week 2 Flashcards
what is affected in RA?
synovium
what mediates RA?
HLA-DR4
describe RA
inflammatory arthritis, symmetirial, F>M. any age, 1% prevalence.
smoking and genetics lead to worse outcome.
presence of auto-antibodies gives worse prognosis.
commonly affected sites in RA
c1/C2, hand joints, wrist, elbow, shoulders, TMJ, knees, hips, ankle, feet. (synovium lined)
what is the hallmark of RA
synovitis. (spongey on examination)
Get inflammatory “pannus” with inflammatory cascade (osteoclasts erode, B cells give Rheumatoid factor, mast cells cause inflammation, and neutrophils….)
early RA and therapeutic window
<2 years, first 3 months best therapeutic window.
PC of RA
- early morning stiffness greater than 30min
- more than one area
- hand joint
- symmetrical
- positive ‘squeeze’ test of MCP/MTP
diagnosis of RA
Hx, Examination,
bloods: FBC (check for anaemia of chronic disease, inc platelets ) CRP + ESR/PV [inflammatory markers]
radiology [for staging ]
autoantibodies [may be negative]
what is tenosynovitis
caused by RA. tendon sheath inflammation. causes carpal tunnel PIP, MCP, MTP joint inflammation.
autoantibodies to check for in RA
rheumatoid factor and anti-CPP (better)
imaging for RA
x-ray hand/feet. US. MRI (gold standard.)
how do you assess RA
DAS-28. <2.6= disease remission and >5.1 is high activity.
management of RA
rheumatologist, drugs, target good DAS28 score, steroid/NSAID’s, patient education.
High high with NSAID + steroids (not tot long as side effects - use as bridging therapy until DMARD’s kick in) initially then drop down once in remission (gain control the reduced drugs)
DMARDs in RA
Methotrexate
sulphasalazine
hydroxycholoroquine
(biologic therapy ).
also gold therapy, penicillamine, azothiaprine.
what do you need to check if giving biological therapy (anti-TNF)
bacterial and TB reactivation
how can steroids be administered in RA
oral, IM, IA.
how is MTX administered and what needs co-prescribed with Methotexate.
weekly injection.
folic acid.
risks of methotrexate
pneumonitis, LFT’s, teratogenic, reduced FBC.
what needs considered when prescribing biological therapy for RA patients
DAS28 score, TB/HIV/Hep B status, methotrexate co-prescibed. no live-attenuate vaccine (EG: yellow fever)
what are the signs of advanced RA
joint damage and deformity. atlanto-axial sublaxation
things to consider in paint with RA on medication
pregnancy, accelerate CVS risk, immunisations, stop smoking, keep DAS28 score good
what is the commonest arthritis
OA (osteoarthritis)
What happens in OA
progressive degenerative disease, thinning of cartilage with loss of joint space and bony spurs formation
pathogenesis of OA
loss of matrix of cartilage, cytokine release (Il-1, TNF, mixed metalloproteinases and prostaglandins).
fibrillated cartilage surface, bone formed not cartilage.
Pc of OA
gradual onset, mechanical pain, crepitius, stiffness, deformity/swellings of joints. reduced function and mobility. effusions and soft tissue swelling present.
common sites of OA
hip, knee, neck, big toes, thumb/fingers. (weight bearing/mechanical overuse/stress joints)
what are hebardons nodes
occur in OA, DIP bony enlagements
what are bouchards nodes
occur in OA, PIP bony enlargements.
what is a Baker’s cyst
synovial bursa in popliteal fossa.
risk factors for OA
age, female, FHx, occupation, obesity, previous joint injury/abnormalities. underlying RA, gout, acromegaly
diagnosis of OA
Hx + Examination.
bloods - inflammatory markers raised usually.
