Rheumatology Mbchb4


Key Points
CT dis (CTD) affect multiple organ systems, but freq have organelle-specific autoantibodies
Confusing terminology reflects poor understanding of the etiologies
Typical feats of SLE – butterfly rash, arthralgia, serositis, renal dis, organic brain syndromes, cytopenias
Consider CTD in any pt w any of the SLE feats in isolation, w unexplained constitutional feats or with multisystem/multiorgan dis
Assessment + Mgt of possible CTD requires early specialist consultation

Major Groups of CTD
SLE – Systemic Lupus Erythematosus
Scleroderma (aka systemic sclerosis)
Polymyositis and Dermatomyositis
Sjogren’s syndr (prim and 2ndry)
Vasculitis (many diff clin syndromes)


Epidem 9:1 (F:M)
Prev per 100,000 = 50 (European), 200 (African/Asian) – 3x ↑ in M/PI + SE Asian immigrants
Most common age of onset 15-40 yrs
Pathophys Deposition of imm complexes believed to explain many of the clinical feats

Organ Pres
Joints Arthritis, Arthralgia
Heart Pericarditis, Valve nodules, atheroma
Blood Anemia, Leukopenia, thrombocytopenia, clots, vasculitis
Lungs Pleurisy, interstitial lung dis
Kidneys Nephrotic syndr, RF
Skin Cutaneous lesions (eg facial rash), photosensitivity
Brain Neuropsychiatric problems, seizures, stroke

Main Clinical Feats of SLE
1. Facial rash – butterfly distbn (nose and cheeks)
2. Most serious manifestations – kidneys and brain
3. 5 yr survival rates >80%
4. Arthritis similar distbn to that of RA (symmetrical polyarthritis of small periph joints) but tends to be non-erosive

Main Differences SLE RA
Onset 20-40 30-60
F:M 9:1 3:1
Facial rash Y N
Pericarditis Y Rare
Nodules N Y
Proteinuria Y Rare
Joint erosions N Y
Neuropsyc probs Y N

Typical Lab Results SLE RA
Hb ↓ (possible hemolysis) ↓ (anemia chr dis)
ESR Mild ↑ ↑
RF 20% + Pos
ANA 95% + 20% +
Anti-DNA 50% + Neg
C3/4 Reduced N

Anti-nuclear antibodies
Immunofluorescent test – detects autoantibodies binding to nuclear components
ANA - Pos in a number of different CTDs – present in ALL SLE patients (and pos in some pts w other CTDs) – normal in 5% popn
Anti-dsDNA and anti-sm - uncommon in healthy individuals – specific to SLE but only 30-50% w SLE test pos
Certain drugs (procainamide and hydrallazine) can cause drug induced SLE – mild + remits once drug stopped (ANA against histones)

Pathogenesis of SLE
Auto-imm but poorly understood – pathological auto-antibodies are impt

I’M DAMN SHARP – SLE Revised Diagnositc Criteria 97 -
1. Immunoglobulins (Positive immunology - anti-DNA, anti-phopholipid, anti-sm)
2. Malar rash
3. Discoid rash
4. ANA (Anti-nuclear antibody)
5. Mucositis (oropharyngeal ulcers)
6. Neurologic dis (siezues, pschosis)
7. Serositis (pericarditis, pleuritis)
8. Hematologic d/os (hemolysis, leucopenia, lypmphopenia, thrombocytopenia)
9. Arthritis
10. Renal dis (proteinuria, casts)
11. Photosensitivity

Sxs incl fever, fatigue, weight loss, nonbacterial verrucous endocarditis, hilar adenoapthy, raynauds phenomenon
Wire loop lesions in kidney w imm complex deposition (w nephrotic synder)
Death from renal failure and infections
False positives on syphilis tests (RPR/VDRL) due to anti-phospholipid antibodies
Labs ANA – sensitive but not specific
Anti-dsDNA – v specific, poor prognosis
Anti-smith antibodies (anti-sm) – v specific, poor prognosis
Antihistone antibodies – drug induced lupus

Mgt Symptomatic tx – analgesics, NSAIDs, sun avoidance, vaccinations
Hydroxychloroquine (skin and joints
Immunosuppressive tx (azathioprine, prednisone for major organ involvement – renal, cns, vasculitis)
Biologic therapy – rituximab (anti-CD20, b cell depletion)
Careful assessment and tx of CV risk


Def Excessive fibrosis and collagen deposition throughout body – 75% F
Commonly sclerosis of skin (but also CV, GI and Kidney)
2 Major categories – Diffuse scleroderma and CREST syndrome

Epidem Most common age onset 20-50 yrs
Feats Early feat = raynauds phenomenon (arteriolar vasospasm of cold extremities causing triphasic color change
Fingers white (vasospasm) then blue (cyanosis) then red (reactive hyperemia)
If severe → gangrene
If mild → common and no need for special tx
If it occurs in isolation (w/o feats of CTD) → referred to as raynauds dis (also occurs in SLE and other CTDs)
Clin feats Scleroderma – thickening, tightening and tethering of the skin
Sclerodactyly – skin changes involving the fingers
Muscles – inflammation
Joints – arthralgia
GI – abnormal esophageal function (dysphagia, reflux) AND bowel (impaired transit, bacterial overgrowth, malabsorption)
Lungs – interstitial fibrosis, pulmonary HT
Kidney – RF, Acute renal crisis
Autoantibodies only present in small proportion of pts
Anti-scl-70 – more severe systemic dis, lung dis
Anti-centromere → CREST syndrome

1. Diffuse Scleroderma
Widespread skin involvement, rapid progression, early visceral involvement
Assoc w anti-scl 70 antibody

2. CREST Syndrome
Form of limited scleroderma → Calcinosis
Esophagus dysmotility
Limited skin involvement, often confined to skin and face
Assoc w anti-centromere antibody
More benign clinical course - Prognosis good but can develop late pulm HT

Scleroderma Tx
Raynauds phenomenon – cold avoidance vasodilators (felodipine, nifedipine), iv prostacyclin if distal ischaemia
Esophagitis PPIs
Renal crisis – ACEIs, renal support
ILD – immunosuppressive therapy (azathioprine, cyclophosphamide)
Pulmonary HT – vasodilators (bosentan, sildenafil, iv/nasal prostacyclin)


Primary or 2ndry SLE
Clin feats - venous thrombosis, arterial thrombosis, pregnancy morbidity (recurrent spontaneous miscarriage, late miscarriage, severe pre-eclampsia)
Presence of lupus anti-coagulant +/- anticardiolipin antibodies
Mgt Thrombosis – LT anti-coag w warfarin
Pregnancy complications – Aspirin +/- LMWH


Inflammatory Arthritis
Spondyloarthritis (ank.spon, psoriatic arth, reactive arth, colitic arth, undifferentiated spondarthritis) – axial joints, RF neg, often HLAB27 pos
Post-infective arthritis (rheumatic fever, reactive arthritis)
Infective (septic) arthritis (virus eg rubella, hep b, mumps etc or bacteria eg staph.aureus)
Crystal deposition (gout, calcium pyrophosphate deposition-cppd)
CT dis (SLE, progressive systemc sclerosis/scleroderma, polymyositis/dermatomysitis)
Vasculitis syndromes (polyarteritis nodosa, temporal arteritis)

Chronic Polyarthritis → may be either inflammatory or degenerative (ie OA)
Acute Monoarthritis → Trauma
Crystal deposition arthritis (monosodium urate - gout / CPPD – pseudogout)
Infective arthritis (staph, gonococcus)
Other inflammatory arthritis (spondyloarthrits, RA, juvenile chr arthritis)

1. Pain Impt Site Scale 1-10
Severity Sleep disturbance, work disturbance, recreational difficulties, analgesia reqd
Character Quality
Mode of onset, duration, ending Diurnal pattern
+ Precipitating and alleviating factors Pain at rest / on exercise
Complaints of disturbed sensation
2. Loss of mobility/function a. Stiffness (esp early morning stiffness)
b. paralysis (due to either neurological or motor dysfunction)
c. Lock or jamming
d. Instabiltiy
e. Pain on movement – may indicate synovitis
f. Loss of range
3. Deformed/Swollen joint Swelling due to bone, soft tis or synovial swelling
Joint deformity occurs with joint damage (involving bone, joint capsule, tendons)
a. Length of abnormality
b. Other joints affected
c. Is it painful
d. Is function normal

1. Hx + Examination Findings
2. FBC Anemia → chr inflam, occasionally hemolysis (SLE)
Leucocytosis → acute infection, inflammation or ?steroids
Leucopenia → autoimm (esp SLE) or drugs
ESR → increases w age
CRP → does not increase w age
3. Liver ↑ ALP/GGT – may occur as part of the acute phase response to inflammation
4. Renal ↑ creatinine in serious kidney dis (SLE or vasculitis)
5. Urine WBC, RBC, casts, protein (Glomerulonephritis in SLE)
6. Uric acid
7. Serological
Streptococcal antibodies >200 or 4x ↑ - antistreptolysin-o (ASO), antihyaluronidase (AHT), Deoxyribonuclease (anti-DNAse B)
Anti-nuclear factor (ANF) – pos in 99% of SLE but also pos in 5% of normal pts, 30% of RA + other CT d/os + chr active hepatitis and some drugs
Anti-DNA auto-antibodies – sig ↑ suggests SLE
C3/4 – low levels found in SLE
Rheumatoid Factors – antibody usu IgM (but sim in other Ig classes) – present 5% normal popn and 50-85% w RA (also SLE, SBE)
Synovial fluid – crystals and culture
HLAB27 – normal Caucasian 6-8%, ankspon 90-95%, Reactive arthritis 60-85% (only useful if high index suspicion spondyloarthropathy)

