Rheumatology 3

Question 1

What is adhesive capsulitis?

Answer 1

Adhesive capsulitis (frozen shoulder) is a common cause of shoulder pain. It is most common in middle-aged females. The aetiology of frozen shoulder is not fully understood.

diabetes mellitus: up to 20% of diabetics may have an episode of frozen shoulder

Question 2

Features of adhesive capsulitis?

Answer 2

external rotation is affected more than internal rotation or abduction
both active and passive movement is affected
patients typically have a painful freezing phase, an adhesive phase and a recovery phase
bilateral in up to 20% of patients
the episode typically lasts between 6 months and 2 years

Question 3

Management of adhesive capsulitis?

Answer 3

no single intervention has been shown to improve outcome in the long-term
treatment options include NSAIDs, physiotherapy, oral corticosteroids and intra-articular corticosteroids

Question 4

Anibodies seen in Dermatomyositis?

Other investigations?

Answer 4

ANA positive in 60%
anti-Mi-2 antibodies are highly specific for dermatomyositis, but are only seen in around 25% of patients
anti-Jo-1 antibodies are not commonly seen in dermatomyositis - they are more common in polymyositis where they are seen in a pattern of disease associated with lung involvement, Raynaud’s and fever

elevated creatine kinase
EMG
muscle biopsy

Question 5

Mangement of dermatomyositis?

Answer 5

prednisolone

Question 6

What are the investigations for Ankolysing spondylitis?

Answer 6

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

Plain XR
MRI

Question 7

What is seen on an XR of Ankylosing spondylitits?

Answer 7

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

Question 8

Managment of Ankylosing spondylitits?

Answer 8

encourage regular exercise such as swimming
NSAIDs are the first-line treatment
physiotherapy
the disease-modifying drugs which are used to treat rheumatoid arthritis (such as sulphasalazine) are only really useful if there is peripheral joint involvement
the 2010 EULAR guidelines suggest: ‘Anti-TNF therapy should be given to patients with persistently high disease activity despite conventional treatments’
research is ongoing to see whether anti-TNF therapies such as etanercept and adalimumab should be used earlier in the course of the disease

Question 9

What does pANCA mostly target withing the cell?

Answer 9

MPO is the major target for pANCA, other targets to lesser amounts include lysosome, cathepsin G and elastase.

Question 10

What does cANCA mostly target withing the cell?

Answer 10

Proteinase 3 (PR3)

Question 11

What types of vasculitis are associated with ANCA?

Answer 11

granulomatosis with polyangiitis
eosinophilic granulomatosis with polyangiitis (Churg-Strauss syndrome)
microscopic polyangiitis

Question 12

Common findings in ANCA associated vasculitis?

Answer 12

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

Question 13

cANCA va pANCA

Answer 13

cANCA - granulomatosis with polyangiitis
pANCA - eosinophilic granulomatosis with polyangiitis + others (see below)

Question 14

Features of OA in the hands?

Answer 14

Usually bilateral
CMCs and DIP joints are more affected that the PIP joints
Episodic joint pain
Stiffness
Heberden’s nodes at the DIP joints
Bouchard’s Nodes at the PIP joints
these nodes are the result of osteophyte formation.

Squaring of the thumbs: Deformity of the carpometacarpal joint of the thumb resulting in fixed adduction of the thumb.

Question 15

How do Bisphosphoates work?

Answer 15

Bisphosphonates are analogues of pyrophosphate, a molecule which decreases demineralisation in bone. They inhibit osteoclasts by reducing recruitment and promoting apoptosis.

Question 16

What are Bisphosphonates used for ?

Answer 16

prevention and treatment of osteoporosis
hypercalcaemia
Paget’s disease
pain from bone metatases

Question 17

Adverse effects of Bisphosphonates?

Answer 17

oesophageal reactions: oesophagitis, oesophageal ulcers (especially alendronate)
osteonecrosis of the jaw
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

Question 18

when is there a higher risk of Bisphosphonates causing osteonecrosis of the jaw?

