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RH22 Rheumatology Toronto Notes 2023

• PAN with major organ manifestations (CNS, cardiac, GI, renal)

induction therapy with high-dose glucocorticoids + cyclophosphamide for 3-6 mo followed by

maintenance therapy with low-dose prednisone and either azathioprinc, M I X, or leflunomide

treatment should be a minimum of 18 mo

• hepatitis B virus-associated vasculitis

prednisone 1 mg/kg/d PO x7 d (then taper and withdraw by 14 d) ± methylprednisolone 15 mg/

kg/d IV xl-3 d

after corticosteroid therapy, treat with plasma exchange + antiviral therapy

Large Vessel Vasculitis s

GIANT CELL ARTERITIS/TEMPORAL ARTERITIS

Table 24. Classification Criteria for GCA*

GCA Criteria

Presence of 3or more criteria yields

sensitivity of 94%, specificity of 9t%

Criteria Description

1.A9eatonsel>50

2.New H/A

3.Temporal artery abnormality

4.Elevated ESN

5.Abnormal arlery biopsy

Oflen temporal

Temporalartery lenderness or decreased pulsations,not dueloarteriosclerosis

ESR >50mm/h

Mononuclear cellinfiltration or granulomatousinflammation,usually withmullinudeated giant cells

'Diagnosed if 3or more of the aboveScriteria present

American College ol Rheumatology.1990

Epidemiology

• most common vasculitis in North America

• patients >50 yr; peak incidence 70-80 yr

• F:M=2:1

• north-south gradient (predominance in Northern Europe and US)

• affects extracranial arteries

Clinical Presentation

• new onset temporal H/A ± scalp tenderness overlying temporal artery

• sudden, painless loss of vision and/or diplopia due to narrowing of the ophthalmic or posterior ciliary

arteries(PCA more common);can affect both eyes

• tongue and jaw claudication (pain in muscles of mastication on prolonged chewing)

• PMR (proximal pain and stiffness, constitutionalsymptoms,elevated HSR) occurs in 30% of patients

• aortic arch syndrome (involvement ofsubclavian and brachial branches of aorta resulting in pulseless

disease), aortic aneurysm ± rupture are late complications

• constitutionalsymptoms (e.g.fever of unknown origin in patients £65 yr) and shoulder/pelvic girdle

pain and stiffness

Investigations

• diagnosis made by clinicalsuspicion, increased HSR,increased CRP, colour Doppler U/S of temporal ±

axillary arteries (+ halo sign), MR1, consider temporal artery biopsy

<§

Medical Emergency

If untreated.GCA can lead to permanent

blindness in 20-25% of patients

Treat on clinical suspicion

Treatment

• if suspect GCA, immediately start high-dose prednisone 1 mg/kg PO in divided doses for 2-4 wk, and

then taper prednisone by 10 mg per 1-2 wk assymptoms resolve; highly effective in treatment and

prevention of blindness and other vascular complications

• considerlow-dose ASA to help decrease visual loss

• if presenting with vision loss at diagnosis,methylprednisolone 1000 mg/d IV for 3d followed by highdose prednisone 1 mg/kg/d PO in divided doses for 4 wk

• tocilizumab, an 1L-6 receptor monoclonal antibody, has also been used in combination with

glucocorticoids to treat GCA (new or relapsing)

Prognosis

• increased risk of thoracic aortic aneurysm and aortic dissection

• yearly CXR ± abdominal U/S asscreening

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RH23 Rheumatology Toronto Notes 2023

Seronegative Rheumatic Disease

Table 25. A Comparison of the Spondyloarthropathies

Feature AS PsA ReA EA

M:F 3:1 1:1 8:1 1:1

AgeolOnset

Peripheral Arthritis

Distribution

Sacroiliitis

Dactylitis

Enthesitis

Skin Lesions

20s 35 45 20s Any

25% 96% 90% Common

Axial,large joints Any If If

100%

Uncommon

Common

40% 80% 20%

Common Occasional Uncommon

Figure 10. Spondyloarthropathy

subsets

Common

Occasional

Keratoderma

blcnnorihaqicd

Less Common

Occasional

Pyoderma, erythema

nodosum

Common

100%

Eventually psoriasis.

70% alonset olarthritis

Occasional

Uncommon

Rare

Uveitis

Urethritis

Common 20% Rare

Rare Common Rare AS shares some features with the

other three types of seronegative

spondyloarthropathies such as feA.EA.

PsA.and U-sPA

HLA 827 90 95% 40% 80% 30%

'LE =lower extremities

Ankylosing Spondylitis

Definition

• chronic Inflammatory arthritis involving the sacroiliac joints and vertebrae

• enthesitis is a major feature (e.g. Achilles tendinitis, plantar fasciitis)

• prototypical spondyloarthropathy Consider AS in the differential for causes

of aortic regurgitation

Table 26. ASAS Classification Criteria for Axial Spondyloarthritis*

1.Back pain of any type for at least 3 mo and age of onset <45 yr

2. Sacroiliitis on imaging plus>1AS feature or HLA-B27 positive plus >2 AS features

AS Features

HLA- B27 positive

Inflammatory back pain

Arthritis

Enthesitis (heel)

Uveitis

Dactylitis

Psoriasis

Crohn'sdisease/colitis

Good response toNSAIDs

EMHx ofSpA

Elevated CRP

Sacroiliitis on Imaging

Active (acute) inflammation on MRI highly suggestive of sacroiliitis associated wilh AS

Rule of 2s

AS occurs in

0.2% of the general population

2% of HLA-B27 positive individuals

20% of HLA B27 positive individuals with

affected family member

OR

Oclinite radiographic sacroiliitis (grade 2 bilaterally or grade 3- 4 unilaterally

