Passmedicine Rheumatology Flashcards
What type of arthritis is gout?
Inflammatory
How do gout episodes typically present?
Episodes lasting several days
Often symptom free between episodes
Acute episodes develop maximal intensity within 12h
What are the symptoms of gout?
Pain
Swelling
Erythema
What joint is most affected in gout?
MTP (podagra = gout affecting this joint)
Apart from the MTP what joints are also commonly affected by gout?
Ankle
Wrist
Knee
What can untreated gout lead to?
Repeated acute episodes of gout can damage the joints –> chronic joint problem
What are the radiological features of gout?
Joint effusion
Punched out erosions with slcerotic margins in a juxta-articular distribution
Eccentric erosions
Soft tissue tophi
Differences between RA and OA: Aetiology
RA: autoimmune
OA: wear + tear –> localised loss of cartilage, remodelling of adjacent bone, assoc. inflammation
Differences between RA and OA: gender
RA: more common in women
OA: similar in men and women
Differences between RA and OA: age
RA: all ages
OA: elderly more common
Differences between RA and OA: typical joints affected
RA: MCP, PIP
OA: large wt bearing joints, CMC, DIP, PIP
Differences between RA and OA: typical hx
RA: morning stiffness, improves with use, systemic upset
OA: pain following use, improves with rest, unilateral symptoms, no systemic upset
Differences between RA and OA: x-ray findings
RA: loss of joint space, juxta-articular osteoporosis, periarticular erosions, subluxation
OA: loss of joint space, subchondral sclerosis, subchondral cysts, osteophytes forming at joint margins
What is the aetiology of systemic sclerosis?
Unknown
What is systemic sclerosis characterised by?
Hardened, sclerotic skin, and other connective tissues
In which gender is systemic sclerosis more common?
Females
What are the three patterns of disease of systemic sclerosis?
- Limited cutaneous systemic sclerosis
- Diffuse cutaneous systemic sclerosis
- Scleroderma (without internal organ involvement)
What are the features of limited cutaneous systemic sclerosis?
Can present with Raynaud’s
Scleroderma of face + distal limbs
What antibody is strongly associated with limited cutaneous systemic sclerosis?
Anti-centromere Ab
Name a subtype of limited cutaneous systemic sclerosis
CREST syndrome
What are the features of CREST syndrome?
Calcinosis Raynaud's Oesophageal dysmotility Sclerodactyly Telangiectasia
What are the features of diffuse systemic sclerosis?
Scleroderma of the trunk + proximal limbs
Commonest cause of death: interstitial lung disease/pulmonary arterial hypertension
HAS POOR PROGNOSIS
What are the commonest complications associated with diffuse systemic sclerosis?
ILD, pulmonary arterial hypertension
Renal disease
HTN
What antibody is strongly associated with diffuse cutaneous systemic sclerosis?
scl-70 antibodies
What are the features of scleroderma (without internal organ involvement)?
Tightening + fibrosis of the skin
May manifest as plaques (morphoea) or linear
What antibodies are associated with systemic sclerosis?
ANA 90%
RF 30%
What is Paget’s disease of the bone?
Disease of increased but uncontrolled bone turnover
What is the aetiology of Paget’s disease?
Primary disorder of osteoclasts, with excessive osteoclastic resorption followed by increased osteoblastic activity
How does Paget’s normally present?
1 in 20 are symptomatic
What bones are most commonly affected by Paget’s disease?
Skull
Spine
Pelvis
Long bones of lower extremities
What are the predisposing factors for Paget’s?
Increasing age
Male
Northern latitude
Family history
What are the clinical features of Paget’s?
Tends to be older male with bone pain + isolated raised ALP
What are the classical features of Paget’s if it is left untreated?
Bowing of tibia
Bossing of skull
What does blood work for Paget’s usually show?
Normal Ca, phosp
Raised ALP
Other markers of bone turnover may be high (e.g. procollagen type 1, N-terminal propeptide, serum C-telopeptide, urinary N-telopeptide + urinary hydroproline)
X-ray of a Paget’s diseased skull would show…
Thickened vault
Osteoporosis circumscripta
What are the indications for the treatment of Paget’s?
Bone pain
Skull/long bone deformity
Fracture
Periarticular Paget’s
How is Paget’s treated?
Bisphosphonates (oral risedronate/IV zoledronate)
Calcitonin
What are the complications associated with Paget’s disease?
Deafness (due to cranial nerve entrapment) Bone sarcoma Fractures Skull thickening High output cardiac failure
What are the new recommendations for the treatment of RA?
Start DMARD ASAP and to include other Rx options, e.g. analgesia, physio + surgery
What is the initial therapy for RA?
DMARD monotherapy +/- bridging course of prednisolone
How do NICE recommend monitoring response to treatment in RA?
CRP + disease activity (e.g. DAS28)
What is the most commonly used DMARD?
Methotrexate
What must you do if you put a patient on methotrexate?
Monitor LFTs and FBC due to risk of myelosuppression and liver cirrhosis
Repeat weekly until stabilised, thereafter monitor every 2-3m
What are the three other DMARDs apart from methotrexate used for RA Rx?
Sufasalazine
Leflunomide
Hydroxychloroquine
When are TNF-inhibitors indicated for Rx of RA?
Inadequate response to 2+ DMARDs including methotrexate
Name 3 TNF-inhibitors
Etanercept
Infliximab
Adalimumab
What is etanercept?
Recombinant human protein, acts as a decoy for TNF-a
s/c administration
What are the side effectsof etanercept?
Demyelination
Reactivation of TB
What is infliximab?
Monoclonal Ab
Binds to TNF-a + prevents it fro binding with TNF receptors
IV administration
What risks are associated with infliximab use?
Reactivation of TB
What is adalimumab?
Monoclonal Ab
s/c administration
What is rituximab?
Anti-CD20 monoclonal Ab
RESULTS IN B CELL DEPLETION
Given as two 1g IV infusions 2 weeks apart
Infusion reactions common
What is abatacept?
Fusion protein that modulates a key signal required for activation of T lymphocytes
–> decreased T cell proliferation + cytokine production
Given as infusion
What is polyarteritis nodosa?
Vasculitis affecting medium sized arteries with necrotising inflammation leading to aneurysm formation
In which groups of people is polyarteritis nodosa most common?
In middle aged men
Associated with HEPATITIS B infection
What are the features of polyarteritis nodosa?
Fever, malaise, arthalgia Wt loss HTN Mononeuritis multiplex, sensorimotor polyneuropathy Testicular pain Livedo reticularis Haematuria, renal failure
What antibody is associated with polyarteritis nodosa?
pANCA
What is pseudogout?
A form of microcrystal synovitis caused by deposition of calcium pyrophosphate dihydrate crystals in the synovium
What are the risk factors for pseudogout?
Haemochromatosis Hyperparathyroidism Acromegaly Low mg, low phosp Wilson's disease
Where does pseudogout tend to affect most?
Knee, wrist, shoulders most commonly affected
What investigations should you do in pseudogout and what will they find?
Joint aspiration: weakly positive birefringent rhomboid shaped crystals
X-Ray: chondrocalcinosis
What is the management of pseudogout?
Aspiration of joint fluid to exclude septic arthritis
NSAIDs/IA/IM/oral steroids
What is gout?
Form of microcrystal synovitis caused by deposition of monosodium urate monohydrate in the synovium
What causes gout?
Chronic hyperuricaemia (>450microm/l)
What is the acute management of gout?
