (e.g. pleurisy) are common -ANA positive in 100%, dsDNA negative -anti-histone antibodies are found in 80-90% -anti-Ro, anti-Smith positive in around 5%

Answer 37

Most common causes procainamide hydralazine Less common causes isoniazid minocycline phenytoin

Answer 38

Antiphospholipid syndrome is an acquired disorder characterised by a predisposition to both venous and arterial thromboses, recurrent fetal loss and thrombocytopenia. It may occur as a primary disorder or secondary to other conditions, most commonly systemic lupus erythematosus (SLE). Around 30% of patients with SLE have positive antiphospholipid antibodies. A key point for the exam is to appreciate that antiphospholipid syndrome causes a paradoxical rise in the APTT. This is due to an ex-vivo reaction of the lupus anticoagulant autoantibodies with phospholipids involved in the coagulation cascade.

Answer 39

Associations other than SLE -other autoimmune disorders -lymphoproliferative disorders -phenothiazines (rare) Features -venous/arterial thrombosis -recurrent miscarriages -livedo reticularis -other features: pre-eclampsia, pulmonary hypertension

Answer 40

Investigations antibodies -anticardiolipin antibodies -anti-beta2 glycoprotein I (anti-beta2GPI) antibodies -lupus anticoagulant thrombocytopenia prolonged APTT

Answer 41

Management - based on EULAR guidelines primary thromboprophylaxis -low-dose aspirin secondary thromboprophylaxis -initial venous thromboembolic events: lifelong warfarin with a target INR of 2-3 -recurrent venous thromboembolic events: lifelong warfarin; if occurred whilst taking warfarin then consider adding low-dose aspirin, increase target INR to 3-4 -arterial thrombosis should be treated with lifelong warfarin with target INR 2-3

Answer 42

Polymyalgia rheumatica (PMR) is a relatively common condition seen in older people characterised by muscle stiffness and raised inflammatory markers. Whilst it appears to be closely related to temporal arteritis the underlying cause is not fully understood and it does not appear to be a vasculitic process.

Answer 43

Features -typically patient > 60 years old -usually rapid onset (e.g. < 1 month) -aching, morning stiffness in proximal limb muscles -weakness is not considered a symptom of polymyalgia rheumatica -also mild polyarthralgia, lethargy, depression, low-grade fever, anorexia, night sweats

Answer 44

Investigations raised inflammatory markers e.g. ESR > 40 mm/hr note creatine kinase and EMG normal Treatment prednisolone e.g. 15mg/od patients typically respond dramatically to steroids, failure to do so should prompt consideration of an alternative diagnosis

Answer 45

Overview -inflammatory disorder causing symmetrical, proximal muscle weakness -thought to be a T-cell mediated cytotoxic process directed against muscle fibres -may be idiopathic or associated with connective tissue disorders -associated with malignancy -dermatomyositis is a variant of the disease where skin manifestations are prominent, for example a purple (heliotrope) rash on the cheeks and eyelids typically affects middle-aged, female:male 3:1

Answer 46

Features -proximal muscle weakness +/- tenderness -Raynaud's -respiratory muscle weakness -interstitial lung disease e.g. fibrosing alveolitis or organising pneumonia seen in around 20% of patients and indicates a poor prognosis -dysphagia, dysphonia

Answer 47

Investigations -elevated creatine kinase -other muscle enzymes (lactate dehydrogenase (LDH), aldolase, AST and ALT) are also elevated in 85-95% of patients -EMG -muscle biopsy -anti-synthetase antibodies anti-Jo-1 antibodies are seen in pattern of disease associated with lung involvement, Raynaud's and fever

Answer 48

Management high-dose corticosteroids tapered as symptoms improve azathioprine may be used as a steroid-sparing agent

Answer 49

Overview -an inflammatory disorder causing symmetrical, proximal muscle weakness and characteristic skin lesions -may be idiopathic or associated with connective tissue disorders or underlying malignancy (typically ovarian, breast and lung cancer, found in 20-25% - more if patient older). Screening for an underlying malignancy is usually performed following a diagnosis of dermatomyositis -polymyositis is a variant of the disease where skin manifestations are not prominent

Answer 50

Skin features -photosensitive -macular rash over back and shoulder -heliotrope rash in the periorbital region -Gottron's papules - roughened red papules over extensor surfaces of fingers -'mechanic's hands': extremely dry and scaly hands with linear 'cracks' on the palmar and lateral aspects of the fingers -nail fold capillary dilatation

Answer 51

Other features -proximal muscle weakness +/- tenderness -Raynaud's -respiratory muscle weakness -interstitial lung disease: e.g. Fibrosing alveolitis or organising pneumonia -dysphagia, dysphonia

Answer 52

Investigations -the majority of patients (around 80%) are ANA positive around 30% of patients have antibodies to aminoacyl-tRNA synthetases (anti-synthetase antibodies), including: -antibodies against histidine-tRNA ligase (also called Jo-1) -antibodies to signal recognition particle (SRP) -anti-Mi-2 antibodies

Answer 53

Systemic sclerosis is a condition of unknown aetiology characterised by hardened, sclerotic skin and other connective tissues. It is four times more common in females.