'SpondylorUnapjIhy: inflammatory joint disease olthe vertebral column

Etiology and Pathophysiology

• inflammation > osteopenia > erosion -) ossification > osteoproliferation (syndesmophytes)

Epidemiology

• M:T=3:1; females have milder disease (may be under-diagnosed), more peripheral arthritis, and upper

spine spondylitis

• 90-95% of patients are HI.A- B27 positive (9% of the general population is HLA-B27 positive)

I

• Spondylitis

• Hip

• Shoulder

Figure 11. Common sites of

involvement of AS

The Bath Ankylosing Spondylitis

Disease Activity Index (BASDAI)

Self-reported scoring system that

focuses on fatigue, axial pain,peripheral

pain,enthesitis.and morning stiffness

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RH24 Rheumatology Toronto Notes 2023

Table 27. Types of Back Pain NORMAL POSTURE

Cervical lordosis

Thoracic kyphosis

Lumbar lordosis

Sacral kyphosis

Parameter Mechanical Inflammatory

!

Past History

Family History

Onset

t

Acute Insidious

<45 yr

++ (worse during 2nd half of night)

Age 15-90 yr

ANKYLOSING SPONDYLITIS

Sleep Disturbance

Morning Stiffness

Involvementof Other Systems

Exercise

t

Increased occiput

to wall distance <30 min >1 h

Increased cervical

flexion

Increased

thoracic kyphosis

Worse 8elter

Rest Better Worse

NSAIO Responsiveness

Radiation of Pain

Sensory Symptoms

Motor Symptoms

-

Anatomic (L5-S1) Olfluse (thoracic,buttock) Decreased lumbar

lordosis

® Cassandra Collin

Clinical Presentation

• axial

Figure12.AS postural change

mid and lower back stiffness, morning stiffness >1 h, night pain, alternating buttock pain, painful

SI joint (+ l-ABER test)

spinal restriction (decreased ROM):lumbar (decreased Schbber), thoracic (decreased chest wall

expansion, normal >5 cm at T4), cervical (global decrease, often extension first)

postural changes:decreased lumbarlordosis + increased thoracic kyphosis + increased cervical

flexion = increased occiput to wall distance (>5 cm)

FABER (Flexion, ABduction. and

External Rotation) Test

fessively flex,abduct,then gently

externally rotate the leg.If pain is

elicited during this movement,the

location of the pain may help determine

the location of the patient's pathology

(e.g. hip joint.SI joint). However,it is

poorly reproducible and inaccurate in

discerning inflammatory vs. mechanical

back pain

• peripheral

asymmetrical large joint arthritis, most often involving lower limb

• enthesitis: tenderness over tibial tuberosity, or Achilles tendon and plantar fascia insertions into

the calcaneus

• dactylitis: toes or fingers

• extra-articular manifestations

• ophthalmic: acute anterior uveitis is common (25-30% patients)

• renal: amyloidosis (late and rare), IgA nephropathy

• gastrointestinal: IBD

• cardiac: aortitis, aortic regurgitation, pericarditis, conduction disturbances, heart failure (rare)

respiratory: apical fibrosis (rare)

neurologic:cauda equina syndrome (rare)

• skin:psoriasis

ft

Modified Schober Test

• Patient must be standing erect with

normal posture

• Mark an imaginary horizontal line

connecting both posteriorsuperior

iliac spines(close to the dimples of

Venus)

• A mark is placed 10 cm above this

horizontal line, and another 5cm

below

• The patient bendsforward

maximally:measure the difference

between these two points

- Report the Increase (in cm to the

nearest 0.1 cm)

• The better of two triesis recorded

Investigations

• x-ray of SI joint:“pseudowidening"

of joint due to erosion with jointsclerosis-> bony fusion (late),

symmetric sacroiliitis

• x-ray ofspine: “squaring of edges” from erosion and sclerosis on corners of vertebral bodies(shiny

cornersign) leading to ossification of outer fibres of annulusfibrosis (bridging syndesmophytes) ->

“bamboo spine” radiographically

• MRI of spine:assess activity in early disease;detection of cartilage changes, bone marrow edema,

bone erosions, and subchondral bone changes. Best seen on T2 short tau inversion recovery (STIR)

images (suppress fat and see bone edema )

• labs:CBC,elevated ESR /CRP, ALP, Ca 2 *.serum protein electrophoresis (SPEP), BMD, HLA-B27

Treatment

• non-pharmacological therapy

prevent fusion from poor posture and disability through: exercise (e.g.swimming), postural and

deep breathing exercises, outpatient PT,and smoking cessation

• pharmacological therapy

» NSAlDs (first line of treatment for peripheral and axial disease)

glucocorticoids(topical eye drops,local injections,occasionally require systemic steroids prior to

other effective Rx)

DMARDs only for peripheral arthritis (SSZ, M I X)

if inadequate response to two NSAlDs (or DMARD for peripheral arthritis only), consider antiTNF agents or anti-IL-17 for axial and peripheral involvement

• manage extra-articular manifestations

• surgical therapy

• hip replacement and vertebral osteotomy for marked deformity (latter rarely performed)

Extra-Articular Manifestations of AS

5As

Anterior uveitis

Apical lung fibrosis

Aortic incompetence

Amyloidosis (kidneys)

Autoimmune bowel disease (ulcerative

colitis)

t

- J

Prognosis

• spontaneous remissions and relapses are common and can occur at any age

• function may be excellent despite spinal deformity

• favourable prognosis if female and age of onset >40 yr

• early onset with hip disease may lead to severe disability;may require arthroplasty