First line: NSAIDs/colchicine + PPI if req.
Consider oral steroids (e.g. 15mg predn) if NSAIDs/colchicine CI
3rd line: IA steroids
Ensure patient continues on allopurinol if already taking
In treating an acute attack of gout, when should the patient be advised to stop taking NSAIDs?
1-2 days after symptoms have settled
What are the indications for urate lowering therapy?
All patients after their first attack of gout
In which patients is urate lowering therapy strongly indicated?
>= 2 attacks in 12 months Tophi Renal disease Uric acid renal stones Prophylaxis if on cytotoxics/diuretics
What is used for urate lowering therapy?
First line: allopurinol (2w after attack) 100mg od initially titrating every few weeks to aim for serum uric acid of <300microm/l
Consider colchicine when starting allopurinol (or NSAID if colchicine not tolerated)
Second line: febuxpstat
How do allopurinol + febuxpstat work?
Xanthine oxidase inhibitors
What lifestyle modifications are helpful in gout?
Reduce alcohol intake
Lose wt
Avoid foods high in purines
What foods are high in purines?
Liver Kidney Seafood Oily fish Yeast products
What drugs might you want to stop in someone with gout?
Precipitating drugs, e.g. thiazides
How does colchicine work?
Inhibits microtubule polymerization by binding to tubulin, interfering with mitosis. Also inhibits neutrophil motility and activity
What are the expected values of serum: Calcium Phosphate ALP PTH in someone with osteoporosis?
Calcium - normal
Phosphate - normal
ALP - normal
PTH - normal
What are the expected values of serum: Calcium Phosphate ALP PTH in someone with osteomalacia?
Calcium - decreased
Phosphate - decreased
ALP - increased
PTH - increased
What are the expected values of serum: Calcium Phosphate ALP PTH in someone with primary hyperparathyroidism?
Calcium - increased
Phosphate - decreased
ALP - increased
PTH - increased
What are the expected values of serum: Calcium Phosphate ALP PTH in someone with chronic kidney disease --> secondary hyperparathyroidism?
Calcium - decreased
Phosphate - increased
ALP - increased
PTH - increased
What are the expected values of serum: Calcium Phosphate ALP PTH in someone with Paget's disease of the bone?
Calcium - normal
Phosphate - normal
ALP - increased
PTH - normal
What are the expected values of serum: Calcium Phosphate ALP PTH in someone with osteopetrosis?
Calcium - normal
Phosphate - normal
ALP - normal
PTH - normal
How do bisphosphonates work?
Analogues of pyrophosphate (a molecule thatdecreases demineralisation in bone)
They inhibit osteoclasts by reducing recruitment + promoting apoptosis
What are bisphosphonates used to treat?
Prevention and treatment of osteoporosis
Hypercalcaemia
Paget’s disease
Pain from bone metatases
What are the AEs of bisphosphonates?
Oesophagitis, oesophageal ulcers (esp. alendronate)
Osteonecrosis of the jaw
Increased risk of atypical stress fractures of proximal femoral shaft
Acute phase response: fever, myalgia, arthalgia following administration
Hypocalcaemia (due to Ca efflux from bone)
How do bisphosphonate tablets need to be taken?
On empty stomach in the morning at least 30m before breakfast
Sitting upright/standing for 30m
Swallow with plenty of water
When should you co-prescribe vitamin D/Ca with bisphosphonates?
Vit D always
Ca if dietary intake is inadequate
When should you stop bisphosphonates?
After 5 years if the patient is <75, femoral neck T score of >2.5 + low risk according to FRAX/NOGG
What is temporal arteritis?
Large vessel vasculitis
What condition overlaps with temporal arteritis?
Polymyalgia rheumatica
What are the features of temporal arteritis?
Patient usually >60 Rapid onset, <1m Headache Jaw claudication Visual disturbances (secondary to anterior ischaemic optic neuropathy) Tender, palpable temporal artery 50% have features of PMR Lethargy, depression, low grade fever, anorexia, night sweats
What are features of PMR?
Aching
Morning stiffness in proximal limb muscles
What investigations should you do for temporal arteritis?
Inflammatory markers, expect ESR >50, elevated CRP
Temporal artery biopsy (NB skip lesions may be present)
CK and EMG normal
How do you treat temporal arteritis?
High dose prednisolone (should be dramatic response if not reconsider diagnosis)
Urgent ophthalmology review for those with visual symptoms (on the day)
What conditions are associated with cANCA antibodies?
Granulomatosis with polyangiitis (wegener’s)
What conditions are associated with pANCA?
Churg strauss syndrome, primary sclerosing cholangitiis, sometimes granulomatosis with polyangiitis
Others: UC, connective tissue dx (e.g. RA, SLE, Sjogren’s), autoimmune hepatitis
What is the most common target for cANCA?
Serine protease 3
What is the most common target for pANCA?
Myeloperoxidase
What is Marfan’s syndrome?
Autosomal dominant connective tissue disorder
What is the aetiology of Marfan’s syndrome?
FBN1 gene defect on chromosome 15 that encodes for the protein fibrillin 1
What are the features of Marfan’s?
Tall stature with arm span to height ratio >1.05
High arched palate
Arachnodactyly
Pectus excavatum
Scoliosis of >20 degrees
Heart: dilatation of aortic sinuses (may –> aortic aneurys, aortic dissection, aortic regurg, mitral valve prolapse)
Lungs: repeated pneumothoraces
Eyes: upward lens dislocation, blue sclera, myopia
Dural ectasia
What is dural ectasia?
Ballooning of the dural sac at the lumbrosacral level
What treatments have extended the life expectancy of those with Marfan’s?
Regular echos, beta-blockers, ACEi
What is osteomalacia?
Normal bony tissue but decreased mineral content
Rickets if growing, osteomalacia after epiphysis fusion
What can cause osteomalacia?
Vit D deficiency, e.g. malabsorption, lack of sunlight, diet Renal failure Drug induced, e.g. anticonvulsants Vitamin D resistant, inherited Liver disease, e.g. cirrhosis
What are the features of Rickets?
Knock-knee, bow legs, features of hypocalcaemia
What are the features of osteomalacia?
Bone pain, fractures, muscle tenderness, proximal myopathy
What investigations should you do in suspected ostemalacia?
25(OH) vitamin D: low
Alk phos: raised
Ca, phos: low
X-Ray: children: cupped, ragged metaphyseal surfaces, adults: translucent bands (Looser’s zones or pseudofractures)
How do you treat osteomalacia?
Ca with vit D supplements
What does the histology of PMR show?
Vasculitis with giant cells
Characteristically skips certain sections of affected artery while damaging others
What arteries are most affected in PMR?
Muscle bed arteries
What are the typical features of PMR?
Patient typically >60
Usually rapid onset (<1m)
Aching, morning stiffness in proximal limb muscles
Also mild polyarthalgia, lethargy, depression, low grade fever, anorexia, night sweats
What investigations should you do in PMR?
ESR > 40 mm/hr
Note CK and EMG normal
How do you treat PMR?
Prednisolone e.g. 15mg od
Expect dramatic response
How does azathioprine work?
It is metabolised to the active compound mercaptopurine, a purine analogue that inhibits purine synthesis
How do you test for azathioprine toxicity?
Thiopurine methyltransferase test - TPMT deficiency predisposes to azathioprine related pancytopenia
What adverse effects are associated with azathioprine?
Bone marrow depression NV Pancreatitis Increased risk of non-melanoma skin cancer Agranulocytosis/myelosupression
What drug should you be careful about prescribing alongside azathioprine?