Answer 54

Limited cutaneous systemic sclerosis Diffuse cutaneous systemic sclerosis Scleroderma

Answer 55

-Raynaud's may be the first sign -scleroderma affects face and distal limbs predominately -associated with anti-centromere antibodies -a subtype of limited systemic sclerosis is CREST syndrome: Calcinosis, Raynaud's phenomenon, oEsophageal dysmotility, Sclerodactyly, Telangiectasia

Answer 56

Diffuse cutaneous systemic sclerosis -scleroderma affects trunk and proximal limbs predominately -associated with anti scl-70 antibodies -the most common cause of death is now respiratory involvement, which is seen in around 80%: interstitial lung disease (ILD) and pulmonary arterial hypertension (PAH) -other complications include renal disease and hypertension -patients with renal disease should be started on an ACE inhibitor -poor prognosis

Answer 57

Scleroderma (without internal organ involvement) tightening and fibrosis of skin may be manifest as plaques (morphoea) or linear

Answer 58

Antibodies -ANA positive in 90% -RF positive in 30% -anti-scl-70 antibodies associated with diffuse cutaneous systemic sclerosis associated with a higher risk of severe interstitial lung disease -anti-centromere antibodies associated with limited cutaneous systemic sclerosis

Answer 59

Raynaud's phenomenon is characterised by an exaggerated vasoconstrictive response of the digital arteries and cutaneous arteriole to the cold or emotional stress. It may be primary (Raynaud's disease) or secondary (Raynaud's phenomenon). Raynaud's disease typically presents in young women (e.g. 30 years old) with bilateral symptoms.

Answer 60

Secondary causes of Raynaud's phenomenon -connective tissue disorders: scleroderma (most common), rheumatoid arthritis, systemic lupus erythematosus -leukaemia -type I cryoglobulinaemia, cold agglutinins -use of vibrating tools -drugs: oral contraceptive pill, ergot -cervical rib

Answer 61

Factors suggesting underlying connective tissue disease -onset after 40 years -unilateral symptoms -rashes -presence of autoantibodies -features which may suggest rheumatoid arthritis or SLE, for example arthritis or recurrent miscarriages -digital ulcers, calcinosis -very rarely: chilblains

Answer 62

Management all patients with suspected secondary Raynaud's phenomenon should be referred to secondary care first-line: calcium channel blockers e.g. nifedipine IV prostacyclin (epoprostenol) infusions: effects may last several weeks/months

Answer 63

Sjogren's syndrome is an autoimmune disorder affecting exocrine glands resulting in dry mucosal surfaces. It may be primary (PSS) or secondary to rheumatoid arthritis or other connective tissue disorders, where it usually develops around 10 years after the initial onset. Sjogren's syndrome is much more common in females (ratio 9:1). There is a marked increased risk of lymphoid malignancy (40-60 fold).

Answer 64

Features -dry eyes: keratoconjunctivitis sicca -dry mouth -vaginal dryness -arthralgia -Raynaud's, myalgia -sensory polyneuropathy -recurrent episodes of parotitis -renal tubular acidosis (usually subclinical)

Answer 65

Investigation -rheumatoid factor (RF) positive in nearly 50% of patients -ANA positive in 70% -anti-Ro (SSA) antibodies in 70% of patients with PSS -anti-La (SSB) antibodies in 30% of patients with PSS -Schirmer's test: filter paper near conjunctival sac to measure tear formation -histology: focal lymphocytic infiltration -also: hypergammaglobulinaemia, low C4

Answer 66

Management artificial saliva and tears pilocarpine may stimulate saliva production

Answer 67

Anti-neutrophil cytoplasmic antibodies (ANCA) are important as they are associated with a number of small-vessel vasculitides, including: -granulomatosis with polyangiitis -eosinophilic granulomatosis with polyangiitis (Churg-Strauss syndrome) -microscopic polyangiitis

Answer 68

ANCA associated vasculitis is more common with increasing age. Whilst each condition has its own distinct features, there are a number of common findings: -renal impairment caused by immune complex glomerulonephritis → raised creatinine, haematuria and proteinuria -respiratory symptoms dyspnoea haemoptysiis -systemic symptoms fatigue weight loss fever vasculitic rash: present only in a minority of patients ear, nose and throat symptoms -sinusitis

Answer 69

General approach to first-line investigations: -urinalysis for haematuria and proteinuria bloods: -urea and creatinine for renal impairment -full blood count: normocytic anaemia and thrombocytosis may be seen -CRP: raised -ANCA testing -chest x-ray: nodular, fibrotic or infiltrative lesions may be seen

Answer 70

There are two main types of ANCA - cytoplasmic (cANCA) and perinuclear (pANCA). There is considerable overlap between which antibodies are found in which condition, but as a rule of thumb: cANCA - granulomatosis with polyangiitis pANCA - eosinophilic granulomatosis with polyangiitis + others (see below)

Answer 71

cANCA - serine proteinase 3 PR3 pANCA - myeloperoxidase MPO

Answer 72

-Some correlation between cANCA levels and disease activity -Cannot use level of pANCA to monitor disease activity

Answer 73

Granulomatosis with polyangiitis - cANCA 90%, pANCA 25% eosinophilic granulomatosis with polyangiits -cANCA low, pANCA 50% Microscopic polyangiitis -cANCA 40%, pANCA 75% UC pANCA 70% PSC pANCA 70% Anti-GBM disease pANCA 25% Crohns disease pANCA 20%

Answer 74

Once suspected, ANCA associated vasculitis should be managed by specialist teams (e.g. renal, rheumatology, respiratory) to allow an exact diagnosis to be made. Kidney or lung biopsies may be taken to aid the diagnosis. The mainstay of management is immunosuppressive therapy.

