Rheumatology Flashcards
What are the main ANCA associated vasculitis conditions?
- granulomatosis with polyangiitis
- eosinophilic granulomatosis with polyangiitis
- microscopic polyangiitis
Common features of ANCA associated vasculitis:
- renal impairment: immune complex GN (haematuria, proteinuria, increased creatinine)
- respiratory: dyspnoea, haemoptysis
- systemic: lethargy, weight loss, fatigue
- vasculitic rash
- sinusitis
cANCA (target, association, monitoring)
- seine proteinase 3
- mostly granulomatosis with polyangiitis
- some microscopic polyangiitis
- some correlation with disease activity
pANCA (target, association, monitoring)
- myeloperoxidase
- mostly eosinophilic granulomatosis with polyangiitis
- some microscopic polyangiitis
- also in UC, primary sclerosis cholangitis, anti GBM, Crohn’s
- no correlation with disease activity
Typical presentation of ankylosing spondylitis:
- HLA-B27 associated spondyloarthropathy
- more common in males 3:1 20-30yo
- present with lower back pain and stiffness, worse in morning, at night, improves with exercise
- reduced lateral flexion, forward flexion and chest expansion
What are the 8 A’s of ankylosing spondylitis:
- apical fibrosis
- anterior uveitis
- achilles tendonitis
- aortic regurgitation
- amyloidosis
- peripheral arthritis
- cauda equina
- AV node block
Investigations and signs of ankylosing spondylitis:
-increased CRP and ESR
-HLA B27 positive
x-ray sacroiliac joints:
-sacroiliitis: subchondral erosion, sclerosis
-squaring of lumbar vertebrae
-bamboo spine (late, rare)
-syndesmophytes
-apical fibrosis on CXR
spirometry: restriction
Management of ankylosing spondylitis:
- exercise
- physio
- NSAIDs
- DMARD if peripheral joint involvement
- anti-TNF for persistent disease (etanercept, adalimumab)
What is antiphospholipid syndrome and what are the typical features?
- acquired disorder of arterial and venous thromboses, recurrent foetal loss and thrombocytopaenia
- paradoxical increase in APTT
- other symptoms: livedo reticularis, pulmonary hypertension, pre-eclampsia
What are the associations of antiphospholipid syndrome and the management?
- associated: SLE, autoimmune, lymphoproliferative disorders, phenothiazines
- primary prophylaxis: aspirin
- secondary prophylaxis: lifelong warfarin (target INR 2-3 for initial and arterial, 3-4 if occurred whilst taking aspirin and warfarin)
What is antisynthetase and the features:
- autoantibodies against aminoacyl-tRNA synthetase e.g. Jo-1
- myositis
- interstitial lung disease
- dry and cracked skin of hands
- Raynaud’s
What is Behcet’s, epidemiology and features?
-multisystem disorder of autoimmune mediated inflammation of arteries and veins
-typically eastern mediterranean, men, young, HLA B51 positive, 30% FHx
Features:
-triad: genital ulcers, oral ulcers, anterior uveitis
-thrombophlebitis and deep vein thrombosis
-aseptic meningitis
-arthritis
-GI: colitis, abdominal pain, diarrhoea
-erythema nodosum
Calcium, phosphate, ALP and PTH levels in osteoporosis, osteopetrosis, Paget’s, CKD and osteomalacia:
- everything normal in osteoporosis and osteopetrosis
- Paget’s: everything normal except ALP increased
- CKD: calcium decreased, everything else increased
- Osteomalacia: calcium and phosphate decreased, everything else increased
What qualifies as CFS?
4 months of disabling fatigue affecting mental and physical function more than 50% of the time
more common in females
What can dactylitis be caused by?
- spondyloarthopathies e.g. psoriatic and reactive arthritis
- sickle cell
- rare: TB, sarcoidosis, syphilis
What is dermatomyositis?
- inflammatory disorder causing symmetrical, proximal muscle weakness and skin lesions
- idiopathic or associated with CTD or underlying malignancy
- polymyositis is variant with less skin manifestation
What are the features of dermatomyositis?
skin:
- photosensitivity
- macular rash over back and shoulder
- heliotrope rash in periorbital region
- mechanic’s hands
- Gottron’s papules
- nailfold capillary dilatation
- proximal muscle weakness and tenderness
- Raynaud’s
- respiratory muscle weakness
- interstitial lung disease
- dysphagia, dysphonia
What are the investigations of dermatomyositis?