X-rays (joint space narrowing, bony cyst, osteophytes, subchondrial sclerosis)
treatment of OA
non-pharam = educate, physio, weight loss, walking aid, footwear
pharma= analgesia, NSAID’s, pain modulators (gabapectin, amitriptyline), IA steroid (only short-term relief )
surgery = arthroscope washout, soft tissue trimming, joint replacement.
what does IA stand for
intraarticular
crystal arthropathies; name the two and their causing crystals
gout (monosodium urate) and psuedogout (calcium pyrophosphate dihydride/CPPD)
what is Gout
inflammartoy arthritis associated with monosodium urate crystal deposition. occurs in older men mostly. (1% population)
Gout pathogeneisis
PURINES from diet and DNA/ RNA sources (due to cell breakdown = cancer, weight loss, sepsis, psoriasis exacerbate) → hypoxanthine → xanthine → plasma Urate→ urine uric acid (water soluble but if dehydrated causes Gout)
what is hyperuracaemia
high uric acid in blood (>7mg/dL). present in 18% population. inc risk of Gout with higher uric acid levels in blood.
diagnosis of Gout
based on radiological finding, not hyperuracemia alone; [acute changes in uric acid levels often lead to Gout.]
however, 25% in acute attack have normal uric acid levels , optimum is 2 weeks after attack.
clinical presentation of Gout
rapid onset, big toe, sever pain, red/hot joint, up to 2 weeks.
DD of Gout
Gout, trauma, septic arthritis, seronegative arthritis (EG:psoriatic)
chronic polyarticular gout
chronic joint inflammation, inc uric acid, recurrent acute attacks, >10years.
investigation for gout
high CRP, ESR/PV. sometimes high WCC.
Xray normal actually, chronic shows erosions, joint destruction, overhanging osteophytes.
Aspirate joint = gold standard (differentiate between septic arthritis)
management of gout
acute= Nsaid’s or colchicine or corticostreroids (oral, IM, IA); analgesia (opiates and paracetamol).
chronic= lifesytle change (reduce red meat, seafood, beans and alcohol.). lose weight, inc fluids (non fructose - no fizzy drinks).
GIVE ALLOPURINOL/FEBUXOSTAT after acute attack stops and at low dose then step up checking uric acid levels. long term → reduce acute attacks.
what is pseudogout
occurs in elderly, calcium deposition in cartilage. related to OA. Alcohol and diet has no relevance
where does pseudogout commonly affect
knees, wrists, ankles.
diagnosis of pseudogout
joint aspirate shows rhomboid shaped crystals with weak +ive birefringence.
what is pseudogout associated with?
hyperparathryoidism, haemochromatosis, haemosidenosis, trauma, amyloidosis, gout, hypothryroidism.
treatment of pseudogout
nsaid’s, colchicine, steroid, rehydrate.
control other conditions. (gout therapy doesn’t work for psuedogout).
stop diuretics
name a rare for of psuedogout caused by hydroxyapatite crystals.
milwalkee shoulder - aggressive acute and rapid deteroration, occurs in females 50-60 years old.
alizain stain shows red clumps. (not seen in tayside)
CTD overview
often autoimmune disease (AID).
includes SLE, sjogre’s, polymyositis, APS, systemic sclerosis, mixed CTD.
CTD is caused by spontaneous overactivity of IS, systemic, autoimmune, every part of the body → inflammation/tissue damage.
SLE - systemic lupus erythematosus. risk factors
ethnicity (chinese/afro-americans/carribeans), female
what factors cause SLE to develop
hormones (oestrogen/HRT), envorinmental (viruses/UV light), genetics, immunology → SLE
pathogenies of SLE
antigen presenting cells → CD4 helper Tcell → Bcells (→ antibodies) + CD8 cytotoxic T cell. → cell death.
dead cells are left in the body too long in lupus and are then seen as antigen/threat triggering autoimmune attack
lupus characteristic disease pathway
inc turnover + longer to clear dead cells → immune complexes formation drives disease (inflammation of blood vessels occurs also) - type III hypersensitivity.
how does SLE causes renal disease? how is it diagnosed?
immune complexes deposited in mesangium; symptomatic and severe → necrosis and scarring (inc blood or protein in urine, seen on urinalysis.)
shows glomerular nephritis, renal biopsy if unsure.
cutanoues signs of SLE
mouth ulcers, hair thinning, butterfly/malar rash (post-UV light), discoid lupus → may scar.
chronic and acute.