Allopurinol
A significant reaction may occur
Use lower doses of azathioprine
What is Sjogren’s syndrome?
An autoimmune disorder affecting exocrine glands –> dry mucosal surfaces
Can be primary/secondary to RA/other connective tissue dx
In which gender is Sjogren’s syndrome more common?
Females
For what condition is there a marked increased in risk of in Sjogren’s syndrome?
Lymphoid malignancy
What are the features of Sjogren’s syndrome?
Dry eyes (keratoconjunctivitis sicca) Dry mouth Vaginal dryness Arthalgia Raynaud's, myalgia Sensory polyneuropathy Recurrent episodes of parotitis Renal tubular acidosis
What antibodies are associated with Sjogren’s syndrome?
RF in nearly 100%
ANA 70%
AntiRo, AntiLa
What test can do you for Sjogren’s syndrome?
Schirmer’s test (filter paper near conjunctival sac to measure tear formation)
What does the histology show in Sjogren’s syndrome?
Focal lymphocytic infiltration
How do you manage Sjogren’s syndrome?
Artificial saliva + tears
Pilocarpine may stimulate saliva production
How does methotrexate work?
It is an antimetabolite that inhibits dihydrofolate reductase (an enzyme essential for the synthesis of purines and pyrimidines)
What are the indications for methotrexate use?
Inflammatory arthritis (esp. RA)
Psoriasis
ALL
What are the adverse effects of methotrexate?
Mucositis Myelosupression Pneumonitis Pulmonary fibrosis Liver fibrosis
What is the BNFs advice on methotrexate + pregnancy?
Avoid pregnancy for at least 6m after treatment cessation
Men should use effective contraception until 6m after treatment
What should you co-prescribe with methotrexate?
Folic acid 5mg
What is the recommended starting dose of methotrexate?
7.5mg
Only one strength of methotrexate should be prescribed - what is this?
2.5mg
What drugs should you avoid co-prescribing with methotrexate?
Trimethoprim
(increases risk of marrow aplasia as trimethoprim + methotrexate are both folate antagonists so –> pancytopenia/myelosuppression putting pt at risk of severe infection/bleeds)
Aspirin
(increases risk of methotrexate toxicity due t reduced excretion)
How do you treat methotrexate toxicity?
Folinic acid
Which HLA allele is reactive arthritis associated with?
HLA-B27
What is Reiter’s syndrome?
Triad of urethritis, conjunctivitis and arthritis
Was originally following dysenteric illness in WW2, but most commonly due to STIs now
What is reactive arthritis?
Arthritis that develops following an infection where the organism cannot be recovered from the joint
What are the features of reactive arthritis?
Develops after 4-6 weeks of initial infection
Symptoms generally last about 4-6m
Asymmetrical oligoarthritis of lower limbs
Dactylitis
Urethritis
Conjuncitivitis, anterior uveitis
Circinate balanitis, keratoderma blenorrhagica
What is keratoderma blenohagica?
Waxy brown/yellow papules on palms/soles
What HLA allele is ankylosing spondylitis associated with?
HLA-B27
In which group of people is ankylosing spondylitis most common?
Men, 20-30yo
What investigations can you use in ankylosing spondylitis?
ESR, CRP typically raised but normal levels do not exclude AS
HLA-B27 not useful as it is +ve in 10% of normal patients
Plain X-Ray of the SI joint is most useful for diagnosis
What are some later changes of ankylosing spondylitis you may see on X-Ray?
Sacroilitis - subchondral erosions, sclerosis
Squaring of lumbar vertebrae
Bamboo spine
Syndesmophytes (due to ossification of outer fibres of annulus fibrosus)
CXR - atypical fibrosis
What might spirometry show in ankylosing spondylitis?
Restrictive pattern due to pulmonary fibrosis, kyphosis, ankylosis of costovertebral joints
What is the management for ankylosing spondylitis?
Regular exercise, e.g. swimming NSAIDs 1st line Physio DMARDs if peripheral joint involvement Anti-TNF therapy should be given to patients with persistently high dx activity despite conventional Rx (e.g. etanercept)
What antibodies tend to be positive in SLE?
ANA 99%
RF 20%
anti-dsDNA very specific to SLE
Anti-Sm - even more specific
Others - anti-u1, SS-A (anti-Ro), SS-B (anti-La)
How do you monitor disease progression in SLE?
ESR (during active dx, CRP characteristically normal)
C3, C4 levels low during active disease (formation of complexes leads to consumption of complement)
Anti-dsDNA titres can be used to monitor disease
What is the different between Raynaud’s disease and Raynaud’s phenomenon?
Raynaud’s disease = primary
Raynaud’s phenomenon = secondary
In which group of people does Raynaud’s most commonly present?
Women in their 30s with bilateral symptoms
In someone presenting with Raynaud’s disease, what factors would suggest underlying connective tissue disease?
Onset after 40 years Unilateral symptoms Rashes Presence of Abs Features which may suggest SLE, RA (e.g. recurrent miscarriages, arthritis) Digital ulcers, calcinosis Chillblains
What are some secondary causes of Raynauds?
Connective tissue dx (scleroderma, RA, SLE) Leukaemia Type 1 cyroglobulinaemia, cold agglutins Use of vibrating tools COCP, ergot Cervical rib
How do you manage Raynaud’s?
First line: CCB, e.g. nifedipine
IV prostacycline infusions
In which group of people is SLE more common?
Women
Afro-carribbean origin
What are the general features of SLE?
Fatigue
Fever
Mouth ulcers
Lymphadenopathy
What are the skin features of SLE?
Malar (butterfly) rash that spares the nasolabial folds
Discoid rash (scaly, erythematous, well demarcated in sun-exposed areas)
Photosensitivity
Raynaud’s phenomenon
Livedo reticularis
Non-scarring alopecia
What are the MSK features of SLE?
Arthalgia
Non-erosive arthritis
What are the CV features of SLE?
Pericarditis
Myocarditis
What are the respiratory features of SLE?
Pleurisy
Fibrosing alveolitis
What are the renal features of SLE?
Proteinuria
Diffuse proliferative GN
What are the neuropsychiatric features of SLE?
Anxiety, depression
Psychosis
Seizures
What is rheumatoid factor?
Circulating antibody (usually IgM) that interacts with the Fc portion of the patients own IgG
How can RF be detected?
Rose-Waaler test: sheep red cell agglutination
Latex agglutination test (less specific)
What % of RA patients have a +ve RF?
70-80%
High titre levels assoc. w. severe progressive dx
In which conditions is RF commonly +ve?
Sjogren's 100% Felty's syndrome 100% Infective endocarditis 50% SLE 20% Systemic sclerosis 30% General pop 5% Rarely: TB, HBV, EBV, leprosy
When can you detect anti-cyclic citrullinated peptide antibody in those with RA?
May be detectable up to 10 years before development of RA
When should you test for anti-CCP antibodies?
In those with suspected RA but negative RF
What are the risk factors for osteoporosis as included in the FRAX risk assessment tool?
Hx of glucocorticoid use RA Alcohol excess Hx of parental hip fracture Low BMI Current smoking
Apart from the ones included on FRAX, what other risk factors are there for osteoporosis?
