Rheumatology Flashcards

Question

What are the clinical features of antiphospholipid syndrome?

Answer 1

``` Paradoxical rise in APTT – reaction of lupus anticoagulant antibodies with phospholipids involve in coagulation cascade Venous/arterial thrombosis Recurrent foetal loss Livedo reticularis Thrombocytopenia Pre-eclampsia Pulmonary hypertension ```

Answer 2

Primary thromboprophylaxis – low dose aspirin Secondary thromboprophylaxis • Initial venous event or any arterial events = warfarin with target INR of 2-3 • Recurrent venous events = warfarin with target INR of 3-4

Answer 3

Definition – Inflammatory arthritis occurring as a result of urate crystal deposits. It is more common in men until age of 60 and twice as common in men of African descent.

Answer 4

Persistently elevated levels of uric acid due to diet and genetic factors. The uric acid crystallises and deposits itself within the join capsule making moving very painful. Triggers – drugs, stress illness and dehydration as well as many drugs, food and drink Decreased excretion of Urate • Drugs – diuretics and high dose aspirin • Chronic kidney disease • Lead toxicity Increased production of urate • Myeloproliferative/lymphoproliferative disorders • Cytotoxic drugs • Psoriasis

Answer 5

Patient have episodes lasting several days during flares with: • Erythema • Pain with maximal intensity within 12 hours • Hot • Swollen – can form tophi which are large swelling of urate deposition Usually affecting the 1st metatarsal-phalangeal joint Other joints commonly affected: ankles, knees, wrists and fingers Without treatment will resolve within a week but repeated episodes can damage the joints resulting in chronic problems

Answer 6

Blood Urate levels Aspiration of synovial fluid if there is any doubt X-ray in chronic disease will show – joint effusion, punched out erosions with sclerotic margins, relative preservation of joint space, eccentric erosions, no periarticular osteopenia (on contrast to RA) and soft tissue tophi may be seen

Answer 7

Acute management NSAIDs at maximum dose until 1-2 days after the symptoms are settled and gastroprotection is usually required Colchicine – slower onset of action and the main SE is diarrhoea If NSAIDs and Colchicine are CI then oral steroids Intraarticular steroid injection Continue allopurinol if already on it

Answer 8

``` Ongoing management Everyone who has had their first attack of gout should be using urate lowering therapy Particularly if: • 2 attacks in 12 months • Tophi • Renal disease • Uric acid renal stones • Prophylaxis if on cytotoxic or diuretic drugs ``` Allopurinol is first line – do not start until 2 weeks post attack/after inflammation has settled as long-term drug decision are best made when not in pain Titrate dose against serum uric acid levels aiming for < 300umol/l Consider Colchicine cover when starting allopurinol and may be required for 6 months Second line agent is Febuxostat (another xanthine oxidase inhibitor) If refractory to treatment, then trial uricase or pegloticase (infusion every 2 weeks) Note losartan has a specific uricosuric action and is particularly useful if hypertensive

Answer 9

Lifestyle Modification Reduce alcohol intake and avoid during an acute attack Lose weight if obese Avoid food high in purines – liver, kidneys, seafood, oily fish (mackerel and sardines) and yeast products Increased vitamin C intake

Answer 10

Pseudogout is an inflammatory arthritis caused by deposits of calcium pyrophosphate crystals within the joint so also known as Acute calcium pyrophosphate crystal deposition disease. The condition often mimics gout, however, is more likely to affect proximal joints, with the knee and wrist being most commonly affected.

Answer 11

Advanced age Hyperparathyroidism, Hypophosphatemia and hypomanesaemia Acromegaly and Wilson’s disease

Answer 12

Knee, wrist and shoulders most commonly affected Acute onset joint swelling Subcutaneous deposits near the affected joint

Answer 13

Diagnosis of pseudogout is also made by joint aspiration and microscopy, which will show weakly-positively birefringent rhomboid-shaped crystals. X-ray – chondrocalcinosis Exclude septic arthritis

Answer 14

Pseudo-gout is treated acutely with NSAIDs | Intra-articular or intra-muscular or oral steroids

Answer 15

Diagnosed after at least 4 months of disabling fatigue affecting mental and physical function more than 50% of the time in the absence of other diseases which may explain the symptoms. It is more common in females.

