YYBC (leukopenia,lymphopenia)

t Cr.proteinuria. RBC casts

a Hb t CRP

Normal WBC

Possibly t Cr. proteinuria

+ Hb

Normal Y/BC

tCK

AIIA-posilivein>90%

Anti- topoisomerase T (diffuse)

Anti- centromere (usually in CRESI. see

Sidebar,CRISI Syndrome. RHI4)

CK elevated in 80%

AHA-positivein 33%

Anti Jo-1.anti Ml 2

Muscle biopsy

Specific AHA-posilive in 98%.

Anli-dsDNA-posilive in 50-70%,

Anti- Sm-positive In 30%,

C3. C4. tola!

hemolytic complement,

false positive VORL (in SLE

subtypes)

EMG

MRI

APIA

* Pulmonary fibrosis,

'

ILD

t Esophageal dysmotility

'

Calcinosis

lEsophageal dysmotility

± ILD

1Calcifications

Radiographs Very early:normal

Early:periarticular osteopenia

Later:join!spacenarrowing

Erosions

Symmelricfconcentric

•110/lung nodules

Hon- erosive

- Osteopenia

t Soft tissue swelling

Rheumatoid Arthritis

Definition

• chronic,symmetric,erosive synovitis ofperipheral joints (c.g. wrists, MCPs,Ml'Hs)

• characterized by inflammatory joint disease ± a number of extra-articular features

• 1 joint with definite clinical synovitis (swelling) not explained by another disease

RA is art independent risk factor for

atherosclerosis and CV disease.RA

is associated with increased overall

mortality/morbidity from all causes:

CV disease,neoplasm (especially

lymphoma).Infection Table 13. 2010 ACR /EULAR Classification Criteria for RA

(score based algorithm: add score ol categories A 0; n score ol 6110 for dcfinilc RA)

Criteria Score Comments

A.Joint involvement {swollen or lender)

1large joint (shoulders, elbows,hips,knees,and ankles)

2-10 large joints

1-3 small joints (MCPs,PIPs. wrists, 2nd-Sth MIPs)

4-10 small joints

>10 joints (at least 1small joint)

6. Serology

Negative RE and negative Anli CCP

Low- positive RF or low-positive Anti-CCP (<3x ULN)

High-positive RF or high-positive Anli-CCP (>3x ULH)

C. Acute phase reactants

Normal CRP and normal ESR

Abnormal CRP and abnormal ESR

0.Duration of symptoms

«6 wk

iSwk

0 Common Presentation

• Morning stiffness >1 h. improves

with use

• Symmetric joint involvement

• Initially involves small joints of hands

and feet

• Constitutional symptoms

1

2

3

S

Total score of e6:definite RA

Musi have rf joint with definite clinical swelling,nol belter

explained by another disease

0

2

3

0

1

r n

LJ

0

1

Arthritis Rheum 2010:62:2569-2581

+

RH9 Rheumatology Toronto Notes 2023

Pathophysiology

• autoimmune disorder, unknown etiology; may have genetic and environmental component

• complex genetic and environment interactions lead to disruption of immune tolerance, ultimately

resulting in synovial inflammation

• genetic predisposition: HLA-DR4/DR 1 association (93% of patients have either HLA type),

cytokine promoters, T cell signaling

• environmental predisposition: induction of enzymes that convert arginine to citrulline caused

by environmental stress (cigarette smoking), propensity for immune reactivity to neoepitopes

created by protein citrullination

• inflammatory process causes transformation ofsynovium into an invasive pannus tissue that

degrades cartilage and bone with absence of repair

elevated TNF level increases osteoclasts and decreases osteoblasts at the site of inflammation

(results in periarticular osteopenia)

upregulation of RANK ligand increases osteoclast-mediated destruction

Epidemiology

• most common inflammatory arthritis: prevalent in 1% of population

• F:M=3:1

• age of onset 20-40 yr

Clinical Presentation

• variable course of exacerbations and remissions

• morning stiffness >1 h, improves with use, worsens with rest

• polyarthritis:symmetric joint involvement (tender, swollen),small joints affected, most commonly in

hands and feet (MCF, PIP, MTP)

• constitutional s

• extra-articular

• limitation of function and decrease in global functional status

• complications of chronic synovitis

signs of mechanical joint damage: loss of motion, instability, deformity, crepitus, joint deformities

swan neck deformity, boutonniere deformity

ulnar deviation and subluxation of MCP, radial deviation of wrist joint

hammer toe, mallet toe, claw toe

flexion contractures

• atlanto-axial and subaxial subluxation

C-spine instability

- neurological impingement (long tract signs)

- difficult/dangerous intubation: risk of worsening subluxation and damage to spinal cord

• limited shoulder mobility, spontaneous tears of the rotator cuff leading to chronic spasm

• tenosynovitis -> may cause rupture of tendons

• carpal tunnel syndrome

• ruptured Baker’

s cyst (outpouching of synovium behind the knee); presentation similar to acute deep

vein thrombosis (DVT)

• poor prognostic factors include: young age of onset, high RF litre, elevated ESR, activity of >20 joints,

and presence of extra-articular features

• Wrist, not 1st CMC

• Elbow

• Shoulder

• Knee

• Ankle

• MTP

• C-spine

*

o

-

Figure 5. Common sites of joint

involvement in RA

ymptoms: profound fatigue, depression, myalgia, weight loss

features

Boutonniere Deformity

Swan Neck Deformity

Claw Toe

Table 14. Extra-Articular Features of RA Classified by Underlying Pathophysiology

Hammer Toe System Vasculitic Lymphocytic Infiltrate

Skin Periungual infarction, cutaneous ulcers,

palpable purpura

Episcleritis,sderitis

Rheumatoid nodules(may have vasculitic

component)

Keratoconjunctivitissicca

Xerostomia. Haslilmoto'sthyroiditis(see

Endocrinology.E31)

Peri-/myocarditis.valvular disease, conduction

defects

Pulmonary fibrosis, pleural effusion, pleuritis,

pulmonary nodules

i

Ocular

Head and Heck Mallet Toe

Cardiac Figure 6. Joint deformities

Pulmonary

Neurologic Peripheral neuropathy:sensory stockingglove, mononeuritismultiplex Syndromes in RA

• SS (common):keratoconjunctivitis

sicca and xerostomia (dry eyes and

mouth)

• Caplan's syndrome (very rare):

combination of RA + pneumoconiosis

that manifests as multiple

intrapulmonary nodules

• Felly's syndrome (rare):arthritis,

splenomegaly, neutropenia

Hematologic

Renal

Splenomegaly,neutropenia (Felty'ssyndrome)

Amyloidosis- caused by accumulation of

abnormal proteins

j

Classification of Global Functional Status in RA

• Class I: able to perform usual activities of daily living (self-care, vocational, avocational)

• Class II: able to perform self-care and vocational activities, restriction of avocational activities

• Class III: able to perform self-care, restriction of vocational and avocational activities