Answer 18

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

Question 19

Advice given to patients when taking bisphosphonates?

Answer 19

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’

Question 20

What is polyarteritis nodosa?

Answer 20

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.

Question 21

Features of Polyarteritis nodosa?

Answer 21

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

Question 22

What is McArdle disease?

Answer 22

McArdle disease, also known as glycogen storage disease type V (GSD V), is a rare genetic disorder that affects muscles

caused by myophosphorylase deficiency
this causes decreased muscle glycogenolysis

Question 23

Features of McArdle’s disease?

Answer 23

muscle pain and stiffness following exercise
muscle cramps
second wind phenomenon
occurs when patients experience an improvement in exercise tolerance after a brief rest or reduction in intensity
due to the body’s switch from glycogen-dependent energy metabolism to increased reliance on circulating glucose and fatty acids
his adaptation allows for better energy utilisation during prolonged activity despite the underlying myophosphorylase deficiency.
rhabdomyolysis & myoglobinuria
low lactate levels during exercise

Question 24

What is Sjogren’s sundrome?

Answer 24

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).

Question 25

Features of Sjogren's syndrome?

Answer 25

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

Question 26

Investigations for Sjogren's syndrome?

Answer 26

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

Question 27

Management of Sjogren's syndrome?

Answer 27

artificial saliva and tears pilocarpine may be helpful to stimulate saliva production

Question 28

What is reactive arthritis?

Answer 28

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.

Question 29

What is temporal arteritis?

Answer 29

Temporal arteritis (also known as giant cell arteritis: GCA) is a vasculitis of unknown cause that affects medium and large-sized vessels arteries

Question 30

Features of Temporal arteritis?

Answer 30

typically patient > 60 years old usually rapid onset (e.g. < 1 month) headache (found in 85%) jaw claudication (65%) 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

Question 31

Why is visual testing important in Temporal arteritis?

Answer 31

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) ## Footnote 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.

Question 32

Investigations for temporal arteritis?

Answer 32

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

Question 33

Treatment for temporal arteritis?

Answer 33

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

Question 34

What is Behcet's syndrome?

Answer 34

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 ## Footnote associated with HLA B51 tends to affect young adults (e.g. 20 - 40 years old)

Question 35

Features of Behcet's syndrome?

Answer 35

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

Question 36

How is Behcet's diagnosed?

Answer 36

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

Question 37

What is Discoid Lupus?

Answer 37

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

Question 38

Features of Discoid lupus?

Answer 38

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

Question 39

Management of Discoid lupus?

Answer 39

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

Question 40

How can Rheumatoid factor be detected?

Answer 40

Rose-Waaler test: sheep red cell agglutination Latex agglutination test (less specific)

Question 41

RF in RA?

Answer 41

RF is positive in 70-80% of patients with rheumatoid arthritis, high titre levels are associated with severe progressive disease (but NOT a marker of disease activity.

Question 42

What conditions are associated with RF?

Answer 42

Felty's syndrome (around 100%) Sjogren's syndrome (around 50%) infective endocarditis (around 50%) SLE (= 20-30%) systemic sclerosis (= 30%) general population (= 5%) rarely: TB, HBV, EBV, leprosy

Question 43

what test is highly specific for anti CCP?

Answer 43

Anti-cyclic citrullinated peptide antibody may be detectable up to 10 years before the development of rheumatoid arthritis. It has a key role in the diagnosis of rheumatoid arthritis, allowing early detection of patients suitable for aggressive anti-TNF therapy. It has a sensitivity similar to rheumatoid factor (around 70%) with a much higher specificity of 90-95%.

Question 44

Features of limited cutaneous sclerosis?

Answer 44

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

Question 45

Features of diffuse cutaneous systemic sclerosis?

Answer 45

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 - captopril is typically used due to its rapid onset and short half-life, allowing for dose titration ACE inhibitors target the underlying mechanism by reducing efferent arteriolar vasoconstriction and limiting renin-angiotensin system activation poor prognosis

Question 46

Early XR changes in Rheumatiod arthritis?