Signs of SLE
renal disease, cutaneous, arthritis, serositis (pleural inflammation), neurological, haemolytic anaemia, thrombocytopenia, leukopenia
neurological signs of SLE
depression, psychosis, peripheral neuropathy.
classification of SLE
mild - joint and skin affected
moderate
severe- life-threatening = renal, ham, neuro affected
immunology of lupus
ana, ANTI-DNA. - best two
anti-Sm, Anti-Ro, Anti-RNP (lupus and others.)
symptoms of SLE
fever, fatigue, weight loss, myalgia, headache, anglarged lymph nodes, joint pain/swelling
what condition often occurs with SLE
APS - anti-phospholipid syndrome.
clots in artery/vein, causes recurrent miscarriage + PE/DVT [high D-dimer]
why are lupus patients more susceptible to infection?
low complement levels.
defective phagocytosis,
steroid/immunosuppressant drugs
investigations for lupus (Bloods only not screening )
ANA (+ive in hep C, HIV, RA, other AID’s)
Anti-double standed DNA (most associated and gives level of disease and associated with kidney disease - BEST)
anti-Ro. presence in pregnant SLE patients predicts neonatal problems (heart block)
anti-phospholipid → 3 blood tests. higher value then inc clot likelihood.
screening of lupus
multi-organ screening.
urinalysis always plus others if symptomatic (e.g.: CXR for lung problems).
flare-up of lupus causes what blood results
inc anti-DNA and reduced C4 level.
also inc PV/ESR but not CRP (never raised in SLE, in other AID’s can be raised )
what does CRP indicate
- infection
- AID’s (apart from SLE)
treatment of SLE (generally)
GENERAL: educate, regular monitoring, avoid UV light, pregnancy issues.
treatment of SLE (mild)
NSAID’s and analgesia, (anti-malaria) hydroxycholoroquine/HCQ, helps with organ protection, joint pain and skin (therefore - everyone with SLE on HCQ)
treatment of SLE (moderate)
steroid is severe (low dose if joints, high dose if kidney)
+ immunosuppressants (1st line is cyclophosphamide, methotrexate, azathioprine ). → leads to reduced IS, bone marrow suppression, potentially teratogenic.
treatment of severe SLE
immunospuressant + steroid (IV and inc dose).
+Biological therapy = anti-CD20 + anti-Blys.
may acutely need Warfarin is haematology’s bad.
what are the symptoms of CTD
arthralgia, fatigue, myalgia, reynaud’s, alopecia, mucosal ulcers, unprovoked thrombosis/ pregancy losses, sicca (dryness) symptoms.
AID’s general points
female > male often overlap, primary or secondary most is B cell mediated (gives antibodies) inc CVS risk
what is APS (anti-phospholipid syndrome)
venous or arterial thrombosis+ adverse pregnancy. can be primary or secondary. [anti-cardiolipin antibody present]
what type of rash is associated with APS (and what causes it?)
Livedo reticulitis
(mottled reticulated vascular pattern that appears as a lace-like purplish discoloration of the skin. caused by swelling of the venules owing to obstruction of capillaries by small blood clots. )
what antibodies are associated with APS (3 of them)
IgM/IgG anti-cardiolipin.
IgM/IgG Beta2-glycoproteins,
lupus anticoagulants
treatment for APS
- life-long anticoagulation for thrombosis;
- aspirin/herpain to reduced pregnancy complications;
- HCQ.
what is Sjogren’s
chrnoic autoimmune inflammatory disorder causing dry eyes/mouth (reduced gland function).
- primary or secondary
- female 50-60 years
PC of sjogrens’
“gritty eyes”
dry mouth/eyes/vagina.
dental caries
joint pains, fatigue, bilateral parotid gland enlargement.
antobodies in Sjogrens
anti-Ro, anti-LA,
inc IgG, inc ESR, inc Rheumatoid factors
diagnosis of Sjogrens
salivary gland US + biopsy
treatment for Sjogren’s
artificial tear supplements, cyclosporin eye drops, punctal plugs, saliva supplements, HCQ, immunosuppression (MTX)
what is systemic sclerosis
fibrosis + vascular endothelial changes.
Skin involved distal to elbow and not torso.
what diseases is associated with systemic sclerosis
raynaud’s.
symptoms/signs of systemic sclerosis
pulmonary hypertension (common complication)
small intestinal bacterial overgrowth.
sclerodactyly, calcinosis, osephageal dysmobility, ILD.
scelroderma (thickening of skin) and telangiectasia (spider veins).
what antibody is associated with systemic sclerosis
anti-centromere antibody
summarise diffuse cutaneous Systemic sclerosis
what is affected
skin involvement proximal to elbows and torso involved. rapid skin change and early organ involvement.