Sedentary lifestyle Premature menopause Caucasians and asians Endocrine disorders (e.g. hyperthyroidism, hypogonadism (e.g. Turner's), growth hormone deficiency, hyperparathyroidism, DM Multiple myeloma, lymphoma IBD, malabsorption, gastrectomy, liver disease CKD Osteogenesis imperfecta, homocystinuria
What medications can worsen osteoporosis?
Glucocorticoids SSRIs Anti-epileptics PPIs Glitazones Long term heparin therapy Aromatase inhibitors, e.g. anastrozole
Why should you investigate osteoporosis for secondary causes?
To exclude diseases that mimic osteoporosis (e.g. osteomalacia)
To identify the cause of osteoporosis + contributory factors
Assess the risk of subsequent fractures
To select the most appropriate form of treatment
What investigations are recommended for diagnosing osteoporosis?
Hx, Ex FBC, ESR/CRP Serum Ca, albumin, creatinine, phosphate, alk phos, liver transaminases TFTs DXA
What other investigations may be useful in osteoporosis for specific indications?
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
What are the minimum baseline bloods that should be ordered for all patients with suspected osteoporosis?
FBC UE LFTs Bone profile CRP TFTs
What is Behcet’s syndrome?
A complex multisystem disorder associated with presumed autoimmune mediated inflammation of the arteries and veins
What is the aetiology of Behcet’s syndrome?
Unknown
What is the classic triad of Behcet’s syndrome?
Oral ulcers
Genital ulcers
Anterior uveitis
In which groups of people is Behcet’s most common?
Eastern Mediterranean countries
Men
20-40yos
What HLA allele is Behcet’s associated with?
HLA B51
What are the features of Behcet’s syndrome?
1. oral ulcers, 2. genital ulcers, 3. anterior uveitis Thrombophlebitis and DVT Arthritis Neurological involvement Abdo pain, diarrhoea, colitis Erythema nodosum
What is used to diagnose Behcet’s syndrome?
No definitive test
Based on clinical findings
Positive pathergy test is suggestive (puncture site following needle prick becomes inflamed with small pustule forming)
Where is the gene for HLA antigens found?
Chromosome 6
What diseases are strongly associated with HLA-A3 antigen?
Haemochromatosis
What diseases are strongly associated with HLA-B51 antigen?
Behcet’s disease
What diseases are strongly associated with HLA-B27 antigen?
Ankylosing spondylitis
Reiter’s syndrome
Acute anterior uveitis
What diseases are strongly associated with HLA-DQ2/8 antigen?
Coeliac disease
What diseases are strongly associated with HLA-DR2 antigen?
Nacrolepsy
Goodpasture’s
What diseases are strongly associated with HLA-DR3 antigen?
Dermatitis Herpetiformis
Sjogren’s syndrome
Primary biliary cirrhosis
What diseases are strongly associated with HLA-DR4 antigen?
T1DM
RA
What is chronic fatigue syndrome?
At least 4 months of disabling fatigue affecting mental + physical function more than 50% of the time in the absence of other disease which may explain symptoms
What are some other features of chronic fatigue syndrome?
Sleep problems Muscle/joint pains Headaches Painful lymph nodes without enlargement Sore throat Cognitive dysfunction (e.g. difficulty thinking, inability to concentrate...) Physical/mental exertion makes worse General malaise, flu like symptoms Dizziness Nausea Palpitations
What investigations should you do in chronic fatigue syndrome and why?
To exclude other pathology
FBC, UE, LFTs, TFTs, CRP, ESR, Ca, ferritin, coeliac screening, urinalysis
How do you manage chronic fatigue syndrome?
CBT
Graded exercise therapy
Pacing (organising activities to avoid tiring)
Low dose amitriptyline may be useful for poor sleep
Referral to pain management if it is a predominant feature
What is Ehler-Danlos syndrome?
AD connective tissue disorder that mostly affects type III collagen
Leads to tissue being more elastic than normal –> joint hypermobility + increased elasticity of skin
What are the features of Ehler-Danlos syndrome?
Elastic, fragile skin
Joint hypermobility + recurrent dislocation
Easy bruising
Aortic regurgitation, mitral valve prolapse, aortic dissection
SAH
Angioid retinal streaks
What is osteogenesis imperfecta?
Group of disorders of collagen metabolism resulting in bone fragility + fractures
How is osteogenesis imperfecta inherited?
AD
What is the aetiology of osteogenesis imperfecta?
Abnormality in type 1 collagen due to decreased synthesis of pro-alpha 1 or pro-alpha 2 collagen polypeptides
If the X-Ray is negative for SI joint involvement in AS but suspicion of AD is high what should be the next step in investigation?
MRI
What imaging findings confirm the diagnosis of AS?
Signs of inflammation in the SI joints (bone marrow oedema)
Name one of the most important risk factors for osteoporosis
Use of corticosteroids
The risk of osteoporosis is thought to rise significantly once an individual is taking what dose of steroids?
Equivalent of prednisolone 7.5mg a day for 3m+
If a patient is going t be taking steroids >3m and are at risk of osteoporosis when should bone protection start?
ASAP
What are the two groups that patients at risk of corticosteroid induced osteoporosis are split into?
- > 65/previously had a fragility fracture –> offer bone protection
- <65 –> offer bone scan + results dependent on T score
> 0 - reassure; 0–>-1.5 - repeat bone density scan in 1-3y,
What is the first line treatment for corticosteroid induced osteoporosis?
Alendronate
Ensure Ca and vit D replete
When is treatment for osteoporosis indicated?
Following osteoporotic fragility fracture in a post-menopausal women confirmed to have osteoporosis (T score -2.5 or less)
(DEXA scan be not be necessary if clinician considers inappropriate/unfeasible)
Who with osteoporosis should be offered vit D/Ca supplements?
All, expect those who are replete
What is the first line treatment for osteoporosis?
Alendronate
What % of pts cannot tolerate alendronate + why is this usually?
25%
Upper GI problems
What is second line treatment for osteoporosis?
Risedronate or etidronate
What treatments are recommended for those with osteoporosis who cannot take bisphosphonates?
Stronium ranelate
Raloxifene
What evidence is there for alendronate/risedronate/etidronate?
Reduce risk of vertebral and non-vertebral fractures
What is the option for a once a month oral bisphosphonate?
Ibandronate
What kind of drug is raloxifene?
Selective oestrogen receptor modulator
What is the evidence behind raloxifene?
Reduces vertebral fractures, prevents bone loss + increases bone density in spine + femur
What are the AEs of raloxifene?
May worsen menopausal symptoms
Increases risk of TE events
What is an additional benefit of raloxifene?
May reduce risk of breast cancer
What is the action of strontium ranelate?
Increases deposition of new bone by osteoblasts (promotes differentiation of pre-osteoblasts to osteoblasts)
Reduces resorption of bone by inhibiting osteoclasts
What is the issue with strontium ranelate?
Concerns re safety profile
Must only be prescribed by a specialist if there are no other treatments
What are CIs for strontium ranelate?
Hx of CV dx or significant CV dx or prev. VTE
What are the AEs of strontium ranelate?
Increased risk of CV event
Increased risk of TE events
Serious skin reactions, e.g. SJS
What is the action of denosumab?
Human monoclonal antibody that inhibits RANK ligand, which in turn inhibits the maturation of osteoclasts
How is denosumab given?
Single sc injection every 6m
What is teriparatide?
Recombinant form of parathyroid hormone
What is teriparatide good at?
Increasing bone mineral density
What evidence does HRT have for osteoporosis management?
Reduces incidence of vertebral fractures + non-vertebral fractures
When is the ONLY situation you would use HRT for osteoporosis management?
