Rheumatology BasicsRheumatology Basics

Kalyani McCullough, MDKalyani McCullough, MD

Clinics and MOP DidacticClinics and MOP Didactic

Purpose of this talkPurpose of this talk

To provide a foundation for: To provide a foundation for: Seeing patients in Rheumatology clinicSeeing patients in Rheumatology clinic Getting started on the work-up of Getting started on the work-up of

suspected rheumatologic diseases in suspected rheumatologic diseases in your clinicyour clinic

Review most common rheumatologic Review most common rheumatologic diseasesdiseases Fast overviewFast overview Resource for laterResource for later

Main diseases you’ll be Main diseases you’ll be seeingseeing

Inflammatory arthritisInflammatory arthritis Rheumatoid, spondyloarthropathiesRheumatoid, spondyloarthropathies

Crystal arthritisCrystal arthritis Gout, PseudogoutGout, Pseudogout

Autoimmune disordersAutoimmune disorders Lupus, Sclerodema, Autoimmune myositisLupus, Sclerodema, Autoimmune myositis

VasculitisVasculitis Large, medium, small vesselLarge, medium, small vessel

What are some clues your patient What are some clues your patient may have a rheumatologic may have a rheumatologic

disease?disease? Constitutional symptomsConstitutional symptoms

Fevers, sweats, weight loss, fatigueFevers, sweats, weight loss, fatigue Subacute time courseSubacute time course

Started over weeks to monthsStarted over weeks to months Characteristic symptomsCharacteristic symptoms

Mono or polyarticular joint pain, multisystem Mono or polyarticular joint pain, multisystem complaints (i.e. skin, lung, GI)complaints (i.e. skin, lung, GI)

Are there signs of an inflammatory Are there signs of an inflammatory process?process? Synovitis, rash, serositis, elevated ESR/CRPSynovitis, rash, serositis, elevated ESR/CRP

How do you get started on the How do you get started on the work-up?work-up?

Thorough physical examThorough physical exam Lab testsLab tests

CBC w diff, ESR, CRP, ANA, targeted CBC w diff, ESR, CRP, ANA, targeted autoantibodiesautoantibodies

RadiographsRadiographs Erosive arthritis, sacroillitisErosive arthritis, sacroillitis

Biopsy?Biopsy? Skin, muscle, kidneySkin, muscle, kidney

Basics of treatmentBasics of treatment NSAIDsNSAIDs

Symptom relief, especially joint painSymptom relief, especially joint pain GlucocorticoidsGlucocorticoids

Acutely, try to use steroid sparing agent if possibleAcutely, try to use steroid sparing agent if possible Disease-modifying antirheumatic drugs Disease-modifying antirheumatic drugs

(DMARDs)(DMARDs) Synthetic DMARDsSynthetic DMARDs

Slow onset, 2-6 monthsSlow onset, 2-6 months Methotrexate, Hydroxychloroquine, Sulfasalazine, Azathioprine, Methotrexate, Hydroxychloroquine, Sulfasalazine, Azathioprine,

Mycophenolate mofetil, CyclophosphamideMycophenolate mofetil, Cyclophosphamide Biologic DMARDsBiologic DMARDs

Bioengineered protein drugs (antibodies or receptor-antibody Bioengineered protein drugs (antibodies or receptor-antibody chimeras )chimeras )

IV or SQ onlyIV or SQ only Rapid onsetRapid onset Screen for and treat LTBI, HBV firstScreen for and treat LTBI, HBV first Infliximab, Etancercept, RituximabInfliximab, Etancercept, Rituximab

Steroid Side EffectsSteroid Side Effects Weight gainWeight gain DiabetesDiabetes CataractsCataracts InsomniaInsomnia Fluid retentionFluid retention HypertensionHypertension Proximal weaknessProximal weakness AlopeciaAlopecia SweatsSweats OsteoporosisOsteoporosis InfectionInfection Psychiatric disturbance (eg, depression, mania, psychosis)Psychiatric disturbance (eg, depression, mania, psychosis) Easy bruising of the skinEasy bruising of the skin StressStress TremorTremor Peptic ulcer diseasePeptic ulcer disease