ILD>pulmonary hypertension. renal crisis may occur.
diffuse cutaneous Systemic sclerosis antibodies
anti-toposiomerarse/anti-SCL-70/anti-RNA III polymerase antibody
treatment of systemic sclerosis
raynauds → CCB’s, phosphodiesterase inhibitors
digital ulcers → iloprost infusions
reflux → PPI/H2 antagonist.
lung disease → immunospuression
pulmoary hypertension → CCB, endothelin receptor antagonist, prostacyclin, O2 (at home).
control BP.
small intestinal bacterial overgrowth → antibiotics
describe MTCD (mixed CTD)
features of SLE, SS, polymyositis.
Pulmonary hypertension is common complication.
MTCD antibody
anti-RNP antibody
MCTD treatment
depends of symptoms and major organ involvement.
polymyositis antibody
anti-Jo1 (and others)
generally how do you investigate and treat CTD’s
investigations = Examination +Hx, bloods, urinalysis and screening = pulmonary function tests/CXR/ECHO/ CT….
treatment = depends on severity. (NSAID’S, steroid short term, HCQ, treat symptoms.)
if joint involvement → DMARD’s/short steroids.
organ involvment → immunosupression and high dose steroid.
tailor treatment to symptoms (except HCQ in SLE for everyone)
define spondylarthropathies
a family of conditions characterised by involvement of both spine and joints (in HLA-b27 predisposed individuals)
what conditions does being HLA-b27 positive increase risk of?
ankylosing spondylitis, crohn’s, uvetitis, reactive, psoriatic, enteropathic arthritis (higher in northern european countries.)
people can be HLA-B27 positive without disease or any symptoms.
back pain difference between mechanical and inflammatory
mechanical - worsened by activity, sore at end of day
inflammatory - helped by movement and worse in morning with stiffness.
what do spondylarthropathies have in common symptoms-wise with rheumatoid disease
SI and spinal involvement, enthesitis, dactylitis, eye inflammation, (rare) heart block/aortic regurgitation
what is ankylosing spondylitis
chronic systemic inflammatory involvement primarily affecting spine.
sarcoiliac common, large joint involvement uncommon
who does AS usually affect and how
> male, adolescent to adulthood, enthesopathy occurs. get fusion of spine (syndemophytes)
how to diagnose AS
Hx and Exam (Schober’s test, and occipital to wall test)
MRI → shows sacroilitis
blood → HLA-B27, ESR, CRP, PV.
X-rays → sacroilitis, syndemophytes, “bamboo spine”.
treatment of AS
physio, OT, NSAID’s, DMD (sulphazine, MTX), anti-TNF and Anti-Il-17(biological)
what is psoriatic arthritis
most patients have psoriasis in skin,
no rheumatoid nodules/rheumatoid factor (RF) negative.
features of psoriatic arthritis
psoraisis, nail pitting, onycholysis, dactylitis, enthesitis, eye disease.
what are the 5 types/subgroups? of psoriatic arthritis
hand/feet, spine, dactylitis, Arthritis mutilans (aggressive+erosive), Oligoarticular (few joints), Polyarticular (many )
how to diagnose psoriatic arthritis
Hx, Exam, bloods (raised inflammatory but -ive RF),
x-rays= “pencil in cup, osteolysis, marginal erosions”
treating psoriatic arthritis
NSAID, corticosteroid, immunosupressant (MTX, AZA). anti-TNF/anti-Il-17.
physio, OT, orthotics.
what is reactive arthritis
infection induced systemic illness, primary inflammatory synovitis with no viable organisms (sterile)
what causes reactive arthritis
post-infection (GU or enterogenic usually)
1-4 weeks delay.