- 80% ANA +ve
- 30% Ab to aminoacyl-tRNA synthetase (Jo-1, SRD, anti-Mi-2)
What are the features of drug induced lupus?
- arthralgia
- myalgia
- malar rash
- pleurisy
- ANA +ve
- dsDNA -ve
- anti-histone Ab +ve
- some anti-Ro, anti-Smith
Causes of drug induced lupus?
common: procainamide, hydralazine
rare: isoniazid, minocycline, phenytoin
What is EDS and what are the typical features?
- autosomal dominant CTD affecting type III collagen
- joint hypermobility
- elastic, fragile skin
- easy bruising
- aortic regurgitation, aortic dissection, mitral valve prolapse
- SAH
- angioid retinal streaks
How can you treat fibromyalgia?
- pregabalin
- duloxetine
- amitriptyline
Presentation of gout:
- form of inflammatory arthritis
- microcrystal synovitis - deposition of monosodium urate monohydrate in synovium
- chronic hyperuricaemia (uric acid >0.45mmol/L)
- episodes last several days with no symptoms in between
- pain, swelling, erythema
- most present 1st MTP joint
Radiological features of gout:
- joint effusion early sign
- well defined erosion with sclerotic margins in juxta-articular distribution
- relative joint space preservation until late
- eccentric erosions
- no periarticular osteopaenia unlike RA
- soft tissue tophi
Predisposing factors of gout:
Decreased uric acid excretion: -drugs: diuretics, aspirin -CKD -lead toxicity Increased uric acid production: -myeloproliferative/lymphoproliferative disorder -cytotoxic drugs -severe psoriasis Lesch-Nyhan syndrome
What is Lesch Nyhan syndrome?
- HGPRTase deficiency
- x-linked recessive (only boys)
- features: gout, renal failure, neuro deficits, learning difficulties, self-mutilation
Management of gout:
Acute:
- NSAIDs or colchicine
- max dose NSAIDs 1-2 days after symptoms settled
- gastroprotection - PPI
- colchicine slower onset (ADR: diarrhoea)
- if CONTRA, oral steroids (prednisolone 15mg/day)
- intra articular steroid injection
- continue allopurinol
Indications for urate lowering therapy in gout:
- > 2 attacks in 12 months
- tophi
- renal disease
- uric acid renal stones
- prophylaxis if on cytotoxic or diuretics
Use of urate lowering therapy in gout:
-allopurinol
-don’t start during attack
-initial 100mg od
-aim serum uric acid <300micromol/L
-lower initial dose if reduced eGFR
-2nd line: febuxostate (also xanthine oxidase inhibitors)
refractory cases:
-uricase - catalyses urate to allantoin
-pegloticase - rapid control hyperuricaemia
Lifestyle modifications for gout:
- reduce alcohol and avoid in acute attack
- lose weight
- avoid food high in purines: kidney, liver, seafood, oily fish, yeast products
How does greater trochanteric pain syndrome present?
- due to repeated movement of fibroelastic iliotibial band
- pain and tenderness over lateral thigh
- most common women 50-70yo
How does neuralgia paraesthetica present?
- compression of lateral cutaneous nerve of thigh
- burning sensation over anterolateral thigh
How does transient idiopathic osteoporosis present?
- uncommon condition sometimes in 3rd trimester
- groin pain associated with limited range of movement in hip
- unable to weight bear
- ESR may be elevated
Which chromosome encodes the HLA genes?
chromosome 6
What is HLA A3 associated with?
haemachromatosis
What is HLA B51 associated with?
Behcet’s
What is HLA-B27 associated with?
- ankylosing spondylitis
- Reiter’s syndrome
- acute anterior uveitis
What is HLA DQ2/8 associated with?
coeliac
What is HLA DR2 associated with?
- narcolepsy
- goodpasture’s
What is HLA DR3 associated with?
- dermatitis herpetiformis
- Sjogren’s
- primary biliary cirrhosis
What is HLA DR4 associated with?