Long term considerations for Long term considerations for most autoimmune diseasesmost autoimmune diseases

Increased risk of CV death due to Increased risk of CV death due to inflammation and accelerated atherosclerosisinflammation and accelerated atherosclerosis Aggressive risk factor reduction: BP<120/80, Aggressive risk factor reduction: BP<120/80,

LDL<100LDL<100 Osteoporosis from glucocorticoidsOsteoporosis from glucocorticoids

Dexa screening, Calcium-Vit D, bisphosphonates Dexa screening, Calcium-Vit D, bisphosphonates prnprn

Infections Infections Increased risk of certain malignanciesIncreased risk of certain malignancies

Lymphoma, Lung/Cervical CA in LupusLymphoma, Lung/Cervical CA in Lupus

Inflammatory ArthritisInflammatory Arthritis

Rheumatoid arthritisRheumatoid arthritis SpondyloarthropathiesSpondyloarthropathies

Axial skeletal involvement and Axial skeletal involvement and polyarthritis of peripheral jointspolyarthritis of peripheral joints

Ankylosing spondylitisAnkylosing spondylitis Reactive arthritisReactive arthritis Psoriatic arthritisPsoriatic arthritis IBD-associated arthritisIBD-associated arthritis

Rheumatoid arthritisRheumatoid arthritis Clinical presentation:Clinical presentation:

Chronic, symmetric polyarthritisChronic, symmetric polyarthritis Often starts with the PIPs, MCPs, MTPsOften starts with the PIPs, MCPs, MTPs

Can affect most synovial joints (wrists, knees, elbows Can affect most synovial joints (wrists, knees, elbows etc.)etc.)

Doesn’t affect DIPsDoesn’t affect DIPs Morning stiffness, pain, swelling (vs. OA: worse with Morning stiffness, pain, swelling (vs. OA: worse with

activity)activity) Labs:Labs:

RF, anti-CCP Ab or both in 70% of patientsRF, anti-CCP Ab or both in 70% of patients RF not specific, anti-CCP 90-98% specificRF not specific, anti-CCP 90-98% specific ACD, ESR, CRPACD, ESR, CRP

Xrays:Xrays: articular erosions and joint space narrowingarticular erosions and joint space narrowing

Joint distribution in RA vs. Joint distribution in RA vs. OAOA

RA – Physical Exam FindingsRA – Physical Exam Findings• Ulnar deviation

• at mcps• Swan neck deformity

• hyperextension of PIPs, flexion of DIPs

• Boutonniere deformity• flexion of PIP, hyperextension of DIP

OA – Physical Exam FindingsOA – Physical Exam Findings

Bony outgrowths/ calcific spurs on PIPs and DIPs

RA – Extra-articular RA – Extra-articular ManifestationsManifestations

Many extra-articular Many extra-articular findings:findings: Rheumatoid nodulesRheumatoid nodules Other organ Other organ

involvement:involvement: Sjogren’s syndromeSjogren’s syndrome ScleritisScleritis Interstitial fibrosisInterstitial fibrosis Pericardial effusionsPericardial effusions Peripheral neuropathyPeripheral neuropathy AmyloidosisAmyloidosis

RA - TreatmentRA - Treatment Early aggressive treatment leads to better Early aggressive treatment leads to better

longterm outcomeslongterm outcomes Glucocorticoids acutelyGlucocorticoids acutely MTX frequently usedMTX frequently used

Start 7.5mg weekly, increase to a max dose of Start 7.5mg weekly, increase to a max dose of 20-25mg weekly20-25mg weekly

Give with folate 1mg daily to reduce toxicityGive with folate 1mg daily to reduce toxicity Check CBC, AST/ALT, Cr q 3 moCheck CBC, AST/ALT, Cr q 3 mo Contraindications:Contraindications: liver disease, HBV/HCV, liver disease, HBV/HCV,

alcohol use, CrCl<30alcohol use, CrCl<30 Toxicities:Toxicities: oral ulcers, nausea, hepatotoxicity, oral ulcers, nausea, hepatotoxicity,

