Rheumatology 3 Flashcards
What is adhesive capsulitis?
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
Features of adhesive capsulitis?
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
Management of adhesive capsulitis?
no single intervention has been shown to improve outcome in the long-term
treatment options include NSAIDs, physiotherapy, oral corticosteroids and intra-articular corticosteroids
Anibodies seen in Dermatomyositis?
Other investigations?
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
Mangement of dermatomyositis?
prenisolone
What are the investigations for Ankolysing spondylitis?
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
What is seen on an XR of Ankylosing spondylitits?
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
Managment of Ankylosing spondylitits?
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
What does pANCA mostly target withing the cell?
MPO is the major target for pANCA, other targets to lesser amounts include lysosome, cathepsin G and elastase.
What does cANCA mostly target withing the cell?
Proteinase 3 (PR3)
What types of vasculitis are associated with ANCA?
granulomatosis with polyangiitis
eosinophilic granulomatosis with polyangiitis (Churg-Strauss syndrome)
microscopic polyangiitis
Common findings in ANCA associated vasculitis?
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
cANCA va pANCA
cANCA - granulomatosis with polyangiitis
pANCA - eosinophilic granulomatosis with polyangiitis + others (see below)
Features of OA in the hands?
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.
How do Bisphosphoates work?
Bisphosphonates are analogues of pyrophosphate, a molecule which decreases demineralisation in bone. They inhibit osteoclasts by reducing recruitment and promoting apoptosis.
What are Bisphosphonates used for ?
prevention and treatment of osteoporosis
hypercalcaemia
Paget’s disease
pain from bone metatases
Adverse effects of Bisphosphonates?
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
when is there a higher risk of Bisphosphonates causing 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
Advice given to patients when taking 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’
What is polyarteritis nodosa?
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.
Features of Polyarteritis nodosa?
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
What is McArdle disease?
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
Features of McArdle’s disease?
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
What is Sjogren’s sundrome?
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).
Features of Sjogren’s syndrome?
dry eyes: keratoconjunctivitis sicca
dry mouth
vaginal dryness
arthralgia
Raynaud’s, myalgia
sensory polyneuropathy
recurrent episodes of parotitis
renal tubular acidosis (usually subclinical)
Investigations for Sjogren’s syndrome?
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
Management of Sjogren’s syndrome?
artificial saliva and tears
pilocarpine may be helpful to stimulate saliva production
What is reactive arthritis?
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.
What is temporal arteritis?
Temporal arteritis (also known as giant cell arteritis: GCA) is a vasculitis of unknown cause that affects medium and large-sized vessels arteries
Features of Temporal arteritis?
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
Why is visual testing important in Temporal arteritis?
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)
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.
Investigations for temporal arteritis?
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
Treatment for temporal arteritis?
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
What is Behcet’s syndrome?
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
associated with HLA B51
tends to affect young adults (e.g. 20 - 40 years old)
Features of Behcet’s syndrome?
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
How is Behcet’s diagnosed?
no definitive test
diagnosis based on clinical findings
positive pathergy test is suggestive (puncture site following needle prick becomes inflamed with small pustule forming)
What is Discoid Lupus?
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
Features of Discoid lupus?
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
Management of Discoid lupus?
topical steroid cream
oral antimalarials may be used second-line e.g. hydroxychloroquine
avoid sun exposure
How can Rheumatoid factor be detected?
Rose-Waaler test: sheep red cell agglutination
Latex agglutination test (less specific)
RF in RA?
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.
What conditions are associated with RF?
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
what test is highly specific for anti CCP?
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%.
Features of limited cutaneous sclerosis?
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
Features of 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 - 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
Early XR changes in Rheumatiod arthritis?
loss of joint space
juxta-articular osteoporosis
soft-tissue swelling
periarticular erosions
subluxation
SLE IN PREGNANCY?
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
What antibody in SLE leads to neonatal CHB?
SLE - antibodies associated with congenital heart block = anti-Ro
Features of drug induced lupus?
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%
causes of drug indiced lupus?
Most common causes
procainamide
hydralazine
Less common causes
isoniazid
minocycline
phenytoin
What are the risk factors for osteoporisis?
history of glucocorticoid use
rheumatoid arthritis
alcohol excess
history of parental hip fracture
low body mass index
current smoking
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
what medications may worsen osteoporosis?
SSRIs
antiepileptics
proton pump inhibitors
glitazones
long term heparin therapy
aromatase inhibitors e.g. anastrozole
Investigating for secondary causes of osteoporosis?
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)
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
Antibodies seen in SLE?
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)
What antibody is most specific for SLE?
anti-Smith: highly specific (> 99%), sensitivity (30%)
Complications of RA?
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
A patient is newly diagnosed with Dermatomyositis what is the most important next step??
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.
What can be used for monitoring of disease in SLE?
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)
How is mixed connective tissue disease managed?
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
What antibody is most specific to mixed connective tissue disease?
Anti-ribonuclear protein (anti-RNP) = mixed connective tissue disease
What is Polymyositis?
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
Features of Polymyositis?
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
Investigations for polymyositis?
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
Management of polymyositis?
high-dose corticosteroids tapered as symptoms improve
azathioprine may be used as a steroid-sparing agent