90% settle in 6 months.
characteristic of reactive arthritis (+ who does it affect)
20-40 year olds, M=F ratio, HLA-B27 +ive,
nail, eye, ulcers, fever, malaise common
diagnosis of reactive arthritis
Hx, Exam, blood (raised inflammatory markers, FBC and U+E, HLA-b27. culture,)
aspirate joints and x-ray affected joints.
treatment of reactive arthritis
self-limiting usually, recurrence/persistance rare usually good prognosis; Nsaids, steroids, (IA once sepsis ruled out/oral), antibiotics for underlying infection.
if chronic- DMARDs (sulphalazine as MTX is tetarogenic).
OT and physio
what is enteropathic arthritis
associated with Crohns/UC, arthritis in several joints (esp knee, ankle, wrists, elbow).
flares worsen in IBD flares. [20% have Sacroiliac involvement.]
symptoms of enteropathic arthritis
loose watery (mucous/bloody) stool, fever, weight loss, skin (pyroderma gangrenosum) and uveitis, enthesitis, aphalanous ulcers.
investigations for enteropathic arthritis
upper/lower GI biopsy, joint aspirate (no organisms/crystals), high CRP/PV, Xray/MRI showing sacroilitis.
USS showing synovitis/tinosynovitis.
treatment for enteropathic arthritis
treat IBD, NSAID not usually good as exacerbates IBD, mild analgesia.
steroid (IM/IA/oral), DMD (MTX, SSZ, AZA). Anti-TNF
(consult GI for advanced treatments)
enthesitis means what?
inflammation where tendons insert into bone
what is vasculitis
presence of leukocytes/immune complexes present in vessel walls
Name some types of vasculitis and where they affect
Many (HSP, Wegeners[Granulomatosis with polyangiitis (GPA], chung-strauss [Eosinophilic granulomatosis with polyangiitis], microspoic polyangitis…)
can affect large medium and small vessels depending on type of vasculitis.
vasculitis can be primary or secondary (to SLE, RA…)
what test can be done for vasculitis to classify
ANCA.
name for chung-strauss and wegener’s
CS -[Eosinophilic granulomatosis with polyangiitis]
W - [Granulomatosis with polyangiitis (GPA],
investigating vasculitis
ELISA, IIF, pairing of results (PR3 + MPO)
→ biopsy affected system(s).
can use BVAS (Birmingham vasculitis assesment score)
treatment of vasculitis
localised → steroid and MTX/AZA.
generalised → cyclophosphamide +steroid or rituximab + steroid (or alternatives). potentially plasma exchanger.
refractory → not working on cycle/steroid → IV immunoglobulins + ritiximab + plasma exchanger.
prognosis of vasculitis
90% 5 year survival rate, 0% if untreated.
polymyositis/dermatomyositis PC
F>M, idiopathic inflammatory myopathies, 40-50 years old, inc malignancy incidence (paraneoplastic syndrome).
WEAKNESS is PC
dermatomyositis signs
dermato = skin involvement [shawl and gottron’s signs and heliotope rash]
histology of polymyosits/dermatomyosisis
fibre necrosis, degredation, regeneration, inflammatory cell inflitrate.
muscle weakness worsening over months, usually symmetrical proximal muscles
polymyosits/dermatomyosisis
other features of polymyosits/dermatomyosisis
lung - ILD +muscle weakness. dysphagia, myocarditis, fever, weight loss, raynaud’s, non-erosive polyarthritis
what age group is malignancy risk particularly associated with in patients with polymyosits/dermatomyosisis
> 45 males.
what to check for in Hx of polymyosits/dermatomyosisis
D.mellitis, thyroid, statins, steroids, FHx, alcohol/ilict drugs
what tests to do in examination for polymyosits/dermatomyosisis
inspect/observe.
confrtonational testing or isotonic testing
how do you diagnoses polymyosits/dermatomyosisis
muscle enzymes (CK), inflammatory markers raised. electrolytes, Ca2+, PTH, TSH, autoantiboideis (ANA+anti-Jo1). EMG (electromyography). Biopsy, MRI
treatment of polymyosits/dermatomyosisis
glucocorticoids, AZA, MTX, ciclosporin, IV immunoglobulin, ritixumab.
what is inclusion body myositis
> 50years, M>F, more insideous onset (slow but harmful), digital muscle weakness.
weakness often asymmetrical and in wrist and finger flexors and quads/tibial muscles leg.
occasionally misdiagnosed as polymyosits
investigations for inclusion body myositis
lower CK levels than polymyositis (PM)
biopsy shows “inclusion bodies”.