BMS, pneumonitisBMS, pneumonitis

SponydloarthropathiesSponydloarthropathies

Inflammatory arthritis with Inflammatory arthritis with involvement of:involvement of: Sacroiliac (SI) jointSacroiliac (SI) joint Axial spineAxial spine Tendon fasciaTendon fascia Ligament insertion points (entheses)Ligament insertion points (entheses) Peripheral jointsPeripheral joints

Ankylosing SpondylitisAnkylosing Spondylitis Psoriatic ArthritisPsoriatic Arthritis

DIPs often involved, assoc with nail DIPs often involved, assoc with nail pittingpitting

Reactive ArthritisReactive Arthritis Triggered by GI/GU infectionTriggered by GI/GU infection

IBD-associated arthritisIBD-associated arthritis Correlates with bowel activityCorrelates with bowel activity

SpondyloarthropathiesSpondyloarthropathies

Ankylosing SpondylitisAnkylosing Spondylitis Clinical presentationClinical presentation

Inflammatory back pain in Inflammatory back pain in young adultyoung adult

Reduction in spinal Reduction in spinal mobility, particularly mobility, particularly lumbar flexionlumbar flexion

Association with anterior Association with anterior uveitisuveitis

LabsLabs Increased relative risk of Increased relative risk of

HLA-B27HLA-B27 •XrayXray- Sacroiliitis- Sacroiliitis

•TreatmentTreatment - PT, NSAIDs- PT, NSAIDs

Crystal ArthritisCrystal ArthritisGout – Natural HistoryGout – Natural History

1) Asymptomatic hyperuricemia1) Asymptomatic hyperuricemia Over production or under excretion (or both)Over production or under excretion (or both)

2) Acute and intermittent gout2) Acute and intermittent gout Attacks triggered by fluctuations in UA level (up Attacks triggered by fluctuations in UA level (up

or down) and deposition of UA crystals in jointor down) and deposition of UA crystals in joint Acute monoarthritis, often 1Acute monoarthritis, often 1stst attack is at 1 attack is at 1stst mtp mtp After years see bony erosions on xrayAfter years see bony erosions on xray

3) Chronic tophaceous gout3) Chronic tophaceous gout

Gout - TreatmentGout - Treatment Acute attackAcute attack – most efficacious if initiate – most efficacious if initiate

treatment within 48h of onsettreatment within 48h of onset NSAIDs – indomethacinNSAIDs – indomethacin

Avoid if h/o PUD or renal impairmentAvoid if h/o PUD or renal impairment Colchisine Colchisine

1.2mg PO x 1, then 0.6mg 1h later and q24h until 1.2mg PO x 1, then 0.6mg 1h later and q24h until symptoms improvesymptoms improve

Side effects: Diarrhea, abdominal pain, NSAIDs better Side effects: Diarrhea, abdominal pain, NSAIDs better toleratedtolerated

Reduce dose if Cr > 1.5, risk of neuromuscular toxicityReduce dose if Cr > 1.5, risk of neuromuscular toxicity GlucocorticoidsGlucocorticoids

Prednisone 20-40mg/d, taper 1-2 wks after symptoms Prednisone 20-40mg/d, taper 1-2 wks after symptoms resolveresolve

Gout - ProphylaxisGout - Prophylaxis Goal UA<6Goal UA<6 Xanthine oxidase inhibitors (decrease production)Xanthine oxidase inhibitors (decrease production)

AllopurinolAllopurinol Start with 100mg daily, gradually increase doseStart with 100mg daily, gradually increase dose Max is 800mg/d, though 300-400mg usually effectiveMax is 800mg/d, though 300-400mg usually effective Reduce dose if diminished CrReduce dose if diminished Cr Hypersensitivity reaction can be fatal, more common in Hypersensitivity reaction can be fatal, more common in

older patients with impaired Cr on diureticsolder patients with impaired Cr on diuretics If develop rash, stopIf develop rash, stop

FebuxostatFebuxostat Metabolized by liver, so better with renal impairmentMetabolized by liver, so better with renal impairment Ok with mild-moderate hepatic insufficiencyOk with mild-moderate hepatic insufficiency