If pt also having vasomotor symptoms
What non-medication treatments may be useful in the management of osteoporosis?
Hip protectors - compliance is an issue
Falls risk assessment - consider for high risk pts
What is the most common organism causing septic arthritis?
Staph aureus
What organism should be considered for causing septic arthritis in young sexually active individuals?
Neisseria gonorrhoea
In adults, where is the most common location for septic arthritis?
Knee
What criteria is used to assess the probability of septic arthritis in kids?
Kocher's criteria - 1 point for each of: - Non wt bearing - Fever >38.5 - WCC >12x10^9/L - ESR >40mm/hr
(2 points = 40% risk, 3 = 93%, 4 = 99%)
How is septic arthritis managed?
IV antibiotics (flucloxacillin/clindamycin) for 6-12w Needle aspiration to decompress the joint Athroscopic lavage may be req.
What should be done before treating septic arthritis?
Take sample of synovial fluid before antibx are started!
What is dermatomyositis?
Inflammatory disorder causing SYMMETRICAL, proximal muscle weakness + skin lesions
What is the aetiology of dermatomyositis?
Idiopathic
Associated with connective tissue dx
Associated with underlying malignancy
What malignancies are most commonly associated with dermatomyositis?
Ovarian, breast, lung
What is polymyositis?
Variant of dermatomyositis where skin manifestations are not prominent
What are the skin features in dermatomyositis?
Photosensitive Macular rash over back + shoulders Helitrope rash in periorbital region Gottron's papules Mechanics hands - v. dry and scaly, with cracks on palmar + lateral aspects of fingers Nail fold capillary dilatation
What are Gottron’s papules?
Roughened red papules over extensor surface of fingers
What are the non-skin manifestations of dermatomyositis?
Proximal muscle weakness +/- tenderness Raynaud's Respiratory muscle weakness Interstitial lung dx, e.g. fibrosing alveolitis/organising pneumonia Dysphagia, dysphonia
What antibody do 80% of those with dermatomyositis have?
ANA
What antibody do 30% of those with dermatomyositis have?
Aminoactyl-tRNA synthases (e.g. Jo-1, Abs to signal recognition particle, anti-Mi-2 antibodies)
What antibody is generally associated with RA?
Anti-CCP antibody
What antibody is generally associated with SLE?
Anti-dsDNA
What antibody is generally associated with diffuse systemic sclerosis?
Anti-Scl-70 antibodies
What is anti-mitochondrial antibodies (AMAs) associated with?
Primary biliary cirrhosis
What two conditions is hydroxychloroquine used in?
RA
Systemic/discoid lupus erythematosus
What adverse effect is associated with hydroxychloroquine?
Bull’s eye retinopathy - my result in severe + permanent vision loss
What 1 examination/investigation is required before starting a patient on hydroxychloroquine?
Baseline ophthalmological examination
thereafter annual screening
Can hydroxychloroquine be used in pregnancy?
Yes
What HLA allele is associated with ankylosing spondylitis?
HLA-B27
What is the typical history of someone presenting with ankylosing spondylitis?
Young man who presents with low back pain + stiffness of insidious onset
Stiffness worse in morning + improves with exercise
Pt may experience pain at night, which improves on getting up
What will you see on examination of someone with AS?
Reduced lateral flexion
Reduced forward flexion (Schober’s test)
Reduced chest expansion
What is Schober’s test?
Draw line 10cm above + 5cm below back dimples (L5)
The distance between the two lines should increase by >5cm when the pt bends as far forward as possible
What are other features associated with AS?
The A's: Apical fibrosis Anterior uveitis (in 1/3rd) Aortic regurgitation Achilles tendonitis AV node block Amyloidosis
Cauda equina syndrome
Peripheral arthritis
When is the typical onset of SLE?
20-40y
What kind of hypersensitivity reaction is SLE?
Type 3
What HLA alleles are associated with SLE?
HLA B8, DR2, DR3
What is thought to cause SLE?
Immune system dysregulation leading to immune complex formation
Immune complexes can deposit in any organ incl. skin, joints, kidneys, brain
What should all pts with OA be offered?
Help with wt loss
Advice re. local muscle strengthening exercises + general fitness
What are the first line analgesics for OA?
Paracetamol + topical NSAIDs (for knee/hand)
What are second-line analgesics for OA?
NSAIDs/COX-2 inhibitors, opioids, capsaicin cream, IA corticosteroids
What must be co-prescribed with COX-2 inhibitors/NSAIDs?
PPI
What drug that if the pt was already on would CI prescribing COX-2 inhibitors/NSAIDs?
Aspirin
What are non-pharmacological treatments for OA?
Supports + braces
TENS
Shock absorbing insoles/shoes
If all conservative measures for OA management fail what are the options?
Refer for consideration of joint replacement
What is glucosamine?
Normal constituent of glycosaminoglycans in cartilage and synovial fluid
What is the evidence re glucosamine use in treatment of OA?
Significant improvement in symptoms + reduces joint space narrowing
However NICE don’t recommend it
What is osteoporosis?
Disorder characterised by loss of bone mass
Define osteoporosis
Bone mineral density of less than 2.5 standard deviations below the young adult mean density
What does osteoporosis put pts at risk of?
Fragility fractures (e.g. neck of femur fracture, which carries significant morbidity + mortality)
What % of post-menopausal women will suffer an osteoporotic fracture at some point?
50%
What are the major risk factors for osteoporosis?
Age, female sex
What are other risk factors for osteoporosis?
Corticosteroids use Smoking Alcohol Low BMI FH
What screening tools can you use for osteoporosis? What do these assess?
FRAX/QFracture
Assess 10 year risk of pt developing a fragility fracture
Which pts should be assessed for osteoporosis?
Those who have sustained a fragility fracture
How is BMD assessed?
Dual energy X-Ray absorptiometry (DEXAscan) from which a T score can be worked out
What bones does the DEXA scan use?
Lumbar spine
Hip
What T score in either the hip or the lumbar spine warrants starting treatment for osteoporosis?
What is the first line treatment for osteoporosis?
Bisphosphonate, e.g. alendronate
When are bisphosphonates contraindicated?
If eGFR <35
What are some respiratory extra-articular complications of RA?
Pulmonary fibrosis, pleural effusion, pulmonary nodules, bronchiolitis obliterans, methotrexate pneumonia, pleurisy
What are some ocular extra-articular complications of RA?
Keratoconjunctivitis sicca, episcleritis, scleritis, corneal ulceration, keratitis, steroid induced cataracts, chloroquine retinopathy
What is an MSK extra-articular complications of RA?
Osteoporosis
What is a CV extra-articular complications of RA?
IHD (has similar risk as T2DM)
What is a psychological extra-articular complications of RA?
Depression
What is an immunological extra-articular complications of RA?
Increased risk of infection
What two conditions are less commonly associated with RA?
Felty’s syndrome
Amyloidosis
What are the features of Felty’s syndrome?
RA
Splenomegaly
Low WCC
What organisms can cause the post-dysenteric form of reactive arthritis?
Shigella flexneri Salmonella typhimurium Salmonella enteritidis Yersinia enterocolitica Campylobacter
What organisms can cause the post-STI form of reactive arthritis?
Chlamydia trachomatis
What is the management of reactive arthritis?
Analgesics, NSAIDs, IA steroids
Sulfasalazine, methotrexate sometimes used for persistent symptoms
How long does it usually take for reactive arthritis to clear up?
