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348-361.

r T

c j

+

Rheumatology

Rachel Goldfarb and Eden Meisels, chapter editors

Karolina Gaebe and Alyssa Li, associate editors

Wei Fang Dai and Camilla Giovino, EBM editors

Dr. Arthur Bookman, Dr. Sahil Koppikar, Dr. Dharini Mahendira, Dr. Ahmed Omar, and

Dr. Medha Soowamber, staff'

editors

Acronyms ...

Anatomy of Joint Pathology

Basics of Immunology.

Immune Mechanisms of Disease

Immunogenetics and Disease

Differential Diagnoses of Common Presentations,

Synovial Fluid Analysis

Septic Arthritis

Degenerative Arthritis:Osteoarthritis

Seropositive Rheumatic Disease

Connective Tissue Disorders

Rheumatoid Arthritis

Systemic LupusErythematosus

Antiphospholipid Antibody Syndrome

Scleroderma (i.e. Systemic Sclerosis)

Inflammatory Myopathy

Sjogren'

sSyndrome

Mixed Connective Tissue Disease

Overlap Syndrome

Vasculitides

Small Vessel Non-ANCA-Associated Vasculitis

Small Vessel ANCA-Associated Vasculitis

Medium Vessel Vasculitis

Large Vessel Vasculitis

Seronegative Rheumatic Disease

Ankylosing Spondylitis

Enteropathic Arthritis

Psoriatic Arthritis

Reactive Arthritis

Crystal-Induced Arthropathies

Pseudogout (Calcium Pyrophosphate Dihydrate Disease)

Non-Articular Rheumatism.

Polymyalgia Rheumatica

Fibromyalgia

Common Medications

Landmark Rheumatology Trials.

References

RH2

,RH2

.RH2

RH3

RH4

RH5

RH5

RH7

RH8

RH18

RH23

..RH27

...RH28

,„....RH31

. RH32

RH35

+

RHl Rheumatology Toronto Notes 2023

R1I2 Rheumatology Toronto Notes 2023

Acronyms

AAV antineutcophil cytoplasmic

antibody-associated vasculitis

Ab antibody

ACPA anti-citrullinated protein

antibodies

Ag antigen

ANA antinuclear antibody

ANCA antineutrophil cytoplasmic

antibody

Anti-RNP antiribonudear protein

Anti-Sm anti-Smith antibodies

CMC carpometacarpal joint

CNS central nervous system

CTD connective tissue disease

CPPD calcium pyrophosphate

deposition disease

CRP C-rcactivc protein

CVA cerebrovascular accident

GPA granulomatosis with polyangiitis PMN

headache

human leukocyte antigen

intra-articular

inflammatory bowel disease PIT

infective endocarditis

immunoglobulin A

immunoglobulin E

immunoglobulin G

interstitial lung disease

interphalangeal joint

idiopathic thrombocytopenic SNRI

purpura

metacarpophalangeal joint SpA

mixed connective tissue disease SS

major histocompatibility

complex

microangiopathic polyangiitis SSc

myeloperoxidase

metatarsophalangeal joint

methotrexate

osteoarthritis

polyarteritis nodosa

proximal interphalangeal joint U-SpA

polymyositis

polymorphonuclear leukocyte

polymyalgia rheumatica

proteinase 3

psoriatic arthritis

partial thromboplastin time

peptic ulcer disease

rheumatoidarthritis

reactive arthritis

rheumatoid factor

range of motion

sacroiliac

serotonin-norepinephrine

reuptake inhibitors

spondyloarthritis

Sjogren's syndrome

Sjogren's syndrome antigen A

Sjogren's syndrome antigen B

systemic sclerosis

sulfasalazin

tumour necrosis factor

thrombotic thrombocytopenic

purpura

upper limit of normal

undifferentiated

spondyloarthropathy

H/A PMR

HLA PR3

IA PsA

IBB

IE PUO

IgA RA

CVS cardiovascular system

OAT direct antiglobulin test

DEXA dual energy x-ray

absorptiometry

Anti-SRP anti-signal recognition particle DIP distal interphalangeal joint

Anti-SSA anti-Sjogren's syndrome antigen DMARD disease-modifying antirheumatic drug