Uricosuric agents (increase excretion)Uricosuric agents (increase excretion) ProbenacidProbenacid

Age <65, good renal function, not on more than ASA 81 Age <65, good renal function, not on more than ASA 81 dailydaily

Side effects: rash and GI symptomsSide effects: rash and GI symptoms

PseudogoutPseudogout

Clinical presentationClinical presentation Intermittent monoarthritis, often knee/wrist, Intermittent monoarthritis, often knee/wrist,

though can be 1though can be 1stst mtp mtp LabsLabs

rhomboid shaped, positively birefringent calcium rhomboid shaped, positively birefringent calcium pyrophosphate dihydrate (CPPD) crystalspyrophosphate dihydrate (CPPD) crystals

Can be associated with other diseases: Can be associated with other diseases: hemochromatosis, thyroid diseasehemochromatosis, thyroid disease

TreatmentTreatment NSAIDs, colchisineNSAIDs, colchisine

Autoimmune disordersAutoimmune disorders

Systemic lupus erythematosis (SLE)Systemic lupus erythematosis (SLE) Antiphospholipid antibody syndromeAntiphospholipid antibody syndrome Raynaud’s phenomenonRaynaud’s phenomenon SclerodermaScleroderma Sjogren’s DiseaseSjogren’s Disease Dermatomyositis and PolymyositisDermatomyositis and Polymyositis Relapsing PolychondritisRelapsing Polychondritis

LupusLupus Clinical presentationClinical presentation

Typically affects women of Typically affects women of childbearing agechildbearing age

Multisystem Multisystem relapsing/remitting diseaserelapsing/remitting disease

Affects skin, Affects skin, musculoskeletal, renal, CV, musculoskeletal, renal, CV, pulmonary, GI, CNS, psychpulmonary, GI, CNS, psych

- Hallmark symptoms: photosensitive rash, - Hallmark symptoms: photosensitive rash, polyarthritis, serositis, fatigue polyarthritis, serositis, fatigue - Renal and CNS involvement -> significant - Renal and CNS involvement -> significant morbidity morbidity

Lupus Lupus LabsLabs

Presence of antinuclear Presence of antinuclear antibodies antibodies

Once ANA positive, no need Once ANA positive, no need to recheckto recheck

Anti-dsDNA and anti-Sm Anti-dsDNA and anti-Sm have great specificity, have great specificity, but lack sensitivity.but lack sensitivity.

Hypocomplementemia Hypocomplementemia may occur during flares. may occur during flares.

C3, C4, CH50C3, C4, CH50

TreatmentTreatment Glucocorticoids, DMARDsGlucocorticoids, DMARDs

Lupus - MonitoringLupus - Monitoring Lupus nephritisLupus nephritis – approx 50% – approx 50%

Typically immune complex glomerulonephritisTypically immune complex glomerulonephritis Screen q3 mo:Screen q3 mo:

Ask about polyuria, nocturia, foamy urineAsk about polyuria, nocturia, foamy urine Look for HTN and edemaLook for HTN and edema Labs: UA – RBC casts, spot prot: Cr ratioLabs: UA – RBC casts, spot prot: Cr ratio

Diagnose with biopsyDiagnose with biopsy Increased risk of malignancyIncreased risk of malignancy: Hodkin’s and : Hodkin’s and

Non-Hodgkins lymphoma, Lung CA, Cervical CANon-Hodgkins lymphoma, Lung CA, Cervical CA Annual cervical CA screeningAnnual cervical CA screening

SclerodermaScleroderma Clinical presentationClinical presentation

Early in disease:Early in disease: msk pain, fatigue, weight loss, GERDmsk pain, fatigue, weight loss, GERD Rare disorder, but symptoms common in primary careRare disorder, but symptoms common in primary care