Usually within 1 y
What would you expect to find of the synovial fluid in reactive arthritis?
Cloudy yellow colour
Culture negative
No crystals
WCC 20, 000/mm
What is the most common Ig?
IgG
What is the action of IgG?
Enhances phagocytosis of viruses/bacteria
Fixes complement + passes to foetal circulation
What is the most predominant Ig in breast milk?
IgA
Where is IgA mostly found?
Secretions of digestive, respiratory and urogenital tracts/systems
What is the action of IgA?
Provides localised protection on mucous membranes
What is the action of IgM?
First Ig to be secreted in response to an infection
Fixes complement b
Does IgM pass to the foetal circulation?
No
What is the role of IgD antibodies?
Largely unknown but involved in activation of B cells
What is the action of IgE?
Mediates T1 hypersensitivity reactions by binding to Fc receptors on the surface of mast cells + basophils
Also provides immunity to parasite, e.g. helminths
What is the least abundant Ig in the serum?
IgE
What is the structure of IgE?
Monomer
What is the structure of IgD?
Monomer
What is the structure of IgM?
Penamer
What is the structure of IgA?
Monomer/dimer
What is the structure of IgG?
Monomer
What can predispose to gout?
Decreased excretion of uric acid
Increased production of uric acid
Lesch-Nyhan syndrome
What things can cause decreased excretion of uric acid?
Drugs, e.g. diuretics
CKD
Lead toxicity
What things can cause increased production of uric acid?
Myeloproliferative/lymphoproliferative disorder
Cytotoxic drugs (e.g. chemotherapy)
Severe psoriasis
What is the pathophysiology of Lesch-Nyhan syndrome?
Hypoxanthine-guanine phosphoribosyl transferase (HGPRTase) deficiency
How is Lesch-Nyhan syndrome inherited?
X-linked recessive
What are the features of Lesch-Nyhan syndrome?
Gout Renal failure Neurological deficits Learning difficulties Self-mutilation
What kind of muscle weakness do you get in PMR?
No true weakness of limb girdles
Weakness of muscles is due to myalgia (pain inhibition)
How would you describe the pain in OA?
Exacerbated by exercise, relieved by rest
What movement is affected first in hip OA?
Internal rotation
What are risk factors for hip OA?
Age
Obesity
Prev. joint problems
When is the pain from inflammatory arthritis most prominent?
Morning
What other features will be present in inflammatory arthritis?
Systemic features, raised inflammatory markers
What features may you see in referred lumbar spine pain?
Femoral nerve compression may cause referred hip pain
Femoral nerve stretch test +ve
What is the femoral nerve stretch test?
Lie pt prone, extend hip joint with straight leg when bend the knee
This stretches the femoral nerve and causes pain if it is trapped
What causes greater trochanteric pain syndrome (Trochanteric bursitis)?
Repeated movement of the fibroelastic iliotibial band
What are the features of greater trochanteric pain syndrome (Trochanteric bursitis)?
Pain + tenderness over lateral thigh
What people tend to get greater trochanteric pain syndrome (Trochanteric bursitis)?
Women aged 50-70
What causes meralgia paraesthetica?
Compression of lateral cutaneous nerve of thigh
What are the symptoms of meralgia paraesthetica?
Burning over anterolateral aspect of thigh
What may avascular necrosis follow?
High dose steroid therapy or hip fracture or dislocation
When is pubic symphysis dysfunction common?
In pregnancy - ligament laxity increases in response to hormonal changes
What symptoms do you get in pubic symphysis dysfunction?
Pain over pubic symphysis with radiation to the groins + medial aspect of thighs
What kind of gait may you see in pubic symphysis dysfunction?
Waddling
When is transient idiopathic osteoporosis seen?
Uncommon condition but more seen in 3rd trimester of pregnancy
How does transient idiopathic osteoporosis present?
Groin pain + limited range of movement in the hip
May be unable to wt bear
ESR may be elevated
What is a T score based off of?
Bone mass of a young reference population
What scores a T score of -1 mean?
Bone mass of one SD below the young reference population
What is the Z score adjusted for?
Age, gender, ethnic factors
T score >-1 =?
Normal
T score of -1 to -2.5 =?
Osteopenia
T score >-2.5
Osteoporosis
What usually results in lateral epicondylitis?
Unaccustomed activity, e.g. playing tennis or house painting
What are the features of lateral epicondylitis?
Pain/tenderness at lateral epicondyle
Worse on wrist extension against resistance/supination of forearm with elbow extended
How long do bouts of lateral epicondylitis tend to last?
6m-2y
What is involved in the management of lateral epicondylitis?
Advice re avoiding muscle overload
Simple analgesia
Steroid injection
Physio
What are anti-jo antibodies also known as?
Ab against aminoacyl-tRNA
What features are associated with antisynthase syndrome?
Myositis
Interstitial lung disease
Thickened + cracked skin of hands
Raynaud’s
What is antisynthase syndrome?
Subtype of dermatomyositis
What are poor prognostic features in rheumatoid arthritis?
RF +ve Poor functional status at presentation HLA DR4 X-ray - early erosions Extra-articular features, e.g. nodules Insidious onset Anti-CCP antibodies Female gender
What are the features of drug induced lupus?
Arthalgia
Myalgia
Skin (e.g. malar rash) + pulmonary involvement (e.g. pleurisy)
What antibodies are positive in drug induced lupus?
ANA 100%
Antihistone in 80-90%
Anti-Ro/anti-Smith less commonly +ve
What are the most common causes of drug induced lupus?
Procainamide
Hydralazine
What are the less common causes of drug induced lupus?
Isoniazid
Minocycline
Phenytoin
In which patients may you consider colchicine instead of NSAIDs for treating an acute attack of gout?
Elderly pts on warfarin (puts them at risk of GI haemorrhage)
What are the rotator cuff muscles?
SItS - small t for teres minor Supraspinatus Infraspinatus teres minor Subscapularis
What is the action of supraspinatus?
Abducts arm before deltoid (first 20 degrees)
What is the action of infraspinatus?
Rotates arm laterally
What is the action of teres minor?
Adducts + rotates arm laterally
What is the action of subscapularis?
Adducts + rotates arms medially
What does calcinosis look like?
White deposits
What symptoms do patients get with oesophageal dysmotility?
Dysphagia
What does sclerodactyly look like?
Thickened skin on tops of hands an inability to straighten fingers
What is telangiectasia?
Excessive number of spider naevi
What is the mechanism of type 1 hypersensitivity reactions?
Antigen reacts with IgE bound to mast cells
Give examples of T1 HS reactions
Anaphylaxis
Atopy (e.g. asthma, hayfever, eczema)
What is the mechanism of type 2 hypersensitivity reactions?
IgG or IgM binds to antigen on cell surface
Give examples of T2 HS reactions
Autoimmune haemolytic anaemia ITP Goodpasture's syndrome Pernicious anaemia Acute haemolytic transfusion reactions Rheumatic fever Pemphigus vulgaris / bullous pemphigoid
What is the mechanism of type 3 hypersensitivity reactions?
Free antigen + antibody combine
Give examples of T3 HS reactions
Serum sickness
Systemic lupus erythematosus
Post-streptococcal glomerulonephritis
Extrinsic allergic alveolitis (especially acute phase)
What is the mechanism of type 4 hypersensitivity reactions?
T-cell mediated
Give examples of T4 HS reactions
TB/tuberculin skin reaction Graft versus host disease Allergic contact dermatitis Scabies Extrinsic allergic alveolitis (especially chronic phase) MS Guillain-Barre syndrome
What is the mechanism of type 5 hypersensitivity reactions?