DMM dermatomyositis

dsDNA double stranded DNA

Iqk ReA

IqG RF

ILD ROM

IP SI

UP

A MCP

APIA antiphospholipid antibodies MCTD

APS antiphospholipid antibody

syndrome

MHC SSA

EA cnteropathic arthritis

activated partial thromboplastin ECASA enteric-coated acctylsalicylic

time

SSB

aPTT MPA

MPO

EGPA eosinophilic granulomatosis and MTP

polyangiitis

FVC forced vital capacity

GC Neisseria gonorrhoeae

gonococcus

GCA giant cell arteritis

acid SS2

AS ankylosing spondylitis

avascular necrosis

B lymphocyte stimulator

calcium channel blocker

cyclic dtrullinated peptide

creatine kinase

INF

AVN t.‘

I X TIP

BlyS OA

CCB PAN ULN

CCP PIP

CK PM

Anatomy of Joint Pathology

Muscl

Bursa one Erosion § Terminology in Rheumatology

Cartilage

destruction1

Arthritis:inflammation in the joint(s)

• Joint swelling:effusion/synovial

thickening

Synovial

'

'membrane

£

-Synovitis £

. Effusion 5

Synovial • Pain

Tendon __ S

Cartilage j

Joint \

capsule

fluid • Warmth

• Erythema -

Cartilage

particle

loss ol

joint space

Osteophyte -

Cartilage

destruction

' Arthralgia:joint pain without

swelling,redness,or warmth oint space Z

narrowing <

JJ

-

Normal Joint Degenerative Joint Inflammatory Joint «9

Figure 1.Structure of normal, degenerative, and inflammatory joint

Innate Immune Cells

Neutrophil (PMN):circulates in

blood and responds to inflammatory

stimuli,kills invading organisms by

phagocytosis, degranulation. and

neutrophil extracellular traps

Natural Killer Cell:innate immunity

against intracellular infections

(especially viruses),killing function,and

produces cytokines

Macrophage:arrives after PMNs,

suppresses PMN efflux and

phagocytoses PMN debris, secretes

pro-inflammatory cytokines in response

to microbial debris

Dendritic Cell: actively phagocytic

when immature,activated by signals

from toll like receptor (ILR). releases

pro-inflammatory cytokines,presents

antigens to T cells in lymph nodes

Eosinophil:responds to inflammatory

cytokines and degranulates.releasing

reactive oxygen species and cytokines,

associated with allergy,asthma,and

parasitic infection

Mast Cell:presents in connective tissue

and mucosa,allergen cross-linking

of IgE bound to mast cell triggers

degranulation and the release of

inflammatory mediators

Basics of Immunology

Immune Mechanisms of Disease

Table 1. Mechanisms of Immune-Mediated Disorders

Type Pathophysiology Examples

IgE-Mcdiated/lmmcdiate Hypersensitivity

fiypcD

Antibody Medinted/Cylotoxic (TypeII)

Allergens bind toIgE antibodies on mast cells, Asthma,allergic rhinitis,anaphylaxis

inducing their degranulation

IqG or IgM antibodies deposit and bindlo cell

membrane- or matrix- associatedantigen

leading to lysis olthe target cell

Autoimmune hemolytic anemia,antiglomerular bascmonlmembrane disease

(Goodpasture syndrome).Graves' disease,

pemphigus vulgaris,rheumalic lever.IIP

SLE,PAN.post-streplococcal

glomerulonephritis,serumsickness,viral

hepatitis

Immune Complex (Type III) Ag-Ab complexes deposit in tissues,

which activates complement and cecruits

inflammatory mediators,resulting in tissue

injury

Release of cytokines by sensitized1cells and1 Contact dermatitis,insect venom,

cell- medialed cytotoxicity

r t

iJ

Cell-Mediated/Delayed Hypersensitivity

(Type IV) mycobacterial proteins (e.g.tuberculin skin

lest)

+

RH3Rheumatology Toronto Notes 2023

Immunogenetics and Disease

Key Cytokine Targets of Biologic Drugs • the short arm of chromosome 6 contains the genes that encode H LA molecules

• in humans, HLAs act as MHCs which present antigens to be recognized by T cell receptors and

identify the self to the immune system such that they must be matched for in organ transplantation