Mgt Goals
5Ds Death
Disability (mobility and function)
Discomfort (pain and other unpleasant physical sxs, psychological sxs)
Drug and other tx side effects
Dollar cost (direct and indirect)

Key Points – Rheumatology Patient
1. Screening questions in Hx a. Any pain or stiffness in arms, legs, back
b. Any problems going up or down stairs
c. Can you dress yourself completely w/o difficulty
2. Key points to elicit in hx a. time course
b. distribution
c. extra-articular feats
d. functional impact
3. GALS screening examination Gait, arms, legs, spine
4. Clinical signs of joint dis a. swelling/deformity
b. tenderness
c. loss of movement/function


Synovitis – inflam synovial membr, when unqualified, same as arth

Def An acute arth caused by crystallisation (precipitation) within joints of monosodium urate (MSU) in a hyperuricemic pt
Epidem M>40 yr, hyperuricemia, obesity, Maori
Pres Rapid onset severe pain (max severity 2-6 hrs) + extreme tenderness
Marked swelling
Red shiny skin
Feats Acute monarticular arth (but can be polyarticular) – asymmetric
Acute attack often follows alcohol or consumption large meal
Classical manifestation - metatarsophalangeal (MTP) joint of great toe (podagra)
Tophus – irreg firm nodules of uric acid deposits in periarticular fibrous tis, cartilage ext ear, Achilles tendon, olecranon bursae, hands, feet
Uric acid stones cause (not MSU) cause renal colic in 10% of gout pts
Ix Joint aspiration – MSU crystals (white + needle shaped + neg birefringence (having >1 refractive index according to dir of transmitted light)
↑ ESR (Rate rbc sedimentation in anti-coag bld - ↑rates often assoc w states anemia or inflam)
↑ wbcs (Neutrophil leucocytosis) + ↑ CRP
Uric acid >0.42 mmol/L (but often <0.42 mmol/L during acute attack)
XR – assess degree of joint damage
Assess renal function (serum creatinine + urine), HT, blood glucose, lipids

Diff Dx Septic arthritis (more subacute in onset, progresses in severity until treated)
Traumatic arth
Viral arth
Reiter’s syndrome (reactive arth)
Psoriatic arth
Reactive arth
Ankylosing spondylitis

Hyperuricemia Uric acid derived chiefly via purine catabolism formed in denovo synth nucleic acids + to lesser extent b/down of dietary purine
Plasma uric acid filtered at glom + reabsorbed by prox tub → Tubular secr accounts for almost all urinary uric acid
Hyperuricemia – due to either incr in endogenous biosynth of purines or reduction in renal excr (or both)
Manip of diet little effect on serum uric acid level (though excess dietary purine may contribute to etiol of acute attack gout)

Primary Gout Almost exclusively M, >40 yrs
2ndry Gout Usu 65+ yrs, chr hyperuricaemia 2ndry to renal impairment or chr diuretic use

1. Underexcretion Uric Acid (Common)
1° Idiopathic (inappropriately low excr rate relative to serum uric acid level) – Inherited isolated renal tubular defect (90%)
2° RF
Diuretics (thiazides + loops)
acute alcohol ingestion
Others - ↓ tubular excr uric acid, toxaemia in preg, DKA, Salicylate (low dose), Dehydration

2. Overproduction Uric Acid (Uncommon)
1° Idiopathic *PRPP excess (↑ PRPP synthetase activity) - Phosphoribosylpyrophosphate
*HGPRT deficiency – Hypoxanthine-guanine phophoribosyltransferase (Lesch-Nyan Syndr)
2° Assoc w ↑ nucleic acid t/o myeloproliferative d/os
lymphoproliferative d/os
chr haemolytic anemias
assoc w ↑ synth de novo
*glucose-6-phosphatase defic

Pathogenesis Acute Gout Attack
1. Precip Events – Dietary excess, Alcohol, Drugs (aspirin, diuretics, allopurinol, uricosuric agents)
Also – trauma, unusual physical exercise, surgery, severe systemic illness, severe dietary restr
2. Cyrstallisation within joints of uric acid in hyperuricaemic pt
3. urate crystals activate Hageman factor → series of reactions → bradykinin + other kinins
4. ↑ capil perm + accum leukocytes (chemotactic factor)
5. vigorous phagocytosis of crystals by neutrophilic leukocytes
6. activation of lysosomal enzymes within cells → release into synovial fluid

Mgt Acute Gouty Arth
Self limiting – 5-14 days return to normal
Aim → pain relief
Do NOT use uricosuric drugs or allopurinol – however continue allopurinol if pt already stabilised on it
Tx NSAIDs – Diclofenac, Naproxen (side effects → renal impairment, CHF, peptic ulceration)
Add low dose colchicine (resistant cases)
Prednisone (when NSAIDs contra)
Joint Aspiration – instant relief
Intra-articular corticosteroid injection – prevents fluid reaccum (can abort an attack)
Manage RFs – weight, alcohol, diuretics, dietary purines

Colchicine Depolymerises microtubules → impairs leukocyte chemotaxis + degranulation
GI side effects (vomiting / diarrhea)
Avoid 2 hourly regimen (GI tox in 80%)

Mgt Chr Gout
Only after acute gouty arth controlled
Not all pts require LT mgt – however most people will have a 2nd attack within 1 yr and the freq of attacks ↑ w time
Later attacks – usu more severe and involve more joints
Eventually – MSU deposition causes joint damage + chr pain
Concurrent anti-inflam meds or colchicine (0.5mg od) usu reqd first few months to prevent acute exacerbation of gout
Pts w tophi may require lifelong colchicine
Indications to ↓ serum uric acid level
Serum uric acid >0.54 mmol/l (consistently)
>1 attack ev 3 months or >2 weeks lost time from work
Evidence of renal involvement – renal impairment, calculi
Tophi or radiological joint destr
Drugs to ↓ serum uric acid –
Uricosuric Drugs - ↑ renal excretion uric acid
Probenecid – inhibits reabsorption of uric acid proximal tubule (also inhibits secr of penicillin)
Allopurinol – inhibits prodn of uric acid (xanthine oxidase inhibitor)
↓ conversion xanthine to uric acid
Starting dose 100-300 mg (100 mg if renal impairment)
→ initial sharp ↓ in tis uric acid levels → can partially dissolve MSU crystals + trigger acute attacks → pt should continue
↑ allopurinol in 100 mg increments until achieve range in lower half of normal (max dose = 900mg)
Also used in lymphoma + leukaemia to prevent tumor lysis-assoc urate nephropathy
Wait 3-4 wks after acute attack before starting (continue at same dose if already stabilised when acute attack occurs)
Build dose up gradually eg by 100mg increments/wk or fortnight
Monitor w regular uric acid estimations (monthly for 3/12)
Aim – serum uric acid <0.36 mmol/L
General Measures Optimal body weight – weight loss + exercise
Avoid severe dietary restrictions
Moderate alcohol consumption acceptable
Dietary Meat + seafood (high purine load) - ↑ risk
Alcohol (esp beer) - ↑ risk
Obesity - ↑ risk
Diary products – ↓ risk
Moderate intake purine rich veges – no ↑ risk

Asx Hyperuricaemia 95% hyperuricaemic subjects never develop gout
Seek cause of hyperuricaemia + correct eg. diuretics
Drug tx justified (uncommon) when persistent/prolonged hyperuricemia + complications likely ie. >0.78 mmol/L


Overview Mechanical wear + tear of joints → destr articular cartilage, cysts, sclerosis, osteophytes, eurnation, Heberdens nodes (DIP) +
Bouchards Nodes (PIP)
Predisposing Factors – age, obesity, joint deformity
Pres – pain in weight bearing joints after use (ie end of day), improving w rest (no systemic sxs)

Feats Chondropathic form of arthritis (rather than synovial inflammatory arthritis like RA)
Final common pway incorp both degradation + repair of a number of diff insults which affect the joints
Clinical syndr which may be helped by a wide range of non-operative txs + stimes surg

Epidem Most common rheumatic dis → sig pain + diability – 2% adult popn / 10% 60+ yrs
Def A heterogenous grp of conditions sharing common path + radiol feats
Focal loss articular cartilage in part of a synovial joint + accompanied by a hypertrophic reaction in the subcondral bone + joint margin
Radiographic changes → joint sp narrowing, subcondral sclerosis, cyst formation + marginal osteophyte formation (bony outgrowth/protrub)
Predilection for knees, hips, hands + apophyseal joints of spine (apophysis = outgrowth/projection esp one from bone)
Often accompanied by use related joint pain, gelling (stiffness) of joints after inactivity + loss of range of mvment

Two Current Paradigms (not mutually excl) – Nature of OA
1. OA viewed as a response to joint injury → initiating both degradative + reparative processes in the joint (involving all tissues)
2. OA regarded as age related d/o of joints dep on joint usage + shape – rapid change in posture, grip + activity of humans + the ↑ post-repro
lives → accum of injury in organisms w ltd repair capacity
Genetic Factors
COL2AI gene implicated in some pedigrees (produces type 11 collagen)
VDR (vit D R) – assoc w radiographic OA of knee