Answer 75

Temporal arteritis (also known as giant cell arteritis: GCA) is a vasculitis of unknown cause that affects medium and large-sized vessels arteries. It occurs in those over 50 years old, with a peak incidence in patients who are in their 70s. It requires early recognition and treatment to minimize the risk of complications such as permanent loss of vision. Hence, when temporal arteritis is suspected, treatment must be started promptly with high-dose prednisolone as well as urgent referral for assessment by a specialist. There is an overlap between temporal arteritis and polymyalgia rheumatica (PMR) - around 50% of patients will have features of PMR.

Answer 76

Features -typically patient > 60 years old -usually rapid onset (e.g. < 1 month) -headache (found in 85%) -jaw claudication (65%) -vision testing is a key investigation in all patients anterior ischemic optic neuropathy accounts for the majority of ocular complications. It results from occlusion of the posterior ciliary artery (a branch of the ophthalmic artery) → ischaemia of the optic nerve head. Fundoscopy typically shows a swollen pale disc and blurred margins -may result in temporary visual loss - amaurosis fugax -permanent visual loss is the most feared complication of temporal arteritis and may develop suddenly -diplopia may also result from the involvement of any part of the oculomotor system (e.g. cranial nerves) -tender, palpable temporal artery around 50% have features of -PMR: aching, morning stiffness in proximal limb muscles (not weakness) -also lethargy, depression, low-grade fever, anorexia, night sweats

Answer 77

Investigations raised inflammatory markers ESR > 50 mm/hr (note ESR < 30 in 10% of patients) CRP may also be elevated temporal artery biopsy skip lesions may be present note creatine kinase and EMG normal

Answer 78

Treatment -urgent high-dose glucocorticoids should be given as soon as the diagnosis is suspected and before the temporal artery biopsy -if there is no visual loss then high-dose prednisolone is used if there is evolving visual loss IV methylprednisolone is usually given prior to starting high-dose prednisolone -there should be a dramatic response, if not the diagnosis should be reconsidered urgent ophthalmology review patients with visual symptoms should be seen the same-day by an ophthalmologist visual damage is often irreversible other treatments -bone protection with bisphosphonates is required as long, tapering course of steroids is required -low-dose aspirin is sometimes given to patients as well, although the evidence base supporting this is weak

Answer 79

Behcet's syndrome is a complex multisystem disorder associated with presumed autoimmune-mediated inflammation of the arteries and veins. The precise aetiology has yet to be elucidated however. The classic triad of symptoms are oral ulcers, genital ulcers and anterior uveitis

Answer 80

Epidemiology -more common in the eastern Mediterranean (e.g. Turkey) -more common in men (complicated gender distribution which varies according to country. Overall, Behcet's is considered to be more common and more severe in men) -tends to affect young adults (e.g. 20 - 40 years old) -associated with HLA B51 -around 30% of patients have a positive family history

Answer 81

Features -classically: 1) oral ulcers 2) genital ulcers 3) anterior uveitis thrombophlebitis and deep vein thrombosis -arthritis -neurological involvement (e.g. aseptic meningitis) -GI: abdo pain, diarrhoea, colitis erythema nodosum

Answer 82

Diagnosis -no definitive test -diagnosis based on clinical findings -positive pathergy test is suggestive (puncture site following needle prick becomes inflamed with small pustule forming)

Answer 83

Polyarteritis nodosa (PAN) is a vasculitis affecting medium-sized arteries with necrotizing inflammation leading to aneurysm formation. PAN is more common in middle-aged men and is associated with hepatitis B infection.

Answer 84

Features -fever, malaise, arthralgia -weight loss -hypertension -mononeuritis multiplex, sensorimotor polyneuropathy -testicular pain -livedo reticularis -haematuria, renal failure -perinuclear-antineutrophil cytoplasmic antibodies (ANCA) are found in around 20% of patients with 'classic' PAN -hepatitis B serology positive in 30% of patients

Answer 85

Features symmetrical muscle weakness (proximal > distal) common problems are rising from chair or getting out of bath sensation normal, reflexes normal, no fasciculation

Answer 86

Causes -inflammatory: polymyositis -inherited: Duchenne/Becker muscular dystrophy, myotonic dystrophy -endocrine: Cushing's, thyrotoxicosis alcohol

Answer 87

Diagnosed after at least 3 months of disabling fatigue affecting mental and physical function more than 50% of the time in the absence of other disease which may explain symptoms Epidemiology more common in females past psychiatric history has not been shown to be a risk factor

Answer 88

Fatigue is the central feature, other recognised features include -sleep problems, such as insomnia, hypersomnia, unrefreshing sleep, a disturbed sleep-wake cycle -muscle and/or joint pains -headaches -painful lymph nodes without enlargement -sore throat -cognitive dysfunction, such as difficulty thinking, inability to concentrate, impairment of short-term memory, and difficulties with word-finding -physical or mental exertion makes symptoms worse -general malaise or 'flu-like' symptoms -dizziness -nausea -palpitations