Late in disease:Late in disease: SkinSkin: thickening, ischemic digital ulcers, pitting, : thickening, ischemic digital ulcers, pitting,

telangectasias on face and palmstelangectasias on face and palms LungsLungs: interstitial fibrosis, pulmonary htn: interstitial fibrosis, pulmonary htn GIGI: GERD, dysphagia: GERD, dysphagia RenalRenal: rare, but Scleroderma Renal Crisis (SRC) is life : rare, but Scleroderma Renal Crisis (SRC) is life

threatening emergencythreatening emergency CardiacCardiac: ischemic injury: ischemic injury MSKMSK: erosive arthritis, tendon friction rub: erosive arthritis, tendon friction rub

CREST (limited scleroderma): calcinosis, raynaud’s, CREST (limited scleroderma): calcinosis, raynaud’s, esophageal dysmotility, sclerodactyly, telangectasiasesophageal dysmotility, sclerodactyly, telangectasias

SclerodermaScleroderma

Digital ulcers

Sclerodactyly Telangectasias

Thickened, tight skin

Scleroderma Scleroderma LabsLabs

If negative ANA, diagnosis is very unlikelyIf negative ANA, diagnosis is very unlikely Indirect immunofluorescence better than ELISAIndirect immunofluorescence better than ELISA

Anti-centromere Ab in 20-40%Anti-centromere Ab in 20-40% Anti-Scl-70 (anti-topoisomerase) 20-40%Anti-Scl-70 (anti-topoisomerase) 20-40%

Correlates with worse prognosisCorrelates with worse prognosis TreatmentTreatment

No No provenproven disease-modifying medication disease-modifying medication Screening and early identification of internal Screening and early identification of internal

organ involvement importantorgan involvement important Organ specific treatmentOrgan specific treatment

Fibrosis – immunosuppresionFibrosis – immunosuppresion Renal crisis – ACEiRenal crisis – ACEi GERD – PPI and behavioral changeGERD – PPI and behavioral change

Autoimmune myositisAutoimmune myositis

Polymyositis (PM)Polymyositis (PM) Dermatomyositis Dermatomyositis

Dermatomyositis sine myositis (just Dermatomyositis sine myositis (just skin)skin)

Dermatomyositis sine dermatitis (classic Dermatomyositis sine dermatitis (classic muscle biopsy findings)muscle biopsy findings)

Immune-mediated necrotizing Immune-mediated necrotizing myopathy (IMNM)myopathy (IMNM) Statin exposureStatin exposure

Clinical presentationClinical presentation Symmetric, Symmetric, proximal proximal muscle weakness that muscle weakness that

develops over weeks to monthsdevelops over weeks to months Difficulty rising from a chair, walking up steps, Difficulty rising from a chair, walking up steps,

washing or brushing hairwashing or brushing hair If severe: dysphagia and respiratory distress from If severe: dysphagia and respiratory distress from

weakness of neck, pharyngeal and diapghragmatic weakness of neck, pharyngeal and diapghragmatic musclesmuscles

Distal weakness very uncommon, suspect another Distal weakness very uncommon, suspect another diagnosisdiagnosis

Autoimmune myositis Autoimmune myositis

DermatomyositisDermatomyositis Clinical Presentation: SkinClinical Presentation: Skin

Gottron papulesGottron papules: raised : raised violaceous lesions at violaceous lesions at extensor surfaces of mcp, extensor surfaces of mcp, pip, dippip, dip

Gottron signGottron sign: : erythematous rash at above erythematous rash at above sitessites

Heliotrope rashHeliotrope rash: : red/purplish discoloration of red/purplish discoloration of eyelidseyelids

DermatomyositisDermatomyositis

Shawl signShawl sign: erythematous rash : erythematous rash across posterior neck and across posterior neck and shouldersshoulders

V signV sign: erythematous rash on : erythematous rash on anterior neck and chestanterior neck and chest

Mechanic’s hands/feetMechanic’s hands/feet: : hyperkeratotic skin thickening, hyperkeratotic skin thickening, often with painful crackingoften with painful cracking

Autoimmune myositis Autoimmune myositis LabsLabs

Elevated CK, aldolase, AST, ALT, LD from Elevated CK, aldolase, AST, ALT, LD from damaged muscle cellsdamaged muscle cells