Antibodies that recognise and bind to cell surface receptors and stimulate them or block ligand binding
Give examples of T5 HS reactions
Grave’s disease
Myasthenia gravis
What drug should those with RA be given as soon as diagnosed?
DMARD + short dose of bridging prednisolone
What are other treatment options for RA?
Analgesia
Physio
Surgery
What should be used to monitor response to treatment in RA?
CRP and disease activity (e.g. DAS28)
How are flares in RA managed?
Corticosteroids (oral/intramuscular)
What is the most widely used DMARD in RA?
Methotrexate
What monitoring is req. for pts on methotrexate?
LFTs + FBC (due to risk of liver cirrhosis + myelosuppression)
What are 3 other DMARDs apart from methotrexate that may be used to treat RA?
Sulfasalazine
Leflunomide
Hydroxychloroquine
If a pt with RA is having an inadequate response to DMARDs what is the next step in Rx?
If inadequate response to at least 2 DMARDs can start TNF-inhibitor
What are the four TNF-inhibitors used in the treatment of RA?
Etanercept
Infliximab
Adalimumab
Abatacept
How does etanercept work?
Recombinant human protein (anti-CD20 monoclonal Ab), acts as a decoy for TNF-a
What are AEs of etanercept?
Demyelination
Reactivation of TB
How is etanercept administered?
SC
How does infliximab work?
Monoclonal Ab, binds to TNF-a and prevents it binding with TNF receptors
How is infliximab administered?
IV
What are the AEs of infliximab?
Reactivation of TB
What is adalimumab?
Monoclonal Ab
How is adalimumab administered?
SC
What cell does rituximab lead to depletion in?
B cells
How does abatacept work?
Fusion protein that modulates a key signal required for activation of T lymphocytes –> decreased T cell proliferation + cytokine production
Does psoriatic arthritis tend to occur before or after the skin changes?
Tends to precede
What % of pts with psoriasis skin lesions develop an arthropathy?
10-20%
What are the types of psoriatic arthropathy?
Rheumatoid like polyarthritis Asymmetric oligoarthritis (typically affects hands/feet) Sacroilitis DIP joint disease Arthritis mutilans
What is arthritis mutilans?
Severe deformity of fingers/hands - ‘telescoping fingers’
How should you treat psoriatic arthropathy?
Like RA
What deformity may seen in hand x-ray of someone with psoaritic arthritis?
Pencil in cup deformity
Plantar spur
When is it appropriate to start trying to use anti-TNFa drugs in someone with axial AS?
If they have tried and failed on 2 different NSAIDs and meets criteria for active disease on 2 occasions 12w apart
List secondary causes of Raynaud’s
Connective tissue dx (e.g. scleroderma most common)
Leukaemia
Type 1 cryoglonulinaemia, cold agglutinins
Use of vibrating tools
Drugs, e.g. COCP, ergot
Cervical rib
What kind of crystals are seen in gout?
Monosodium urate
Needle-shaped, negatively birefringent under polarised light
What kind of crystals are seen in pseudogout?
Calcium pyrophosphate
Rhomboid positively birefringent under polarised light
What crystals are seen in OA?
Calcium phosphate due to degeneration of cartilage no birefringence
What crystals are see in RA?
Cholesterol crystals
Rhomboid + negatively birefringent
What mnemonic can be used to remember some causes of gout?
DART - diuretics, alcohol, kidney disease, trauma
If a patient on allopurinol for gout prophylaxis has an acute attack, should their allopurinol be stopped?
No - continue it
List possible differentials for polyarthritis
rheumatoid arthritis SLE seronegative spondyloarthropathies Henoch-Schonlein purpura sarcoidosis tuberculosis pseudogout viral infection: EBV, HIV, hepatitis, mumps, rubella
What are interferons and cytokines in the body released in response to?
Viral infections
Tumours
INF-a and INF-b bind to what type of receptors?
Type 1
What type of receptors does IFN-gamma bind to?
Type 2
What cells produce INFa?
Leucocytes
What is the action of INFa?
Antiviral action
In which conditions is INFa helpful?
Hepatitis B and C
Kaposi sarcoma
Metastatic renal cancer
Hairy cell leukaemia
What are adverse effects of INFa?
Depression
Flu like symptoms
What cells produce INFb?
Fibroblasts
What is the action of INFb?
Antiviral
What condition is treated with INFb?
MS (can reduce freq. of exacerbations in RRMS)
What cells produce INF-g?
Natural killer cells mostly + T helper cells
What is the action of INF-g?
Antiviral action, but more of a role in immunomodulation, esp. macrophage activation
In what diseases may INF-g be helpful?
Chronic granulomatous disease, osteopetrosis
Why can TA cause visual symptoms?
Can cause occlusion of ophthalmic artery –> blindness (irreversible)
Transient visual problems may precede complete occlusion
What is dactylitis?
Inflammation ofa digit
What can cause dactylitis?
Spondyloarthritis: psoriatic/reactive
Sickle cell disease
Rarer - TB, sarcoidosis, syphillis
What score is used to assess for hypermobility?
Beighton score
What beighton score is +ve in kids?
6/9
What beighton score is +ve in adults?
5/9
Why might you get a single central radiodense line in the spine of someone with AS?
Ossification of the supraspinous and infraspinous ligaments
Known as dagger sign
What is fibromyalgia?
Syndrome characterised by widespread pain throughout the body with tender points in specific areas
What is the causes of fibromyalgia?
Unknown
Which gender does fibromyalgia affect more?
Women
What are the features of fibromyalgia?
Chronic pain - at multiple sites or sometimes all over
Lethargy
Cognitive impairment - ‘fibro fog’
Sleep disturbance, headaches, dizziness
How is fibromyalgia diagnosed?
Clinically - American college of rheumatology classification criteria lists 9 pairs of tender points on body, if pt tendering at least 11 points fibromyalgia more likely
What is involved in the management of fibromyalgia?
Explanation
Aerobic exercise
CBT
Medications - pregabalin, duloxetine, amitriptyline
What two things are required for diagnosis of AS?
Radiological feature - sacroiliitis
Clinical feature
NOTE: squaring of vertebrae and bamboo spine are all signs but are not part of the diagnostic criteria
How long may anti-CCP antibodies may detectable for before diagnosis of RA?
10 years
What test can you do to differentiate between statin induced myopathy and PMR?
ESR -
Raised in PMR, normal in statin induced myopathy
What ages tend to get Still’s disease?
Bimodal age distribution - 15-25y and 35-46y
What are the features of Still’s disease?
Arthalgia Elevated serum derritin Salmon pink, maculopapular rash Pyrexia Lympadenopathy RF and ANA -ve
What is the pattern of the pyrexia in Still’s disease?
Typically rises in late afternoon/early evening in daily pattern + accompanies worsening of joint symptoms + rash
What criteria can be used to help diagnose still’s disease?
Yamaguchi criteria
What is the management of Still’s disease?
NSAIDs - first line to manage fever, joint pain + serositis
Trial at least a week before steroids added
If symptoms persist then consider methotrexate or IL-1/anti-TNF
What is the mechanism of action of penicillamine?
Thought to reduce IL-1 synthesis and prevent maturation of newly synthesized collagen
When might penicillamine be used?
RA Mx
What are adverse effects of penicillamine?