Answer 89

Investigation NICE guidelines suggest carrying out a large number of screening blood tests to exclude other pathology e.g. FBC, U&E, LFT, glucose, TFT, ESR, CRP, calcium, CK, ferritin, coeliac screening and also urinalysis Diagnosis NICE publish diagnostic criteria NICE a diagnosis is typically made if the symptoms persist for 3 months

Answer 90

Management refer to a specialist CFS service if the diagnostic criteria are met and symptoms have persisted for 3 months energy management a self-management strategy that involves a person with ME/CFS managing their activities to stay within their energy limit, with support from a healthcare professional physical activity and exercise do not advise people with ME/CFS to undertake exercise that is not part of a programme overseen by an ME/CFS specialist team should only be recommended if patients 'feel ready to progress their physical activity beyond their current activities of daily living' graded exercise therapy used to be recommended but is now specifically not recommended by NICE cognitive behavioural therapy NICE stress this is 'supportive' rather than curative for CFS

Answer 91

Fibromyalgia is a syndrome characterised by widespread pain throughout the body with tender points at specific anatomical sites. The cause of fibromyalgia is unknown. Epidemiology women are around 5 times more likely to be affected typically presents between 30-50 years old Features chronic pain: at multiple site, sometimes 'pain all over' lethargy cognitive impairment: 'fibro fog' sleep disturbance, headaches, dizziness are common

Answer 92

Diagnosis is clinical and sometimes refers to the American College of Rheumatology classification criteria which lists 9 pairs of tender points on the body. If a patient is tender in at least 11 of these 18 points it makes a diagnosis of fibromyalgia more likely

Answer 93

The management of fibromyalgia is often difficult and needs to be tailored to the individual patient. A psychosocial and multidisciplinary approach is helpful. Unfortunately there is currently a paucity of evidence and guidelines to guide practice. The following is partly based on consensus guidelines from the European League against Rheumatism (EULAR) published in 2007 and also a BMJ review in 2014. explanation aerobic exercise: has the strongest evidence base cognitive behavioural therapy medication: pregabalin, duloxetine, amitriptyline

Answer 94

Ehler-Danlos syndrome is an autosomal dominant connective tissue disorder that mostly affects type III collagen. This results in the tissue being more elastic than normal leading to joint hypermobility and increased elasticity of the skin.

Answer 95

Features and complications -elastic, fragile skin -joint hypermobility: recurrent joint dislocation -easy bruising -aortic regurgitation, mitral valve prolapse and aortic dissection -subarachnoid haemorrhage -angioid retinal streaks

Answer 96

Osteogenesis imperfecta (more commonly known as brittle bone disease) is a group of disorders of collagen metabolism resulting in bone fragility and fractures. The most common, and milder, form of osteogenesis imperfecta is type 1 Overview autosomal dominant abnormality in type 1 collagen due to decreased synthesis of pro-alpha 1 or pro-alpha 2 collagen polypeptides

Answer 97

Features -presents in childhood -fractures following minor trauma -blue sclera -deafness secondary to otosclerosis -dental imperfections are common Investigations adjusted calcium, phosphate, parathyroid hormone and ALP results are usually normal in osteogenesis imperfecta

Answer 98

Paget's disease is a disease of increased but uncontrolled bone turnover. It is thought to be primarily a disorder of osteoclasts, with excessive osteoclastic resorption followed by increased osteoblastic activity. Paget's disease is common (UK prevalence 5%) but symptomatic in only 1 in 20 patients. The skull, spine/pelvis, and long bones of the lower extremities are most commonly affected. Predisposing factors increasing age male sex northern latitude family history

Answer 99

Clinical features - only 5% of patients are symptomatic -the stereotypical presentation is an older male with bone pain and an isolated raised ALP -bone pain (e.g. pelvis, lumbar spine, femur) -classical, untreated features: bowing of tibia, bossing of skull

Answer 100

Investigations bloods -raised alkaline phosphatase (ALP) -calcium and phosphate are typically normal. Hypercalcaemia may occasionally occur with prolonged immobilisation other markers of bone turnover include -procollagen type I N-terminal propeptide (PINP) -serum C-telopeptide (CTx) -urinary N-telopeptide (NTx) -urinary hydroxyproline x-rays -osteolysis in early disease → mixed lytic/sclerotic lesions later -skull x-ray: thickened vault, osteoporosis circumscripta bone scintigraphy -increased uptake is seen focally at the sites of active bone lesions

Answer 101

Management indications for treatment include bone pain skull or long bone deformity fracture periarticular Paget's bisphosphonate (either oral risedronate or IV zoledronate) calcitonin is less commonly used now

Answer 102

Complications -deafness (cranial nerve entrapment) -bone sarcoma (1% if affected for > 10 years) -fractures -skull thickening -high-output cardiac failure

Answer 103

Osteomalacia describes softening of the bones secondary to low vitamin D levels that in turn lead to decreased bone mineral content. If this occurs in growing children it is referred to as rickets, with the term osteomalacia preferred for adults.