Auto antibodies (anti-Jo-1, anti PL-7)Auto antibodies (anti-Jo-1, anti PL-7) ANA positive in >50%ANA positive in >50% Antisynthetase syndrome in dermatomysoitis: Antisynthetase syndrome in dermatomysoitis:

also with ILD, arthritis, fevers, raynaud’salso with ILD, arthritis, fevers, raynaud’s

MRI:MRI: muscle edema, fascial inflammation muscle edema, fascial inflammation EMG:EMG: irritable myopathy irritable myopathy Muscle biopsy:Muscle biopsy: generally nonspecific generally nonspecific

findings, but rules out non-autoimmune findings, but rules out non-autoimmune myopathiesmyopathies DM: perifascicular atrophy is specificDM: perifascicular atrophy is specific

TreatmentTreatment Glucocorticoids to control acute diseaseGlucocorticoids to control acute disease

Taper to lowest effective doseTaper to lowest effective dose Steroid sparing agent: MTX, azathioprineSteroid sparing agent: MTX, azathioprine Exercise: especially isometric, avoid Exercise: especially isometric, avoid

heavy weight liftingheavy weight lifting

Autoimmune myositis Autoimmune myositis

Autoimmune myositis vs. Autoimmune myositis vs. PMRPMR

Polymyalgia Rheumatica (PMR) Polymyalgia Rheumatica (PMR) aching and stiffness of neck, shoulders, aching and stiffness of neck, shoulders,

hips (vs. weakness)hips (vs. weakness) Elevated ESR >40Elevated ESR >40 Age >50Age >50 Rapid response to prednisone 20mg/d or Rapid response to prednisone 20mg/d or

lessless Association with GCA, but can occur Association with GCA, but can occur

independently tooindependently too

Mixed Connective Tissue Mixed Connective Tissue DiseaseDisease

Overlap syndrome with features of Overlap syndrome with features of SLE, Scleroderma and PolymyositisSLE, Scleroderma and Polymyositis

Characteristic clinical symptoms: Characteristic clinical symptoms: Raynaud phenomenon, hand edema, Raynaud phenomenon, hand edema,

synovitis, inflammatory muscle disease, synovitis, inflammatory muscle disease, sclerodactyly sclerodactyly

High titers of anti-U1 RNP High titers of anti-U1 RNP autoantibodyautoantibody

VasculitisVasculitis

Inflammatory destruction of blood Inflammatory destruction of blood vesselsvessels

Occlusion, rupture, thrombus can Occlusion, rupture, thrombus can lead to tissue ischemialead to tissue ischemia

Vary in severity and presentation Vary in severity and presentation based on vessels affectedbased on vessels affected

Vasculitis Vasculitis Clinical presentationClinical presentation

Constitutional symptomsConstitutional symptoms Subacute Subacute Signs of inflammationSigns of inflammation Multisystem diseaseMultisystem disease

i.e. Mononeuritis multiplexi.e. Mononeuritis multiplex Distinct/named peripheral nerves infarcted one at a timeDistinct/named peripheral nerves infarcted one at a time Due to vasculitis of vasa nervorum leading to ischemiaDue to vasculitis of vasa nervorum leading to ischemia Hallmarks are asynchrony and asymmetryHallmarks are asynchrony and asymmetry

LabsLabs Diagnose with biopsyDiagnose with biopsy

TreatmentTreatment Disease specific, often immunosuppressive therapyDisease specific, often immunosuppressive therapy

In SummaryIn Summary Suspect a rheumatologic process in patients with Suspect a rheumatologic process in patients with

subacute onset of constitutional symptoms, signs subacute onset of constitutional symptoms, signs of inflammation and multi system involvementof inflammation and multi system involvement

Get work-up started with thorough PE, targeted Get work-up started with thorough PE, targeted labs and xrayslabs and xrays

Consult with Rheum and consider getting Consult with Rheum and consider getting prednisone started to control acute disease, with prednisone started to control acute disease, with a goal of tapering to the lowest effective dose a goal of tapering to the lowest effective dose when possiblewhen possible

Monitor for the longterm complications of Monitor for the longterm complications of autoimmune diseaseautoimmune disease

Questions?Questions?