• Class IV:limited ability to perform self-care, vocational, and avocational activities

+

RH10 Rheumatology Toronto Notes 2023

Investigations

• Woodwork

RF:80% sensitivity but non-specific; may not be present at onset of symptoms; levels do not

correlate with disease activity

« can be associated with more erosions, more extra-articular manifestations, and worse

function

anti-CCP:80% sensitivity but more specific (94-98%); may precede onset ofsymptoms

• increased disease activity is associated with decreased Hb (anemia of chronic disease) and increased

platelets, HSR, and CRP

• imaging

bilateral hands/wrists, ankles/feet x-ray

first change is periarticular osteopenia, followed by erosions

(1-spine x-ray (may be normal at onset, required for preoperative assessment in long-standing

disease)

U/S (with power Doppler) -often changes of synovitis/erosion noted in advance of those seen on

plain x-ray

MR1 may fee used to image hands to detect early synovitis and erosions

MR1T’l inflamed synovium is hypointense and hyperintense on T2; bone marrow edema can be

seen as well as areas of increased uptake gadolinium contrast

Poor prognostic features of RA include:

young age of onset, high RF litre,

elevated ESR, activity of >20 joints,and

presence of e xtra-articular features

Side Effects of Steroids

• Weight gain

• Osteoporosis

. AVN

• Cataracts, glaucoma

. PUD

• Susceptibility to infection

• Easy bruising

. Acne

. HTN

. Hyperlipidemia

. Hypokalemia, hyperglycemia

• Mood swings

Treatment

• goals of therapy: remission or lowest possible disease activity

key is early diagnosis and early intervention with DMARDs

“window of opportunity”

= early treatment within first 3 mo of disease may allow better control/

remission

assess poor prognostic factors at baseline (Rl'

-positive,functional limitations,and extra-articular

features)

• behavioural

exercise program: active,gentle ROM and isometric exercise during flares; aquatic/aerobic/

strengthening exercise between flares

job modification, assistive devices as necessary

interventionsto reduce cardiovascular disease,smoking cessation,lipid control

• pharmacologic: alter disease progression

DMARDs and biologies (not analgesics or NSAlDs) can alter the course of RA

• DMARDs

treatment with DMARDs should be started assoon as RA diagnosisis made and should be

aimed at reaching sustained remission

MIX is the gold standard and is first-line unless contraindicated

- prior to M I X therapy:CBC profile, liver enzymes(ALT), Cr (Cr clearance), hepatitis B

and Cserology, and a CXR should be done

- monitor and if inadequate response (3-6 mo) -> combine orswitch

- consider combination therapy to MTX if patients have poor prognostic features or high

disease activity

- therapy includes:hydroxychloroquine,SSZ, leflunomide, biologies

- contraindicationsinclude liver disease,significant alcohol intake, pregnancy,and

lactation

- if contraindication to MTX, then hydroxychloroquine, SSZ, and/or leflunomide should

be considered with the former being considered as a weaker agent and the latter as more

potent

• biologies (bDMARDs)

should be used if inadequate response to DMARDs

should be combined with DMARD therapy (initiating with combination therapy is associated

with faster response rates and longer duration of effect)

first-line (anti-TNF) options:infliximab, etanercept, adalimumab, golimumab, and

certolizumab

non-anti

-TNl agents include anakinra (almost never used for RA), abatacept, rituximab, and

tocilizumab

reassess every 3-6 mo and monitor disease activity (predominantly via assessing swollen joint

count)

JAR inhibitors (including tofacitinih and upacitinib) are oral small molecule synthetic

DMARDs; used if other DMARDs and biologies fail

• pharmacologic:supportive to reduce inflammation and pain

NSAlDs

individualize according to efficacy,tolerability, and comorbidities

contraindicated /cautioned in some patients(e.g. PUD, ischemic cardiac disease, pregnancy,

CKD, anticoagulant use)

add acetaminophen for synergistic pain control

corticosteroids

local:injections to control symptoms in a specific joint

DMARDs. prednisone, and biologies

(bOMARDs) but not analgesics or

NS AIDs. alter the course of RA

r -)

L J

+

RH11 Rheumatology Toronto Notes 2023

systemic (oral prednisone) or 1M

- low dose (5-10 mg/d) useful forshort-term to improve symptoms if NSAlDs are

ineffective and to bridge gap until DM ARDs take effect

- do baseline DEXA bone density scan and consider bone supportive pharmacologic

therapy (e.g. bisphosphonates) if using corticosteroids 7.5 mg/d >3 mo, particularly in

those with other risk factors

- cautions/contraindications: active infection,TB, osteoporosis, H

'

l

'

N, gastric ulcer, DM

•surgical

• indicated for structural joint damage

surgical options include:synovectomy, joint replacement, joint fusion, reconstruction /tendon

repair

Follow-Up Management and Clinical Outcomes

•clinical reassessment every mo initially, then 3-6 mo ifstill ongoing activity, then 6-12 mo after

inflammation has been suppressed

•examine jointsfor active inflammation -if active, consider adjusting medications, physical therapy/

occupational therapy (PT/OT)

• RA patients should be screened and managed for cardiovascular disease given increased risk

• if assessment reveals joint damage - consider analgesia, referral to PT/OT,surgical options

•outcome depends on disease activity, joint damage, physical functionalstatus, psychological health,

and comorbidities

•functional capacity is a useful tool for determining therapeutic effectiveness; many tools for

evaluation have been validated

• patients with RA have an increased prevalence of other serious illnesses:infection (e.g. pulmonary,

skin, joint), osteoporosis, mental health disorders,renal impairment, lymphoproliferative disorders,

cardiovascular disease (correlates with disease activity and duration)

• risk of premature mortality, decreased life expectancy (most mortality not directly caused by RA)

Systemic Lupus Erythematosus

• see Nephrology, NP26 Diagnostic Criteria of SLE

Definition

• chronic autoimmune disease of unknown etiology resulting in multi-system inflammation

• characterized by production of autoantibodies and diverse clinical manifestations

MD SOAP BRAIN

Malar rash

Discoid rash

Scrositis

Oral ulcers

ANA

Photosensitivity

Blood

Renal

Arthritis

Immune

Neurologic

Table 15. Classification Criteria of SLE*

Entry criterion:ANA at a titre of >1:80 and Additive Criteria

1. Do not count criterion il there is a more likely explanation than SLE

2. Occurrence ola criterion on atleast one occasion is sufficient

3. Within each domain,only the highest weighted criterion is counted towards the total score

Clinical Domains and Criteria Score

Constitutional

Hematologic

Fever

leukopenia

thrombocytopenia

Autoimmune hemolysis

Delirium

Psychosis

Seiture

Non-scarring alopecia

Oral ulcers

Subacute cutaneous or discoid lupus

Acute cutaneous lupus

Pleural or pericardial effusion

Acute pericarditis

Joint involvement

Proteinuria (»0.5 g!24 h)

Renal biopsy Class II or V lupusnephritis

Renal biopsy Class IIIor IV lupus nephritis

2

3

4

A Systematic Review of Guidelines lor Managing

Rheumatoid Arthritis

EMC Rheumatol 2019:3:42

Five generalprinciples formanagement:

• Start OMAROs assoon as possible following the

diagnosis.