Answer 104

Causes -vitamin D deficiency malabsorption lack of sunlight diet -chronic kidney disease -drug induced e.g. anticonvulsants -inherited: hypophosphatemic rickets (previously called vitamin D-resistant rickets) -liver disease: e.g. cirrhosis -coeliac disease

Answer 105

Features -bone pain -bone/muscle tenderness -fractures: especially femoral neck -proximal myopathy: may lead to a waddling gait

Answer 106

Investigation -bloods low vitamin D levels low calcium, phosphate (in around 30%) raised alkaline phosphatase (in 95-100% of patients) -x-ray translucent bands (Looser's zones or pseudofractures)

Answer 107

Treatment -vitamin D supplmentation a loading dose is often needed initially -calcium supplementation if dietary calcium is inadequate

Answer 108

Advancing age and female sex are significant risk factors for osteoporosis. The prevalence of osteoporosis increases from 2% at 50 years to more than 25% at 80 years in women. There are many other risk factors and secondary causes of osteoporosis. We'll start by looking at the most 'important' ones - these are risk factors that are used by major risk assessment tools such as FRAX: history of glucocorticoid use rheumatoid arthritis alcohol excess history of parental hip fracture low body mass index current smoking

Answer 109

Other risk factors -sedentary lifestyle -premature menopause -Caucasians and Asians endocrine disorders: -hyperthyroidism, hypogonadism (e.g. Turner's, testosterone deficiency), growth hormone deficiency, hyperparathyroidism, -diabetes mellitus -multiple myeloma, lymphoma gastrointestinal disorders: -inflammatory bowel disease, -malabsorption (e.g. coeliac's), gastrectomy, liver disease chronic kidney disease osteogenesis imperfecta, homocystinuria

Answer 110

Medications that may worsen osteoporosis (other than glucocorticoids): -SSRIs -antiepileptics -proton pump inhibitors -glitazones -long term heparin therapy -aromatase inhibitors e.g. anastrozole

Answer 111

we should order the following bloods as a minimum for all patients: -full blood count -urea and electrolytes -liver function tests -bone profile -CRP -thyroid function tests

Answer 112

The risk of osteoporosis is thought to rise significantly once a patient is taking the equivalent of prednisolone 7.5mg a day for 3 or more months. It is important to note that we should manage patients in an anticipatory, i.e. if it likely that the patient will have to take steroids for at least 3 months then we should start bone protection straight away, rather than waiting until 3 months has elapsed. A good example is a patient with newly diagnosed polymyalgia rheumatica. As it is very likely they will be on a significant dose of prednisolone for greater than 3 months bone protection should be commenced immediately.

Answer 113

The RCP guidelines essentially divide patients into two groups. 1. Patients over the age of 65 years or those who've previously had a fragility fracture should be offered bone protection. 2. Patients under the age of 65 years should be offered a bone density scan, with further management dependent: T score Management Greater than 0 Reassure Between 0 and -1.5 Repeat bone density scan in 1-3 years Less than -1.5 Offer bone protection The first-line treatment is alendronate. Patients should also be calcium and vitamin D replete.

Answer 114

Basics T score: based on bone mass of young reference population T score of -1.0 means bone mass of one standard deviation below that of young reference population Z score is adjusted for age, gender and ethnic factors T score > -1.0 = normal -1.0 to -2.5 = osteopaenia < -2.5 = osteoporosis

Answer 115

Patients >= 75 years of age Patients who've had a fragility fracture and are >= 75 years of age are presumed to have underlying osteoporosis and should be started on first-line therapy (an oral bisphosphonate), without the need for a DEXA scan. It should be noted that the 2014 NOGG guidelines have a different threshold, suggesting treatment is started in all women over the age of 50 years who've had a fragility fracture - 'although BMD measurement may sometimes be appropriate, particularly in younger postmenopausal women.'

Answer 116

If a patient is under the age of 75 years a DEXA scan should be arranged. These results can then be entered into a FRAX assessment (along with the fact that they've had a fracture) to determine the patients ongoing fracture risk.

Answer 117

Key points include treatment is indicated following osteoporotic fragility fractures in postmenopausal women who are confirmed to have osteoporosis (a T-score of - 2.5 SD or below). In women aged 75 years or older, a DEXA scan may not be required 'if the responsible clinician considers it to be clinically inappropriate or unfeasible' vitamin D and calcium supplementation should be offered to all women unless the clinician is confident they have adequate calcium intake and are vitamin D replete alendronate is first-line around 25% of patients cannot tolerate alendronate, usually due to upper gastrointestinal problems. These patients should be offered risedronate or etidronate strontium ranelate and raloxifene are recommended if patients cannot tolerate bisphosphonates

Answer 118

the T-score criteria for risedronate or etidronate are less than the others implying that these are the second line drugs if alendronate, risedronate or etidronate cannot be taken then strontium ranelate or raloxifene may be given based on quite strict T-scores (e.g. a 60-year-old woman would need a T-score < -3.5) the strictest criteria are for denosumab

Answer 119

Raloxifene - selective oestrogen receptor modulator (SERM) has been shown to prevent bone loss and to reduce the risk of vertebral fractures, but has not yet been shown to reduce the risk of non-vertebral fractures has been shown to increase bone density in the spine and proximal femur may worsen menopausal symptoms increased risk of thromboembolic events may decrease risk of breast cancer