Rashes
Taste disturbance
Proteinuria
What can penicillamine cause in patients with Wilson’s disease?
Membranous glomerulonephropathy
Offer prophylactic bisphosphonates to those with a T score of _____ if they are on steroids/going to be on steroids for 3+ months (even if <65y)
1.5
What does joint aspirate in RA show?
High WCC (predominantly PMNs)
Yellow and cloudy
No crystals
What are typical features of RA?
Swollen, painful joints in hands + feet
Stiffness worse in morning
Gradual gets worse with larger joints becoming involved
Presentation usually insidious over a few m
Positive squeeze test
What is a squeeze test?
Discomfort on squeezing across the metacarpal or metatarsal joints
What deformities are late features of RA?
Swan neck deformity and boutonniere deformities
What is palindromic rheumatism?
Relapsing/remitting monoarthritis of different large joints
What is chondrocalcinosis?
Calcification of the cartilage
What is antiphospholipid syndrome?
Acquired disorder characterised by predisposition to both venous and arterial thromboses, recurrent foetal loss, thrombocytopenia
What is the aetiology of antiphospholipid syndrome?
Primary disorder
Secondary to other conditions, e.g. SLE
Antiphospholipid syndrome causes a paradoxical increase in what?
APTT + low platelets - due to ex-vivo reaction of lupus anticoagulant autoantibodies with phospholipids involved in the coagulation cascade
What are the features of antiphospholipid syndrome?
Venous/arterial thrombosis Recurrent foetal loss Livedo reticularis Thrombocytopenia Prolonged APTT Pre-eclampsia, pulmonary HTN
What conditions are associated with antiphospholipid syndrome?
SLE - most common
Other autoimmune disorders
Lymphoproliferative disorders
Phenothiazines
How should you manage antiphospholipid syndrome?
Initial VTE: warfarin with INR target of 2-3 for 6m
Recurrent VTE - lifelong warfarin (increase target INR to 3-4 if VTE occur while on warfarin)
Arterial thrombosis treat with lifelong warfarin aiming for INR 2-3
What might you see on the skull x-ray of someone with paget’s?
Thickening of calvarium
Ill-defined sclerotic and lucent areas
What antibody is associated with antiphospholipid syndrome?
Anti-cardiolipin antibody and lupus anticoagulant (La)
What is sulfasalazine used to treat?
IBD
RA
What kind of drug is sulfasalazine?
5-ASA
How does sulfasalazine work?
Decreases neutrophil chemotaxis alongside supressing proliferation of lymphocytes + pro-inflammatory cytokines
What are cautions for sulfasalazine use?
G6PD deficiency
Allergy to aspirin/sulphonamides (e.g. co-trimoxazole)
What adverse effects are associated with sulfasalazine?
Olgiospermia
SJS
Pneumonitis/lung fibrosis
Myelosupression, Heinz body anaemia, megaloblastic anaemia
May colour tears –> stained contact lenses
Is sulfasalazine safe to use in pregnancy and breastfeeding?
Yes
When does OI tend to present?
Childhood
What are the features of OI?
Fractures following minor trauma
Blue sclera
Deafness secondary to otosclerosis
Dental imperfections common
What things do you have to take into consideration when a patient with RA is undergoing surgery under GA?
Do lateral and anteroposterior cervical spine radiographs to screen for alantoaxial subluxation - to ensure pt goes into surgery with a Cspine collar and spine is not hyperextended on intubation
Why might you get a normal temporal biopsy in TA?
Skip lesions
What should be prescribed in RA to reduce need for NSAIDs/COX2 inhibitors?
Simple analgesia, e.g. paracetamol, codeine
What two blood tests must be negative to diagnose Still’s disease?
RF and ANA
What is a very common SE of colchicine?
Diarrhoea
What are vasculitides?
Group of conditions characterised by inflammation of BV walls
What vasculitides affect the aorta and its branches?
Takayasu’s arteritis
Buergers disease
Giant cell arteritis
What vasculitides affect large and medium sized arteries?
Buergers disease
Giant cell arteritis
Polyarteritis nodosa
What vasculitides affect medium sized muscular arteries?
Polyarteritis nodosa
Wegeners granulomatosis
What vasculitides affect small muscular arteries?
Wegeners granulomatosis
Rheumatoid vasculitis
What is Takayasu’s arteritis?
Inflammatory, obliterative arteritis affecting aorta and its branches
What are features of Takayasu’s arteritis?
Upper limb claudication
Diminished/absent pulses
ESR raised in acute phase
What is Buergers disease?
Segmental thrombotic occlusions of small and medium sized lower limb vessels
Who is Buergers disease most common in?
Young male smokers
What are the features of Buergers disease?
Proximal pulses usually present but pedal pulses loss
Acute hypercellular occlusive thrombus often present
What might you see on angiography in Buergers disease?
Tortuous corkscrew shaped collateral vessels
What kind of lesions might you see in GCA temporal artery biopsy?
Granulomatous lesions
What might you see on angiography in polyarteritis nodosa?
Saccular/fusiform aneurysms and arterial stenoses
What is Wegeners granulomatosis?
Systemic necrotising granulomatous vasculitis
What cutaneous lesions might you see in Wegeners granulomatosis?
Ulceration
Nodules
Purpura
What might you see in sinus imaging in Wegeners granulomatosis?
Mucosal thickening and air fluid levels
What are the main treatments for vasculitides?
Immunosupression
What HLA allele is associated with seronegative spondyloarthropathies?
HLA-B27
What does seronegativemean in seronegative spondyloarthropathies?
RF -ve
What are the common features of seronegative spondyloarthropathies?
Peripheral arthritis, usually asymmetrical
Sacroilitis
Enthensopathy, e.g. Achilles tendonitis, plantar fasciitis
Extra-articular manifestations e.g. uveitis, pulmonary fibrosis (upper zone), amyloidosis, aortic regurg
What are the seronegative spondyloarthropathies?
ankylosing spondylitis
psoriatic arthritis
Reiter’s syndrome (including reactive arthritis)
enteropathic arthritis (associated with IBD)
What kind of hearing loss do you get in Paget’s?
Sensorineural
After someone is on bisphosphonates for how many years can you consider stopping them?
5 years or 3 for IV zolendronate - reassess need for ongoing treatment, if T score >-2.5 can stop and review in 2y
What things would make you keep someone on bisphosphonates indefinitely?
Age >75 Glucocorticoid therapy Previous hip/vertebral fractures Further fractures on treatment High risk on FRAX scoring T score
What criteria can be used to diagnose RA?
2010 American College of Rheumatology criteria
Who should you consider a diagnosis of RA in?
Those with:
- At least 1 joint with definite clinical synovitis
- synovitis is not better explained by another disease
What score is needed on the 2010 American College of Rheumatology criteria for a diagnosis of RA?
6/10
What is the 2010 American College of Rheumatology criteria for a diagnosis of RA?
A) JOINT INVOLVEMENT 1 large joint = 0 2-10 large joints = 1 1-3 small joints = 2 4-10 small joints = 3 10 joints (at least 1 small) = 5
B. SEROLOGY
-ve RF + ACPA = 0
low +ve RF or ACPA = 2
high positive RF or ACPA = 3
C. ACUTE PHASE REACTANTS
Normal CRP + ESR = 0
Abnormal CRP or ESR = 1
D. DURATION OF SYMPTOMS
<6w = 0
>6w = 1
What investigation should you do before starting someone on TNF inhibitors?
CXR - TNF inhibitors can cause reactivation of TB