Answer 46

loss of joint space juxta-articular osteoporosis soft-tissue swelling periarticular erosions subluxation

Question 47

SLE IN PREGNANCY?

Answer 47

risk of maternal autoantibodies crossing the placenta leads to a condition termed neonatal lupus erythematosus neonatal complications include congenital heart block strongly associated withanti-Ro (SSA) antibodies

Question 48

What antibody in SLE leads to neonatal CHB?

Answer 48

SLE - antibodies associated with congenital heart block = anti-Ro

Question 49

Features of drug induced lupus?

Answer 49

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. 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%

Question 50

causes of drug indiced lupus?

Answer 50

Most common causes procainamide hydralazine Less common causes isoniazid minocycline phenytoin

Question 51

What are the risk factors for osteoporisis?

Answer 51

history of glucocorticoid use rheumatoid arthritis alcohol excess history of parental hip fracture low body mass index current smoking ## Footnote 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

Question 52

what medications may worsen osteoporosis?

Answer 52

SSRIs antiepileptics proton pump inhibitors glitazones long term heparin therapy aromatase inhibitors e.g. anastrozole

Question 53

Investigating for secondary causes of osteoporosis?

Answer 53

The following investigations are recommended by NOGG: History and physical examination Blood cell count, sedimentation rate or C-reactive protein, serum calcium, albumin, creatinine, phosphate, alkaline phosphatase and liver transaminases Thyroid function tests Bone densitometry ( DXA) ## Footnote Other procedures, if indicated Lateral radiographs of lumbar and thoracic spine/DXA-based vertebral imaging Protein immunoelectrophoresis and urinary Bence-Jones proteins 25OHD PTH Serum testosterone, SHBG, FSH, LH (in men), Serum prolactin 24 hour urinary cortisol/dexamethasone suppression test Endomysial and/or tissue transglutaminase antibodies (coeliac disease) Isotope bone scan Markers of bone turnover, when available Urinary calcium excretion

Question 54

Antibodies seen in SLE?

Answer 54

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)

Question 55

What antibody is most specific for SLE?

Answer 55

anti-Smith: highly specific (> 99%), sensitivity (30%)

Question 56

Complications of RA?

Answer 56

A wide variety of extra-articular complications occur in patients with rheumatoid arthritis (RA): respiratory: pulmonary fibrosis, pleural effusion, pulmonary nodules, bronchiolitis obliterans, methotrexate pneumonitis, pleurisy ocular: keratoconjunctivitis sicca (most common), episcleritis, scleritis, corneal ulceration, keratitis, steroid-induced cataracts, chloroquine retinopathy osteoporosis ischaemic heart disease: RA carries a similar risk to type 2 diabetes mellitus increased risk of infections depression Less common Felty's syndrome (RA + splenomegaly + low white cell count) amyloidosis

Question 57

A patient is newly diagnosed with Dermatomyositis what is the most important next step??

Answer 57

In patients with a new diagnosis of dermatomyositis, urgent malignancy screen is needed Almost a quarter of individuals diagnosed with dermatomyositis have an underlying malignancy (typically ovarian, breast and lung cancer), this prevalence increases in the elderly.

Question 58

What can be used for monitoring of disease in SLE?

Answer 58

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)

Question 59

How is mixed connective tissue disease managed?

Answer 59

No large-scale trials - patients have been included in trials for SLE/SSc and show similar levels of response to immunosuppression/DMARDs Calcium channel blockers may be used for the treatment of Raynaud's Proton pump inhibitors for reflux disease Endothelin receptor antagonists/prostacyclin analogues in pulmonary hypertension Smoking cessation, moderate exercise

Question 60

What antibody is most specific to mixed connective tissue disease?

Answer 60

Anti-ribonuclear protein (anti-RNP) = mixed connective tissue disease

Question 61

What is Polymyositis?

Answer 61

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

Question 62

Features of Polymyositis?

Answer 62

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

Question 63

Investigations for polymyositis?

Answer 63

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

Question 64

Management of polymyositis?

Answer 64

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