• The best ir tie’ treatment is MIX.

• Monitor disease activity regularly.

• Bio'og csshould be initiated in patients with

pertstentlyactive disease despite MIX treatment.

• Goals ol treatment should be aimed at low disease

activity or remission.

4

Neuropsychiatric 2

3

S

Mucocutaneous 2

2

4

6

Serosal 5

Environment

Stress, viruses, sun

6

Musculoskeletal 6

Renal

Genetic Hormonal

4 HLA

8 T cells irugs

10 r T

L J

Immunology Domains and Criteria Score

Antiphospholipid antibodies

Complement proteins

Anti- cardiolipin antibodies or Anti-|!2PG1 antibodies or lupus anticoagulant 2

Low C3 or low C4

lowC3andlswC4

Anh- dsDHA or Anti Srn antibodies

I

—Formation of —,

Auto-Ab

Cytotoxic Ah Immune complexes

3

4 +

SLE specific antibodies 6 i

Cell damaye/dealh Inflammation

’Classification of SLE requires total score of >10 with>1clinical criterion

Sindhu R.Johnson. Thomas Dorner.Ray Naden. et aL Arthritis & Rheumatology (71,9),p.1400. copyright 2020.Modilied byPermission of John

Wiley andSons Figure 7. Multi-factorial etiology of

SLE

RH12 Rheumatology Toronto Notes 2023

Etiology and Pathophysiology

• production of cytotoxic autoantibodies and immune complex formation

• multi-factorial etiology

• genetics

common association with HLA-B8/DR3;

-10% have positive family history

• strong association with defects in apoptotic clearance > fragments of nuclear particles captured

by antigen- presenting cells > develop ANAs

cytokines involved in inflammatory process and tissue injur)': BlyS, 1L-6, 1L-17, IL-18, TNl-

'

-a

• environment

UV radiation, cigarette smoking, infection, vitamin D deficiency, silica dust

• estrogen

• increased incidence after puberty, decreased incidence after menopause

• men with SLE have higher concentration of estrogenic metabolites

increased risk of SEE associated with use of combined oral contraceptive pills and hormone

replacement therapy

• infection

viral (non-specific stimulant of immune response)

• drug-induced

• antihypertensives (hydralazine), anticonvulsants (phenytoin), antiarrhythmics (procainamide),

isoniazid, biologies

anti-histone Abs are commonly seen in drug-induced SLE

symptoms resolve with discontinuation of offending drug

Drug-Induced SLE

Often presents atypically with systemic

features and serositis;usually associated

with anti

-histone Ab

Epidemiology

• prevalence: 0.05% overall

• E:M = I0:I

• age of onset in reproductive yr (15-45)

• more common and severe in Hispanic and Asian individuals, and individuals of African descent

• bimodal mortality pattern

• early (within 2 yr)

active SLE, active nephritis, infection secondary to steroid use

late

inactive SLE, inactive nephritis, atherosclerosis likely due to chronic inflammation

Clinical Presentation

• characterized by periods of flares and remission

Table 16. Signs and Symptoms of SLE

System Symptoms

Systemic

Hematologic

fatigue, malaise,weight loss,fever, lymphadenopathy

Anemia ol chronic disease, hemolytic anemia, leukopenia, neutropenia, thrombocytopenia, pancytopenia,

thrombosis,splenomegaly

Hematuria,proteinuria (glomerulonephritis).HTN. peripheral edema,renal failure

Photosensitivity, malar rash, discoid rash,oral ulcers, alopecia (hair loss), purpura, panniculitis (inflammation of

subcutaneouslat and muscle tissue), urticaria

Polyarthralgias, polyarthritis, myalgias.AVN.reducible deformities of hand (Jaccoud's arthritis)

Keratoconjunctivitissicca,episcleritis,sderitis, cytoid bodies (cotton wool exudates on fundoscopy -infarction

ol nerve cell layer of retina)

Pericarditis.CAD.nonbacterial endocarditis(Libman-Sacks).myocarditis

Note:SLEis an independent risk factor for atherosclerosis and CAD

Raynaud's phenomenon, livedo reticularis(mottled discolouration of skin due to narrowing of blood vessels,

characteristic lacy or net-like appearance), vasculitis

Pleutilis, ILD.pulmonary HIN. PE.alveolar hemorrhage

Pancreatitis. SLE enteropathy, hepatitis, hepatomegaly, dysphagia, esophagitis, intestinal pseudo-obstruction,

peritonitis, mesenteric vasculitis

Cardiac: coronaiy vasculitis, malignant HIN.tamponade

Hematologic:hemolytic anemia, neutropenia,thrombocytopenia.TIP, thrombosis

Neurologic:seizures.CVA.stroke

Respiratory: pulmonary HIN. pulmonary hemorrhage, emboli

Raynaud's Phenomenon

Vasospastic disorder characteristically

causing discolouration of fingers and

toes (white

*

blue »red)

Classic triggers:cold and emotional

stress

Renal

Dermatologic

Musculoskeletal

Ophthalmic

Cardiac

Vascular

Respiratory

Gastrointestinal

Neurologic/Psychiatric

lifo/Organ-Ihrcalcning

Investigations

• ANA (98% sensitivity,but poor specificity -> used as a screening test; ANA titres are not useful to

follow disease course, see (.

'

/loosing Wisely Recommendations, RH5 )

• anti

-dsDNA and anti-Sm are specific (95-99%)

• anti-dsDNA titre and serum complement (C3, C4) are useful to monitor treatment response in patients

who are clinically and serologically concordant (anti-dsDNA increases, C3and C4 decrease with

disease activity)

• AFI.A (anti-cardiolipin Ab, SLE anticoagulant, anti

-|52 glycoprotein-1 Ab), may cause increased risk of

clotting and increased aPT'T

ri

L J

Consider SLE in a patient who has

involvement of 2 or more organ systems +

RH13Rheumatology Toronto Notes 2023

Treatment

• goals of therapy

aim for remission, prevention of flares

• hydroxychloroquine ± glucocorticoid

treat early and avoid long-term steroid use, if unavoidable see Endocrinology, E4b for

osteoporosis management

if high doses ofsteroids are necessary for long-term control, taper when possible and add

immunosuppressive therapies(MTX, azathioprine, mycophenolate)

• treatment is tailored to organ system involved and severity of disease

• moderate refractory disease can be treated with belimumab

all medications used to treat SLH require periodic monitoring for potential toxicity

• dermatologic

• sunscreen, avoid UV light and estrogens

• topical steroids, hydroxychloroquine

• musculoskeletal

NSAlDs ± gastroprotective agent for arthritis(also beneficial for pleuritis and pericarditis)

