approach to rheum pt_

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General Approach to the

Rheumatology patient

History

Cardinal rheumatological symptoms

Pain Swelling

Joint dysfunction (stiffness and loss of function)

Other symptoms

Fever Rash

Eye symptoms

Bowel/urinary symptoms



Examination

Joint examination

(exposure), Inspection, Palpation, Movements, Specialtests

General examination

Skin and eyes

Blood pressure Cardiorespiratory

Abdominal





Investigations (targeted to exclude or confirm

the differential diagnosis)

X-rays - particularly for degenerative andinfectious joint disease

Blood tests

To detect inflammation-ESR or CRP

To detect disease-associated antibodies - eg ANA,Rheumatoid factor

Others - eg Urate

Synovial fluid analysis





Patterns in rheumatology

Acute (hours) vs subacute (days) vs chronic

(months)

Monoarthritis (1) vs oligoarthritis (2-5) vspolyarthritis (>5)

Symmetrical vs assymetrical joint

involvement

Peripheral vs axial joint involvement

inflammatory vs mechanical symptoms



Patterns of joint pain

Degenerative (Osteoarthritis)

Chronic onset and progression

Pain worse with movement and improved by rest(Mechanical pain)

Little swelling or stiffness

Specific joints involved - DIPs, PIPs, 1st CMC,

hips, knees, 1st MTP, lumbar and cervical spine



Inflammatory arthritis (eg rheumatoid arthritis,

gout, reactive arthritis)

Acute or sub acute onset Pain improved by movement and worsened by

rest

Early morning stiffness or hours

Swelling prominent Pattern of joint involvement usually defines the

diagnosis




Patterns of inflammatory joint involement

Acute monoarthritis

Consider gout or sepsis Subacute symmetrical polyarthritis

Consider rheumatoid arthritis or SLE

Subacute assymetrical oligo-polyarthritis

Consider spondyloarthritis (reactive arthritis etc) Chronic axial and peripheral oligoarthritis

consider ankylosing spondylitis




Other clues to diagnosis

Rashes

Psoriasis (Psoriatic arthritis), sun exposed rashes (SLE),

exanthems (viral arthritis, Stills¶ disease) Eyes

Anterior and posterior inflammatory eye disease (Iritis,

uveitis) - consider spondyloarthritis, retinal lesion (SLE)

Kidneys

Glomerular red cells (SLE)

Serosal involvement

Pleurisy/pericarditis - consider SLE or rheumatoid arthritis




Laboratory Investigations

Guided by patient history

If no diagnosis after history and exam, odds

of making diagnosis with lab is poor ³arthritis panel´ should not be used

judicious appropriate testing warranted

Bayesian Analysis



Labs cont¶d

A few general principals:

When diagnosis unclear, do not order broad

screening test

Order tests that address most likely diagnosis

Start with least invasive tests

Choose most specific test

Choose subsequent tests to refine diagnosis,monitor disease progress, ensure safety of Rx



Synovial fluid analysis

Early examination crucial if infection possible

examined promptly in the laboratory

normal fluid is clear, slightly amber, high viscosity,< 95 WBC/ul

WBC >3000/ul indicates inflammation

80,000/ul indicates infection esp > 90% PMN

damaged joint more easily infected investigate for crystals, culture



Immunological tests

Commonly Used:

Rheumatoid factor ANA

ANCA

Antiphospholipid antibody

Complement levels



Rheumatoid factor

RF is any immunoglobulin which binds the Fc

portion of another Ig (they are classically IgM

but IgG and IgA RFs are described) Rheumatoid arthritis - 75-80% positive RF

Sjogren¶s syndrome - 75-95%

MCTD - 50-60%

Mixed cryoglobulinaemia - 40-100%

SLE - 15-35%

PM/DM - 5-10%



The higher the level of RF the higher the

likelihood of disease

RF levels are not useful in monitoring RA RF should be ordered in patients with a

high pretest probability of RA or Sjogren¶s

syndrome

RF is associated with nodules and

vasculitis in RA patients

RF is cheap

Rheumatoid factor



Anti-nuclear Antibodies (ANA)