poor response to therapy.
how does polymyalgia rheumatica present
STIFFNESS AND PAIN
> 50years, 1% prevelence, ache in shulder/hip girdle, morning stiffness, symmetrical, fatigue, fever, weight loss, reduced movement of shoulders, neck and hips. Muscle strength is normal
what is PMR associated with
giant cell arteritis/temporal arteritis.
giant cell arteritis/temporal arteritis symptoms
symptoms - which is granulation arteritis of large vessels in cranium causing jaw claudication, headache, scalp tenderness and visual loss. (sue to temporal artery supplying optic nerve.) - get tender artery with no pulse
giant cell arteritis/temporal arteritis treatment
15mg prednisolone as test and clears up instantly
diagnosing PMR
exclude other diagnoses, ESR/PV/CRP raised, temporal artery biopsy.
treatment for PMR
rapid and dramatic response to low dose steroid (prednisolone). 40mg if no visual involvement and 60mg if visual disturbances. reduce dose slowly over 2 years.
what is Fibromyalgia
PAIN and SLEEP DISORDER
common, not associated with inflammation, unknown cause (psychological as may begin after emotion/physical trauma) 20-50year old women, 2-5% prevelence.
PC of fibromyalgia
pain in shoulder, lower back, chest wall.
diffuse and chronic and varies in intensity, symptoms worsen on exacerbation, stress or fatigue.
get unrefreshing sleep, IBS, poor concentration, headache.
excessive tenderness on palaption (18 points) no other MSK abnormalities
how to diagnose fibromyalgia
no diagnositc test, inflammatro markers normal, absence of explanation of symptoms
treatment of fibromyalgia
educate, graded excretes response, CBT, complementary medicine, analgesia, low grade ant-depressants, gabapentin/pregabalin
side effects of steroids
osteoporisis so give Ca2+/Vit D supplements weight gain [long term]. (inc appetite and water retention) cataracts/glaucoma easy bruising/skin thinning infection worsening of diabetes hypertension inc body hair growth
summarise autoimmune diseases
self-reaction, high titres of auto-antiboidies or auto-reactive T cells.
rarely monogenic usually polygenic
examples of autoimmune diseases
graves, MG, sacroid, RA, vitiligo, type 1 diabetes, MS, pernicous anaemia, SLe, sjorgen’s…. F>M
give example for monogenic AID
IPEx, x-linked, FOXP3 gene (essential for Tc ell regulation).
early childhood with overwhelming autoimmunity causing diahoirrea, eczema, infection, diabetes.
how do you treat IPEX
imunosupression, total perental care, bone marrow transplant, insulin
what does the FOXP3 gene do
regulates Tcells, il-10 and TGF-beta deactivate self-reactions.
where are the MHC/HLA class molecules on genome
chromosome 6 short arm
strep M5 protein causes what ?
rheumatic fever (post-strep throat infection) may leads to mitral stenosis as heart proteins same as M5 on strep.
what are the mechanisms of AID
molecular memory,
super-antigens,
antigen sequestration,
unrelated bystander activation
SLE is what type AID
hypersensitivty type 3.
insoluble immune complexes are deposited and cause AID (activate compliment and phagocytes). Uv light, infection, wound cause cell death and inc SLE.
mutation in what genes affect cell clearance therefore causing lupus?
C1q or Mac-1
how is any inflammatory arthritis treated
DMARD (MTX, SAS, HCQ, biologicals) and symptoms relief (NSAID, paracetamol, opiates, atypical analgesia)
paracetamol in inflammatory arthritis
pure analgesic [little anti-inflammatory action]
component of many anlgesic e.g. co-codamol/codydramol. safe unless overdose
analgesic prescription
non-opiod,mild opiod, strong opiod (until pain is controlled).
options include co-codamol, dihydrocodene, tramadol, amitriptyline, gabapentin
NSAIDS in arthritis
used in inflammatory arthritis, mechanical pain, pleuitic pain and other painful conditions [e.g. gout.]
adverse affects of NSAID’s
dyspepsia, oseophagitis, gastritis, PEPTIC ULCER, small/large bowl ulceration, RENAL impairment, ASTHMA exacerbation, inc CVS risk
types of NSAIDs
aspirin, ibuprofen, Celecoxib…
Cox2 inhibitors.