• certain HLA haplotypes are associated with increased susceptibility to autoimmune diseases

TNF

• Source of cytokine: T cells,

macrophages/monocytes

• Major functions:apoptotic cel

death,cachexia,induces other

cytokines. T cell stimulation,

induces metalloproteinases and

prostaglandins,increases expression

of adhesion molecules;increases

vascular permeability,leading to

increased entry of IgG.complement

and cells into tissues

Table 2. Classes of MHCs

MHC Class Types Location Function

HUS-A.B.C Recognized by CD8-(cytotoxic)

T lymphocytes

Ag presenting cells(mononuclear Recognized by CD4-(helper)

phagocytes.B cells,etc.)

In plasma

I All nucleated cells

II HU-DP.DO.DR

Ilymphocytes

Some components of the

complement cascade

Chemotaxis.opsonization,lysis of

bacteria and cells

III

lnterleukin-6 (IL-6)

• Source of cytokine:many

cells including monocytes and

macrophages

• Major functions:anemia of

inflammation (hepcidin production),

proliferation of B and T cells,acute

phase reactant induces natural

protease inhibitor,promotes

erosions,induces elevated CRP

Table 3.HLA-Associated Rheumatic Diseases

HLA Type Associated Conditions Comments

B27 AS Relative risk -20x for developing AS and ReA

ReA

EA (axial)

PsA (axial)

InRA.relativerisk - 2-10x:found in 933s of patients

DR3 is associated withthe producbon of anli-Ro/SSA and

anti-laSSB antibodies

DR4.DR1 RA

DR3 ss

SLE

Adaptive Immune Cells

• B cell:produces antibodies after

activation by specific antigen and B

cell co-receptor,additional signals

provided by CD4+ T helper cells

• Cytotoxic T cell:CD8- ceil,directs

cytotoxicity of target cells at sites

of infection,kills via lytic granules

and FasL-Fas interaction,recognizes

specific antigen and MHCI

• Helper T cell:subset of CD4- cells,

activates and helps other types of

cells carry out immune defense

(activates macrophages,helps B

cells,releases cytokines)

• Regulatory T cell:subset of CD4

-

cells, suppresses activation of name

autoreactive T cells

Differential Diagnoses of Common

Presentations

Joint Pain

I

Articular Non-Articular

T

Inflammatory Degenerative

1 1

I

*

T

*

I

Seropositive Seronegative Crystal Infectious/Septic

Gonococcal

Pseudogout Non-gonococcal

Hydroxyapatite Lyme disease

Viral

Mycobacterial

Fungal

Primary Secondary

0A Metabolic

Hemophilic

Neuropathic

Trauma

Localized Generalized

PMR

Tendinitis Fibromyalgia

Capsulitis Myofascial pain

Muscle sprain syndrome

RA Gout Bursitis

SLE

Scleroderma

DMM/PM Causes of Joint Pain

SS SOFTER TISSUE

Sepsis

OA

Symmetrical Asymmetrical Fracture

Tendon/musde

Epiphyseal

Referred

Tumour

Ischemia

Seropositive arthritides

Seronegative arthritides

Urate (gout)Zother crystal

Extra-articular rheumatism (PMR/

fibromyalgia)

AS ReA

EA PsA

Figure 2. Clinical approach to joint pain

Table 4. Differential Diagnosis of Acute Monoarthritis

Non-lnflammatory Inflammatory

Crystal

-Induced Infectious

Monosodium urate (MSU- gout),CPPO.1

pseudogout,hydroxyapatite

Gonococcal non-gonococcal,mycobacterial,

and fungal

Hemarthrosis.internal derangement (e,g.

loose body,tommeniscus)

Table 5. Differential Diagnosis of Oligoarthritis/Polyarthritis

Patterns of Joint Involvement

• Symmetrical vs. asymmetrical

• Small vs.large

• Mono vs. oligo (2-4 joints) vs.

polyarticular (>5 joints)

• Axial vs. peripheral

Acute (

‘

6 wk) Chronic (>6 wk)

Post-viral infection (parvovirus

B19.HIV)

Post-bacterial infection (GC and

non-GC.rheumatic fever)

Crystal-induced

Other (sarcoidoss.Lyme disease)