- T1DM
- RA
Type I hypersensitivity reaction:
- anaphylactic
- antigen reacts with IgE on mast cells
- anaphylaxis, atopy
Type II hypersensitivity reaction: (7)
- cell bound
- IgG or IgM binds to antigen on cell surface
- autoimmune haemolytic anaemia, ITP, good pasture’s, pernicious anaemia, acute haemolytic transfusion reactions, rheumatic fever, pemphigus vulgaris
Type III hypersensitivity reaction: (4)
- immune complex
- free antigen and antibody combine
- serum sickness, SLE, post-streptococcal GN, extrinsic allergic alveolitis (acute phase)
Type IV hypersensitivity reaction: (7)
- delayed hypersensitivity
- T cell mediated
- tuberculosis, GVHD, allergic contact dermatitis, scabies, extrinsic allergic alveolitis (chronic phase), MS, Guillain Barre
Type V hypersensitivity reaction:
- Grave’s
- Myasthenia Gravis
What is Langerhans cell histiocytosis?
- abnormal proliferation of histiocytes
- typically child with bony lesions
- bone pain (especially skull or femur)
- cutaneous nodules
- recurrent otitis media/mastoiditis
- tennis racket shaped Birbeck granules on electromicroscopy
What is lateral epicondylitis?
- typically after unaccustomed activity in 45-55yo affecting dominant arm
- worse on wrist extension against resistance with elbow extended or supination of forearm with elbow extended
What is Marfan’s syndrome incl features and therapy?
- autosomal dominant CTD
- defect FBN1 gene on chromosome 15 (codes for fibrillin1)
- tall stature with arm span to height >1.05
- high arched palate
- arachnodactyly
- pectus excavatum
- pes planus
- scoliosis >20 degrees
- heart: dilation aortic sinuses leading to aneurysms, dissection, regurgitation, mitral valve prolapse
- lungs: repeated pneumothoraces
- eyes: upwards lens dislocation, blue sclera, myopia
- dural ectasia
- therapy: regular echocardiography monitoring and beta blockers/ACEi
What is McArdle’s disease?
- autosomal recessive type II glycogen storage disease
- myophosphorylase deficiency
- causes decreased muscle glycogenolysis
- myalgia and stiffness after exercise, cramps, myoglobinuria, decreased lactate levels during exercise
Causes of myopathies:
- polymyositis
- Duchenne/Becker muscular dystrophy, myotonic dystrophy
- endocrine: Cushing’s, thyrotoxicosis
- alcohol
Osteoarhritis vs Rheumatoid differences:
Osteoarthritis:
-mechanical wear and tear
-localised loss of cartilage, remodelling of adjacent bone, associated inflammation
-mostly in elderly
-large weight bearing joints, carpometacarpal joints, DIP, PIP joints
-pain following use, improves with rest, unilateral, no systemic
Rheumatoid arthritis:
-autoimmune
-more in women
-all ages
-MCP, PIP joints
-morning stiffness, improves with use, bilateral, systemic upset
X-ray findings in osteoarhtirtis and rheumatoid arthritis:
Osteoarthritis: -loss of joint space -subchondral sclerosis -subchondral cyst -osteophytes forming at joint margins Rheumatoid: -loss of joint space -juxta-articular -osteoporosis -periarticualr erosions -subluxation
Management of osteoarthritis:
- weight loss, muscle strengthening
- paracetamol and topical NSAIDs
- second line: oral NSAIDs/COX-2 inhibitors (+PPI), opioids, capsaicin cream, intraarticular corticosteroids
- joint replacement
- glucosamine: part of glycosaminoglycans in cartilage and synovial fluid
Osteogenesis imperfecta, features and investigations:
- brittle bone disease
- type I collagen - decreased synthesis of pro-alpha 1 or pro-alpha 2 collagen polypeptides
- autosomal dominant
- presents in childhood
- family history following minor trauma
- blue sclera
- deafness secondary to otosclerosis
- dental imperfections
- adjusted calcium, phosphate, PTH and ALP normal
Osteomalacia features and treatment:
- normal bone tissue but decreased mineral content
- rickets if whilst growing: knock-knee, bow leg, features of hypocalcaemia
- osteomalacia if after epiphysis fusion: bone pain, fractures, muscle tenderness, proximal myopathy
- Tx: calcium and vit D tablets
Investigations of osteomalacia:
- reduced 25 (OH) vit D
- increased ALP
- reduced calcium and phosphate
- x-ray: children have cupped, ragged metaphysical surfaces, adults have translucent bands
What is osteoporosis?
- loss of bone mass
- bone m mineral density <2.5 SD below young adult mean density
- increased risk of fragility fractures
What are the risk factors for osteoporosis?