• hydroxychloroquine improveslong-term control and prevents flares

bisphosphonates, calcium, vitamin D to combat osteoporosis

• other considerations

smoking cessation

• immunizations (influenza); live vaccines are generally not recommended

• for women with APLA, avoid estrogen-containing contraceptives because of increased risk of

thrombosis

• organ-threatening disease

high-dose oral prednisone or IV methylprednisolone in severe disease

• steroid-sparing agents:azathioprine, MTX, mycophenolate (can use mofetil orsodium)

• IV cyclophosphamide for serious organ involvement (e.g. cerebritis or lupus nephritis) for clinical

features of lupus nephritis

refractory disease can be treated with rituximab

The arthritis of SLE can be deforming

but it is non-erosive (in contrast to RA)-

called Jaccoud'

s arthritis

Antiphospholipid Antibody Syndrome

Definition

• multi-system vasculopathy manifested by recurrent thromboembolic events,spontaneous abortions,

and thrombocytopenia

• circulating antiphospholipid autoantibodies interfere with coagulation

• primary APS:occurs in the absence of other disease

• secondary APS: occurs in the setting of a connective tissue disease (including SLH), malignancy, drugs

(hydralazine, procainamide, phenyloin, interferon,quinidinc), and infections ( HIV,TB, hepatitis C.

‘

.

infectious mononucleosis)

• catastrophic APS:development within 1 wk of small vessel thrombotic occlusion in >3organ systems

with positive APLA (high mortality)

Manifestations of APLA

• Thromboembolic events

• Spontaneous abortions

• Thrombocytopenia

• Associated with livedo reticularis,

migraine headaches

Arterial and venous thrombosis are

usually mutually exclusive

Table 17. Classification Criteria of APS*

Criteria Description

CLINICAL

Vascularthrombosis One or more clinical episodes of arterial, venous, or small vessel thrombosis in any tissue or organ

Must be conlrrmcd by imaging or histopalliology

1. >1death ol morphologically normal fetus (confirmed by U /S or fetal exam) at >10 wk gestation:OB

2. >1premature birth ol morphologically normal neonate belore 34 wit gestation doe to eclampsia,

preedampsia.or placental insufficiency;OR

3. >3 consecutive spontaneous abortions -

'

10 wk gestation (excluding maternal anatomic and hormonal

abnormalitres or palernal/mateinal chromosomal causes)

Pregnancy morbidity

Labs must be positive on 2 occasions,at least 12 wk apart

Present in plasma,detected according to the guidelines of the International Society on Ihrombosisand

Haemostasis

LABORATORY

See Landmark Rheumatology Trials.

RH32lor more information on the

TULIP-2 trial. It examined the efficacy of

anifrolumab for the treatment of SLE.

Lupus anticoagulant

Anti cnrdiolipin Ab IgG and/or IgM. plasma or serum, present in medium high Hire (i.e. >40 CPI or MPl, or *99lh percentile),

measured by ELISA

Anti-p2 glycoprotein !Ab IgG and/or IgM.plasma or serum,present in high litre (i.e.>99th percentile), measured by ELISA

*1clinicill and1laboratory criteria must be present

J ThrombHaemost 200G;4:29D- 30G

Clinical Presentation

• see clinical criteria ( Table 17)

• hematologic

• thrombocytopenia, hemolytic anemia, neutropenia

• dermatologic

» livedo reticularis, Raynaud’s phenomenon, purpura, leg ulcers,gangrene

+

RHl I Rheumatology Toronto Notes 2023

Treatment

• thrombosis

• lifelong anticoagulation with warfarin

target1NR 2.0-3.0 for first venous event, >3.0 for recurrent event, target 1NR >3.0 for arterial

event, or target 1NR 2.0-3.0 + ASA

• recurrent fetal loss

• heparin/low molecular weight heparin ± ASA during pregnancy

• catastrophic APS

• high-dose steroids, anticoagulation, cyclophosphamide, plasmapheresis

Scleroderma (i.e. Systemic Sclerosis)

Definition

• a non-inilammatory autoimmune disorder characterized by widespread small vessel vasculopathy,

production of autoantibodies, and fibroblast dysfunction causing fibrosis CREST Syndrome

Cal cinosis

Raynaud's phenomenon

Esophageal dysmotility

Sderodactyly

Telangiectasia

Sclorodortna

li e.systemic sclerosis)

I

*

Localized

(no involvement ol internal organs)

•Mostly children and young adults

Generalized

I

I

T

*

Limited systemic sclerosis

•Skin sclerosis restricted to

hands,face, neck

•3rd to 4th decade

•Pulmonary HTN common

•CREST

Diffuse systemic sclerosis

•Widespread skin disease

( proximal to wrist, can

involve trunk), tendons

•Early visceral involvement

(renal, pulmonary fibrosis)

Scleroderma isthe most common cause

of secondary Raynaud's phenomenon

Morphea

•Hard oval patches

on the skin

Linear

•Line of thickened skin

Figure 8. Forms of scleroderma

Etiology and Pathophysiology

• idiopathic vasculopathy (not vasculitis) leading to atrophy and fibrosis of tissues

characterized by several hallmark pathogenic features:small vessel vasculopathy resulting in

tissue hypoxia, production of autoantibodies, and fibroblast dysfunction leading to increased

deposition of extracellular matrix

• resembles malignant HTN

• lung disease is the most common cause of morbidity and mortality

Cyclophosphamide vs. Mycophcoolitc Mofctil in

Scleroderma lung Disease

L arret Respir Wed 2016;4:708-719

Study Double ; 'd. randomized, parallel group

MI

Purpose: locompare the toxicity and efficacy of

cyclophosphamide vs. mycoptierrolate mofetil on

lung function.

Results: In both treatment groups,(be adjusted

percent predctedfVC Improved from baseline In 24

no.Mycophenotate mofetil was associated with less

tonicity and was better tolerated.

Conclusion: Treatment of SSc-ltD with

mycophenolatemofetil for 2 yr oe cyclophosphamide

lor1yr both result in improved long function.

However,mycophenolatemofetil isthe current

preference for treatment of SSc-tlO due to its better

Mtnbllity.

Table 18. The American College of Rheumatology (ACR)/European League Against Rheumatism

(EULAR) Criteria for the Classification of Scleroderma*

Item Sub-item Score

1.Skin thickening of fingers of both hands

extending proximal to the MCP (sufficient

criterion)

2.Skin thickening of the lingers

9

Fully lingers

Sderodactyly

Oigital tip ulcers

fingertip pilling scats

2

3.fingertip lesions 4

4. Telangiectasia 2 Raynaud's Phenomenon DDx

5.Abnormal nailfoldcapillaries

6.Pulmonary arterial HTNiILD (max score 2)

3 COLD HAND

Cr yoglobulins/Cryofibrinogens

Obstruction/Occupational

Lupus erythematosus, other connective

tissue disease

DM/Drugs

Hematologic problems (polycythemia,

leukemia, etc.)