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RH25 Rheumatology Toronto Notes 2023

Enteropathic Arthritis

Definition

• see Gastroenterology. Inflammatory Bowel Disease,G22

Clinical Presentation

• MSK manifestations in the setting of either ulcerative colitis (UC) or Crohn'

s disease (CD) include

peripheral arthritis (large joint, asymmetrical),spondylitis, and hypertrophic osteoarthropathy

• non -arthritic MSK manifestations can occur secondary to steroid treatment of bowel inflammation

(arthralgia, myalgia, osteoporosis, AVN)

Both AS and BA feature symmetric

sacroiliitis

Table 28. Comparing Features of Spondylitis vs. Peripheral Arthritis in EA

Parameter Spondylitis Peripheral Arthritis

HLA-B27 Association

Gender

Onset Before IBD

ParallelsI8D Course

Type of IBD

Treatment

Yes No

M*F M-F

Yes No

No Yes

UC'CO

NSAIDs (use cautiously,may exacerbate bowel NSAIDs. DMARDs:INF inhibitors ifresistant

disease):TNF inhibitors if resistant

CD

Psoriatic Arthritis

Definition

• arthritic inflammation associated with psoriasis

Etiology and Pathophysiology

• unclear but many genetic, immunologic,and some environmental factors involved (e.g.bacterial,

viral,and trauma)

Check “hidden"areas(or psoriatic

lesions(eats, hairline, umbilicus,gluteal

cleft nails)

TNF inhibitors are effective treatments

for PsA with no important added risks

associated with their short-term use

Epidemiology

• psoriasis affects 1% of the population

• arthropathy in 15% of patients with psoriasis

• 15-20% of patients will develop joint disease before skin lesions appear

Clinical Presentation

• dermatologic

• psoriasis: well-demarcated erythematous plaques with silvery scale

• psoriatic nail changes (potential predictor for PsA): pitting, transverse or longitudinal ridging,

discolouration,subungual hyperkeratosis, onycholysis, and oil drops

• musculoskeletal

• 5 general patterns

• asymmetric oligoarthritis (<5 small and/or large joints affected in asymmetric distribution;

most common - 70%)

• arthritis of DIPs with nail changes

* symmetric polyarthritis (similar to RA)

sacroiliitis and spondylitis(usually older, male patients)

» arthritis mutilans (destructive and deforming small joint polyarthritis)

• other findings:dactylitis, enthesopathy, morning stiffness >30 min (50%)

• ophthalmic

conjunctivitis, iritis (anterior uveitis)

• cardiac and respiratory (late findings)

aortic insufficiency

• apical lung fibrosis

• neurologic

• cauda equina syndrome

• radiologic

floating syndesmophytes

pencil-in-cup appearance at IPs

osteolysis, periostitis r->

L J

Treatment

• treatskin lesions (e.g.steroid cream,salicylic and/or retinoic acid,tar, UV light)

• NSAIDs and/or 1A steroids(as an adjuvant), benefitshould be seen within a few wk,should not be the

sole therapy >3 mo

• DMARDs to minimize erosive disease (use earlv in peripheral joint involvement)

non-biologic DMARDs(MTX,SSZ, or leflunomide)

biologic therapies include anti-TNl-

'

agents, anti-lL-17 (secukinumab), and anti-lL-12/23

(ustekinumab)

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RH26 Rheumatology Toronto Notes 202.

'

Table 29. CASPAR Criteria for PsA*

Criterion Description

1.Evidence of psoriasis

2. Psoriatic nail dystrophy

3. Negative results for RE

4.Dactylitis

5.Radiological evidence

Current,past,or lamily history

Onycholysis,pitting,hypetheralosis

Preferably by ELISA,ncphclometry

Current or past history

Juxta-articular bone formation on hand or foot x-rays

"To meet the CASPAR (ClASsrfication criteria for Psoriatic ARthritis) criteria,a patientmust have inflammatory articular disease (joint,spine,or

enthese

Arthritis

al) with >3 poi

Rheum 2006

nts from the above 5 cat

Aug54(8):2665-2673.C

ries.

fication criterialor PsA development

egor

lassi

Reactive Arthritis

Definition

• one of the seronegative spondyloarthropathies in which patients have a peripheral arthritis (>1 mo

duration) accompanied by one or more extra-articular manifestations that appearsshortly after

certain infections of the Cil or (ill tract

• this term should not be confused with rheumatic fever or viral arthritidcs

Clinical Triad of Reactive Arthritis

• Arthritis

• Conjunctivitis/uveitis

• Urethritis/cervicitis

Etiology

• onset following an infectious episode either involving the G1 or CiU tract

• Gl: Shigella, Salmonella,Campylobacter, Yersinia,C. difficile species

GU:Chlamydia (isolated in 16-44% of ReA cases), Mycoplasma species

• acute clinical course

• onset 1-4 wk post-infection

• lasts wk to mo

• often recurring

• spinal involvement persists

“Can't See, Can’t Pee, Can't Climb a

Tree”

T riad of conjunctivitis,urethritis, and

arthritis is 99% specific (but 51%

sensitive) for ReA

Epidemiology

• in HLA-B27 patients, axial > peripheral involvement

• M>1-

Clinical Presentation

• musculoskeletal

• asymmetric peripheral arthritis, spondylitis/sacroiliitis, enthesitis (Achilles tendinitis, plantar

fasciitis), dactylitis

• ophthalmic

iritis(anterior uveitis), conjunctivitis

• dermatologic

keratoderma blennorrhagicum (hvperkeratotic skin lesions on palms and soles) and balanitis

drdnata (small,shallow, painless ulcers of glans penis and urethral meatus) are diagnostic