- corticosteroids
- smoking
- alcohol
- low BMI
- FHx
- RA
- sedentary
- premature menopause
- caucasians and asians
- endocrine
- multiple myeloma, lymphoma
- GI disorders: IBD, malabsorption, gastrectomy, liver disease
- CKD
- osteogenesis imperfecta, homocystinuria
- other meds: SSRIs, anti epileptics, PPI, glitazones, long term heparin therapy, aromatase inhibitors e.g. anastrozole
DEXA scan values:
T score (based on bone mass of young reference population)
->1.0 normal
- -1.0 to -2.5 osteopenia
-
Management of osteoporosis:
- if osteoporotic fragility fracture in postmenopausal women (DEXA not needed >=75yo)
- vitamin D and calcium supplementation
- alendronate 1st line
- if not tolerated, risedronate or etidronate
- if not tolerate, strontium ranelate and raloxifene
Bisphosphonates:
- post menopausal and glucocorticoid induced osteoporosis
- reduces risk of both vertebral and non vertebral fractures
- alendronate and risderonate superior to etidronate
- ibandronate once monthly oral bisphosphonate
Raloxifene:
- selective oestrogen receptor modulator
- prevent bone loss and reduce risk of vertebral fractures
- increase bone density in spine and proximal femur
- may worsen menopausal symptoms
- increased risk of thromboembolic events
- decreases risk of breast cancer
Strontium Ranelate
- dual action bone agent
- increased new bone by osteoblasts and decreased resorption by osteoclasts
- increased risk of CV events and thromboembolic
- may cause skin reaction e.g. Stevens Johnson syndrome
Denosumab:
- single subcutaneous injection every 6 months
- monoclonal Ab that inhibits osteoclast maturation
Teriparatide
- recombinant PTH
- very effective at increased bone mineral density
HRT
- decreased incidence vertebral fractures and non-vertebral fractures
- increased risk CVD and breast cancer
How do you assess patients for osteoporosis after a fracture?
>=75yo -assumed to have underlying osteoporosis -start on 1st line bisphosphonates -no scan needed <75yo -DEXA -FRAX assessment
How do you manage glucocorticoid induced osteoporosis:
- increased risk if equivalent of prednisolone 7.5mg/day for 3 or more mo
- start bone protection
- patients >65yo or fragility fracture offer bone protection
- <65yo offer bone density scan and further management
- 1st line alendronate
- should be calcium and vitamin D replete
Paget’s disease of bone, features:
- increased and uncontrolled bone turnover
- disorder of osteoclasts
- predisposing: age, male, northern latitude, family history
- typically older male with bone pain and isolate increase ALP
- bowing of tibia, bossing of skull, thickened vault, osteoporosis circumscripta
- calcium and phosphate normal
- markers bone turnover: PINP, CTx, NTx, urinary hydroxyproline
- treatment if: bone pain, skull or long bone deformity, fractures, periarticular Paget’s - bisphosphonates, calcitonin
Paget’s disease complications:
- deafness (cranial nerve entrapment)
- bone sarcoma
- fractures
- skull thickening
- high output cardiac failure
Polyarteritis nodosa and features:
- vasculitis affecting medium-sized arteries with necrotising inflammation - aneurysm
- more common middle aged men and hep B associated
- fever, malaise, arthralgia, weight loss, HTN, mono neuritis multiplex, sensorimotor polyneuropathy, testicular pain, lived reticular, haematuria, renal failure, pANCA, hep B positive
What causes poly arthritis?
- RA
- SLE
- seronegative spondyloarthropathies
- HSP
- sarcoidosis
- TB
- pseudogout
- viral infection
Polymyalgia reumatica, features, investigations, treatment:
-closely related to temporal arteritis
Features
->60yo
-rapid onset <1 month
-aching, morning stiffness in proximal limb muscles (not weakness)
-mild polyarthralgia, lethargy, depression, low grade fever, anorexia, night sweats
-investigations: raised inflammatory markers, creatinine kinase, EGM normal
-treat with prednisolone e.g. 15mg/od
Polymyositis:
- inflammatory disorder causing symmetrical proximal muscle weakness
- T cell mediate cytotoxic process against muscle fibres
- idiopathic or associated with CTD
- associated with malignancy
- Raynauds, respiratory muscle weakness, ILD, dysphagia, dysphonia
- investigations: increased creatinine kinase, other muscle enzymes, EMG, muscle biopsy, anti-synthetase Ab (anti-Jo-1)
What will joint aspiration show in gout?