Diagr pg 21 (Locomotor course book)

Classification of OA
1. Classification by joints involved
Monoarticular, oligoarticular, polyarticular
Chief joint site + localisation within joint
Hip – sup pole, medial pole, concentric
Knee – medial, lateral, patello-femoral c/ments
Hand – DIP, PIP joints + 1st CMC (thumb base)
Spine – apophyseal joints, intervertebral discs
2. Classification into primary + 2ndry forms of OA (primary = idiopathic / 2ndry = likely identifiable cause)

2ndry OA Etiology
1. Metabolic – Eg. Ochronosis, acromegaly, hemochromatosis, calcium crystal deposition
2. Anatomic – Eg. Slipped femoral epiphysis, epiphyseal dysplasias, perthe’s dis, congenital dislocation hip, leg length inequality, hypermobility syndromes
3. Traumatic – Eg. Major joint trauma, fracture through joint or osteoneocrosis, joint surgery, chr injury
4. Inflammatory – Eg. Any inflammatory arthropathy (incl RA, PSA)
5. Classification by the presence of specific feats – Eg. Inflammatory OA, erosive OA, atrophic or destructive OA, OA w chondrocalcionosis


1. Non-Invasive
Education Pt contact (monthly telephone contact)
General exercise + activity
Specific physical therapy exercises
Tapes + bandages
Sticks, canes + other walking aids
Shock absorbing footwear
OA joints – not necessarily painful or a cause of disability (ie mild radiographic changes → severe pain / severe joint damage → no sxs)
Theory – general health (esp psychosocial status) impt determinants of both pain + disability
Muscle weakness is an indep RF for ↓ func
Helps explain efficacy of interventions such as patient contact + mus strengthening exercises

2. Drug Therapy
Analgesics – Paracetamol (avoid opiates) – most pts probably txed adequately on simple analgesics
NSAIDs (oral or topical) – nonselective or COX2 selective
Try NSAIDs after paracetamol
COX2 inhibitors – may be useful in those w GI intol/peptic ulceration (alternatively consider non-selective NSAID + PPI)
Elderly age grp → be cautious regarding GI + renal side effects
Local Intra-articular corticosteroid injection
Stimes provide pain relief up to 3 months
Less effective than in FA (probably bec less active inflam within an OA joint)
Elderly pts – generally well tolerated but can stimes precipitate facial flushing (transient) + disturb blood glucose in diabetics
Hyaluronic Acid (HA) Injections
HA normal component of healthy articular cartilage – exists as a large macro-polymer
Broken down in OA
3 weekly injections → provides pain relief + improved mobility 3-9 months in some pts
Expensive but only easily used for OA of knee
Glucosamine + Chondroitin Sulphate
Absorbed from GI tract
Appears to be capable of ↑ proteoglycan synth in articular cartilage
Matrix metalloprotein (MMP) Inhibitors (experimental)
Inhibit enzymes such as collagenase which belong to the MMP family


Polymyalgia Rheumatica

Epidem Age >50 yrs
Pres Shoulder girdle and hip girdle pain
Pronounced morning stiffness
No true muscle weakness – but may be unwilling to move 2ndry to pain
Etiology Unknown – suspected viral infection
Assoc w tempral arteritis – more serious
Findings Systemic sxs of inflam
↑ acute phase markers – CRP/ESR
No distinctive path feats
Pos temporal art biopsies found in 10-15% of GCA pts w no clinical feats of GCA
Tx Dramatic response to low dose corticosteroids → Prednisone 10-15mg/day (can confirm dx)
Most pts need tx for at least 2 yrs
Relapses freq on attempted steroid reduction (monitor dis activity using ESR)

Giant Cell Arteritis (Temporal Arteritis)

Epidem F>M 2:1, mean age onset 70 yrs (rare <50 yrs)
Etiology Inflammatory dis of the blood vessels (most freq temporal arterty branching from ext carotid) – form of vasculitis
¼ cases coexist w PMR (sudden onset pain + stiffness in muscles esp pelvis, shoulder) and seen in the elderly
Other related diseases – SLE, RA + severe infections
Suspected viral infection
Vasculitis immunologically mediated (CD4 T cells implicated) - Assoc w HLA DRB*04
Pres Headache, scalp tenderness, jaw claudication, blurred vision/acute visual loss, fever, malaise, weight loss, fatigue (constitutional sx)
Inflam may affect blood supply to eye (ophthalmic art) → medical emergency
Findings Tender, non-pulsatile, thickened temporal art
Systemic sxs of inflam
Ix Temporal art biopsy → large vessel vasculitis featuring giant cells - false negatives common (skip lesions, wrong side biopsied etc)
Extra-cranial arteritis
Tx Prednisone 40-80mg/day
Don’t delay tx while awaiting biopsy
Gradually taper prednisone over 2-5 yrs
Osteoporosis prophylaxis (Prednisone side effect) → Bisphosphanates/Calcium, HRT, Vit D
Consider steroid sparing txs – azathioprine or methotrexate

Continuum – PMR (mild) → GCA (severe)

Diff Dx Late onset RA (RA → prominent periph joint synovitis – can be confusing bec many elderly pts have pos RF w/o RA)
Polymyositis – clinical muscle weakness
Prodrome viral inf
Other systemic illness – eg neoplasia, metabolic disorders (vit d defic)

LT corticosteroid Use – Side Effects
Weight gain/ central obesity
Skin atrophy and easy bruising
Impaired gluc tol/DM
Infection risk
Mood disturbance
Raised intraocular pres/glaucoma
Mus weakness


Def Arthritis resulting from deposition of calcium pyrophosphate dihydrate crystals within the joint

Clinical feats (variety of forms)
1. Pseudogout Common in elderly
Pres – monoarthritis often in knee or wrist (acute joint inflam)
Differentials – sepsis, gout, other inflam arth
May be triggered by minor trauma
2. Assoc w OA progressive degen joint changes w/o acute episodes
may have superimposed episodes of pseudogout
3. Subactue arthritis mimicking RA
4. Clinically silent – radiological chondrocalcinosis w/o sxs

Metabolic diseases may be assoc w CPPD arthropathy (esp in younger pts) – include hematomachrosis, hyperparathyroidism

Dx Joint aspiration reveals rhomboid shaped crystals, pos bifringence on phase contrast m/scopy
Radiology Chondrocalcinosis often seen within menisci or hyaline cartilage at knee
Deposits at triangular fibrocartilage wrist
Tx Intra-articular steroid injection useful
Colchicine (occasionally beneficial)


Objectives clinical feats, ix, tx, recog when pts require specialist assessment

RA Autoimm inflam d/o affecting synovial joints + pannus formation in joints (MCP, PIP), subcut rheumatoid nodules, ulnar dev, subluxation
80% pos for RF (rheumatoid factor) – anti-IgG antibody
Pres – morning stiffness improving w use, symmetric joint involvement, systemic sxs (fever, fatigue, pleuritis, pericarditis)

Dx of RA (ARA) – at least 4, present for >6 wks
1. morning stiffness >1 hr
2. arthritis of 3+ joints
3. involvement of hands
4. symmetrical arthritis
5. presence of nodules
6. presence of erosions
7. RF pos

Intro Common
Mildest form – pts may never consult a dr
Severe form – carries 5 yr mortality worse than severe ischaemic heart dis and many malignancies
Impt cause of morbidity in young, previously healthy productive people
Est 200K per pt/ lifetime
Median life expectancy - ↓ by 3-7 yrs

Presentation Symmetrical small joint polyarthritis
Small joint – hands + feet (but not DIP joints)
PIP, MCP, MTP, wrist + tarsal joints + others (cervical spine)
Other common sites – ankle, knee, hip, elbow, shoulder, TMJ (not involved w/o involvement of small joints at same point in dis)
Arthritis = Objective inflam of joint detectable on clinical examination
Arthralgia = pain in joint but not necessarily inflamed
Polyarthritis – tender soft tis swelling due to synovitis, ↑ temp (SF or med-large joints), redness (v SF joints eg PIP) + loss of
function (impaired range of motion)

Epidem Incidence 1-2% of popn (incl pts w mild dis or that which spontaneously remits)
0.2-0.5% severe, chr RA
F>M 4:1 (becomes equal after 60 yrs)
Males – show a slight excess w severe extra-articular dis
European popn – more common + severe (due to different HLA-DR4)
Begins any age – juvenile onset form mimics adult RA (peak incidence 30-60 yrs)
1’ relative w RA → ↑ x4 (the closer the relative + the more relatives affected → the higher the risk)
90% no family hx

Hx DIP joint involvement → psoriatic arth or OA
Inflam forms of arth – typically worse in the morning (morning stiffness loosens up later on + time taken for this = index of how active dis is)
Pts feel better after mvment
In contrast – OA/mechanical probs – mvment generally worsens the sxs
RA – at least partial improvement w NSAIDs (but OTC doses usu too small)
Extra articular feats – pleural effusion, splenomegaly
Effect on patient – life, work, function etc