Answer 16

``` Sleep problems – insomnia, hypersomnia, unrefreshing and disturbed sleep-wake cycle Muscle and/or joint pains Headaches Painful lymph node enlargement Sore throat Cognitive dysfunction General malaise Dizziness Nausea Palpitations ``` Physical or mental exertion make symptoms worse

Answer 17

Mostly to exclude other pathology – FBC, U&E, LFT, Glucose, TFT, CRP, Calcium, CK, ferritin, Coeliac and urinalysis

Answer 18

CBT – very effective Graded exercise therapy – formal supervised program Pacing – organising activities to avoid tiring Low dose amitriptyline if poor sleep Referral to pain management clinic if this is the main symptoms Better prognosis in the young

Answer 19

Fibromyalgia is a syndrome characterised by widespread pain throughout the body with tender points at specific anatomical sites. The cause of fibromyalgia is unknown. Women are around 5 times more likely to be affected and it typically presents between 30-50 years old.

Answer 20

Chronic pain: at multiple site, sometimes 'pain all over' Lethargy Cognitive impairment known as fibro fog Sleep disturbance, headaches and dizziness are common

Answer 21

Diagnosis is clinical The American College of Rheumatology classification criteria 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 22

The management of fibromyalgia is difficult Psychosocial and multidisciplinary approach is helpful Unfortunately, there is currently a paucity of evidence and guidelines to guide practice Explanation Aerobic exercise: has the strongest evidence base Cognitive behavioural therapy Medication: pregabalin, duloxetine, amitriptyline

Answer 23

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 24

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 Mild polyarthralgia, lethargy, depression, low-grade fever, anorexia, night sweats

Answer 25

Raised inflammatory markers | Creatine kinase and EMG normal

Answer 26

Prednisolone e.g. 15mg/od Patients typically respond dramatically to steroids, failure to do so should prompt consideration of an alternative diagnosis

Answer 27

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 28

Tall stature with arm span to height ratio > 1.05 High-arched palate Arachnodactyly long fingers and toes Pectus excavatum Pes planus – loss of medial longitudinal arch of the foot Scoliosis of > 20 degrees Heart – dilation of the aortic sinuses (seen in 90%) which may lead to aortic aneurysm, aortic dissection, aortic regurgitation and mitral valve prolapse (75%) Lungs – repeated pneumothoraces ``` Eyes – upwards lens dislocation (superotemporal ectopia lentis), blue sclera and myopia dural ectasia (ballooning of the dural sac at the lumbosacral level) ```

Answer 29

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. However, aortic dissection and other cardiovascular problems remain the leading cause of death.

Answer 30

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 31

Elastic, fragile skin Joint hypermobility leading to recurrent joint dislocation Easy bruising Aortic regurgitation, mitral valve prolapse and aortic dissection Subarachnoid haemorrhage Angioid retinal streaks

Answer 32

Also known as brittle bone disease, is a group of disorders affecting metabolism of collagen resulting in bone fragility and fractures. Type 1 is the most common and is autosomal dominant.

Answer 33

``` Presents in childhood Fractures following minor trauma Blue sclera Deafness secondary to otosclerosis Dental imperfections are common ```

Answer 34

Anti-neutrophil cytoplasmic antibodies (ANCA) are associated with a number of small vessel vasculitides such as granulomatosis with polyangiitis, eosinophilic granulomatosis with polyangiitis (Churg-Strauss Syndrome) and microscopic polyangiitis. ANCA is more common with increasing age.

Answer 35

Renal impairment – immune complex glomerulonephritis Respiratory symptoms such as dyspnoea and haemoptysis Systemic symptoms – fatigue, weight loss and fever Vasculitis rash – minority of patients ENT symptoms such as sinusitis

Answer 36

Urinalysis for haematuria and proteinuria Bloods – U&Es, FBC (normocytic anaemic and thrombocytosis) CRP ANCA testing Chest X-ray – nodular, fibrotic or infiltrative lesions Kidney or lung biopsies

Answer 37

There are two main types of ANCA – cytoplasmic and perinuclear both are seen in most ANCA conditions but are much more common in some • cANCA – granulomatosis with polyangiitis (90%), Eosinophilic granulomatosis with polyangiitis (low) and microscopic polyangiitis (40%) • pANCA – granulomatosis with polyangiitis (25%), Eosinophilic granulomatosis with polyangiitis (50%) and microscopic polyangiitis (75%). Also seen in UC (70%), primary sclerosing cholangitis (70%), Anti-GBM (25%) and Crohn’s (20%).

Answer 38

Via specialist teams e.g. renal, rheumatology and respiratory Immunosuppressive therapy is the mainstay of treatment

Answer 39

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).