Very early rheumatoidarthritis

(VERA)

Seropositive inflammatory

arthritis

Seronegative inflammatory

arthritis

Degenerative

OA

RA AS

SLE EA

Scleroderma

DMM’PM

PsA

ReA

Crystal (polyarticular gout) +

RillRheumatology Toronto Notes 2023

Table 6. Symptoms of Inflammatory Arthritis vs. Degenerative Arthritis

Inflammatory Degenerative

The presence of synovitis often indicates

articular as opposed to non-articular

joint pain:synovitis presents with:soft

tissue swelling,effusion,warmth,and

stress pain (passive movement of the

joint through its range, plus a little bit

further)

Pain attest,relieved with activity

Morning stiffness >1h

Cardinal signs of inflammation (warmth,swelling,erythema,

tenderness,loss offunction)

Malalignmenl/delormity (late finding)

Extra-articular manifestations

Nighttime awakening due to pain

Pain with motion,relieved by rest

Morning stiffness <1h

Joint instability,buckling,gelling

Bony enlargement,malalignment/deformity (late finding)

Eveningfendof day pain

Table 7. Seropositive vs. Seronegative

Seropositive

Rheumatic Diseases

Seronegative Monitoring

G

CRP vs.ESR

• CRP is more sensitive for

inflammation than ESR

• CRP responds more quickly to

changes in the clinical situation

than ESR

• False negative and false positive

results are more common with ESR

• ESR is increased by renal disease,

female sex,older age, pregnancy,

and other chronic diseases such

as DM,multiple myeloma,and

congestive heart failure

• ESR can be useful at detecting lowgrade bone and joint infections and

monitoring disease activity in CTDs

such as SLE.PMR,and GCA

• Do not order ESR for acute

inflammation

Demographics

Peripheral Arthritis

F»M M -F

Symmetrical

Small (PIP, MCP) and medium joints (wrist,

knee,ankle, elbow) common

DIP less often involved

Usually asymmetrical

Usually larger joints,lower extremities

(exception:PsA)

DIP in PsA

DactylitisI

'sausage digit')

Pelvk/Axial Disease No (except for C-spine) Ves

fnthesitis

Extra-Articular

No Ves

Nodules

Vasculitis

Sicca

Raynaud's phenomenon

Rashes,internal organ involvement (lung,

cardiac)

Entrapment neuropathies|i.e.carpal tunnel

syndrome)

Iritis (anterior uveitis)

Oral ulcers

Gastrointestinal

Dermatological (psoriasis,nail pitting,

onycholysis,or keratoderma)

Genitourinary inflammation

Synovial Fluid Analysis Enthesitis

m :inflammation of tendon or

ligament at site of attachment to bone

•synovial fluid is an ultrafiltrate of plasma plus hyaluronic acid; it lubricates joint surfaces and

nourishes articular cartilage

Indications

•diagnostic: to clarify cause of inflammation; to analyze fluid for culture, crystal, and cell count to

differentiate inflammatory vs. degenerative;septic vs. crystal-induced vs. hemarthrosis

•therapeutic: drainage of blood, purulent or tense effusions; corticosteroid injection in the absence of

sepsis

Contraindications to Joint Aspiration or Injection

•absolute: open lesion or suspected infection of overlying skin or soft tissue

•relative: bleeding diathesis, thrombocytopenia, prosthetic joint

Synovial Fluid Analysis

•most important to assess the 3 Cs: cell count (WBC) and differential, culture and Ciram stain, and

crystal analysis

•other parameters to consider are listed in Table 8

Table 8. Synovial Fluid Analysis

Parameter Normal Non* Inflammatory Septic Hemorrhagic

Inflammatory

Colour

Clarity

WBC/mm’

Vellow to while

Opaque/purulcnt

»50000

Red/brown

Sangurnous

Variable

Pate yellow

Clear

Pale yellow

Cleat

-> 2000

Pale yellow

Opaguc

»2000

(crystal-induced

arthritis - often much

higher than 2000)

‘

200 Most Important Tests of Synovial Fluid

3 Cs

Culture andGram stain

Cell count and differential

Crystal examination ‘

25% ‘

% PMN 25% »50% »75% Variable

Culture/Gram Slain

Examples

Usually positive

Seropositive

Seronegative Gram negative

Crystal arthropathies GC »dilficult to

culture (may have

low WBC)