Exam Examine ALL joints – quick GALS style screening exam is not adequate
Is there objective arthritis?
General physical exam – extra articular feats, complications of RA or therapy (anemia, peptic ulcer)
Other inflam diseases – eg psoriasis, IBD – both assoc w arth

Ix Lab ↑ ESR, ↑ CRP (↑ other acute phase reactants)
Normocytic anemia
↑ wcc + platelets
low albumin, raised globulins
RF 80%
Anti-nuclear antibodies 15%
HLA-DR tying not indicated – research stage only
Synovial fluid – predom neutrophils, negative culture + no urate crystals (Gout + RA practically never co-exist)
Rad soft tis swelling
Osteopenia (↓ calcification or density of bone)
Erosions – usu at edge of cartilage zone “marginal”
↓ joint space (represents cartilage loss)
deformity / misalignment
2ndry OA

Extra-articular feats
Skin vasculitic ulcers, nail fold infarcts, rheumatoid nodules
Muscle wasting
Bone osteoporosis
Tendons tensynovitis, nodules, rupture
Eyes keratoconjunctivitis, scleritis
CVS pericarditis, valvulitis, myocarditis, vascultis
Resp pleuritis, effusion,s bronchiolitis
Haem anemia, hypers;oensim
Nerous periph n entrapments, polyneuropathy, sp cord compression
Gi blood loss
Renal renal impairment (NSAIDs)

Differential Dx SLE
Psoaritic Arthritis
Viral inf (rubella, parovirus, hep b, arboviruses)
Lyme dis (not nz)

Prognosis RA chr – many pts have spontaneous cycles of remission + relapse (flares = bad patches)

unknown (est 1/3 genetic)
Main known genetic factor = HLA-DR (esp DR4)
RA is only assoc w HLA-DR which have partic seq at a part of 2 molecule that binds 2 processed antigenic peptides
This seq referred to as the shared epitope
Theory – DR4 causes predis to RA bec it uniquely binds certain antigenic peptides (identity of peptides unknown)
Maori/PI – less RA bec they have protective DR4 subtypes which cant bind the mystery antigen
HLA effects contribute 1/3 to genetic component – other genes coding for CKs (eg TNFa) + oth imm modulatory molecules implic
Autoimm – prevailing theory – RA autoimm triggered by a virus and mediated by T lymphocytes
Various autoantibodies (eg RF, antibodies against collagen) - none really a/cs for the dis (may be incidental or 2ndry 2 oth dam)
Many CD4 cell accum in the synovium
CKs – dominant ones found in inflamed RA joint → IL1/6/8, TNFa, VEGF, GM-CSF (mainly made by fblasts/mphages)
IL1 + TNF → activate chondrocytes + osteoclasts → cartilage + bone resorption (respectively) – also help activate B+T cells
IL6 – mimics IL1 (mediates acute phase response)
IL8 – potent neutrophil attracter + activator
GM-CSF – activates mphages
VEGF – promotes growth of blood vessels in synovium
Synovial lining cells (normally 1-2 cells thick) → proliferate enormously (synovium thickens + called “pannus”)
Damage to joint – reactive o2 species (free radicals) generated by activated neutrophils – they may be ↑ by cycles of ischaemia +
reperfusion (during joint mvment) as intra-articular pres gets high enough to occlude blood flow into synovium → oxidative damage to DNA/proteins
Imm Complexes – B cell activated – some produce RF within joint – when this binds IgG → imm complexes formed → activate compl + phag
Enzymes – more damage as phagocytes release many enzymes which damage cartilage + bone (incl collagenase + stromelysin)
PGs + LKs – released by activated mphages + fibroblasts – potent pro-inflam mediators + produce pain

Tx Hospitalisation only reqd for severe flares, complications or joint surgery – usu outpt mgt sufficient
1. Patient Education
Written info helpful
Arthritis foundation – literature, dvds, support grps
2. Rest + Exercise
Rest → ↓ synovitis (splints appropriate for certain joints eg wrists)
Bedrest occasionally indicated in severe flares (but leads to loss of bone mineral density, mus bulk, exercise capacity etc)
Additional problem → devt of joint contractures (eg flexion deformities at knees/elbows)
Prevent contractures by range-of-motion exercises
Stay fit – most pts ok to walk 20-30 mins 3x/wk within limits of their joint pain
Any activity exposing joints to high mechanical stress (eg running, contact sports) should be avoided
Swimming – safe for almost all pts
Mobilising exercises – easier in a warm pool (hydrotherapy pool)
3. Diet + alternative therapies
Chinese herbs – some contain potent quantities of corticosteroids + other inflam agents (some aldutered w heavy metals)
Herbal teas – many contain hepatotoxic alkaloids
Omega 3 polyunsat FAs (PUFA) – taken as fish oil capsules – a real but modest beneficial effect if taken in large dose (unpleasant)
Green lipped mussel extract – further research needed
Collagen – more research needed
Total fasting – effective but works by producing malnutrition hence immunodeficiency (risks outweigh benefits)
4. Health professionals
Physio – range of motion exercises, education joint care, hydrotherapy, topical heat + cold
Occup therapist – daily living assessment, provision aids + appliances, modification of home/work evt
Social worker – dis impact, benefits, community resources, alternative accom, conselling, fam therapy
5. Drugs
Early + aggressive – irreversible joint damage begins v early in the dis (often first few months)
Prob – some pts remit either spontaneously or have relatively mild dis (expos to potentially toxic therapy unjustified)
Solution – identify those w worse prog – however no single clin or lab indiactor that reliably predicts poor prognosis
Approach – DMARDs (disease modifying anti-rheumatic drugs) → slow joint dam
Paracetamol - moderate effect, well tolerated
Opiates - avoid if possible (not esp effective for the MS pain of RA, ever incr dosing reqd, inappropr for non-malignant chr dis)
NSAIDs – marked (+ unpredicatable) inter pt variation in efficacy + side effects – Ibuprofen, naproxen, diclofenac, indomethacin, ketoprofen
COX2 Selective Inhibitors – Rofecoxib (Vioxx) + Celecoxib (Cerebrex) – not subsidized
Selective inhibition COX2 isoform of COX enzyme (which mediates inflam via PG prodn), but leave COX1 isoform intact (constitutive
gastroprotective PGs not affected) – alternative non-selective NSAID + PPI
NSAIDs Side Effects → Peptic ulceration + Renal impairment (due to PG inhibition)
Methotrexate – 1/wk, much smllr doses than ca chemo
Action – uncertain (possible inhibition neutrophil enzymes) – promotes adenosine accum (anti-inflam)
Tox – cytopenias (esp wcc), nausea, rash, abnormal LFTs +/- liver fibrosis, acute pulm alveolitis
Folic acid ↓ some side effects (nausea)
Leflunomide – 3x100 mg loading dose then 20 mg /day – enterohepatic recirc + v long half life
Action – interferes w pyrimidine synth
Tox – diarrhea, skin rash, cytopenias (are), teratogenic
Choestyramine – used to wash out drug (eg preg)
Sulphasiazine – antibiotic + salicylate combo
Action – may work as subtle immunomodulator
Tox – nausea, rash, neutropenia, hepatitis
Gold – IM inj 1/wk (eventually 1/month)
Action – unclar, possible interference mphage func
Tox – may be severe, rash, ulcers, cytopenias, nephropathy (proteinuria)
Hydrochloroquine – weak agent but well tolerated
Action – changes pH in endocytic vesicles in APCs – inhibits prodn of mphage derived CKs
Tox – possible retinal tox (ophthalmic monitoring reqd)
Action – effects on T lymphocytes, dendretic cells, mphages
Tox – Renal tox limits the safe dosage
Often used in conj w methotrexate
Interactions w other drugs common
Action – SH grp thought to bind various inflam molecules
Tox – nausea, taste turbance, cytopenias, proteinuria
Selection – Efficacy → hydrochloroquine + oral gold weaker than others
Methotrexate – most effective + best tolerated in LT (but concerns about potential tox)
Corticosteroids – injections of depot preps directly into active joints
Systemic – prednisone for resis dis
Monoclonal antibodies to TNFa → Infliximab, adalimumab) + soluble TNFa R (etanercept) – not subsidized – expensive, effective, well
tolerated, but no LT data
Many studies – TNF blockers prevent progr of erosions → definite improvement over older RA drugs
No drugs biologically curative – dis usu relapses when drug discontinued

Complications 2’ to RA or 2’ to drug tx
Osteoporosis – Calcium, VIt D, BIsphophanates, HRT
Depr – counseling, antidepressants, pain mgt
Peptic ulcer – H2 antagonists, PPI, misoprostol

Orthopaedic surgery
Despite best available therapy – many RA pts → irreversible cartilage + bone damage + eventually require joint replacements

Transfering Pt to a specialist
At least one specialist assessment early in dis – essential as the majority of pts will need early aggressive therapy soon after dis begins
If uncertainty about dx
Considering 2nd line therapy – most pts
Erosions or other bone dam, extra-articular dis
Complications needing surgery
Specific probs (eg co-morbidity complicating drug therapy)


Case 1

28 F
Pres 1 month hx of morning stiffness and pain in fingers
PMHx Soreness and swelling of wrists 3 months prior following attack of flu – took neurofen and this cleared in 2 wks
Anxious about working future as solo mother w 7 yr old