Answer 40

Raynaud's disease typically presents in young women (e.g. 30 years old) with bilateral symptoms. Typical white, blue then red colour change

Answer 41

``` Connective tissue disorders Scleroderma (most common) Rheumatoid arthritis Systemic lupus erythematosus Leukaemia Use of vibrating tools Drugs: oral contraceptive pill, ergot Cervical rib ```

Answer 42

Factors suggesting underlying connective tissue disease Onset after 40 years Unilateral symptoms Rashes Presence of autoantibodies Features suggesting rheumatoid arthritis or SLE Digital ulcers, calcinosis

Answer 43

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

Answer 44

Increased and uncontrolled bone resorption followed by excessive and chaotic bone deposition. It is common, occurring in 1 in 20 people in the UK but only symptomatic in 1 in 20 of those with it.

Answer 45

Increasing age Male sex Northern Latitude Family history

Answer 46

Affects (in order) spine, skull, pelvis and femur Older male with bone pain and isolated raised serum alkaline phosphatase Untreated features – bowing of tibia and bossing of skull Calcium and phosphate are usually normal Risk of high output cardiac failure with >15% bony involvement Small risk of sarcomatous change – 1% if affected for > 10 years Deafness from cranial nerve entrapment Skull thickening Fracture

Answer 47

Abnormal thickened, sclerotic bone on x-ray | Bone profile and PTH

Answer 48

Only treat if symptomatic i.e. pain, deformity, fracture, or periarticular Paget’s Bisphosphonates either oral risedronate or IV zoledronate

Answer 49

These are often termed HLA-B27 Seronegative Spondyloarthropathies. This is because they are associated with HLA-B27 and are seronegative for rheumatoid factor. These include ankylosing spondylitis, reactive arthritis, psoriatic arthritis and enteropathic arthritis.

Answer 50

Definition – chronic inflammatory disease of the spine and sacroiliac joints. Typical presentation is a man less than 30. It is a HLA B27 associated spondyloarthropathy however, HLA-B27 not useful for diagnosis as although 90% of patients have it positive, 10% of normal patients are also positive for it

Answer 51

Gradual onset lower back pain and stiffness Worse during the morning Spinal morning stiffness relieved by exercise Pain can radiate from sacroiliac joints to the buttocks Gradual loss of spinal movements – lateral and forward flexion – schober’s test Reduced chest expansion and loss of thoracic volume ``` Other associations Can have AV heart block Eye problems – anterior uveitis Artic regurgitation Achilles tendonitis Amyloidosis ```

Answer 52

Clinical diagnosis Inflammatory markers are typically raised X-ray looking at sacroiliac joint (normal early on) – sacroiliitis, squaring on lumbar vertebrae, bamboo spine, syndemophytes (ossification of outer fibres of annulus fibrosus CXR – apical fibrosis MRI useful to confirm active disease if X-ray negative but suspicion high Spirometry – restrictive defect

Answer 53

Regular exercise NOT rest such as swimming NSAIDs for pain relief Physiotherapy Anti-TNF alpha if severe DMARDs only useful if there is peripheral joint involvement Surgery for replacement of hip or shoulder involvement

Answer 54

Reactive arthritis is one of the HLA-B27 associated seronegative spondyloarthropathies. It encompasses what was formerly called Reiter's syndrome. Reactive arthritis is defined as an arthritis that develops following an infection where the organism cannot be recovered from the joint e.g. Sexually acquired reactive arthritis – SARA. Post-STI form much more common in men (e.g. 10:1). Post-dysenteric form equal sex incidence.

Answer 55

Classic triad of urethritis, conjunctivitis and arthritis following a n infection Typically develops within 4 weeks of initial infection and lasts 4-6 months Typically asymmetrical oligoarthritic of lower limbs Dactylitis – inflammation of the a digit Can't see, pee or climb a tree

Answer 56

Post-dysenteric form – Shigella, salmonella, Campylobacter | Post STI form – chlamydia

Answer 57

Symptomatic – analgesia, NSAIDs and intra-articular steroids Sulfasalazine and methotrexate are sometimes used if persistent Symptoms rarely last more than 12 months

Answer 58

Complex multisystem disorder presumed to be autoimmune inflammation of arteries and veins. The classic triad of symptoms are oral ulcers, genital ulcers and anterior uveitis. It is more common in men, particularly from easter Mediterranean e.g. Turkey, tends to affect young adults and is associated with HLA B51. Often there is a family history

Answer 59

Classical triad – oral ulcers, genital ulcers, and anterior uveitis Thrombophlebitis and DVT Arthritis Aseptic meningitis GI – abdominal pain, diarrhoea, and colitis Erythema nodosum

Answer 60

An inflammatory disorder causing symmetrical, proximal muscle weakness and characteristic skin lesions. polymyositis is a variant of the disease where skin manifestations are not prominent.

Answer 61

Idiopathic Associated with connective tissue disorders Underlying malignancy (typically ovarian, breast and lung cancer, found in 20-25% - more if patient older).

Answer 62

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 ``` Other features Proximal muscle weakness +/- tenderness Raynaud's Respiratory muscle weakness Interstitial lung disease: e.g. Fibrosing alveolitis or organising pneumonia Dysphagia and dysphonia ```

Answer 63

Screening for an underlying malignancy is usually performed following a diagnosis of dermatomyositis Majority of patients are ANA positive (80%) 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 64

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. Typically affects middle-aged, female:male 3:1

Answer 65