Answer 120

Strontium ranelate 'dual action bone agent' - increases deposition of new bone by osteoblasts (promotes differentiation of pre-osteoblast to osteoblast) and reduces the resorption of bone by inhibiting osteoclasts concerns regarding the safety profile of strontium have been raised recently. It should only be prescribed by a specialist in secondary care due to these concerns the European Medicines Agency in 2014 said it should only be used by people for whom there are no other treatments for osteoporosis increased risk of cardiovascular events: any history of cardiovascular disease or significant risk of cardiovascular disease is a contraindication increased risk of thromboembolic events: a Drug Safety Update in 2012 recommended it is not used in patients with a history of venous thromboembolism may cause serious skin reactions such as Stevens Johnson syndrome

Answer 121

Denosumab human monoclonal antibody that inhibits RANK ligand, which in turn inhibits the maturation of osteoclasts given as a single subcutaneous injection every 6 months initial trial data suggests that it is effective and well tolerated Denosumab is a relatively new treatment for osteoporosis. It is a human monoclonal antibody that prevents the development of osteoclasts by inhibiting RANKL. Remember that osteoblasts build bone, osteoclasts eat bone. It is given as a subcutaneous injection, at a dose of 60mg, every 6 months. A larger dose of denosumab (120mg) may also be given every 4 weeks for the prevention of skeletal-related events (i.e. pathological fractures) in adults with bone metastases from solid tumours. For example, you may have noticed some of your breast cancer patients have been prescribed denosumab.

Answer 122

Denosumab is generally well tolerated. Dyspnoea and diarrhoea are generally considered the two most common side effects, occuring in around 1 in 10 patients. Other less common side effects include hypocalcaemia and upper respiratory tract infections. What does the Drug Safety Update add? Cases of atypical femoral fractures have been noted in patients taking denosumab. Doctors are advised to look out for patients complaining of unusual thigh, hip or groin pain.

Answer 123

Teriparatide recombinant form of parathyroid hormone very effective at increasing bone mineral density but role in the management of osteoporosis yet to be clearly defined

Answer 124

Hormone replacement therapy has been shown to reduce the incidence of vertebral fracture and non-vertebral fractures due to concerns about increased rates of cardiovascular disease and breast cancer it is no longer recommended for primary or secondary prevention of osteoporosis unless the woman is suffering from vasomotor symptoms Hip protectors evidence to suggest significantly reduce hip fractures in nursing home patients compliance is a problem Falls risk assessment no evidence to suggest reduced fracture rates however, do reduce rate of falls and should be considered in management of high risk patients

Answer 125

The general consensus is that patients do not require assessment of bone mineral density once bone protection has been started. This is partly because there is limited evidence of any link between improvement in bone mineral density and reduction in fracture risk. With respect to length of treatment, the NOGG state the following in their patient-information leaflet (more detail seems to be given here than the guidelines aimed at healthcare professionals!) A treatment review is recommended after 5 years of treatment for alendronate, risedronate or ibandronate and after 3 years for zoledronic acid. The review is likely to involve a recalculation of your fracture risk and a DXA scan.

Answer 126

Bisphosphonates are analogues of pyrophosphate, a molecule which decreases demineralisation in bone. They inhibit osteoclasts by reducing recruitment and promoting apoptosis. Clinical uses prevention and treatment of osteoporosis hypercalcaemia Paget's disease pain from bone metatases

Answer 127

Adverse effects -oesophageal reactions: oesophagitis, oesophageal ulcers (especially alendronate) -osteonecrosis of the jaw -substantially greater risk for patients receiving IV bisphosphonates in the treatment of cancer than for patients receiving oral bisphosphonates for osteoporosis or Paget’s disease -poor dental hygiene/prior dental procedures are also a risk factor increased risk of atypical stress fractures of the proximal femoral shaft in patients taking alendronate acute phase response: fever, myalgia and arthralgia may occur following administration hypocalcaemia: due to reduced calcium efflux from bone. Usually clinically unimportant

Answer 128

The BNF suggests the following counselling for patients taking oral bisphosphonates 'Tablets should be swallowed whole with plenty of water while sitting or standing; to be given on an empty stomach at least 30 minutes before breakfast (or another oral medication); patient should stand or sit upright for at least 30 minutes after taking tablet

Answer 129

Hypocalcemia/vitamin D deficiency should be corrected before giving bisphosphonates. However, when starting bisphosphonate treatment for osteoporosis, calcium should only be prescribed if dietary intake is inadequate. Vitamin D supplements are normally given. The duration of bisphosphonate treatment varies according to the level of risk. Some authorities recommend stopping bisphosphonates at 5 years if the following apply: patient is < 75-years-old femoral neck T-score of > -2.5 low risk according to FRAX/NOGG

Answer 130

benign 'overgrowth' of bone, most typically occuring on the skull associated with Gardner's syndrome (a variant of familial adenomatous polyposis, FAP)

Answer 131

most common benign bone tumour more in males, usually diagnosed in patients aged < 20 years cartilage-capped bony projection on the external surface of a bone