• gastrointestinal

• oral ulcers, diarrhea

• genitourinary

• urethritis, prostatitis, cervicitis, cystitis,sterile pyuria; presence not related to site of initiating

infection

Investigations

• diagnosis is clinical plus laboratory

• evidence of antecedent or concomitant infection (stool culture, urine, and genital swab testing)

• blood work: norntocytic, normochromic anemia, and leukocytosis

• sterile cultures

• serology: HLA-B27 positive, elevated ESR/CRP

Treatment

• antibiotics for non-articular infections

• NSAIDs (naproxen 500 mg BID/TID, diclofenac 50 mg HD, indomethadn 50 mgTTD/QlD), PT,

exercise

• local therapy

IA steroid injection (triamcinolone acetonide)

• topical steroid for ocular involvement

• systemic therapy

corticosteroids (starting dose 20 mg/d)

DMARDs (for refractory reactive arthritis with peripheral joint involvement only) (SSZ, MT'

X)

TNP-ct inhibitors for spinal inflammation (for disease refractory to NSAIDs, DMARDs)

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RH27 Rheumatology Toronto Notes 2023

Prognosis

• self-limited, typically 3-5 mo, varies based on pathogen and patient'

s genetic background

• chronic in 15-20% of cases

Crystal-Induced Arthropathies

Table 30. Gout vs. Pseudogout

Parameter Gout Pseudogout

Gender M»F M-f

Age Middle- aged males

Post menopausal females

Usually elderly

Onset of Disease Acute

Can become chronic if high uric acid untreated, Chondrocalcinosis isasymptomatic but the

people with renal failure,kidney transplant clinical featureis generally acute

Monosodium urate

Negative birefringence (yellow when parallel Positive birefringence (bluewhen parallel),

to compensator filter),needle-shaped

First MIP classically:also midfoot,ankle,

knee,or polyarticular

Radiology (notefindings arenonspecific) Erosions

Acule

S

2

% Crystal Type CPPD

rhomboid- shaped 1

S

Distribution Knee,wrist:monoarticular,or polyarticular

ilchronic

3

• 1st MTP - podagra

• Ankle

• Knee

-

Chondrocalcinosis

OA (knee,wrist,2nd and 3rd MCP)

NSAIDs,corticosteroids Figure 13. Common sites of

involvement of gout (asymmetric

joint involvement)

Acute:NSAIOs.corticosteroids,colchicine

Chronic:tallopurinol.febuxostat

Treatment

Gout

Definition

• derangement in purine metabolism resulting in hyperuricemia; monosodium urate crystal deposits in

tissues(tophi) and synovium (microtophi)

An acute gout attack may mimic

cellulitis; however, joint mobility is

usually preserved in cellulitis unless it

overlaps a joint

Etiology and Pathophysiology

• uric acid can be obtained from the diet or made endogenously by xanthine oxidase,which converts

xanthine to uric acid

• an excess of uric acid results in hyperuricemia

• uric acid can deposit in the skin/subcutaneous tissues (tophi),synovium (microtophi),and kidney,

where it can crystalize to form monosodium urate crystals that lead to gout

• non-modifiable risk factors include:genetic mutations, male gender, and advanced age

• modifiable risk factors include:diet (alcohol, purine rich foodssuch as meats and seafoods,fructose/

sugar sweetened foods;see list of precipitants below)

• other risk factors:renal failure, metabolic syndrome, dehydration (e.g. diuretics)

Precipitants of Gout

Drugs are FACT

Furosemide

Aspirin 1 (low-dose)/Alcohol

Cyclosporine

Thiazide diuretics Clinical Presentation

• single episode progressing to recurrent episodes of acute inflammatory arthritis

• acute gouty arthritis

severe pain, erythema, joint swelling, usually involving lower extremities

• joint mobility may he limited

• attack will subside spontaneously within d to wk (5-10 d ); may recur

Foods are SALT

Seafood

Alcohol (beer and spirits)

Liver and kidney

Turkey (meat)

• tophi

• urate deposits on cartilage, tendons, bursae,soft tissues, and synovial membranes

• common sites:first MTP, ear helix, olecranon bursae, tendon insertions (common in Achilles

tendon)

2020 American College olRheumatology

Guideline for the Managementol Goul

• kidney Arthritis Rheumatol 2020:72:879-95

• gouty nephropathy

» uric acid nephrolithiasis

•Inflate urate awering therapy (IW)lor patents

viitli :

•

>1SC tophi

•Radiographic damage attributable to gout

•Freguentgoutflares (»2/yr)

• Allopurino!is preferred over at other ULTsas a firstlineagent for allpatientsRnctjdi-g CKO stage »3|

•Initiate concomitant anti-indamnratory prophylaxis

(e.g.colchicine.NSAIDs.predn sore prednisolone)

lor 3 -6 mo

• Conl-.nue 01!to target and maintain strum urate

0 mgfdl

•In patients with frequent gout Daiesor

nomesolvingSC tophi who have failedloacheve

serum urate <0 mgfdlon uticosutlcs.ualhine

oxidase inhibitors,and other interventions,

peglotitase should be initiated and the current ULI

should be discontinued

• tout flares should he managedwith NSAIOs.

low-dose colchicine,nr glucocorticoids as trst-lloe

agents

Investigations

• joint aspirate:>90% of joint aspiratesshow crystals of monosodium urate (negatively birefringent,

needle-shaped) if done early in course of presentation

• x-rays may show tophi assoft tissue swelling, bone/joints - punched-out lesions, erosion with “overhanging"

edge

• U/S shows double-contour sign

• correlated with hyperuricemia in the blood

Treatment

• acute gout

• NSAIDs: high-dose, then taper as symptoms improve

• corticosteroids: 1 A, oral, or IM (if renal, cardiovascular, or (il disease and/or if NSAIDs

contraindicated or failed). IV for patients with multiple joints flaring, unable to take oral

medication, and already have IV line

colchicine 1.2 mg at the first signs of an attack followed by 0.6 mg 1 h later and 0.6 mg BID on

subsequent days until the attack has resolved

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RH28 Rheumatology Toronto Notes 2023