Arterial problems(atherosclerosis)/

Anorexia nervosa

Neurologic problems (vascular tone)

Orscasc of unknown origin (idiopathic)

Pulmonary arterial HTN 2

ILD

7.Raynaud’s phenomenon 2

8.Scleroderma-related Ab Anti-centromere 2

Anti- toporsomcraseI

Anti RNA polymeraseIII

'Score ol >9 issufficient to classify a patient as having definite scleroderma (sensitivity 0.95.spedlicity 0.93)

Epidemiology

• I :M=3- 4:I , peaking in 5th decade

• associated with HLA-DR1 and environmental exposures (silica, epoxy resins, toxic oil,aromatic

hydrocarbons, polyvinyl chloride)

• limited systemic sclerosis has a higher survival prognosis (>70% at 10 yr) than diffuse systemic

sclerosis (40-60% at 10 yr)

r m

L J

+

RHl5 Rheumatology Toronto Notes 2023

Clinical Presentation

Table 19. Clinical Manifestations of Scleroderma Features of Pathologic Raynaud’s

Syndrome

• New onset

• Asymmetric

• Precipitated by stimuli other than

cold or emotion

• Associated with distal pulp pitting or

tissue reabsorption

• Digit ischemia

• Capillary dilatation by capillaroscopy

System Features

Dermatologic Painless non pitting edema »skin tightening

Ulcerations, calcinosis, periungual erythema, hypo/hyperpigmenlation. pruritus,telangiectasias

Characteristic lace: mask-like (acies with light lips, beak nose,radial perioral furrows

Raynaud'

s phenomenon •» digital pits, gangrene

Thrombosis

Distal esophageal hypomolilily » dysphagia

Loss ollower esophageal sphincter lunction * gastroesophageal reflux disease (GERD), ulcerations,strictures

Small bowel hypomotility *bacterial overgrowth, diarrhea,bloating,cramps,malabsorption, weight loss

Large bowel hypomolilily

-

wide mouth diverticula are pathognomonic radiographic finding on barium study

Mild proteinuria,Cr elevation, KIN

"Scleroderma renal crisis" (10-15%) may lead to malignant arterial HIN, oliguria, and microangiopathic hemolytic

anemia

Interstitial librosis. pulmonary HTN. pleurisy, pleural effusions

lelt ventricular dysfunction, pericarditis, pericardial effusion, arrhythmias

Polyarthralgias

"Resorption of distal tufts” (radiological finding)

Proximal weakness 2° to disuse, atrophy, low grade myopathy, tendon friction rubs

Hypothyroidism

Vascular

Gastrointestinal (

-90%)

Renal

Pulmonary (

-SOS)

Cardiac

Musculoskeletal

Endocrine

Investigations

•blood work

CBC.Cr. ANA

anti-topoisomerase l /anti-Scl-70 antibody:specific but notsensitive for diffuse systemic sclerosis

anti-centromere antibody:favours diagnosis of CREST (limited systemic sclerosis)

• anti-RNA polymerase 111 antibody: associated with severe skin involvement, increased risk of

renal crisis

•P1-

'

T

assess and monitor for 1LD

•echocardiogram

• rule out pulmonary HTN

•imaging

baseline CXR to rule out ILL)

Treatment

• dermatologic

• good skin hygiene

• low-dose prednisone (>20 mg may provoke renal crisis if susceptible). M I X (limited evidence)

• vascular

Raynaud’s:keep hands and body warm,smoking cessation

vasodilators (CCBs,local nitroglycerine cream,systemic PGE2 inhibitors, PDE5 inhibitors),

fluoxetine

• gastrointestinal

GERD:PPls are first-line, then H2-receptor antagonists

• small bowel bacterial overgrowth: broad spectrum antibiotics (tetracycline, metronidazole)

motllltydisturbanccs: prokinetics

• renal disease

ACE inhibitor for hypertensive crisis

see

• pulmonary

early interstitial disease: mycophenolate mofetil (less toxicity) or cyclophosphamide

pulmonary HTN:vasodilators (e.g. bosentan, epoprostenol, and PDE5 inhibitors)

rapidly progressive disease at risk of organ failure: consider hematopoietic stem cell

transplantation

• cardiac

pericarditis:systemic steroids

• musculoskeletal

arthritis: NSAIDs

• myositis:systemic steroids

r 1

+

RH16 Rheumatology Toronto Notes 2023

Inflammatory Myopathy 0

Definition

• autoimmune diseases characterized by proximal muscle weakness ± pain

• muscle becomes damaged by a non-suppuralive lymphocytic inflammatory process

• associated with malignancy

increased risk of malignancy: age >50, DMM > PM, elevated CK, peak incidence of malignancy

at onset of myositis or within 1st yr, dysphagia, ulcerative skin lesions, cutaneous vasculitis,

anti-P155/140 antibody

• associated with other CTDs, Raynaud'

s phenomenon, autoimmune disorders

Classification

• PM/DMM

• adult and juvenile forms

• newly characterized entities:

focal necrotizing myopathy (secondary to statin)

amyopathic myopathy (anti-synthetase syndrome, MDA-5 syndrome)

Inclusion Body Myositis

• age >50, M>1-

'

,slowly progressive, vacuoles in cells on biopsy

• patient unresponsive to treatment

• distal and proximal muscle weakness

• muscle biopsy positive for inclusion bodies

POLYMYOSITIS/DERMATOMYOSITIS

Definition

• PM and DMM arc idiopathic inflammatory myopathies characterized by inflammation and proximal

skeletal muscle weakness

• notably, DMM often presents with characteristic skin manifestations Signs of DMM

Cottron's papules and Gottron'ssign ate

pathognomonic of DMM (occur In 70%

Etiology of patients)

and Pathophysiology

• PM is a T cell-mediated process with myocytes being the primary target, characterized by focal

endomysial infiltrates (CD8+ T cells) surrounding muscle fibres, found in adults

• DMM is a complement mediated process with perivascular inflammatory infiltrates (CD4+ T cells >

CD8+ T cells) leading to perifascicular atrophy of muscle fibres

Clinical Presentation

• progressive symmetrical proximal muscle weakness (shoulder and hip) developing over wk to mo;

difficulty lifting head off pillow,arising from chair, climbing stairs

• dermatological

DMM has characteristic dermatological features(1

'

>M, children and adults)

Gottron’s papules

- pink-violaceous,flat-topped papules overlying the dorsal surface of the MCP and IP

Gottron’ssign

- erythematous,smooth orscaly patches over the extensorsurface of elbows, knees, or

medial malleoli

heliotrope rash: violaceous rash over the eyelids; usually with edema

shawl sign: poikilodermatous, erythematous rash over neck, upper chest, and shoulders

mechanic'

s hands: dry, crackled lesions on palmar and lateral surfaces of digits, especially

over the pulp space, also seen in a subtype of myositis called anti

-synthetase syndrome

periungual erythema

Malignancies Associated with DMM

- Breast

. Lung

. Colon

• Ovarian

• cardiac

• arrhythmias, congestive heart failure, conduction defect, ventricular hypertrophy, pericarditis