Trauma Irauma

Hemophilia

S. auieus r m

0A L

Neuropathy

Hypertrophic -

arthropathy

+

RH5 Rheumatology Toronto Notes 2023

Septic Arthritis

Choosing Wisely Canada

Recommendations

1. Do not order ANAas a screening test

in patients without specific signs or

symptoms of SIE or another CTD

2. Do not order an HLA-B27 unless

spondyloarthritis issuspected based

on specific signs or symptoms

3. Do not repeat DEXA scans more

often than every 2 yr

4. Do not prescribe bispliosphonates

for patients at low risk of fracture

5. Do not perform whole body bone

scans (e.g.scintigraphy) for

diagnostic screening for peripheral

and axial arthritis in the adult

population

6. Do not prescribe opioidsfor

management of chronic rheumatic

diseases before optimizing the use

of non-opioid approaches in pain

management

7. Do not delay or avoid palliative

symptom management and advance

care planning for a patient with lifelimiting rheumatic diseases because

they arc pursuing disease-directed

treatment

Definition

• invasion of the joint by an infectious agent

• septic arthritisis a medical emergency;it can lead to rapid joint destruction and has a 10-15% risk of

mortality

• knee and hip are most commonly affected joints, with knee accounting for approximately 50% of cases

. poor prognostic factors:older age, immunocompromised,delay in treatment, previously damaged

joint, and joint prosthesis

Clinical Presentation

• acute onset of:joint pain,swelling, erythema, immobility, and heat

Pathophysiology

• most commonly caused by hematogenousspread of bacterial infection (Gram-positive cocci > Gramnegative bacilli)

Risk Factors

• very young or very old age (>80 yr), portal of entry (IV drug use, hemodialysis), recent infection with

STIs,RA (related to prior joint damage and immunosuppressed state of host), type 2 DM

Investigations

• synovial fluid analysis: VVBC count with differential, crystal analysis, Gram stain, and culture (see

Table 8, RH4)

• blood work: GBG and C&S

• ± endocervical, urethral, rectal, and oropharyngeal swabs (if gonococcal septic arthritisis suspected)

• ± plain x-ray to establish joint baseline and to monitor treatment

Treatment

« consider empiric IV antibiotic therapy untilseptic arthritis is excluded or until cultures come back to

narrow antibiotic choice

• source control and joint decompression

• see Infectious Diseases.1D13 and Orthopaedic Surgery.Septic Joint OR11

Septic arthritis is a medical emergency:

it leadsto rapid joint destruction and

there is a10-15% risk of mortality

Degenerative Arthritis:Osteoarthritis

•see Family Medicine. l-M-l

-l

Definition

•progressive deterioration of articular cartilage and surrounding joint structures caused by genetic,

metabolic, biochemical,and biomechanical factors with secondary components of inflammation

Classification (Based on Etiology)

•primary (idiopathic)

most common, unknown etiology

•secondary

post-traumatic or mechanical

post-inflammatory (e.g. RA) or post-infectious

heritable skeletal disorders (e.g.scoliosis)

• endocrine disorders (e.g. acromegaly, hyperparathyroidism, hypothyroidism)

• metabolic disorders(e.g.gout, pseudogout, hemochromatosis, Wilsons disease, ochronosis)

neuropathic (e.g. Charcot joints), atypical joint trauma due to peripheral neuropathy (e.g. DM,

svphilis)

• AVN

other (e.g.congenital malformation)

Pathophysiology

•the process appears to be initiated by abnormalities in biomechanical forces and/or,less often, in

cartilage

•elevated production of local pro-inflammatory cytokines isimportant in OA progression

•tissue catabolism > repair

•contributing factors (mechanisms unknown): genetics, alignment (bow-legged - varus, knockkneed - valgus), joint deformity (hip dysplasia), joint injury (meniscal or ligament tears),obesity,

environmental, mechanical loading, age, and gender

•considered to be a systemic musculoskeletal disorder rather than a focal disorder of synovial joints

Epidemiology

•most common arthropathy (accounts for -75% of all arthritides)

•increased prevalence with increasing age (35% of 30 y/o, 85% of 80 y/o)