Answer 132

tumour of multinucleated giant cells within a fibrous stroma peak incidence: 20-40 years occurs most frequently in the epiphyses of long bones X-ray shows a 'double bubble' or 'soap bubble' appearance

Answer 133

most common primary malignant bone tumour seen mainly in children and adolescents occurs most frequently in the metaphyseal region of long bones prior to epiphyseal closure, with 40% occuring in the femur, 20% in the tibia, and 10% in the humerus x-ray shows Codman triangle (from periosteal elevation) and 'sunburst' pattern mutation of the Rb gene significantly increases risk of osteosarcoma (hence association with retinoblastoma) other predisposing factors include Paget's disease of the bone and radiotherapy

Answer 134

small round blue cell tumour seen mainly in children and adolescents occurs most frequently in the pelvis and long bones. Tends to cause severe pain associated with t(11;22) translocation which results in an EWS-FLI1 gene product x-ray shows 'onion skin' appearance

Answer 135

malignant tumour of cartilage most commonly affects the axial skeleton more common in middle-age

Answer 136

Ca -N Phos - N ALP - N PTH - N

Answer 137

Ca -low Phos - low ALP - high PTH - high

Answer 138

Ca -high Phos - low ALP - high PTH - high

Answer 139

Ca -low Phos - high ALP - high PTH - high

Answer 140

Ca -N Phos - N ALP - high PTH - N

Answer 141

Ca -N Phos - N ALP - N PTH - N

Answer 142

Loss of joint space Osteophytes forming at joint margins Subchondral sclerosis Subchondral cysts

Answer 143

NICE updated its guidelines on the management of osteoarthritis (OA) in 2022 -all patients should be offered help with weight loss, given advice about local muscle strengthening exercises and general aerobic fitness -topical NSAIDs are first-line analgesics. Topical NSAIDs may be particualrly beneficial for patients with OA of the knee or hand NICE -second-line treatment is oral NSAIDs -a proton pump inhibitor should be co-prescribed with NSAIDs these drugs should be avoided if the patient takes aspirin NICE recommend we do not offer paracetamol or weak opioids, unless: NICE -they are only used infrequently for short-term pain relief and -all other pharmacological treatments are contraindicated, not tolerated or ineffective glucosamine and strong opioids are not recommended -non-pharmacological treatment options include walking aids for knee and hip OA -intra-articular steroid injections may be tried if standard pharmacological treatment is ineffective patients should be aware that they only provide short-term relief (2-10 weeks) if conservative methods fail then refer for consideration of joint replacement

Answer 144

Uric acid NICE recommends measuring uric acid levels in suspected gout (i.e. in the acute setting) a uric acid level ≥ 360 umol/L is seen as supporting a diagnosis if uric acid level < 360 umol/L during a flare and gout is strongly suspected, repeat the uric acid level measurement at least 2 weeks after the flare has settled

Answer 145

Synovial fluid analysis needle shaped negatively birefringent monosodium urate crystals under polarised light Radiological features of gout include: -joint effusion is an early sign -well-defined 'punched-out' erosions with sclerotic margins in a juxta-articular distribution, often with overhanging edges -relative preservation of joint space until late disease -eccentric erosions -no periarticular osteopenia (in contrast to rheumatoid arthritis) -soft tissue tophi may be seen

Answer 146

Acute management -NSAIDs or colchicine are first-line the maximum dose of NSAID should be prescribed until 1-2 days after the symptoms have settled gastroprotection (e.g. a proton pump inhibitor) may also be indicated -colchicine inhibits microtubule polymerization by binding to tubulin, interfering with mitosis. Also inhibits neutrophil motility and activity has a slower onset of action may be used with caution in renal impairment: the BNF advises to reduce the dose if eGFR is 10-50 ml/min and to avoid if eGFR < 10 ml/min BNF the main side-effect is diarrhoea -oral steroids may be considered if NSAIDs and colchicine are contraindicated. a dose of prednisolone 15mg/day is usually used -another option is intra-articular steroid injection -if the patient is already taking allopurinol it should be continued

Answer 147

Indications for urate-lowering therapy (ULT) the British Society of Rheumatology Guidelines now advocate offering urate-lowering therapy to all patients after their first attack of gout ULT is particularly recommended if: ->= 2 attacks in 12 months -tophi -renal disease -uric acid renal stones -prophylaxis if on cytotoxics or diuretics

Answer 148

allopurinol is first-line -initial dose of 100 mg od, with the dose titrated every few weeks to aim for a serum uric acid of < 360 µmol/l CKS -a lower target uric acid level below 300 µmol/L may be considered for patients who have tophi, chronic gouty arthritis or continue to have ongoing frequent flares despite having a uric acid below 360 µmol/L -a lower initial dose of allopurinol should be given if the patient has a reduced eGFR -colchicine cover should be considered when starting allopurinol. NSAIDs can be used if colchicine cannot be tolerated. The BSR guidelines suggest this may need to be continued for 6 months the second-line agent when allopurinol is not tolerated or ineffective is febuxostat (also a xanthine oxidase inhibitor) in refractory cases other agents may be tried: uricase (urate oxidase) is an enzyme that catalyzes the conversion of urate to the degradation product allantoin. It is present in certain mammals but not humans in patients who have persistent symptomatic and severe gout despite the adequate use of urate-lowering therapy, pegloticase (polyethylene glycol modified mammalian uricase) can achieve rapid control of hyperuricemia. It is given as an infusion once every two weeks