• chronic gout

• conservative

avoid foods with high purine content (e.g. visceral meats,sardines,shellfish, beans, peas)

avoid drugs with hyperuricemic effects(e.g. pyrazinamide, ethambutol, thiazide, alcohol)

additional management of lifestyle factors:limiting alcohol intake, limiting high-fructose

corn syrup, for overweight/obese patients weight lossis recommended (regardless of activity

level)

medical

antihyperuricemic drugs (first line:allopurinol (not nephrotoxic)second line:febuxostat):

decrease uric acid production by inhibiting xanthine oxidase. Start low and titrate up. Do not

use febuxostat if history of cardiovascular disease

uricosuric drugs (probenecid,sulfinpyrazone): very rarely used in combination with

allopurinol or febuxostat in patients in whom hyperuricemia is not controlled with the latter

• prophylaxis with low-dose NSAlD/colchicine should be started with urate-lowering therapy

• in renal disease secondary to hyperuricemia, use low-dose allopurinol nnd monitor Cr

• indications for treatment with antihyperuricemic medications include

• attacks (>2/yr), tophi, bone erosions/arthritis

Pseudogout (Calcium Pyrophosphate Dihydrate Disease)

Definition

• joint inflammation caused by calcium pyrophosphate (CCP) crystal deposition in connective tissue

Etiology and Pathophysiology

• acute inflammatory arthritis due to phagocytosis of IgG-coated CPPD crystals by neutrophils and

subsequent release of inflammatory mediators within jointspace

• usually monoarticular but can be polyarticular

• slower onset in comparison to gout, lasts up to 2-3 wk but isself-limited

Risk Factors

• old age, advanced OA, neuropathic joints

• other associated conditions:hyperparathyroidism, hypothyroidism, hypomagnesemia,

hypophosphatasia (low ALP), DM, hemochromatosis

-

• Polyarticular wrist

• Hand (MCPI

• Foot (1st MTPI

r;

I

• Hip

Clinical Presentation

• affects knees, wrists, MCPs, hips,shoulders; lesslikely elbows, ankles,big toe,spine

• asymptomatic crystal deposition (seen on radiograph only)

• acute crystal arthritis(self-limited flares of acute inflammatory arthritis resembling gout)

• pseudo-OA (progressive joint degeneration,sometimes with episodes of acute inflammatory arthritis)

• pseudo-RA (symmetrical polyarticular pattern with morning stiffness and constitutionalsymptoms)

• frequently triggered by dehydration, acute illness,surgery, trauma

Investigations

• must aspirate joint to rule out septic arthritis and gout

• CPPD crystals: present in 60% of patients, often only a few crystals, positive birefringence (blue) and

rhomboid shaped

• x-rays show chondrocaldnosis in 75%: radiodensities in fibrocartilaginousstructures (e.g. knee

menisci) or linear radiodensities in hyaline articular cartilage

Treatment

• acute CPP: joint aspiration,steroid injection, cool packs, temporary rest, and protection

• chronic CPP: NSAlDs with gastroprotection and/or low-dose prophylactic colchicine 0.6-1.2 mg/d PO

(controversial)

Figure 14. Common sites of

involvement of CPPD

EULAR Rccornmendationsfor the Management

of CPPD

Ann RheumOis 2011;10:511-5

1. Pharmacological and non-pharmacologicai

treatment mould troth be used to manage CPP0.

2. treating acute CPP crystal arthritis with ice or cool

packs,rest, jointaspmation. and Uiojecbon of

long-acting glucocoitrcoids(CC$) may be sufficient

for many patients.

3. Acute CPP crystal arthritis can be treated

systemically with HSAIDs and low-dose oral

colchicine, although their use may be Imited in

older patients by tonicity and comorbidity.

4.A brief taperingcourse of oral or parenteral CCS

or MTU may be effective for acute CPP crystal

arthritisthatis not amenable to IA6CS injection.

5. Low-dose oral colchicine ixNSAIO can be used as

prophylaxis againstfrequent recurrent acuteCPP

crystal arthritis.

6. For patients with OA and CPPD. management goals

and options are the same asthose for 0A alone.

7.Ibe order of pharmacological preference(or

chronic CPP ciyslal inflammatory art hubs is USAID

andlor colchicine, low-dose corticosteroid. MIX

and hydroxychloroquine.

I. Associated conditionsshould be treated d

detected.

9. Ihere are nodisease-modrfyieg treatmentslor CTP

crystal arthritisand no treatment isMruMfor

asymptomatic cboodrocaldnosis.