Arthritis Joint inflammation characterised by rubor, calor, dolor, tumor (4 cardinal signs) – stimes loss of function added to this
Differentials RA, Reactive arthritis (post viral polyarthritis), Psoriatic arthritis, CTD (SLE)
Morning stiffness Non-specific sx pointing to inflammatory joint dis (common in RA, CTD, AS)
Prognoses RA → v good tx options available
Post viral → often resolves w/o further problems
Not necessarily chr if tx started early

Pt returns 1 month later
Obvious swelling both knees
Knee pain when climbing up/down stairs
↑ soreness of hands
Obvious swelling MCP and prox IP joints
Tingling in R hand waking her at night and during the day after knitting
PMHx She has had RF and an appendicectomy, never been told she has a heart murmur
No sig FHx gout or arthritis but paternal grandfather walked w stooped posture and as a youth, backache, walked w stiff gait and complained of arthritics

New Info suggests -
↑ no s/s suggests a chr inflam arthritis
Suggests dx of RA or CTD as opposed to post-viral arthritis
Polyarthritis – suggestive of RA
FHx AS – HLAB27 assoc – incr risk of spondylarthropathies

Tingling Carpal tunnel syndr – parathesia, weakness of finger mus (median n compression) – wrist synovitis causing CTS
Tx via prednisone, wrist splints, local corticosteroid injections, surgery
RF Hx Not that sig in this case

Following 11 months
Shoulders, wrists and feet – stiffness and swelling
Pain in back of head and front of her ear for 1 month → C-sp involvement (RA of synovial joints - Atlanta-axial joint) + TMJ involvement
V tired → lack of sleep and pain + systemic inflam causes fatigue + anemia of chr dis or via NSAID related gastric bleeding
She is worried about keeping her job and is becoming increasingly bad tempered w her son and at work
chr pain → low mood → difficulty managing pain → sleep disturbance → pain exacerbation

O/E Fit, thin, pulse 80 and regular, BP 150/80
Small nodule at L elbow, ↓ light touch sensation of skin of palm over thenar eminence and index finger
Ixs Further imaging looking for feats of instability as complications possible eg cord compression
Likely Dx RA → small joints hand and feet, polyarthritis, relatively symmetrical, nodule on elbow

Clinical Feats of RA
Symmetrical involvement
Small joint involvement
Morning stiffness
Chr and progressive dis

Ixs CRP – better indicator of acute inflam than ESR
RF – if pos, suggests RA (but 30% of RA pts are neg)
Anti-citrullinated protein antibodies (ACPA) – more specific for RA than RF (detects 80% of all RA pts, but rarely pos in non-RA pts (98% specific)
ACP antibodies can often detect early stages of dis, or even before dis onset
Anti-CCP (cyclic citrulinated peptide) test most common for ACP antibodies
FBC – anemia, bone marrow suppression, CTD (low wcc, low platelet count)
Creatinine – bec on NSAID tx (ensure normal renal function)
Liver function – many meds cause hepatic dysfunction
XR – hands and feet (establish early baseline – unusual to see RA changes within 6 months)
Radiographic feats of RA on xr
1. Narrowing of joint space
2. Periarticular osteopenia
3. Juxta-articular bony erosions
4. Subluxation and gross deformity
5. Periarticular soft tis swelling

Mgt Plan 1. NSAIDs – sx relief only, no impact on underlying process
2. DMARD – early and aggressive eg Methotrexate is first line defence

Case 2

63 F
Pres Pain in both knees
1 week earlier, on feet all day, then next morning could harly move
Some ant knee discomfort climbing up/down stairs or when gardening past few years (esp during winter), but never this bad
Always had a weight problem, current 89kg, unchanged for some years
Daughter-in-law recently has started her on a vegetarian diet w celery and boron supplements

Most common arthritis affected 63F in both knees → OA
Factors in hx supporting this dx and her current pres → ↑ weight causing ↑ joint load, age (post-menop), use of knees (eg gardening)
Diet → weight loss v impt, no proven evidence supporting a celery/boron diet

Case cont
Further hx – pt also remembers playing netball when young, but stopping due to knee probs, decided against an operation back then
O/E Small effusion both knees, tender over medial joint line each side, collat and cruciate ligs intact, full ROM, some patellofemoral crepitus
Feet/ankles normal, some bony enlargement of the IP and pIP joints of fingers of both hands, and bases of both thumbs, these joints not painful

Past hx of knee trouble significance → meniscal injuries predispose to OA
Likely nature of effusions → synovial fluid (low grade effusions), possible CPPD could a/c for worsening sxs (clarify via aspirate)
Is a hip exam impt → Yes, many pts w hip dis pres w knee pain (referred pain)
Nature of swelling of finger joints if not painful → bone swelling (osteophytis typical in OA), or nodes

Case cont
Pt prescribed paracetamol
1 wk later – L knee settled but R knee remains painful and swollen
XR – moderate loss joint space on weight bearing view, more marked in medial c/ment, subchondral sclerosis, mild osteophyte formation
Blood tests normal

NSAIDs more effective than Paracetamol but less safe
XR taken weight bearing – to assess physiological loss of joint space (joint widens spuriously if not weight bearing)
Blood tests to consider – ESR, CRP, Ca2+ pyrophosphate
Tiger balm effectiveness – possibly some effect, cheap and generally non-toxic
Knee support effectiveness – not advised as incr mus wasting leading to greater instability, pts w knee dis req quad strength to stabilise joint
Refer pt to physiotherapists for quad strengthening program

Case cont
Pt R knee continues to give pt probs and over next 2 yrs becomes more and more painful (weight bearing and at rest) – she has given up work
Additional tx options – Knee replacement

Case 3

M 56 Former maori all black
Pres Acute pain + swelling R ankle after spending most of weekend on golf course (no recollection ankle trauma) + evening celebrating
Woken at 5am mon w ankle pain becoming progressively worse over preceding 8 hrs
Hopped into surgery in bare feet – ankle obviously swollen, red, hot and tender to touch

Differentials Trauma (eg sprained ankle), Gout (most likely), Septic arthritis
Hx suggesting gout Alcohol (esp beer) – large purine load → acute hyperuricaemia
Injured joints - ↑ risk of gout
Gout attacks – triggered by release of gout crystals into joint (exacerbating by incr walking golf course
Ethnicity M/PI – higher prev – 3x ↑ risk – present earlier at with more severity

Case cont
PMHx Gout – R 1st toe MTP joint 5 yrs ago when out pig hunting and couldn’t get to dr
Excruciating pain 3-4 days followed by complete resolution
2-3 similar episodes since then involving one or other of his great toe MTP joints – responded to indomethacin
Last occasion 2 wks ago attended A/E – prescribed allopurinol 300mg/day in addition to indomethacin
Bloods Normal blood screen, ESR 35, serum urate 0.4 mmol/l (normal <0.42), serum creatinine normal
XR Normal

Previous hx gout → likelihood of recurrent attack
Acute gouty arthritis if serum urate normal → there is often a big ↓ in serum uric acid levels at onset of attack (unclear why)
Definitive Dx → joint aspirate – MSU crystals under m/scope – concurrently check for infection
Allopurinol → likely harming this pt – NEVER give a pt w an acute attack of gout allopurinol (wait >1 month before starting)

Case cont
O/E Small soft tis swelling over R elbow olecranon process
Random sitting BP 170/110
↑ thirst and urinary freq in recent months
15kg weight gain over 20 yrs

Tophus → collections of uric acid crystals within joint/subcutaneous tis (often elbows, ears, feet or any area of pres) – explains soft tis swelling elbow
Polydipsia/Polyruria → Type 11 DM query as gout has a strong assoc to metabolic syndrome and type 2 DM – always testing fasting glucose in a gout pt
BP → ↑ risk of HT with gout (due to metabolic syndr or diabetic associate renal impairment) → ↓ excretion uric acid – always test creatinine
Thiazide diuretics can also exacerbate hyperuricaemia
Also consider lipid screen and overall assessment of CV risk factors
Lifestyle factors Weight loss – ↑ abdo girth → ↑ uric acid levels
Diet – avoid seafood/meat (high in purines)
Low purine diet
Drink low fat milk
↓ alcohol consumption (esp beer) – wine is better

Case 4

F 45
Pres Pain all over last 3 months – esp aching discomfort hands, forearms, shoulders, neck, hips, knees, ankles
Early morning stiffness
Puffy joints (esp hands and wrists)
Intermittent numbness and tingling in hands and both legs
Freq tired and hx of migraines
Recently reviewed at gastro clinic for diarrhea and IBS

Differentials SLE
Fibromyalgia – chr MS pain, abnormalities in pain sensation, longstanding localised pain/tenderness (esp spine, thigh, elbows, knees)
Inflammatory arthritis related to IBD
Chr pain d/o

Case cont
Sleeping poorly waking several times per night (Sleep disturbance → worsen chronic pain + vice versa)
Currently taking herbal meds as NSAID tablets cause GI discomfort
Multiple allergies and mention she doesn’t like taking tablets
O/E Widespread tenderness small joints of hand incl MCP, PIP, DIP joints
No definite swelling noted
Marked tenderness at midpoint of forearm bilaterally and over trapezius muscles
Marked tenderness bilaterally over lateral aspect thigh, medial aspect knee prox to joint line – gait quite normal
Ixs FBC normal, ESR 9, ANA 1:160 (speckled pattern), anti-dsDNA antibodies and RF neg
XR – normal hands, but degen changes noted on old films of lumbrosacral sp that she bought with her