needle shaped negatively charged birefringent crystals under polarised light
Confirming diagnosis of anti-phospholipid?
anti-cardiolipin Ab
Features of pseudo gout:
- strongly associated with increasing age
- if younger: haemachromatosis, hyperparathyroidism, hypomagnasaemia and hypophosphataemia, acromegaly, Wilson’s disease
- knee, wrist and shoulder most common
- joint aspiration: weakly positive birefringent rhomboid shaped crystals
- x-ray: chondrocalcinosis (e.g. knee - linear calcifications of meniscus and articular cartilage)
Management of pseudo gout:
- aspiration of joint, to exclude septic arthritis
- NSAIDs or intra-articular, intramuscular or oral steroids as for gout
Psoriatic arthropathy:
-correlates poorly with cutaneous psoriasis and often precedes development of skin lesions
types:
- rheumatoid like polyarthritis
- assymmetrical oligoarthritis (typically hands and feet) - pencil in cup appearance
- sacroilitis
- DIP joint disease
- arthritis mutilans
- managed by rheumatologist
- treat as RA but better prognosis
What is Raynaud’s phenomenon?
- exaggerated vasoconstrictive response of digital arteries and cutaneous arteriole to cold or emotional stress
- primary: disease
- secondary: phenomenon
Secondary causes of Raynaud’s phenomenon:
- CTD - RA, scleroderma, RA, SLE
- leukaemia
- type I cryoglobulinaemia, cold agglutins
- use of vibrating tools
- drugs: COCP, ergot
- cervical rib
Factors suggesting CTD with Raynaud’s phenomenon:
- onset after 40yo
- unilateral symptoms
- rashes
- presence autoAb
- digital ulcers, calcinosis
- rarely chilblains
Management of Raynaud’s phenomenon:
- secondary care
- calcium channel blockers e.g. nifedipine
- IV prostacyclin infusions (epoprostenol)
Reactive arthritis:
- HLA B27 seronegative spondyloarthropathies
- following an infection: can’t see, can’t pee, can’t climb up a tree
- post STI: chlamydia trachomatis
- post dysenteric: shigella, salmonella typhimurium and enteritidis, yersinia enterocolitica, campylobacter
- also known as Reiter’s syndrome
Features of reactive arthritis:
- within 4 weeks of initial infection
- symptoms 4-6 months
- typically asymmetrical oligoarthritis of lower limb
- dactylitis
- urethritis
- eye: conjunctivitis, anterior uveitis
- skin: circinate balanitis, keratoderma blenorrhagica
Management of reactive arthritis:
- symptomatic: analgesia, NSAIDs, intra-articular steroids
- sulfasalazine and methotrexate for persistent
- symptoms rarely more than 12 months
Septic arthritis:
- most commonly staph aureus
- typically young, sexually active adults - neisseria gonorrhoea (disseminated gonococcal infection)
- most haematogenous spread
- knee in adults
- acute, swollen joint, restricted movement, warm, fever
Investigations for septic arthritis:
- synovial fluid sampling obligatory before Abx - urgent orthopaedic review
- blood cultures
- joint imaging
Management of septic arthritis:
- IV Abx for gram +ve cocci
- flucloxacillin or clarithromycin
- needle aspiration to decompress
- arthroscopic lavage may be required
Seronegative spondyloarthropathy:
- associated with HLA-B27
- rheumatoid factor negative
- peripheral arthritis, usually asymmetrical
- sacroiliitis
- extra articular manifestations: uveitis, pulmonary fibrosis, amyloidosis, aortic regurgitation
e. g. ankylosing spondylitis, psoriatic arthritis, Reiter’s syndrome, enteropathic arthritis
Sjogren’s disease overview:
- autoimmune disorder affecting exocrine glands
- dry mucosal surfaces
- primary or secondary to RA or other CTD
- female 9:1
- increased risk of lymphoma
Sjogren’s features:
- dry eyes: keratoconjunctivitis sicca
- dry mouth
- vaginal dryness
- arthralgia
- Raynaud’s, myalgia
- sensory polyneuropathy
- recurrent episodes of parotitis
- RTA
Investigations for Sjogren’s:
- rheumatoid factor positive 50%
- ANA 70%
- anti Ro Ab 70%
- anti-La Ab 30%
- Schirmer’s test - measure tear formation