Non-Articular Rheumatism

Definition

• disorders that primarily affect soft tissues or periarticular structures

• includes bursitis, tendinitis, tenosynovitis,fibromyalgia, and PMR

Polymyalgia Rheumatica

Definition

• characterized by pain and stiffness of the proximal extremities (girdle area)

• closely related to GCA (15% of patients with PMR develop GCA)

• no muscle weakness +

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RH29 Rheumatology Toronto Notes 2023

Table 31. PMR Classification Criteria Scoring Algorithm*

Required criteria:age >50 yr.bilateral shoulder aching,and abnormal ESR.CHP

Points without U/S (0-6) Points with AbnormaI

U/S"(0-8)

Morning stillness duration'

45 min

Hip pain or limited ROM

Absence of RForACPA

Absence olother joint involvement

At least one shoulder with subdeltoid and/or biceps tenosynovitis and/or

glenohumeral synovitis (either posterior or axillary) and at least one hip with

synovitis and/or trochanteric bursitis on U/S

Both shoulders withsubdeltoid bursitis,biceps tenosynovitis,or glenohumeral synovitison U/S

2 2

1 1

2 2

1 1

N:A 1

M/A 1

'A score oi 4 or more is categorized as PMR in the algorithm without U/S and a score ot 5 or more is categorized as PMR inthe algorithm withU/S

"OptionalU/S criteria

Ann Rlieum Ols 2012:71:484- 492

Epidemiology

• incidence: 50 in 100000 per yr in those >50 yr

• age of onset typically >50 yr, T:M=2:I

Clinical Presentation

• constitutional symptoms prominent (fever, weight loss, malaise)

• pain and stilTness ofsymmetrical proximal muscles (neck,shoulder and hip girdles, thighs)

• gel phenomenon (stiffness after prolonged inactivity)

• physical exam reveals tender muscles, but no true weakness or atrophy

Investigations

• blood work:often shows anemia of chronic disease, elevated platelets, elevated HSR and CRP, and

normal CK; up to 5% of PMR reported with normal inflammatory markers

Treatment

• goal of therapy:symptom relief

• start with prednisone 12.5-25 mg PO once daily, reconsider diagnosis if no response within several

days

• taper slowly with improvement over 1 yr period with close monitoring, if in remission taper until

discontinued

• relapsesshould be diagnosed and treated on clinical basis; do not treat a rise in HSR as a relapse

• treat relapses aggressively (50% relapse rate)

• monitor for steroid side effects, glucocorticoid-induced osteoporosis prevention, and follow for

symptoms of GC/\

Fibromyalgia

Definition

• chronic (>3 mo), widespread (axial, left- and right-sided, upper and lower segment), non-articular

pain with characteristic tender points

Diagnosis

Table 32. 2010 ACR Preliminary Diagnostic Criteria for Fibromyalgia

Criteria Comments

Y/idespreadPam Index - number ol areas in which thepalienlhad pain A paticnl satisfies diagnostic critena lor fibromyalgia IIthe following 3

over the last wk (max score 19):

L and R:shoulder girdle,upper arm.lower arm.hip.upper leg.lower

leg.jaw

One Area:chest,abdomen,upper back, lower back,neck

Symptom Severity (SS) Score * sum of:

a) severity of fatigue

b) waking unrefreshed

c) cognitive symptoms over the past wk

d) extent ol somatic symptoms (IBS, N/A.abdominal pain/cramps,

dry mouth,fever,hives,ringing in ears, vomiting,heartburn,dry

eyes. SOB.loss of appetite,rash,hair loss,easy bruising,etc.)

All(a d) rated on 0 3 scale:0 *no problem.1*mild.2 •moderate.

3 > severe

conditions are met:

1.Widespread Pain Index (WPI) >7 and SS score >5 or WPI 3 6 and

SS score >9

2.Symptoms have been present at a similar level lor at least 3 mo

3.Ihe patient does not have a disorder that would otherwise explain

the pain

r i

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Arthrit Care amt Res2010:62(5):600-610

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RH30 Rheumatology Toronto Notes 2023

Epidemiology

. I-

'

:M=3:1

• primarily ages 25-45,some adolescents

• prevalence of 2-5% in general population

• overlaps with chronic fatigue syndrome and myofascial pain syndrome

• strong association with psychiatric illness

Clinical Presentation

• widespread aching,stiffness

• easy fatigability

• sleep disturbance: non-restorative sleep, difficulty falling asleep, and frequent wakening

• symptoms aggravated by physical activity, poor sleep, emotional stress

• patient feels that joints are diffusely swollen although joint examination is normal

• neurologic symptoms of hyperalgesia, paresthesias, allodynia

• associated with irritable bowel or bladdersyndrome, migraines,tension H/As, restlessleg syndrome,

obesity, depression, and anxiety

• physical exam should reveal only tenderness with palpation of soft tissues, with no specificity for

trigger/tender points

Investigations

• blood work:includes TSH; all typically normal unless unrelated, underlying illness present

• serology: do not order ANA or Rl- unless there is clinical suspicion for a CTD or inflammatory

arthritis

• laboratory sleep assessment

Treatment

• non-pharmacological therapy

graded exercise programs including aerobic (>2() min/d, 2-3 d/wk) and resistance training (>8

repetitions per exercise, 2-3d/wk)

other therapies with some evidence:acupuncture, CBT, hydrotherapy, meditative movement

(yoga,Tai chi)

there is no evidence for biofeedback, chiropractics, hypnotherapy, meditation

• pharmacological therapy (to help with symptoms, not curative)

low-dose tricyclic antidepressant (e.g. amitriptyline)

for sleep restoration

select those with lower anticholinergic side effects

SNR1:duloxetine, milnacipran

anticonvulsant: pregabalin.gabapentin

analgesics may he beneficial for pain that interferes with sleep (NSAIDs, not narcotics)

Prognosis

• variable; usually chronic, waxes and wanes,svith some pain and fatigue that usually persists

Table 33. Clinical Features of Inflammatory Myopathy vs. Polymyalgia Rheumatica vs.