OA of MCPs can be seen in

hemochromatosis or CPPD-related

disease (chondrocalcinosis)

• Hand (DIP, PIP. 1st CMC)

• Hip

• Knee

• IstMTP

• L-spine (L4-L5. L5-S1)

• C-spine

•Uncommon: ankle,shoulder,

elbow. MCP rest of wrist

r

L

-

a

I +

Figure 3.Common sites of joint

involvement in OA

Risk Factors

•genetic predisposition, advanced age, obesity (for knee and hand OA),female, and trauma

RII6 Rhcunialologv Toronto Notes 2023

Table 9. Signs and Symptoms of OA

Signs Symptoms

Joint line tenderness;stress pain t joint effusion

Bony enlargement at affected joints

Malalignmonl/deformily (angulation)

Limited ROM

Crepitus on passive ROM

Inflammation (mild if present!

Periarticular muscle atrophy

Joint pain with motion; relieved with rest

Short delation of stiffness|<1/ 2 h) after immobility, called gelling

Joint inslabilityfbuckling lotion due to liqdmcntousinstability)

Joint locking due to "joint mouse" (boneot cartilage fragment)

loss ol function (e.g. meniscal tear or other internal derangements)

Insidious onset ol pain, localised to affected joints

Fatigue,poor sleep,impact on mood

1.Thumb squaring

2.Heberden's nodes

j.Bouchard's nodes

Figure 4. Hand findings in OA

Table 10. Radiographic Features of Specific Arthritides

Radiographic Hallmarks of Osteoarthritis Radiographic Hallmarks of Inflammatory Arthritis

Jointspace narrowing -typically non- uniform

Subchondrial sclerosis

Subchondrral cyst formation

Osteophytes

Knee, hip. OIP joints

Older, overused joint

Joint space narrowing -typically uniform

Soft tissue swelling

Erosions

Periarticular osteopenia

Rheumatoid:C-spine. carpus, MCP joints. MIP joint

Often younger

Nevr bone formation|i.e. psoriatic arthritis)

Joint Involvement

• generalized OA:3+ joint groups

• asymmetric (knees usually affected bilaterally)

• hand

• DIF (Heberden's nodes = osteophytes > enlargement of joints)

• FIF (Bouchards nodes)

CMC (usually thumb squaring)

Ist MCF (other MCFs are usually spared)

usually presents as groin pain ± dull orsharp pain in the trochanteric area, internal rotation and

abduction are lost first

pain can radiate to the anterior thigh but generally does not go below the knee

initial narrowingof one compartment, medial > lateral:seen on standing x-rays, often patellar-femoral

joint involved

• foot

common in 1st M I F and midfoot

• lumbarspine

very common, especially L4-L5,L5-S1

degeneration ofintervertebral discs and facet joints

• reactive bone growth can contribute to neurological impingement (e.g. sciatica, neurogenic claudication)

orspondylolisthesis(forward or backward movement ofone vertebra over another)

• cervical spine ’

commonly presents with neck pain that radiates to scapula,especially in mid-lower cervical area (C5-C6)

Differential Diagnosis of Elevated ESR

• Systemic inflammatory diseases

• Localized inflammatory diseases

• Malignancy

• Trauma

• Infection

• Tissue injury/ischemia

• hip

• knee

The

E

Radiographic Hallmarks of OA

• Joint space narrowing

• Subchondral sclerosis

• Subchondral cysts

• Osteophytes

Emcise for Osteoarthritis of the Knee:

A CochraneSystematic Review

B r J Sports Med 2015:49:1554 1557

Purpose: 1o determine if land-based therapeutic

exercise s beneficial for people with knee OS in

reducing pain,improving physical function,and

improving quality of life.

Methods: five databases searchedforiandumiied

cl nical trials comparing therapeut < eieitrse with a

noaeiercisc control.

Results, lid studies identified.Resultsfrom 44

trials indicate thatexercise significantly reduced

pam (12 poirtshOO:95% Cl 10 lo15) and improved

physical function (10 pointsHOO:95% Cl S to13)

after treatment. Additionally,13studiesshowed

hpioved quality of life with exercise.12studies

showed reduced knee pern (6 pointed®)

:95% Cl 3 to

19) end 10 studiesshowed i mproved physical function

(3 po nts.'

lOO; 95% Cl 1 to 5) with eiercse 2 6 mo

after treatment.