- histology: focal lymphocyte infiltration
- hypergammaglobulinaemia, low C4
Management of Sjogren’s:
- artificial saliva and tears
- pilocarpine - saliva production
Still’s disease features:
- arthralgia
- increased serum ferritin
- salmon-pink maculopapular rash
- pyrexia in late afternoon in daily pattern with worsening symptoms and rash
- lymphadenopathy
- rheumatoid and ANA negative
- Yamaguchi criteria sensitivity 93.5%
Management of Still’s disease:
- NSAIDs (1st line, trialled week before steroids)
- steroids (won’t improve prognosis)
- methotrexate, IL1 and anti-TNF if persistent
Overview of SLE:
- more common in females 9:1
- Afro-caribbean and asian
- onset 20-40yo
- autoimmune type III hypersensitivity
- HLA B8, DR2, DR3
- immune complex deposition affecting skin, joints, kidneys and brain
Features of SLE:
- general: fatigue, fever, mouth ulcers, lymphadenopathy
- skin: malar rash (not nasolabial), discoid rash, photosensitivity, Raynaud’s, livedo reticularis, non-scarring alopecia
- MSK: arthralgia, non-erosive arthritis
- CV: pericarditis, myocarditis
- respiratory: pleurisy, fibrosing alveolitis
- renal: proteinuria, GN
- neurospych: anxiety and depression, psychosis, anxiety
Investigations for SLE:
-99% ANA positive (useful to rule out)
-20% RF positive
-anti-dsDNA most sensitive test
-anti Smith, anti U1 RNP, SSA (anti-Ro) and SSB (anti-La)
monitoring:
-inflammatory markers
-decreased C3, C4
-anti-dsDNA for monitoring
Types of systemic sclerosis:
- limited cutaneous
- diffuse cutaneous
- scleroderma
Limited cutaneous systemic sclerosis:
- Raynaud’s may be 1st sign
- associated with anti-centromere Ab
- scleroderma affects face and distal limbs
- CREST: calcinosis, Raynaud’s, oesophageal dysmotility, sclerodactyly, telangiectasia
Diffuse cutaneous systemic sclerosis:
- scleroderma affects trunk and proximal limbs
- associated with scl-70 Ab
- respiratory involvement most common death
- other complications: renal disease and HTN
- poor prognosis
Scleroderma:
- positive anti-centromere
- without internal organ involvement
- tightening and fibrosis of skin
- manifest as plaques or linear
Antibodies in systemic sclerosis:
- ANA 90% positive
- RF 30% positive
- anti-scl-70 Ab associated with diffuse cutaneous
- anti-centromere Ab associated with limited cutaneous
Temporal arteritis features:
- large vessel vasculitis
- skip lesions
- typically >60yo
- rapid onset <1mo
- headache
- jaw claudication
- visual disturbances - check vision, secondary to anterior ischaemic optic neuropathy
- tender palpable temporal artery
- lethargy, depression, low fever, anorexia, night sweats
Investigations for temporal arteritis:
- inflammatory markers increased
- temporal artery biopsy (skip lesions)
- creatinine kinase and EMG normal
Treatment of temporal arteritis:
- high dose prednisolone (dramatic response)
- urgent ophthalmology review same day, irreversible
Azathioprine (MOA, ADR, interaction, pregnancy)
- active component: mercaptopurine (inhibits purine synthesis)
- thiopurine methyltransferase (TPMT) test for people prone to azathioprine toxicity
- ADR: bone marrow depression, n&v, pancreatitis, increased risk non-melanoma skin cancer
- significant interaction with allopurinol (decrease dose of azathioprine)
- safe in pregnancy
Bisphosphonates (MOA, uses, ADR, how to take)
- analogues of pyrophosphate (decreases demineralisation and inhibits osteoclasts by reducing recruitment and increasing apoptosis)
- uses: osteoporosis, hypercalcaemia, Paget’s disease, pain from bone metastases
- ADR: oesophagi’s, ulcers (especially aldendronate), jaw osteonecrosis, increased risk atypical stress fracture at proximal femoral shaft (alendronate), cue phase response (fever, myalgia, arthralgia), hypocalcaemia
- correct hypocalcaemia and vit D before
- take 30 mins before breakfast with water and sit up for 30 mins
What are the conditions for stopping bisphosphonates at 5 years?