Sig of tenderness at small joints of hands → generalised ms tenderness (global not local)
Fibromyalgia tenderpoints (exquisite tenderness) → occipit, traps, lat elbow, lat thigh, med knee
ANA = anti-nuclear antibody – although neg, pt may still have SLE (5-10% of normal popn also test pos for ANA)
Anti-dsDNA – more specific for lupus than ANA

Case cont
Pt prescribed low dose amitriptyline and refered to physiotherapy
Drug stopped after a few days due to drowsiness
Physiotherapy causes her ↑ pain – pt stops attending
She returns after 1 month – no improvement of sxs

Mgt options Refer to pain clinic
Refer to physiotherapist skilled in chr ms pain
Education on pain mgt strategies
Group or psyc therapy
Gaba-pentin (anticonvulsants)

Fibromyalgia (FM or FMS)
Syndr of chr pain ms origin but uncertain cause (possible genetic predisposition)
Dx criteria – pain on both sides of body, both above and below waist, as well as in an axial distbn (cervical, thoracic, lumbar or ant chest) + point tenderness in at least
11/18 specified sites
Diffuse or specific mus, joint, or bone pain, fatigue + wide range of other sxs
F>M 9:1 – 3-6% gen popn (dx usu betw ages 20-50)
Defining sxs – Chr, widespread pain and tenderness to light touch (usu moderate to severe fatigue)
Allodynia – heightened sensitivity of skin
Skin tingling
Achiness in mus tissues, prolonged mus spasms, weak limbs, nerve pain
Chr sleep disturbance
Other sxs often attributed to fibromyalgia incl myofascial pain syndr, chr parasthesia, physical fatigue, IBS
Can (but not always) starts due to some trauma (eg MVA, major surgery, dis)


1. 65 F w RA suddenly develops more severe pain, swelling, heat in R knee
Action → take temp, aspirate knee (look for MSU crystals, infection) + request FBC, ESR and XR
2. 50 F w RA 10 yrs duration on prednisone for 5 yrs presents w ankle pain after twisting injury → suspect # (prednisone causes osteoporosis)
3. 25 F pres painful, warm, swollen knee of spontaneous onset and 3/52 duration – no hx of injury, other arthritis, evidence of systemic illness
Action → aspirate (infection, crystals), CRP
Differentials → gout, sepsis, seroneg spondylarthropathies (eg reactive arth)
4. Pt presents w polyarthrits and involvement DIP joints of fingers may have – OA, OA + gout, Psoriatic arth
Psoriatic arthritis → typically polyarthritis of PIP joints
Not RA as PIP joints not involved
5. Low back pain – questions to differentiate an inflammatory from mechanical cause –
Specific injury
Morning stiffness
Duration of sxs/stiffness
Mech back pain → worse on exertion, bending over (inflammatory back pain improves during the day or on exertion)
6. Erosive changes in a joint w arthritis is een earlier in small joints
7. M 40 Polynesian presents w shoulder pain, unable to sleep, moderately overweight, serum uric acid 0.64 mmol/l
Differentials → gout (many pts hyperuricaemic but no gout), rotator cuff tear/dis, OA (AC joint) due to previous trauma
8. Nodules on elbow assoc w → gout (tophi), SLE, RA, RF
9. Which diseases are more common in Polynesians compared w Caucasians → RF, gout



Chr progr arth distinguished by involvement of sacroiliac + spinal apophyseal joints in addition to inflam of periph jints + tendon attachments (enthesitis)
Characterised by progr stiffness + fusion of axial skeleton

Clin Feats
Prevalence -0.5%
Racial variation – esp Pima and Haida Indians (high prev HLA B27)
M>F (3:1)
Early onset – 20-30 yrs (insidious – months/years w recurring episodes of low back pain + marked stiffness)
Unlike mech back pain – sxs extend over many spinal segments + are axial and symmetrical in distbn
Nocturnal back pain w morning stiffness – relieved by exercise (duration >3 months)
Sacroiliac joints (+ spinal apophyseal joints) always involved
Lumbosacral area usu first + worst affected region – dis tends to ascent spine slowly + eventually whole spine may be affected (yrs)
As spine becomes progressively ankylosed (stiff), spinal rigidity + 2ndry osteoporosis predis to spinal fracture (acute severe localised pain)
Periph arth (esp hips + knees)
Enthesitis – inflam at site where tendons, ligaments or capsules insert into bone (eg plantar fasciitis)
Complications - Iritis (25%), Heart block (10%), Amyloidosis (6%), Aortitis/aortic incompetence (4%)
Early physical signs
Failure to obliterate lumbar lordosis on forward flexion
Pain on sacroiliac compr
Restr of lumbar spine mvments – all directions
As dis progresses – stiffness ↑ throughout spine + chest expansion restricted
Spinal fusion varies in extent – a few pts marked kyphosis of dorsal + cervical spine interfering w forward vision
Extraspinal feats
Pleuritic cp – aggrav by breathing (involvement of costovertebral joints)
Plantar fasciitis, Achilles tendonitis + tenderness over bony prominences (iliac crest, gr trochanter – from enthesopathy)
Fatigue (chr interruption sleep due to pain)
40% extraspinal synov joint involvement

Ex Schobers test – back dimples (PSIS)
Bend forward, if under 40 yrs → PSIS rises >5cm (in AS → <5cm due to restrictive mvment)
↓ chest expansion
Sacroiliac stress test – knee flexed, push straight down, pain

Clinical Tests to detect early AS
Sacroiliac compression Local tenderness
Chest expansion <3cm
Finger to floor inability to touch floor
Schobers test of spinal flexion ↑ to <5cm on full flexion
Occiput to wall unable to touch the wall

Ix XR Strongest evidence (but may take yrs to develop)
Sacroiliac joint irreg (fusion) – (irregularity + loss of cortical margins, widening of joint space + subseq sclerosis, narrowing + fusion)
Sacro-ilitis – also present in pts w reactive arth, psoriatic arth, enteropathic arth
ESR ↑ in 80%
Serum RF Negative
HLA B27 Present in 96% (normal 8%)
Also - ↑ freq reactive arth, psoriatic spondylitis, spondylitis of IBD, Ant uvelitis (iritis)

Mgt Aims – relieve pain + stiffness, maintain max range skeletal mobility + avoid deformity
Education + appropr physical activity (cornerstones)
Reg daily back extensions (morning wake up routine) + punctuate prolonged inactive periods w regular breaks (eg driving)
Swimming ideal exercise
Poor bed + chair posture must be avoided
Anti-inflam meds
NSAIDs – effective sx tx (but do not alter course of dis)
Spinal + breathing exercises (phsyio → ↑ neck mobility + ↓ LT deformity)
Sulphasalazine + methotextrate moderately effective (periph arth only)
Anti-TNFa agents – v effective for both spinal + periph joint inflam (trials) – Etanercept + Infliximab (also use in RA)

Prog -75% of AS pts able to remain in employment + enjoy good QOL
Even if severe ankylosis develops – functional limitation may not be as marked as long as the spine is fused in erect posture

Major differences betw RA + AS
Feature RA AS
M:W 1:4 3:1
Sacroiliac joints rare early involvement, symmetrical
Spinal (axial) joints c-spine often invariably involved
Thoracic/lumbar sp rare
Costovertebral joints not involved early, diffuse
Periph joints invariable – bilat + symmetr presents in up to 30% - asymmetr + large joints
Recurrent iridocyclitis not ↑ present in up to 30%
Subcut nodules up to 20% not found
RF up to 85% (adults) no ↑ freq
10-20% (juvenile)
HLA B27 Normal (same freq) found in up to 96%


Def A dis of predom youngmen (sex ratio 15:1) + possibly most common cause of inflam arth in men aged 16-35 (can occur at any age)
Betw 1 and 2% of pts w non-specific urethritis seen at STD clinics have reactive arthritis
Feats acute onset w development of urethritis, conjunctivits (50%) + inflam oligoarth affected large + small joints of lower limbs
1-3 weeks following expos or attack of dysentery
possibly consid systemic sxs – fever, weight loss (diff dx – septic arth)
Reiters Dis Classic Triad 1. Non-specific urethritis, 2. Conjunctivitis, 3. Reactive arthritis
Other signs mucocutaneous lesions (buccal mucosal ulcers, keratoderma blennorrhagica), +/- skin lesions
Precipated by –
Bacterial dysentery – mainly salmonella, shigella, campylobacter, yersinia or
Sexually acqd inf w Chlamydia


Def Inflam arth occurring in a seronegative nodule-free pt w psoarisis
10% approx of psoriasis pts
may preced devt of skin lesions (may be minimal) – nail pitting, onycholysis
Dactylitis + enthesitis
Clin Types asymm oligoarth
Symm polyarth (indistinguishable from RA)
Predom DIP involvement (often w dactylitis)
Psoriatic spondylitis
Arthritis mutilans
Tx As for RA
Salazopyrin + Methotextrate preferred 2nd line or slowing acting anti-rheumatic drugs (SAARDs)
Anti-TNFa agents v effective (etanercept)