Conclusion In people w < tli knee 0A. lend based

therapeutic exercise providesshort term benefit that

a susta rned a lew m o after treatrre nt.

Investigations

• Woodwork

• normal CBC.KSR,and CRF

• negative Rl- and ANA

• radiology:4 hallmark findings,see sidebar

• synovial fluid:non-inflammatory (see Table8,RH4)

Treatment

• presently, no treatment alters the natural history of OA

• prevention: prevent injury, weight management, physical activity (maintenance of muscle strength)

non-pharmacological therapy

• weight loss(minimum 5-10 lb loss) ifoverweight

exercise:more effective ifsupervised,often by physiotherapists or in a classsetting;Tai chi isstrongly

recommended for hip/knee OA

self-efficacy and self-management programs(goal-setting, positive thinking,education on the disease)

thermal intervention: heat or cold

• occupational therapy: aids,

splints,cane,walker, bracing

• pharmacological therapy (see Table:35, R H M )

• stepped approach to therapy (local > systemic therapy)

• local therapy:

topical NSAlDs, topical capsaicin ( knee, hand OA)

injections:1A glucocorticoids(knee,hip OA)

systemic therapy:

acetaminophen,oral NSAlDs

centrally acting agents(e.g.duloxetine)

• the following are not recommended based on lack of high-qualilv evidence: opioids and medical

cannabinoids(for pain), hyaluronatcs, platelet-rich plasma,stem cell injections, chondroitin, and

glucosamine

• surgical treatment

total and/or partial joint replacement, joint debridement (not shown to be effective),osteotomy,fusion

r n

L J

+

RH7 Rheumatology Toronto Notes 2023

Seropositive Rheumatic Disease

• diagnosis vs. classification in rheumatology

• diagnostic criteria are selected for sensitivity as opposed to specificity and thus may misdiagnose

some cases

• classification criteria are developed for specificity so well- defined cases can be studied in clinical

trials

modern classification criteria are more sensitive and specific for diagnostic use in studies of

earlier disease

• seropositive arthropathies are characterized by the presence of a serologic marker such as positive Rl

or ANA

• a small subset of the vasculitides (i.e. the small vessel ANCA-associated vasculitides) has a measurable

serological component, but they are often considered a separate entity from seropositive disease by

experts

Table 11. Autoantibodies and Their Prevalence in Rheumatic Diseases

Autoantibody Disease Healthy Controls Comments

BA 8(To

SS 50%

Sit 20%

S-25% Serologic hallmark ol RA

Autoantibodies directed against Fc domain ol IgG

Sensitive In RA (can be negative early in disease course)

RF is associated with more aggressive joint disease and extra -articular features(e.g.

nodules)

May be presentin AHA- positive diseases,often in lower litre

Nonspecific:may be present in IE.IB. hepatitis C,silicosis,sarcoidosis

Specific for RA (94-98%)

May be useful in early disease and to predict persistent and erosive disease:can occur

before clinical disease becomes apparent

Associated with increased extra-articular RA manifestations

Ab against nudearcomponents (DNA. RNA. histones, centromere)

Sensitive but not specific foi SLE

Given high false positive rate - only measure when high pre test probability o( CIO

RF

R A 80'

Anti J

- CCP

SLE 98%

MOD100%

SS 40-70%

CRESI syndrome 60-80%

(Often seen in other CIDs)

SLE 50-70%

High litres1:640 <5%

low litres1:40

Op to 30%.