what are DMARD’s.
disease modifying anti-rheumatic drugs; MTX usually 1st line, HCQ (milder).
use aggressively then wear off (as adverse steroid/NSAIDS effects.)
slow acting (weeks-months), so give steroid until effect kicks in. There are pure anti-inflm=ammatories and lower CRP, ESR, and reduce rate of joint damage.
dangers of MTX [methotrexate]
regular monitoring for drop in WBC,
LFTs for hepatotoxicity,
pulmonary function tests regularly as pneumonitis and
pulmonary fibrosis occur (rare)
kidney failure
rash and mouth ulcers (ulcerative stomatitis)
teratogenic.
co-prescribe folic acid. (mechanism unknown but evidence is good)
when to use DMARDs
new onset RA, active inflammatory disease.
why use leflunomide?
similar efficacy/side effects to MTX. also teratogenic. used if TMX not suitable
why use MTX?
RA, CTD, psoriatic arthritis, vasculitis
why use SAS?
often combined with MTX in early inflammatory arthritis.
causes naesea, SJS, rash/mouth ulcers, hepatitis, neutropenia, reversible oligozoospermon (reduced sperm count temporarily)
HCQ used in?
no effect on joint damage, used in CTD (lupus, Ra, sjogren’s).
retinopathy rare and irreversible side effect
Other DMARD’s [sodium acrothromalate (gold) and penicillamine oral ] used for what and their side effects include?
sodium acrothromalate (gold) and penicillamine oral (used in RA)
side effects - bone marrow suppression, glomerulitis, rash, mouth ulcers, → monitor FBC, and urine for protein
anti-TNF is used for what?
RA, AS, psoartic arthritis, subcutanrous (DAS28 score of >5.1 with previous MTX and DMARD’s tried)
Anti-TNF side effects/risks
inc risk of infection (esp TB; so screen for Hepatitis B/C and HIV and TB beforehand).
malignant uncertainty
contraindicated in P.fibrosis or H.Failure (safe in pregnancy )
which biologics are used in RA?
RA = anti-TNF, rituximab (anti-CD20 B cells), Tocilzumab (Il-6) and abatecept (CTLA-4 Ig)
which biologics are used in psoriatic arthritis?
anti-TNF, ustekinumab (il-12+23), secukinimab (il-17)
which biologics are used in CTD?
rituximab
which biologics are used in AS?
anti-TNF, secukinimab
Gout acute treatment
NSAID/colchicine if unsiutable (side effect is diahorrea), prednisolne (oral, IA, IM).
gout prophylaxis
allopurinol (wait until post-acute attack) or febuxostat
both uricosurics = lower rate in blood by inc in urine
allopurinol mechanism of action and side effects.
-xanthine oxidase inhibitor, rapid reduction in uric acid levels may induce exacerbation of gout is prescribed acutely.
- vasculitis/skin rash common (switch to febuxostat).
- patients with pre-existing renal impairment need to lower dose and azathioprine interaction can cause irreversible bone marrow suppression.
gout pathway
purine → xanthine → uric acid → crystal deposit and gout
what can neither febuxostat or allopurinol be prescribed with and why
- azathioprine (interaction)
- can cause irreversible bone marrow suppression
febuxostat mechanism of action and side effects
also xanthine oxidase inhibitor, for those who cannot tolerate allopurinol.
safe in renal impariement.
used in caution with IHD (ischemic heart disease)
what do uricosurics do?
inc uric acid in urine and therefore reduced in blood.
indications for corticosteroids
CTD, vasculitis, RA, PMR, giant cell arteritis
given oral, IA, IM, IV, soft tissue injections - use short term
adverse effects of steroids
high BP, inc weight (centripetal obesity due to inc appetite and fluid retention), muscle wasting, skin atrophy, diabetes, osteoporosis (give Ca2+/Vit D supplements), cushingoid appearance and buffalo hump at neck. cataract, glaucoma, fluid renetion, adrenal suppression, immunosupression, AVN of femoral head(seen in lupus)
to reduce toxicity - short-term, lowest possible dose, wear off to other immunosupressants, watch CVS risk factor, osteoporosis prophylaxis