Arth assoc w IBD – UC + Crohns


Polymyalgia Rheumatica and Giant Cell Arteritis

1. Polymyalgia Rehumatica (PMR)
a. Epidemiology
i. Age >50 yrs
ii. F>M
b. Etiology
i. Unknown
ii. Assoc w GCA
c. Presentation
i. Shoulder / Hip girdle pain
ii. Morning stiffness
d. Ixs
i. ↑ ESR / CRP
ii. +ve temporal artery biopsy in 10-15%
e. Tx
i. Prednisone 10-15 mg / day >2 yrs (confirmation of dx)
2. Giant Cell Arteritis (GCA) aka temporal arteritis
a. Definition
i. Inflammatory dis of the blood vessels, most frequently the temporal artery
b. Epidemiology
i. F:M 2:1
ii. Mean age onset 70 yrs
c. Etiology
i. ¼ of cases co-exist w PMR (continuum - PMR mild → GCA severe)
d. Symptoms
i. Headache
ii. Scalp tenderness
iii. Jaw claudication
iv. Blurred vision/Acute VL (ophthalmic artery affected)
v. Constitutional sxs – fever, malaise, weight loss, fatigue
e. Examination
i. Tender, non-pulsatile thickented temporal artery
f. Ixs
i. ↑ CRP/ESR
ii. Temporal artery biopsy → large vessel vasculitis featuring giant cells
g. Tx
i. Prednisone 40-80 mg / day (start tx before biopsy results)
ii. Manage complications → Osteoporosis prophylaxis (Bisphosphonates, Calcium, HRT, Vit D)
iii. Consider steroid sparing agents → azathioprine, methotrexate
3. Adverse effects of LT corticosteroid use
a. Weight gain / Central obesity
b. Skin atrophy and bruising
c. Osteoporosis
d. Impaired glucose tolerance / DM
e. Infection risk
f. HTN
g. Mood disturbance
h. Cataracts
i. Raised intraocular pressure / Glaucoma


1. Definition
a. Arthritis characterised by focal loss of articular cartilage and a subsequent hypertrophic reaction in the subchondral bone
b. Mainly weight bearing joints – ie knee, hip
2. Epidemiology
a. 10% > 60 yrs age
3. Risk Factors
a. ↑ Age
b. Joint deformity
c. Obesity
4. Etiology
a. Primary OA – idiopathic
b. 2ndry OA –
i. Metabolic – eg acromegaly
ii. Anatomic – eg slipped femoral epiphysis, leg length discrepancy
iii. Traumatic – eg # through joint
iv. Inflammatory – eg RA
5. Presentation
a. Pain in weight bearing joints after use, improving with rest
6. Ixs
a. XR
i. Joint space narrowing
ii. Subchondral sclerosis
iii. Cysts
iv. Osteophytes
7. Management
a. Non-invasive – education, physical therapy, walking aids, shock absorbing footwear, tapes/bandages
b. Paracetamol
c. NSAIDs – caution due to GI and renal side effects
d. Local intra-articular corticosteroid injection
e. ?Glucosamine (appears to ↑ proteoglycan synthesis in articular cartilage)


1. Definition
a. Acute arthritis caused by crystallisation (precipitation) within joints of monosodium urate (MSU) in a hyperuricemic patient
2. Epidemiology
a. M>F
b. >40 yrs age
c. Maori
d. Obese
3. Etiology
a. Primary vs 2ndry Gout
i. Primary gout → Typically obese male >40 yrs age
ii. 2ndry gout → Typically 65+ yrs, chr hyperuricaemia due to renal impairment or diuretics
b. Underexcretion of uric acid
i. Idiopathic – inherited isolated renal tubular defect
ii. Renal failure
iii. Diuretics
iv. Acute alcohol congestion
c. Overproduction of uric acid (uncommon)
4. Presentation
a. Monoarticular joint paint (esp MTP joint big toe) – severe, rapid onset (over 2-6 hours)
b. Swelling
c. Red shiny skin
d. Tophus – irregular firm nodules or uric acid deposits in periarticular fibrous tis (eg ear cartilage, Achilles tendon, olecranon bursae, hands, feet)
5. Ixs
a. Joint aspirate – MSU crystals (white, needle shaped, negative beirefringence (ie does not refract light))
b. Bloods
i. ↑ ESR / CRP
ii. Serum uric acid >0.42 mmol/L (but can decrease during an acute attack)
c. XR – assess joint damage
6. Differentials
a. Septic arthritis
b. Cellulitis
c. Pseudogout
d. RA
e. Psoriatic arthritis
7. Management
a. Acute gouty arthritis
i. Self limiting 5-14 days
ii. Do not start or change dose of uricosuric drugs or allopurinol
iii. NSAIDs
iv. Add low dose colchicine – in resistant cases
v. Prednisone (if NSAID contra)
vi. Joint aspiration (instant relief)
vii. Intra-articular corticosteroid injection - prevents fluid accum (can abort an attack)
viii. Manage RFs – weight, alcohol, diuretics, dietary purines
b. Chronic gout
i. Wait 3-4 weeks after acute attack before initiating
ii. Allopurinol – ↓ uric acid production uric acid (xanthine oxidase inhibitor)
1. 100-300 mg starting dose then gradually titrate in 100mg increments to achieve <0.36 mmol/L
2. Initially causes ↓ in tis uric acid levels → partially dissolves MSU crystals → triggers acute attack
iii. Uricosuric drugs - ↑ renal excretion uric acid (Probenecid, Sulphinpyrazone)
iv. Indications to ↓ uric acid levels
1. serum uric acid level >0.54
2. >1 attack every 3 months
3. renal involvement (renal impairment or calculi)
4. tophi or radiological joint destruction
v. Lifestyle
1. weight loss
2. diet – reduce alcohol, meat and seafood
vi. Asx hyperuricaemia – 95% will never develop gout, seek cause but tx not justified unless severely hyperuricemic

Rheumatoid Arthritis

1. Definition
a. Chronic symmetrical polyarthritis
2. Epidemiology
a. 1-2%
b. Peak 30-50 yrs age
c. F:M 3:1 (prior to 60 yrs age then equal)
d. ↑ incidence in those with family hx
3. Etiology
a. Unknown
b. Systemic auto-immune d/o assoc w extra-articular involvement
4. Pathology
a. Synovitis (inflammation of synovial lining of joints)
b. Erosion of bone and cartilage
c. ↑ Synovial fluid
d. Pannus formation (thickened synovium) – synovium proliferates and gorws out over the cartilage surface producing a mass known as a pannus which then destroys the articular cartilage and subchondral bone producing erosions)
e. Subcutaneous nodules (rheumatoid nodules)
5. Presentation
a. Pain + Morning stiffness
b. Swelling in the small joints of hands and feet – MCP and PIP joints
i. Spindling of fingers (caused by swelling of PIP but Ø DIP joints)
c. Subluxation (partial dislocation) and deformity – caused by weaknening of joint capsules
i. Z shaped thumb
ii. Boutonnieres and swan-neck deformities
d. Extra-articular manifestations
i. Periarticular features – bursitis, tenosynovitis, muscle wasting, subcutaneous nodules
ii. Systemic – fever, fatigue
iii. Neurological – carpal tunnel syndrome, atlanto-axial subluxation
iv. Blood – Anemia (chronic dis, NSAID induced GI blood loss, hemolysis), Thrombocytosis
v. CVS - pericarditis
6. ARA Dx of RA – 4+ for >6 weeks
a. Morning stiffness > 1 hour
b. Arthritis – 3+ joints
c. Involvement of the hands
d. Symmetrical arthritis
e. Presence of nodules
f. Presence of erosions
g. RF positive
7. Ixs
a. Dx usu clinical
b. Blood count → anemia, thrombocytosis, ESR and CRP ↑
c. Serum autoantibodies →
i. RR positive in 80% (not specific for RA)
ii. ANA in 15%
d. Radiology →
i. deformity / misalignment
ii. soft tissue swelling
iii. joint narrowing (cartilage loss)
iv. erosions at joint margins
v. osteopenia or porosis of periarticular bone (↓ calcification/density of bone)
vi. features of 2ndry OA
e. Synovial aspirate → sterile, high neutrophil count
8. Differentials
a. Psoriatic arthritis
b. SLE
9. Management
a. Non-invasive
i. Education
ii. Rest – in severe flares (to ↓ synovitis)
iii. Range of motion exercises (prevent contractures developing)
iv. Exercise – ideally swimming in a warm pool
b. MDP
i. PT – exercises, education re joint care, hydrotherapy
ii. OT – provision of aids/appliances etc
c. Paracetamol or NSAIDs → relief of pain and stiffness (does Ø slow disease progression)
d. DMARDs (disease modifying anti-rheumatic drugs)
i. Give early (but some pts will spontaneously remit or only have mild disease)
ii. Prevent irreversible effects of LT inflammation of joints
iii. Act mainly through inhibition of inflammatory CKs → ↓ inflammation + slow devt of joint erosions
iv. Hydroxychloroquine and Sulfasalazine → mild to moderate dis
v. Methotrexate → more active disease, best therapeutic outcome but potential toxicity
1. Adverse effects → mouth ulcer, diarrhea, liver fibrosis, pulmonary fibrosis, renal impairment
vi. Leflunomide
vii. Azathioprine and Gold used less frequently
e. Anti-CK agents (anti TNFa agnets)
i. Eg – etanercept, infliximab, adalimumab
ii. Slow or halt erosion formation in up to 70% of pts
f. Corticosteroids
i. Suppress dis activity but dose reqd is often large + considerable risk of LT toxicity
ii. Only used in elderly pts or those w explosive RA or those w severe extra-articular manifestations
g. Surgery → synovectomy (prevention of joint destruction/deformity) or joint replacement (restore function)
10. Prognosis
a. Variable
b. Recurrent cycles of remission and relapse
c. Some pts will become severly disabled