Prevalenceol non-diseaserelated AHA rises with age

ANA

Anti-dsDHA 0% Specific for SLE (95%)

levels correlate with disease activity (i.e.SLE flare)

Specific but notsensitive lor SIE

Does not correlate with SLE disease activity

It positive,will remain positive through disease course

Seen in SS

Also seen in subacute cutaneous SIE (74%)

May be the only Ab present in ANA negative SIE

Presence in piegnancy increasesrisk of having a child with neonatal lupus syndrome and

congenital heart block

Usually occurs with anti-Ro

Specific for SS and SLE when anti- Ro is also positive

Increasesrisk of having a child with neonatal lupussyndrome

By definition, present in APS

Only small subset of SLE patients develop clinical syndrome ol APS

It positive, will often get a false positive VDRL test

Highly specific lor drug-induced SIE

Anti-Sm SLE «30% |

J

SS 40-95%

SSc 21%

SLE 32%

HA 15%

Anti-Ro (SSA) 0.5%

Anti-La (SSB) SS 40%

SLE 10%

M

APS100%

SLE 31-40%

Antiphospholipid Ab ( LAC. oCLA. «5%

aB2GP)

Anti-Histone Drug-induced SLE 95%

SLE 30 80%

MCI0 20%

0%

0%

Anti RNP High titles present in MCIO:present in many other CIOs (especially SLE)

SLE

Limited SSc (CREST) >80%

Diffuse SSc 26-76%

Anti-Centromere

Anti-Topoisomerasc I (formerly

Scl-70)

Anti-Jol

0% Specific for CRESI.limited cutaneous varianlof systemic sclerosis

Specific for SSc

Increased risk lor pulmonary fibrosisin SSc

less frequent for 0MM

Associated with interstitial pulmonary fibrosis and anti-synthetase syndrome

Specific 80-95% for GPA

Sensitivity can vary between moderate to high depending on technique and timing of

sample. ELISA method|anti-PR3) is more specific than IF

Nonspecific and poor sensitivity (lound in ulcerative colitis. PAN. microscopic polyangiitis.

E6PA, rapidly progressive glomerulonephritis).ELISA method (anti-MPO) is more specific

than IF

0

PM 0MM 0%

c-AHCA Active GPA 90%

MPA 25%

EGPA <5%

6 PA 10

MPA 50-60%

EGPA 50-70%

0%

p- ANCA 0%

r m

L J

0MM 15-20% Specific but not sensitive (not available in all centres)

Perform DAI. test Hb. reticulocyte, leukocyte, platelet count, and antiplatelel Abs

Sensitive and specific

Anti- Mi-2

Ab Against RBCs, WBCs, or Platelets SLE

Anti-Mitochondria Primary biliary cholangitis 0% +

Note:some individuals in thenormal population test positive for RF ardor ANA,but do not have the conditions listed above

RH8 Rheumatology Toronto Xotcs 2023

Connective Tissue Disorders

Table 12. Features of Seropositive Arthropathies

RA SLE Scleroderma Dermatomyositis

CLINICAL FEATURES

History Symmetrica! polyarthritis (small joint

involvement)

Morning stillness|>1h)

Dyspnea on exertion |IL0) in '

30%

Skin lightness, stillness ol fingers. Heliotrope rash (periorbital). Goltron's papules

Raynaud's,heartburn, dysphagia.SOB (violaceous papules over knuckles and IPs)i

on exertion due to pulmonary Hill or poikiloderma

ILO.lenal crisis with new onset Hill or Shawl sign:photosensitivity,macular erythema

hypertensive urgency/emergency over chcsl and shoulder

Proximal muscle weakness » pain,dyspnea on

exertion

Check BP.rash, mouth ulcers. Skin tightness on dorsum ol hand. Heliotrope rash. Goltron's papules, shawl sign,

alopecia. Raynaud's phenomenon, facial skin lightening,telangiectasia. proximal muscle weakness (usually painless),

serositis,s cflused (typically calcinosis, non effused joint,

small) joints (can bemimmal.look inspiratory crackles, features olrightfor soil tissue swelling)

Multisystem disease:rash,

mouth ulcers,photosensitivity,

Raynaud's,alopecia,cardiac

and pulmonary serosilis. CHS

symptoms, glomerulonephiilis

Physical Examination Early:clluscd joints, tenosynovitis,

subcutaneous nodules,

other extra articular manifestations

Late:join!deformities,

bone-on-bone crepitus in advanced

disease, inspiratory crackles

inspiratory crackles

side hear!failure

LABORATORY

Nonspecific t ESRin 50-60%

t CRP

•Platelets

» Hb (chronic disease)

« V/BC (neutropenia rare)

Rf-positive in"

80%

Anli-CCP-posilivein "80%

« ESR

Platelets (autoimmune)

•Hb (autoimmune)

*