- <75yo
- femoral neck T-score >-2.5
- low risk according to FRAX/NOGG
Hydroxychloroquine (MOA, ADR, pregnancy)
- management of RA and systemic/discoid lupus erythematosus
- similar to chloroquine to treat malaria
- ADR: bull’s eye retinopathy (may cause severe and permanent loss)
- fine in pregnancy
Interferon alpha
- produced by leucocytes
- antiviral action
- used in hep B, C, Kaposi’s sarcoma, metastatic RCC, hairy cell leukaemia
- ADR: flu-like symptoms and depression
Interferon beta
- produced by fibroblasts
- antiviral action
- reduced frequency of exacerbations in patients with relapsing-remitting MS
Interferon gamma
- predominantly NKC, also T helper cells
- weaker antiviral action, more in immunomodulation esp. macrophage activation
- useful chronic granulomatous disease and osteoporosis
Methotrexate (MOA, indications, ADR, pregnancy)
- antimetabolite inhibits dihydrofolate reductase (used for purine and pyrimidine synthesis)
- used for inflammatory arthritis, psoriasis, some chemotherapy acute lymphoblastic leukaemia
- ADR: mucositis, myelosuppression, pneumonitis, pulmonary fibrosis, liver fibrosis
- avoid in pregnancy for 6 months after treatment stopped
- men use contraception 6 months after
How is methotrexate prescribed?
- take weekly until stable
- monitor every 2-3 months
- folic acid 5mg once weekly, take >24 hours after methotrexate
- start at 7.5mg weekly
- only one dose strength
Interactions of methotrexate:
- avoid trimethoprim or co-trimoxazole (increased risk of marrow aplasia)
- increased dose of aspirin - methotrexate toxicity due to reduced excretion
- methotrexate toxicity treatment is folinic acid
Penicillamine (use and ADR)
- used for RA
- decreased IL-1 synthesis and decreased maturation of newly synthesised collagen
- ADR: rashes, disturbance of test, proteinuria
Sulfasalazine (MOA, cautions, ADR, pregnancy)
- pro drug for 5-ASA
- decreased neutrophil chemotaxis and decreased proliferation lymphocytes and pro-inflammatory cytokines
- cautions: G6PD deficiency, allergy to aspirin or sulphonamide
- ADR: oligospermia, Steven-Johnson syndrome, pneumonitis/lung fibrosis, myelosuppression, Henz body anaemia, megaloblastic anaemia, may colour tears (stained contact lenses)
- safe in pregnancy and breast feeding unlike other DMARDs
Supraspinatus
- abducts arm before deltoid
- most commonly injured
Infraspinatus
-rotates arm laterally
Teres minor
- adducts
- rotates arm laterally
Subscapularis
- adducts
- rotates arm laterally
Rotator cuff muscles:
- supraspinatus
- infraspinatus
- teres minor
- subscapularis
IgG (frequency, shape etc.)
- 75%
- monomer
- enhance phagocytosis of bacteria and viruses
- fixes complement and passes to foetal circulation
- most abundant isotope in blood serum
IgA (frequency, shape etc.)
- 15%
- monomer/dimer
- IgA is predominant immunoglobulin found in breast milk
- also found in secretions of digestive, respiratory, urogenital tracts
- provides localised protection on mucous membranes
- most commonly produced in body but lower serum conc that IgG
IgM (frequency, shape etc.)
- 10%
- pentamer
- first secreted in response to infection
- fixes complement but does not pass into foetal
IgD (frequency, shape etc.)
- 1%
- monomer
- role in immune system largely unknown
- involved in activation of B cells
IgE (frequency, shape etc.)
- mediates type I hypersensitivity reactions
- binds to Fc receptors found on man cells and basophils
- provides immunity to parasites such as helminths
- least abundant isotope in serum
Typical finding in arthrocentesis of reactive arthritis:
- cloudy yellow colour
- no crystals
Arthrocentesis in RA:
- high WBC
- turbic yellow
- no crystals
Septic arthritis arthrocentesis:
same as RA but systemic symptoms and precipitate by trauma
Most common organism septic arthritis in children:
strep pyogenes
Most common organism septic arthritis after joint replacement:
staph epidermidis