Answer 149

Lifestyle modifications reduce alcohol intake and avoid during an acute attack lose weight if obese avoid food high in purines e.g. Liver, kidneys, seafood, oily fish (mackerel, sardines) and yeast products

Answer 150

Other points -consideration should be given to stopping precipitating drugs (such as thiazides) -losartan has a specific uricosuric action and may be particularly suitable for the many patients who have coexistent hypertension -increased vitamin C intake (either supplements or through normal diet) may also decrease serum uric acid levels

Answer 151

Decreased excretion of uric acid drugs: diuretics chronic kidney disease lead toxicity

Answer 152

Increased production of uric acid myeloproliferative/lymphoproliferative disorder cytotoxic drugs severe psoriasis

Answer 153

Lesch-Nyhan syndrome hypoxanthine-guanine phosphoribosyl transferase (HGPRTase) deficiency x-linked recessive therefore only seen in boys features: gout, renal failure, neurological deficits, learning difficulties, self-mutilation

Answer 154

Pseudogout is a form of microcrystal synovitis caused by the deposition of calcium pyrophosphate dihydrate crystals in the synovium. For this reason, it is now more correctly termed acute calcium pyrophosphate crystal deposition disease.

Answer 155

Pseudogout is strongly associated with increasing age. Patients who develop pseudogout at a younger age (e.g. < 60 years) usually have some underlying risk factor, such as: haemochromatosis hyperparathyroidism low magnesium, low phosphate acromegaly, Wilson's disease

Answer 156

Features -knee, wrist and shoulders most commonly affected -joint aspiration: weakly-positively birefringent rhomboid-shaped crystals -x-ray: chondrocalcinosis -in the knee this can be seen as linear calcifications of the meniscus and articular cartilage

Answer 157

Management aspiration of joint fluid, to exclude septic arthritis NSAIDs or intra-articular, intra-muscular or oral steroids as for gout

Answer 158

HLA-A3 -haemochromatosis

Answer 159

HLA-B51 Behcet's disease

Answer 160

ankylosing spondylitis reactive arthritis acute anterior uveitis psoriatic arthritis

Answer 161

HLA-DQ2/DQ8 coeliac disease

Answer 162

HLA-DR2 narcolepsy Goodpasture's

Answer 163

HLA-DR3 dermatitis herpetiformis Sjogren's syndrome primary biliary cirrhosis

Answer 164

HLA-DR4 type 1 diabetes mellitus rheumatoid arthritis - in particular the DRB1 gene (DRB1*04:01 and DRB1*04:04 hence the association with DR4)

Answer 165

Marfan's syndrome is an autosomal dominant connective tissue disorder. It is caused by a defect in the FBN1 gene on chromosome 15 that codes for the protein fibrillin-1. It affects around 1 in 3,000 people.

Answer 166

Features tall stature with arm span to height ratio > 1.05 high-arched palate arachnodactyly pectus excavatum pes planus scoliosis of > 20 degrees heart: dilation of the aortic sinuses (seen in 90%) which may lead to aortic aneurysm, aortic dissection, aortic regurgitation mitral valve prolapse (75%), lungs: repeated pneumothoraces eyes: upwards lens dislocation (superotemporal ectopia lentis) blue sclera myopia dural ectasia (ballooning of the dural sac at the lumbosacral level)

Answer 167

The life expectancy of patients used to be around 40-50 years. With the advent of regular echocardiography monitoring and beta-blocker/ACE-inhibitor therapy this has improved significantly over recent years. Aortic dissection and other cardiovascular problems remain the leading cause of death however.

Answer 168

Overview -autosomal recessive type V glycogen storage disease -caused by myophosphorylase deficiency -this causes decreased muscle glycogenolysis

Answer 169

Features muscle pain and stiffness following exercise muscle cramps myoglobinuria low lactate levels during exercise

Answer 170

SItS - small t for teres minor Supraspinatus Infraspinatus teres minor Subscapularis Muscle Notes Supraspinatus aBDucts arm before deltoid Most commonly injured Infraspinatus Rotates arm laterally teres minor aDDucts & rotates arm laterally Subscapularis aDDuct & rotates arm medially

Answer 171

Anaphalactic/Atopy` -Antigen reacts with IgE bound to mast cells

Answer 172

Type II - cell bound -IgG or IgM binds to antigen on cell surface * Autoimmune haemolytic anaemia * ITP * Goodpasture's syndrome * Pernicious anaemia * Acute haemolytic transfusion reactions * Rheumatic fever * Pemphigus vulgaris / bullous pemphigoid

Answer 173

Type III - Immune complex -Free antigen and antibody (IgG, IgA) combine * Serum sickness * Systemic lupus erythematosus * Post-streptococcal glomerulonephritis * Extrinsic allergic alveolitis (especially acute phase)

Answer 174

Type IV - Delayed hypersensitivity -T-cell mediated * Tuberculosis / tuberculin skin reaction * Graft versus host disease * Allergic contact dermatitis * Scabies * Extrinsic allergic alveolitis (especially chronic phase) * Multiple sclerosis * Guillain-Barre syndrome