• gastrointestinal

• oropharyngeal and lower esophageal dysphagia, reflux

• pulmonary

• weakness of respiratory muscles, ILD, aspiration pneumonia

Investigations

• general lab tests:CK, CBC, ESR and/or CRP,TSH

• serologic tests:ANA, anti-)o-l (DMM), anti-Mi-2, anti-SRP (usually not available at commercial labs)

• imaging:MR1 may be used to localize biopsy site

• EMG:characteristic findings of muscle inflammation and damage

• muscle biopsy can aid in diagnosis, however not needed in those with classic skin findings and muscle

weakness

r ->

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RH17 Rheumatology Toronto Notes 2023

Treatment

• non-pharmacological treatment

P I and OT,speech-language therapy for esophageal dysfunction

• pharmacological treatment

high-dose glucocorticoid (e.g.prednisone 1 mg/kg/d) usually not exceeding 80 mg daily and slow

taper after patient improvement (

-6 wk)

• add immunosuppressive agents (azathioprine,MIX)

• 1V1G if severe or refractory

hydroxychloroquine for DMM rash

• malignancy surveillance

• detailed history and physical (breast, pelvic, and rectal exams)

• CXR, abdominal and pelvic VIS,fecal occult blood, Fap test, mammogram ± CT scan (thoracic,

abdominal, pelvic)

Sjogren’s Syndrome

Definition

• autoimmune condition characterized by dry eyes (keratoconjunctivitissicca/xerophthalmia) and dry

mouth (xerostomia), caused by lymphocytic infiltration ofsalivary and lacrimal glands

• exists on a spectrum and may evolve into a systemic disorder (20%) with diminished exocrine gland

activity and extraglandular features

• primary and secondary forms (associated with RA, SLH. DMM, and HIV )

• prevalence 0.5%, F»M at 10:1,40-60 yr

• increased risk of non-Hodgkin’

slymphoma (lifetime incidence 6-7%)

Table 20. The American College of Rheumatology (ACR)ZEuropean League Against Rheumatism

(EULAR) Classification Criteria for Primary Sjogren’s Syndrome (at least 1inclusion criteria, no

condition in exclusion criteria, score >4)

Criteria Score Comments

iry gland biopsy with focal lymphocytic 3

with focusscorea1foois.'

4mmi

Focusscores are histopathologic grading systems

Strongly associated with phenotypic ocularand serological

components of Sjogren'

s

Labial saliva

sialadenitis

Anti-SSA- or Ro-positive

Ocular staining score >5 (or van Gi jsterfeld score >4 1

on at least one eye)

Schirmer'

stest <5 mm/5min on at least one eye 1

Unstimulated whole saliva flowrate <03mL/min 1

3

Ocularstaining score based on fluorescein dye examination of

conjunctiva and cornea to determine clinical changes

Inclusion criteria (positive response to at least one question):1) Have you had daily,persistent,troublesome dry eyesfor more than 3 mo? 2) Do

you have a recurrentsensation of sand or gravel in the eyes? 3) Do you use tear substitutes more than 3 bmes a d? 4) Have you had a daily feeling

of dry mouth for more than 3 mo? 5) Do you frequently drink liquidsto aid in swallowing dry food?

Exclusion criteria include prior diagnosis of any of the foi:owing conditions:1) History of head and neck radiabon treatment.2) Active hepatitis C

infection (with confirmation by polymerase chain reacton.3) AIDS.4)Sarco.dosis.5) Amyloidosis.6) Graftversus- host disease, 7) lgG 4-related

disease

Arthritis Rheumatol. 2017:69:35-45

Clinical Presentation

• “sicca complex":dry eyes (keratoconjunctivitissicca/xerophthalmia),dry mouth (xerostomia),

complicated by staphylococcal blepharitis

• dental caries, oral candidiasis, angular cheilitis (inflammation and Assuring at the labial commissures

of the mouth)

• extra-glandular manifestations

fatigue, low-grade fever

• autoimmune thyroid dysfunction

• arthralgias, arthritis

• subclinical diffuse ILD. xerotrachea leading to chronic dry cough

• renal disease, glomerulonephritis

palpable purpura, vasculitis

• peripheral neuropathy

• lymphoma risk greatly increased

Treatment

• ocular

artificial tears/tear gel if severe, moisture retaining eyewear,humidifiers,orsurgical punctal

occlusion for dry ev es

• good dental hygiene, hydration

• avoid alcohol and tobacco

• parasympathomimetic agents thatstimulate salivary flow (e.g. pilocarpine)

topical nystatin or clotrimazole x4-6 wk for oral candidiasis

• systemic treatments (e.g. hydroxychloroquine,corticosteroids) are ineffective, rituximab can be used

in severe organ-threatening disease (e.g.vasculitis)

Classic Triad (identifies 93% of

Sjogren'

s patients)

• Dry eyes

• Dry mouth (xerostomia) »dysphagia

• Arthritis (small joint,asymmetrical.

non erosive) but may be associated

with rheumatoid arthritis, in which

case, the arthritis is erosive and

symmetric

L J

• oral

+

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RH18 Rheumatology Toronto Notes 2023

Mixed Connective Tissue Disease

Definition

• syndrome with features of 3 different (

"

I Ds (e.g. SLE,scleroderma, myositis)

• common symptoms: Raynaud’

s phenomenon,swollen fingers

Investigations

• blood work:anti-RNP (see Table 12, RHS)

Treatment

• treatment is generally guided by the severity ofsymptoms and organ system involvement

Prognosis

• prognosis is variable:some individuals go into remission, others develop a distinct connective tissue

disease (e.g.SLE, SSc), and others develop a severe disease course

• pulmonary arterial HTN is a major cause of death

Overlap Syndrome

Definition

• syndrome with sufficient diagnostic features of 2+ different CT'

Ds

Vasculitides

• inflammation and subsequent necrosis of blood vessels leading to tissue ischemia or infarction of any

organ system

• diagnosis

clinical suspicion:suspect in cases of unexplained multiple organ ischemia or systemic illness

with no evidence of malignancy or infection; constitutional symptomssuch as fever, weight loss,

anorexia,fatigue

• labs non-specific: anemia, increased WBC and CRP, abnormal U/A

» investigations:biopsy if tissue accessible;angiography if tissue inaccessible

• treatment generally involves corticosteroids and/or immunosuppressive agents

Features of Small Vessel Vasculitis

. Palpable purpura

. Vesicles

• Chronic urticaria

Table 21 • Superficial ulcers (erosions)

. Classification of Vasculitis and Characteristic Features

Classification Characteristic Features

SMAU

Non-ANCA

VESSEL

-assooated m

Anh CBM (Goodpaslure's disease)

Immune complex-mediated (most commonmechanism)