``` Proximal muscle weakness +/- tenderness Raynaud's Respiratory muscle weakness Interstitial lung disease: e.g. fibrosing alveolitis or organising pneumonia Dysphagia and dysphonia ```

Answer 66

Raised creatine kinase Other muscle enzymes (lactate dehydrogenase (LD), aldolase, AST and ALT) raised 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 67

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 68

``` Dry eyes: keratoconjunctivitis sicca Dry mouth Vaginal dryness Arthralgia Raynaud's Sensory polyneuropathy Recurrent episodes of parotitis Renal tubular acidosis (usually subclinical) ```

Answer 69

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 shows focal lymphocytic infiltration Blood tests show hypergammaglobulinaemia and low C4

Answer 70

Artificial saliva and tears | Pilocarpine may stimulate saliva production

Answer 71

Autoinflammatory disease that has a bimodal age distribution - 15-25 yrs and 35-46 yr

Answer 72

Arthralgia Elevated serum ferritin Salmon-pink, maculopapular rash Pyrexia that typically rises in the late afternoon/early evening in a daily pattern and accompanies a worsening of joint symptoms and rash Lymphadenopathy Rheumatoid factor (RF) and anti-nuclear antibody (ANA) negative

Answer 73

This is done clinically but the diagnosis of Still's disease in adults can be challenging. The Yamaguchi criteria is the most widely used criteria and has a sensitivity of 93.5%.

Answer 74

NSAIDs – first line to manage fever, joint pain and serositis and trialled for at least a week before steroids are added Steroids may control symptoms but won't improve prognosis If symptoms persist, the use of methotrexate, IL-1 or anti-TNF therapy can be considered

Answer 75

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. There are three patterns of disease

Answer 76

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

Answer 77

Diffuse cutaneous systemic sclerosis Scleroderma affects trunk and proximal limbs predominately, associated with 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. This has a poor prognosis.

Answer 78

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

Answer 79

* ANA positive in 90% * RF positive in 30% * Anti-scl-70 antibodies associated with diffuse cutaneous systemic sclerosis * Anti-centromere antibodies associated with limited cutaneous systemic sclerosis

Answer 80

Definition – multisystem connective tissue disorder causing: Calcinosis, Raynaud’s Phenomenon, Oesophageal dysmotility, Sclerodactyly and Telangiectasia. Sometimes also known as the Limited Cutaneous form of Systemic sclerosis. Autoimmune disease caused by antibodies against centromeres and nucleus.

Answer 81

Calcinosis – thickening and tightening of the skin with deposition of calcified nodules Raynaud’s Phenomenon – Exaggerated vasoconstriction in the periphery causing very cold hands with poor circulation Oesophageal Dysmotility – sensation of dysphagia, chest pain and cough. This occurs as a result of atrophy of the GI tract smooth muscle Sclerodactyly – localised thickening of the skin around the fingers causing ulcerations. Usually this only occurs distal to the metacarpophalangeal joints Telangiectasia – dilated capillaries on the skin surface Other symptoms include: exhaustion, dyspnoea, badly healing wounds, pulmonary hypertension and the ensuing cor pulmonale.

Answer 82

Detectable antibodies against centromeres and nucleus Easily mimics other disease so can be missed. Diagnosis is made when 3 of the 5 symptoms are found. Assays for the autoantibodies will confirm this diagnosis.

Answer 83

Immunosuppressive therapy Symptoms management especially of GORD, pulmonary hypertension and raynaud’s phenomenon. Steroid medication for inflammation