Seronegative Spondylarthropathies

1. Defintion – group of conditions that share certain clinical features
a. Predilection for axial (spinal + sacroiliac) inflammation
b. Asymmetrical peripheral arthritis
c. Negative RF (seronegative)
d. Strong assoc w HLA B27
2. Conditions include –
a. Ankylosing spondylitis (AS)
b. Reactive arthritis (Reiters)
c. Psoriatic arthritis

Ankylosing Spondylitis
1. Definition
a. Chr progressive arthritis distinguished by involvement of sacroiliac and spinal apophyseal joints
b. In addition to inflammation of peripheral joints and tendon attachments (enthesitis)
c. Characterised by progressive stiffness and fusion of axial skeleton
2. Epidemiology
a. Prev 0.5%
b. M>F 3:1 (men affected more severely)
c. Onset 20-30 yrs age (insidious)
3. Presentation
a. Recurrent episodes of lower back pain and stiffness (improvement with exercise but not with rest)
b. Other features – Achilles tendonitis, plantar fasciitis (enthesitis), iritis
c. Peripheral arthritis – esp hips and knees
4. Examination
a. Loss of lumbar lordosis and ↑ kyphosis
b. Limitation of lumbar spine motility in sagittal and frontal planes (reduced spinal flexion demonstrated by Schobers test - <5 cm increase on forward flexion at level of PSIS)
c. ↓ chest expansion
5. Ixs
a. Bloods
i. ↑ ESR / CRP
ii. Serum RF negative
iii. HLA B27 (in 96%) – vs normal popn 8%
b. XR – may be normal but can show erosion and sclerosis of the sacroiliac joints
i. Squaring of the vertebrae (erosion of corners)
ii. Progressive calcification of interspinous ligaments (bamboo spine)
6. Management
a. Education
b. Exercise (eg daily back extensions) → twice daily, to maintain posture and mobility
c. NSAIDs – sx tx only
d. Sulphasalazine + Methotrexate – moderately effective against peripheral arthritis
e. Anti-TNFa agent (etanercept, infliximab) → effective against spinal and peripheral inflammation (trials)
7. Prognosis
a. Most pts able to lead normal life and remain at work
b. Severe cases – spine may become brittle → risk of # and cord compression

RA vs AS
M:F 1:4 3:1
Sacroiliac joints Rare Early involvement, symmetrical
Spinal (axial) joints C-spine often, Thoracolumbar rare Invariably involved
Costovetrebral joints Not involved Early, diffuse
Peripheral joints Invariable – bilateral and symmetrical ~30% - asymmetric
Rheumatoid factor Up to 85% (adults) No ↑ freq
HLA B27 Normal 96%

Reactive Arthritis (Reiters syndrome)
1. Definition
a. A sterile synovitis occurring after an infection, commonly;
i. GI – shigella, salmonella, campylobacter
ii. STD – non-specific urethritis or cervicitis (Chlamydia or ureaplasma)
2. Epidemiology
a. M:F 15:1
b. Young adults
3. Presentation
a. Acute arthritis after an enteric or venereal infection (<4 wks)
b. Asymmetrical joint involvement (esp lower limbs)
c. Skin lesions resemble psoriasis
d. Reiters syndrome – classical triad (cant see, cant pee, cant climb a tree)
i. Non-specific urethritis
ii. Conjunctivitis
iii. Reactive arthritis
4. Ixs
a. Joint aspirate – sterile + high neutrophil count
5. Management
a. NSAIDs + joint aspirate and corticosteroid injection (for acute inflammation)
b. A/Bs (tx of infection)
c. Sulfasalazien or azathioprine (for chr dis)
6. Prognosis
a. Acute arthritis resolves within a few months
b. 50% develop recurrent arthritis, iritis or AS

Psoriatic Arthritis
1. Epidemiology - ~5% of pts w psoriasis
2. Presentation variable –
a. Asymmetrical involvement of small joints of the hand
b. Symmetrical seronegative polyarthritis resembling RA
c. Arthritis mutilans – severe form w destruction of small bones in hands/feet
3. Ixs → XR may show erosions and periarticular osteoporosis in the terminal IP joints
4. Tx
a. Analgesia + NSAIDs
b. Intra-articular corticosteroid injections
c. Methotrexate, Ciclosporin or Anti-TNFa agents (in severe cases)

Connective Tissue Disease (aka autoimmune diseases)

1. CT Diseases
a. SLE (systemic lupus erythematous)
b. Systemic sclerosis (scleroderma)
c. Polymyositis and dermatomyositis
2. SLE
a. Defintion
i. Multi-system disease with varied clinical presentation
ii. Characterised by presence of serum antibodies against nuclear components
iii. Discoid lupus – a benign variant in which skin dis may be the only the feature
b. Epidemiology
i. Prev 0.1% of popn
ii. 1:9 M:F
iii. Age onset typically 15-40 yrs
c. Etiology
i. Unknown but probably multifactorial (genetic and immunological factors, drugs, infection)
d. Pathophysiology
i. Poorly understood - Autoimmune
ii. Current explanation – antibody formation + development and deposition of immune complexes
e. Presentation varied
i. MS → small joint arthralgia (similar to RA but non-erosive), myalgia
ii. General → tiredness, fever, depression
iii. Skin → butterfly rash, vasculitis, urticaria, photosensitivity, alopecia, raynauds phenomenon
iv. Blood → anemia, leucopenia, lymphopenia, thrombocytopenia
v. Lungs → pleurisy, pleural effusions
vi. Kidneys → GMN (all types)
vii. Nervous system → epilepsy
f. Ixs
i. FBC
1. Anemia, neutropenia, lympphopenia, thrombocytopenia
2. ESR often ↑
ii. Serum auto-antibodies
1. ANA (anti-nuclear antibodies) – almost all cases of SLE, present in other CT diseases, 5% of normal popn
2. Anti-dsDNA (double stranded DNA) – specific for SLE, but only 50% of cases
3. Anti-cardiolipin antibodies – in ~40%
4. Anti-sm (smith) – v specific, poor prognosis
g. Mnemonic → I’M DAMN SHARP
i. Immunoglobulins – anti-DNA, anti-phospholipid, anti-sm)
ii. Malar rash
iii. Discoid rash
iv. ANA (anti-nuclear antibody)
v. Mucositis (oropharyngeal ulcers)
vi. Neurologic dis (seizures, psychosis)
vii. Serositis (pleuritis, pericarditis)
viii. Hematologic d/os (hemolysis, leucopenia, lymphopenia, thrombocytopenia)
ix. Arthritis
x. Renal disease
xi. Photosensitivity (sunlight is an exacerbating factor in most pts)
h. Management
i. Avoid excessive sunlight
ii. NSAIDs – if mild disease + arthralgia
iii. Corticosteroids (mainstay) – moderate to severe disease
iv. Immunosuppressives (azathioprine) + corticosteroids – for severe manifestations (renal or cerebral dis)
v. Topical steroids – for discoid lupus
i. Prognosis
i. 10 year survival rate ~90%
ii. Death typically from renal failure or infections
3. Systemic Sclerosis (Scleroderma)
a. Definition
i. Chr multisystem dis predominantly affecting skin and usu accompanied by raynauds phenomenon
b. Epidemiology
i. M:F 1:4
ii. Presents 30-50 yrs age
c. Etiology
i. Complex, not completely understood → uncontrolled and irreversible proliferation of CT, thickening of vascular walls + narrowing of lumen
d. Clinical features
i. Limited cutaneous scleroderma – 60% (previous known as CREST syndrome)
1. Starts initially with Raynauds phenomenon (arteriolar vasospasm to cold extremities causing triphasic colour change – white→blue→red)
2. Skin – thickening, tightening and tethering of skin and sclerodactyly
3. Joints – arthralgia
4. GI – abnormal esophageal and bowel function
5. Lungs – interstitial fibrosis, pulmonary HTN
6. Kidney – renal failure
a. Calcinosis (palpable subcut nodules of calcium deposition in the fingers)
b. Raynauds phenomenon
c. Esophageal involvement
d. Sclerodactyly (tapering of fingers, see picture)
e. Telangiectasia
ii. Diffuse cutaneous scleroderma – 40%
1. Widespread skin involvement
2. More rapid progression
3. Early visceral and other organ involvement
e. Ixs
i. Serum atuo-antibodies
1. ANA – often positive
2. Anti-centromere antibodies → limited cutaneous scleroderma
3. Anti-topoisomerase (Scl 70) → diffuse cutaneous scleroderma
ii. XR of hands → calcium deposits around fingers
iii. High resolution CT → fibrotic lung involvement
iv. Barium swallow → impaired esophageal motility
f. Management
i. Symptomatic – no specific tx (eg PPI, vasodilators for raynauds)
ii. ACEI – tx of HTN and prevention of kidney damage
g. Prognosis
i. 10 yr survival – 70 and 55% respectively
ii. Death usually caused by pulmonary fibrosis or pulmonary HTN

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