Autoantibodies targeting type IV collageninboth glomerular basement

membrane and alveoli causing glomerulonephntisandor pulmonary findings

Specific autoimmune disorder with at least 6mo of urticaria with Clg

complement deficiency with various systemic findings

Also known as hypersensitivily/leukocytKlasbc vasculitis

Vascular deposition of IgA causing systemic vasculitis (skin.61.renal),usually

self-limiting:most common in childhood

Systemic vasculitis caused by circulating cryoproteins forming immune

complexes;60-80% of cases are due to hepatitis C.5 -10% are due to a CID

(SLE.DA.SS).5-10% are due to a lymphoprotiferative disorder,and the

remaining 5-10% are idiopathic or'

essential.'CV may beassociated with

underlying infection (e.g. hepatitis C) or CTO

Granulomatous inflammation of vessels of respiratory badand kidneys

leading topulmonary hemorrhage and glomerulonephritis:initially may have

upper respiratory tradinfection (URTI) symptoms (sinusitis):most common

inmiddle age

Granulomatous inflammation of vessels with hypereosinophilia and

eosinophilic tissue infiltration,frequentlung involvement (asthma,allergic

rhinitis),associated with MPO-ANCAin 40-50% of cases.Other manifestations

include peripheral neuropathy (70%).Gl involvement myocarditis,and rarely

coronary arteritis;average age 40s

Fauci-immune necrotizing vasculitis,affects kidneys (necrotizing

glomerulonephritis),lungs (capillaritis and alveolar hemorrhage),and skin;

most common in older age

. c-ANCA (e.g.pR3-ANCA):

cytoplasmic anti-neubophil

cytoplasmic Ab associated with

anti-PR3

. p-ANCA (eg.MPO-ANCA):

perinuclear anti-neutrophil

cytoplasmic Ab associated

with multiple antigens,e.g.

myeloperoxidase,lactoferrin (IBD).

cathepsin.etastase.etc.Of these,

only antibodies to myeloperoxidase

have been associated with the

development of vasculitis

Anti-Clg vasculitis (hypocomplemenlemic urticarial vasculitis

syndrome)

Predominantly cutaneous vasculitis

IgA vasculitis (formerly Henoch-Schonlein purpura (BSP))

(see Paediatrics.P98)

Cryoglobuinemic vasculitis (CV)

ANCA-associated(i.e.PR3-ANCA)

Granuiomatosis with polyangiitis (GPA.formerly Wegener'

s)

PR3 (c-ANCA) > MP0|p-ANCA)

EGPA Triad

• Allergic rhinitis and asthma (often

quiescent at time of vasculitis)

• Eosinophilic infiltrative disease

resembling pneumonia

. Systemic vasculitis often

mononeuritis multiplex'

peripheral

neuropathy and peripheral

eosinophilia

EGPA.formerly Churg-Strauss syndrome (50% AHCA positive)

Microangiopathic polyangiitis (MPA)

(70% ANCA positive,usually MPO)

<- J

ME0IUM VESSEL

Segmental,non granulomatous necrotizing inflammation

Unknown etiology in most cases,any age (average 40-50s).M*

F

Arteritis and mucocutaneous lymph node syndrome

PAN Features of Medium Vessel Vasculitis

• Livedo reticularis

• Erythema nodosum

• Raynaud'

s phenomenon

• Nodules

• Digital infarcts

• Ulcers

Kawasaki disease (see Paediatrics.P98) +

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RH19 Rheumatology Toronto Notes 2023

Table 21. Classification of Vasculitis and Characteristic Features

Classification Characteristic Features

LARGE VESSEL

GCA Temporal arteritis Inflammation predominantly of Ihe aorta andits branches

Ages »50.F*

M

Temporalheadache,jaw claudication,scalp tenderness,risionloss

'

Pulseless disease." unequal peripheral pulses,chronic inflammation,most

often the aorta and itsbranches

Host common inyoung adults of Asian descent,ages10-40.f -M.risk of aortic

aneurysm

lakayasu's

OTHER VASCUllTIDES

Buerger'

s disease

("Thromboangiitis Obliterans")

Inflammationand clotting of small and medium- sued arteries and veinsof

distal entremities.may lead to distal daudicabon and gangrene,the most

important etiologic factor is cigareltesmoking. Host commonin young Asian

males.M>F

Behcet'

s disease Multi system disorder presenting withocular involvement (uveitis),recurrent

oral and genitalulceration,venous thrombosis,skin and joint involvement

Most commonin Mediterranean and Asian populations,average age 30y/o.

M>f

Vasculitis mimicry (i.e.pseudovasculitis) Cholesterol emboli,atrial myxoma,subacute bacterialendocardibs|SBE).APS

Takayasu'sateiitis

Kawasaki disease

Small Vessel Vasculitis ANCA-Associatcd Vasculitis

Non- ANCA-AssociatedVasculitis

Cryoglobulinemic vascuCbs

IgA vasulitisllgAV)

Hypocomplementennc urtcanal vasculibs

CWIIOM Tjr-B 2031

Figure 9. Classification of vasculitides by vessel sire

J.C. Jcrrelte.R.J. Falk.P. A.Bacon,et al.Arthritic & Rheunototogy(65.t).p.1.copyright 2020.ModifiedbyPermaiion of John Wiley andSons

Small Vessel Non-ANCA-Associated Vasculitis

CUTANEOUS VASCULITIS

• subdivided into:

drug-induced vasculitis

serum sickness reaction

vasculitis associated with other underlying primary diseases (CTD, infections,malignancieshematologic > solid tumours)

Etiology and Pathophysiology

• cutaneous vasculitis following:

• drug exposure (allopurinol, gold,sulfonamides, penicillin, phenytoin )

• viral or bacterial infection

• idiopathic causes

• small vessels involved (post-capillary venules most frequently)

• usually causes a leukocytoclastic vasculitis:debrisfrom neutrophils around vessels

• sometimes due to cryoglobulins which precipitate in cold temperatures

Clinical Presentation

• palpable purpura (usually on lower extremities) ±vesicles and ulceration, urticaria,macules,papules,

bullae,subcutaneous nodules

renal or joint involvement may occur, especially in children

ri

L -

I

Investigations +

• vascular involvement (both arteriole and venule) established by skin biopsy

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RH20 Rheumatology Toronto Xotes 2023

Treatment

• stop possible offending drug; treat underlying primary disease

• NSAIDs, low-dose corticosteroids

• immunosuppressive agents in resistant cases

• usually self-limiting

Small Vessel ANCA-Associated Vasculitis

GRANULOMATOSIS WITH POLYANGIITIS

(GPA, formerly known as Wegener’s Granulomatosis)

Definition

• granulomatous inflammation of vessels that may affect the upper airways(rhinitis,sinusitis), lungs

(pulmonary nodules,infiltrates caused by pulmonary hemorrhage), and kidneys (glomerulonephritis,

renal failure)

• highly associated with c-ANCA by indirect immunofluorescence (11F) and PR3-AXCA by HL1SA;

however, changes in ANLA levels do not predict remission or relapse

• incidence:2-3 in 100000;more common in Northern latitudes

Classic Features of GPA

• Necrotizing granulomatous vasculitis

of lower and upper respiratory tract

• Focal segmental glomerulonephritis

Table 22. Classification Criteria for GPA*

See Landmark Rheumatology Trials

RH34 for more information on the

RAVE trial. It examined the efficacy

of rituximab for the induction and

maintenance of remission in patients

with ANCA-associated Vasculitides.