Fibromyalgia

Polymyositis PMR Fibromyalgia

Epidemiology

Muscle Involvement

Weakness

F>M.40-50 yr

Proximal muscle

F>M.>50 yr

Proximal muscle

F»M, 25-45 yr

Diffuse

Yes No No

Pain

Stiffness

Painful

Significant morning and gelling May have morning stiffness

stiffness (shoulders, neck, hips)

Muscle biopsy.CK , EMC.ruleout ISR/CRP.rule out CCA

malignancy

Usually normal

High-dose steroids,

immunosuppressants

Painless

Present

Painful

Investigations Sleep assessment. ISH

ESRCRP Markedly elevated

Low-dose steroids

Normal

Treatment Exercise,sleep restoration

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RH3IRheumatology Toronto Notes 2023

Common Medications

Table 34. Common Medications for Osteoarthritis

Contraindications Adverse

Effects

Class Generic Drug Trade Name Dosing (PO) Indications

Name

Analgesics acetaminophen Tylenol:

1000 mg 110 q4 h 1st line

(3 g dailymail

Severe liver disease/

impairment

Hepatoloiicity.

overdose.

potentiates

warfarin

Nausea, tinnitus,

vertigo,rash,

dyspepsia.Gl

bleed.PUD.

hepatitis,

renal failure.

HIN.nephrotic

syndrome

SameasNSAIOs

above

NSAIDs ibuprofen

diclofenac

diclofenac/

misoprostol

naproien

meloucam

Advil -

Voltaren

Arlhrotec:

Naprosyn 1

Aleve:

Mobicoi

200-600 mg TID 2nd line

25- SOmg TID

50-75/200 mg TI0

125-500 mg BID

7.5-15 mg once

Gl bleed,renal

impairment,allergy

to ASA.NSAIDs.

pregnancy (T3).

anticoagulants

daily

Celebrex : COX-2 Inhibitors celecoiib 200 mg once daily Dyspepsia/GERD Renal impairment,

cardiovascular

disease.Gl Bleed

Other Treatments Comments

Combination analgesics (acetaminophen codeine,

acetaminophen NSAIDs)

IA corticosteroid injection

Enhanced short- term effect compared to acetaminophen alone

More adverse effects: sedation.constipation,nausea.Gl upset

Short-term (wk-mo).joint specific treatment

Decrease in pain and improvement in function

Used for managcmenl of an IA inflammatory process when infection has been ruled out

Used for mild-moderate OAof the knees;however,little supporting evidence and not

considered to be effective

Precaution with chicken/egg allergy

Topical diclofenac (Pennsaid'

.Voltaren Emulgcl '

)

May use for patients who fail acetaminophen treatment and who wish to avoid

systemic therapy,better on small joints

Mild decrease inpain

Limited evidence of benefitin 0A knee.No regulation by Health Canada

IA hyaluronic acid q6 mo

Topical NSAIDs

Capsaicin cream

Glucosamine sulfate *

chondroitin

Table 35. DMARDs

Generic Drug Name Trade Name Dosing Contraindications Adverse Effects

COMMONLY USED

hydroxychloroquine Plaqueml '

400 mgP0 once daily Retinal disease.GGPD

initially deficiency

200-400 mg POonce

daily maintenance

(5 mg/kg ideal body

weight per day to a

maximum of 400 mg/d)

1000 mg P0 BID-TID Sulfa/ASA allergy, kidney

disease.GGP0 deficiency

Bone marrow

Gl symptoms,skin rash,macular

damage,neuromyopathy

Requires annual ophthalmological

screening tomonitor for retinopathy

$

sulfasalazine Salaaopyrim

Arullidme '

(US)

Rheumatrex :

Folexj

'Mexate 3

Gl symptoms,rash,H/A.leukopenia

S

7.5-25 mg PO/SC

weekly

Oral ulcers.Gl symptoms,cirrhosis,

suppression,liver disease, myelosuppression.pneumonitis,

significant lung disease. tubular necrosis

immunodeficiency,

pregnancy.EtOHuse

methotrexate

S

leflunomide Arava ’

10 -20 mg P0 once daily Liver disease,lung disease. Alopecia.Gl symptoms,liver

ss pregnancy dysfunction,interstitial pulmonary

fibrosis. HIN

NOT COMMONLY USED

Neoral '

2.5-3 mg/kg/d divided Kidney/liver disease,

and given in 2 doses P0 infection.HIN

50 mg IM weekly after IBD.kidney/liver disease

gradual introduction

2 mg/kg/dP0 once Kidney/liver disease

thiopurine

S- methyItransferase (TPMI) vomiting.diarrhea

deficiency

Kidney/liver disease,

neutropenia

HTN.decreased renal function,hair

growth, tremors,bleeding

Rash,mouth soreness/ulcets,

proteinuria,marrow suppress!on

cyclosporine

Si

gold (injectable) Solganal 3

Myochrysine®

Imuran'

s

aialhiopiine Rash,pancytopenia (especially

* S daily WBC. t AS!.ALT),biliary stasis,

r T

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Cytoxan '

1q/m

'

/mo IV as per

protocol

Cardioloxicity,Gl symptoms,

hemorrhagic cystitis,nephrotoxicity,

bone marrow suppression,sterility,

bladder cancer

cyclophosphamide

s

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RH32 Rheumatology Toronto Notes 2023

Table 35. DMARDs

Generic Drug Name Trade Name Dosing Controindicotions Adverse Effects

NEWER DMARDs (Biologies)

Enbrel:

25 mg biweekly or 50 Fusion protein of INF receptor and Fc portion of IgG

mg weekly SC

3-5 mg/kg IV q8 wk Chimeric mouse/human monoclonalanti INF

etanercept

sss

infliximab Remicade

SSS

adalimumab Humira 40 mg SCq2 wk ' Monoclonal anti-INF

SSS

Simponi' 50 mg SC q1mo or 2 Monoclonal anti-INF

mg/kg q8 wk

400 mg SC q2 wk «3 PEGylated monoclonal anti-INF

then 200 mg SC q4 wk

Day1:10 mg (AM) P0, PDE4 inhibitor which reduces production of INFo

titrate up to 30 mg BID

by day 6

500-1000 mgIV

infusion ql mo or 125

mgSCqlwk

1g x 2 IV infusions, 2 wk Causes 8 cell depletion,binds to CD20

apart q6 mo

4-8 mg/kg IV q4 wk or IL- 6 receptor antagonist

162 mg SCq1-2 wk

5 mg 8ID

golimumab

SSS

Cimna'

certolizumab

SSS

apremilast Oterla

SSS

Orencia abataccpt ' Coslimulalion modulator ofIcell activation

SSS

rituximab Rituxan '

SSS

Actemra;

tocilizumab

SSS

Selective JAK 1/3 inhibitor and thus interferes with JAK-SIAT

signaling pathway

Selective JAK1inhibitor and thus interferes withJAK-STAT signaling

pathway

Blocks IL-17A

tofacitmib Xcl|anr '

S$

upadacitinib Rinvoq:

15 mg once daily

ss

secukmumab Coscnlyx 150 mg monthly

SSS

Landmark Rheumatology Trials

Trial Name Reference Clinical Trial Details

RHEUMATOID ARTHRITIS

COMET Lancet 2008:372:375 82 Title:Comparison of Methotrexate Monotherapy with a Combination of Methotrexate and Etanercept in Active.Early.Moderate to

Severe Rheumatoid Arthritis (COME!): A Randomised,Double Blind,Parallel Treatment Trial

Purpose: To compare the efficacy ol MIX monotherapy or MIX plus etaneiccpt for remission and radiographic non-progression in RA

patients.

Methods:542 RA MTX-naive outpatients with moderale-to- severe disease for 3-24 mo were randomly assigned to MIX alone (titrated

from 7.5-20 mgfwk) or MIX (same titration) plus etanercept 50 mg/wk.

Results: Clinicalremission was achieved in 50% ol patients on combined treatment vs. 28% taking MIX alone (difference.22.05%:

P'

0.0001).80% and 59%,respectively,achieved radiographic non-progression (difference.20.98%:P'

0.0001).Both groups

experienced similar adverse events.

Discussiond yr of Ireatment with etanercept plus MIX can achieve clinical remission and radiographic non-progression in early severe

RA ,

ERA NEJM 2000:343:1586- 93 Title:A Comparison of Etanercept and Methotiexate inPatients with Early Rheumatoid Arthritis

Purpose:To investigate the efficacy of etanercept inreducing disease activity and joint damage inpatients withearly and active RA.

Methods: 632 patients received either SC etanercept (10 or 25 mg/wk) twice weekly or oral MIX (19 mg/wk) for 12 mo.Clinicalresponse

was defined by criteria of the AmericanCollege olRheumatology.

Results:Patients on 25 mg etanercept improved quicker than those on MIX, with significantly mote improvements in disease activity

within 6 mo (P'

0.05).During the first 6 and12 mo,there vrere significantly greater increases in mean erosion scores in the MIX group

(P‘0.007).Fewer adverse events (P‘

0.02) and infections (P‘

0.006) vrere seen in 25 mg etanercept.

Conclusion:Inpatients with early active RA. etanercept more rapidly reduced symptoms and slowed joint damage as compared to MIX.

Title:Clinical and Radiographic Outcomes ol Four Different Treatment Strategies in Patients with Early Rheumatoid Arthritis (the 8eSl

Study):A Randomized.Controlled Trial

Purpose:To identify the optimal therapeutic strategy for preventing long term joint damage and functional decline in RA.

Methods: 508 patients were randomly assigned to1of 4 therapeutic strategies:(1) sequential disease-modifying antirheumatic

diug monotherapy.(2) step up combination therapy.(3) initial combination therapy with tapered high- dose prednisone,or (4) initial

combination therapy withinfliximab.

Results:At 3 mo.groups 3 and 4 showed significantly greater functional improvement (as defined by the Dutch version of the Health

Assessment Questionnaire (D- HA0)) with mean scores of 0.6.as compared lo mean scores of 1.0 in groups1and 2 (P'

0.001).At 1yr.

mean D- HA0 scores in groups 3 and 4 were 0.5,as compared to 0.7 in groups1and 2 (P‘0.009).

Conclusion: As compared tosequential monotherapy or step-up combination therapy,initial combination therapy withpiednisone or

infliximab led loearlier functional improvements and less radiographic damage in patients with early RA.

BeSt Arthritis Rheum

2005:52:3381-90

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Infliximab and MIX NEJM 2000:343:1594-602 Title: Infliximab and Methotrexate in the Treatment of Rheumatoid Arthritis.Anti-Tumor Necrosis Factor Trial in Rheumatoid Arthritis

with Concomitant Therapy Study Group

Purpose:lo assess infliximab for potential sustained benefits and effects on|Oint damage in RA.

Methods:428 patients whohad active RA despite MIX therapy were treated with IV infliximab (3 or 10 mg/kg every 4 or 8 wk plus oral

MIX for 54 wk) or placebo.

Results: As compared lo MIX alone,infliximab plus MIX significantly reduced signs and symptoms of RA (clinical response. 51.8%

vs.17.0%:P'

0.001).Ihere was grealer evidence of joint damage on MIX alone but not on infliximab plus MIX (mean change in

radiographic score,7.0 vs.0.6.P'

0.001).

Conclusion:Repeated doses of infliximab plus MTX inpersistently active RA was clinically effective and slowed the progression of joint

damage.

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