ANA detected using indirect

immunofluorescence on HEp2 cells

(human epithelial cell tumor line) ANA result is titre (usually dilutions from

1:40 to 1:640) and pattern (homogenous,

speckled, nucleolar and centromere)

ANA targets include - ssDNA, dsDNA,

histones, RNA protein complexes, non-

histone nuclear material



Anti- s D A Ab

Anti- ist neAnti-nucleosome

Homogenous

Anti- m

Anti- / AAnti- o/

Anti-topo-isomer se

Speckled

Anti- A pol mer seI

Anti-fibrill rinAnti- -

ucleol r entr omer e

ANA


Utility of staining patterns



ANA titre -the higher titre the higher the

likelihood of autoimmune disease

False positive usually low titre (eg 1:40,32%, 1:80, 13%, 1:320, 3%) - ie ANA has

very low specificity if applied in the wrong

group - without a high pretest probability)

ANAs with Ro, La, PCNA, Ku and Jo-1

specificities may be missed by ANA

screening (thus the HEp2000 cell)




Extractable Nuclear Antigens

(ENAs)

Generally detected using counter

immunoectrophoresis (CIEP) where a gel

is used to precipitate the antibody and theantigen (from rabbit thymus and human

spleen) - a bank of reference sera are

used to detect ENAs which form a ³line of

identity´ with the test serum if positive

Reference sera include - Ro, La, Jo-1,

Topo-isomerase, Ku, PCNA, Sm, Mi-1 and

others



ENAs

Anti-Ro seen in 30% of SLE and up to 70% of

Sjogren¶s - associated with congenital

heartblock and neonatal lupus, subacutecutaneous lupus and photosensivity

Anti-La seen in 15% of SLE and 60% of

Sjogren¶s syndrome - associated with CHB

and neonatal lupus and a low prevalence of renal disease in SLE



Anti-ds DNA antibodies

Highly specific for SLE

Levels fluctuate with disease activity - routine

monitoring may predict flares but one studyhas not shown that pre-empting flares

improves outcomes

High levels predict renal involvement

May be pathogenic - eluted from lupus

kidneys



Anti-neutrophil cytoplasmic

antibodies (ANCA)

ANCA detected by indirect

immunofluorescence on ethanol fixed human

neutrophils

Two patterns cytoplasmic (c-ANCA, mainly

anti-proteinase 3 antibodies) and perinuclear

(p-ANCA, anti-myeloperoxidase elastase,

lactoferrin, lyzosyme and cathepsin B)



Wegener¶s Granulomatosis - 80-95% are c-

ANCA positive - mainly anti-PR3, most of the

remainder have p-ANCA - may fluctuate with

disease (cf anti-ds DNA antibodies

Microscopic polyarteritis (polyangiitis) 40-

80% will have p-ANCA with anti-MPO

antibodies


antibodies (ANCA)



Churg-Strauss vasculitis - ANCA is less

frequent (25-60%)

p-ANCA is detected in many connectivetissue diseases

p-ANCA also detected in up to 80% of

ulcerative colitis patients

Hydralazine, minocycline and propylthiouracil

may induce ANCA (usually p-ANCA/MPO)


antibodies (ANCA)



Lab cont¶d

Complement

C3 and C4 low in active SLE particularly nephritis

Complement deficiency states predispose to SLE



Imaging studies

Plain radiographs

cartilage loss, bone erosions, deformities,

tumors, displaced #

CT: good for evaluating boneabnormalities

isotope bone scan: #, infection, tumors

MRI calibrating spinal canal with lumbar stenosis

choice in investigating disc space infection

excellent for joint evaluation-KJ & Sjoints



Principles of management

Appreciate the following:

chronicity

remissions and relapses treatment guided by presentation and severity



Chronicity

Most systemic CTD are chronic

Therapeutic plan designed according to their

longterm positive and negative effects OA also longterm ongoing treatment.