Clinical Criteria Score

Criteria Description

Crusting,ulcers,epistaxis. congestion,blockage,or septal defect' *3

perforation

Ear/nose cartilage inflammation,hoarseness or stridor,endobronchial *2

involvement,or saddle nose deformity

Conductive or sensorineural

Nasal involvement

Cartilaginous mvohrtment

o

Nearing loss *r

Laboratory.Imaging,and Biopsy Criteria

See Landmark Rheumatology Trials

RH34 for more information on the

MAINRITSAN3trial.It examined the

efficacy of extended maintenance

rituximab in patients with ANCAassociated Vasculitides

c-ANCA or anti-FR3-positive

Pulmonary nodules,mass,or cavitation on chest imaging

Granuloma,extravascu'ar granulomatous inflammation,or giantcells on biopsy

Inflammation,consolidation,or effusion of nasal/paranasal sinuses, or mastoiditis on imaging

Pauci-immune glomerulonephritison biopsy

p-ANCA or anti-MPO-positive

Blood eosinophil comt >1x10

*

l/

5

<2

»2

A

»1

•1

•4

‘Diagnosed if a5

American College of Rheumatology. 2022

Etiology and Pathophysiology

• pathogenesis depends on genetic susceptibility and environmental triggers (e.g.infection)

• dysregulated immune response due to loss of B and T cell tolerance

• acute vascular injury mediated by neutrophils and monocytes

Clinical Presentation

• systemic

malaise,fever, weakness, weight loss

• head, eyes, ears, nose, and throat (HHENT)

• sinusitis or rhinitis, nasal crusting and bloody nasal discharge, nasoseptal perforation,saddle

nose deformity

• proptosis due to:inflammation/vasculitis involving extraocular muscles,granulomatous

retrobulbarspace-occupying lesions or direct extension of masses from the upper respiratory

tract

hearing loss due to involvement of cranial nerve (CN) VIII

• pulmonary

cough, hemoptysis, granulomatous upper respiratory tract masses,tracheal and bronchial

stenosis

• renal

hematuria, proteinuria,elevated Lr, glomerulonephritis

• other

• joint,skin, eye complaints-iritis, vasculitic neuropathy

Investigations

• blood work: anemia ( normal mean corpuscular volume (MCV)),increased WBC,increased Lr,

increased CRP,elevated platelet count, ANCA (HR3 > MPO)

• urinalysis: proteinuria, hematuria, RBL casts

• CXR/CT: pneumonitis, lung nodules, infiltrations, cavitary lesions

• biopsy for confirmation of disease:skin, renal (segmental necrotizing glomerulonephritis),lung

(vasculitis, necrosis)

• LRP may be used to monitor response to treatment in some patients

+

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RH21 Rheumatology Toronto Notes 2023

Treatment

• severe, life or organ-threatening disease

• induction therapy: IV glucocorticoids + either IV or oral cyclophosphamide OR rituximab

glucocorticoid: methylprednisolone 0.5-l.0 g/d IV xI -3 d followed by prednisone 1 mg/kg/d PO

x2-4 wk and then gradual taper

• cyclophosphamide: 2 mg/kg/d (max 200 mg/d) PO for maximum of 3-6 mo OK 15 mg/ kg IV (max

1200 mg) every 2 wk for 3doses, then every 3 wk for 3-6 doses (dose adjust for older age and renal

failure)

rituximab: 375 mg/m2 x4 weekly infusions

» maintenance therapy:initiated once remission is achieved, consider corticosteroid-sparing agents

such as rituximab for maintenance, azathioprine, M I X, and mycophenolate are reasonable

alternatives

• plasma exchange can be an adjunct treatment for patients with severe organ involvement (renal

failure, pulmonary hemorrhage) not responding to conventional induction treatment

• non-organ-threatening disease

prednisone 0.5-1 mg/kg/d PO and MTX 15-25 mg PO/SC weekly OR azathioprine 2 mg/kg/d

• screening and prophylaxis

all patientsshould receive screening and prophylaxis for corticosteroid-induced osteoporosis,

PUD prevention, and Pneumocystis jirowci prophylaxis (trimethoprim/sulfamethoxazole 160/800

mg PO 3x/wk)

Medium Vessel Vasculitis

POLYARTERITIS NODOSA

Definition

• systemic, necrotizing vasculitis of medium-sized vessels, defined as visceral arteries and their

branches

• ANCA-negative, classically lung-sparing

• 5-10% associated with hepatitis B positivity

• incidence: 0.7 in 100000; affects individuals between 40-60 yr; M:l

;

»2:l

Table 23. Classification Criteria for PAN'

Criteria Description

>4 kg.not due to dieting or other factors

Oilfuse myalgiasor muscle weakness

Mottled,reticular pattern over skin

Mononeuropalhy.mononeuropathy multiplex, or polyneuropathy

Not due to infection,trauma, or other causes

Development of BIN with dBP »90 mmHg

Cr >130 pmot/L (1.5mg/dL), DUN >14.3 mmol/L (40 mg/dL)

Presence of hepatitis Bsurface antigen or Ab

Commonly aneurysms

Presence of granulocytes and/or mononuclear leukocytes in the artery wall

1.Weight loss

2. Myalgias,weakness, or leg tenderness

3.livedo reticularis

4. Neuropathy

5.Testicular pain or tenderness

6.dBP >90 mmHg

7.Elevated Cr or BUN

8.Hepatitis B positive

9.Arteriographic abnormality

10.Biopsy of artery

'Diagnosed if 3 or more of the above to criteria present

American College of Rheumatology,1990

Etiology and Pathophysiology

• focal pan-mural necrotizing vasculitis in small and medium-sized arteries

• thrombosis, aneurysm, or dilatation at lesion site may

• healed lesions show proliferation of fibrous tissue and endothelial cells that may lead to luminal

occlusion

occur

Clinical Presentation

• systemic:fatigue, weight loss, weakness, fever, arthralgias

• dermatologic:livedo reticularis, nodules, purpura, eruptions

• renal: renal insufficiency leading to HTN

• neurologic: mononeuropathy multiplex in both motor and sensory nerves

• abdominal: abdominal pain, mesenteric arteritis

Investigations

• blood work:CBC,CRP, Cr, BUN, urinalysis,liver enzymes, p-ANCA, hepatitis B and C serology

• imaging:CT or MR1 angiography shows beading appearance of blood vessels seen

• biopsy of affected organ (e.g.skin, nerve);biopsy of highly vascular tissues(e.g.liver) not

recommended due to risk of aneurysm rupture

Treatment

• PAN with no major organ manifestations

glucocorticoids ± azathioprine

n

L J

+