Remission and relapses:

varies from PT to PT

steady VS intermittent

Should taper and discontinue med if possible

because eof side-effects



Treatment guided by disease

and presentation

Timing and alteration of therapy guided by

disease activity

types and doses guided by inflammatory level

specific outcomes defined

serial assessment of pain, stiffness, functional level,

radiograph, ESR, CRP

tests defining organ function - creatinine, LFT etc.

eye examination



NSAIDS

Inhibit cyclo-oxygenase thus blocking the

formation of pro-inflammatory prostaglandins

Effective in reducing pain and inflammation in

arthritis (and other conditions) but do not alter the course of the disease (ie they are not

disease-modifying)

Risks of using NSAIDs increase with age

Long acting and high doses of NSAIDs havehigher risk



NSAIDs

High incidence of gastric side effects particularly

gastritis and gastric ulcer

Gastric ulcers are more common in patients

taking NSAIDs who are > 65 yoa, with a previoushistory of GU, who take corticosteroids or warfarin

NSAIDs may also increase BP, worsen renal

function (particularly in the elderly), worsen CCF,

cause abnormal liver function tests



Other antirheumatic drugs

Disease-modifying anti-rheumatic drugs

(DMARDs)

A group of drugs used in rheumatoid arthritis and

other forms of inflammatory arthritis which decreasedisease activity and reduce joint damage

All take 6-8 weeks to reduce the inflammatory

response and are generally used in conjunction with

NSAIDs or corticosteroid

Toxicity varies depending on the drug - monitoring is

generally required



DMARDs

Hydroxychloroquine

Indications - Rheumatoid arthritis, SLE

Dose- 400mg daily for three months and then200mg daily

Side effects - Rash (1/200), retinal toxicity

(1/15,000), dizziness

Efficacy - modestly active drug in RA, veryeffective in SLE arthritis



DMARDs

Sulphasalazine

Indications - Rheumatoid arthritis,

spondyloarthritis, inflammatory bowel disease

Dose - 2-3g daily (commence at 1g and gradually

increase)

Side effects - Nausea (common), rash, abnormal

LFTs, neutropenia, oligospermia

Efficacy - very effective in RA, modestly effective

in the peripheral joint component of

spondyloarthritis



DMARDs

Methotrexate

Indications - Rheumatoid arthritis,

spondyloarthritis, SLE arthritis

Dose - 5-25mg weekly (commmence at 5-10mg

daily and increase depending on response)

Side effects - Nausea, mouth ulcers, neutropenia,

thrombocytopenia, abnormal LFTs

Efficacy - Highly effective drug in all forms of

inflammatory arthritis



Other rheumatological drugs

Azathioprine

Indications - steroid sparing agent in many

connective tissue diseases

Dose 50-150mg daily

Side effects - Acute hepatitis, rash, nausea,

neutropenia, thrombocytopenia

Efficacy - moderately effective steroid sparingagent



Cyclophosphamide

Indications - life-threatening autoimmune disease

- proliferative glomerulonephritis, vasculitis

Dose 50-150mg orally daily or 500mg-1.2g IV

monthly

Side effects - nausea, pancytopenia,

haemorrhagic cystitis, infertility, mouth ulcers,

rash

Efficacy - highly effective

Other rheumatological drugs



Corticosteroids Indications/Doses

Low dose (0-10mg) - RA, SLE arthritis

Intermediate dose (10-25mg) - Polymyalgia

rheumatica and sometimes RA, SLE etc High dose (25-60mg) - Vasculitis, proliferative

glomerulonephritis

Side effects

Dose and duration dependent Osteoporosis, hypertension, hyperglycaemia,

increased infections (eg reactivation of TB),

obesity, skin changes, mania, insmonia, sweats



Corticosteroid cont¶d

Selected patients, consider the following:

gastroprotection

osteoporosis protection - estrogen, Ca + vit D,

calcitonin infection surveillance - influenza and pneumococcal

vaccine

treat steroid induced diabetes

understand pharmacology of steroids 0.75mgs dexamethasone=4mgs methylprednisolone=5mgs

prednisone=20mgs hydrocortisone

approach to rheum pt_

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