Treatment of Arthritis and Treatment of Arthritis and Connective Tissue DiseaseConnective Tissue Disease

Dr SinDr Sinééad Harneyad Harney

Dept of Rheumatology CUH/UCCDept of Rheumatology CUH/UCC

10-03-1110-03-11

OutlineOutline

How to treat Rheumatoid Arthritis?How to treat Rheumatoid Arthritis?

How to treat Connective Tissue How to treat Connective Tissue Disease/Vasculitis?Disease/Vasculitis?

Rheumatoid Arthritis: Rheumatoid Arthritis: Treatment dilemma 1Treatment dilemma 1

• 34-year-old woman with 3-year history of RA34-year-old woman with 3-year history of RA• Morning stiffness = 3 hoursMorning stiffness = 3 hours• 2 to 3+ swelling of MCP, PIP, wrist, elbow, knee, and 2 to 3+ swelling of MCP, PIP, wrist, elbow, knee, and

MTP jointsMTP joints• Ulnar deviation, swan neck deformities, decreased Ulnar deviation, swan neck deformities, decreased

ROM at wrists, nodules on elbowsROM at wrists, nodules on elbows

• RF positive, x-rays show erosions of wrists and RF positive, x-rays show erosions of wrists and MCP joints bilaterallyMCP joints bilaterally

• Currently on low-dose prednisone + MTX, SSZ, Currently on low-dose prednisone + MTX, SSZ, and hydroxychloroquineand hydroxychloroquine

Rheumatoid Arthritis: Rheumatoid Arthritis: Treatment dilemma 1contdTreatment dilemma 1contd

• AssessmentAssessment• Very active disease in spite of aggressive Very active disease in spite of aggressive

combination therapycombination therapy• Evidence of extensive joint destructionEvidence of extensive joint destruction

• Treatment options are manyTreatment options are many• Step-down oral prednisone, 60 mg qd tapered to 10 Step-down oral prednisone, 60 mg qd tapered to 10

mg qd over 5 weeks, can be used for immediate relief mg qd over 5 weeks, can be used for immediate relief of symptomsof symptoms

• Consider TNF inhibitor – 3 different agents currently Consider TNF inhibitor – 3 different agents currently in usein use

• Other biologics include – Anti-CD20, CTLA-Ig, Anti-Other biologics include – Anti-CD20, CTLA-Ig, Anti-IL6IL6

Rheumatoid Arthritis: Rheumatoid Arthritis: Treatment Plan SummaryTreatment Plan Summary

• A variety of treatment options are availableA variety of treatment options are available

• Treatment plan should matchTreatment plan should match• The current disease activity The current disease activity • The documented and anticipated pace of joint The documented and anticipated pace of joint

destructiondestruction

Rheumatoid ArthritisRheumatoid ArthritisTreatment dilemma 2Treatment dilemma 2

68-year-old woman with 3-year history of RA is 68-year-old woman with 3-year history of RA is squeezed into your clinic as a new patientsqueezed into your clinic as a new patient

She presents with 4 weeks of increasing fatigue, She presents with 4 weeks of increasing fatigue, dizziness, dyspnea, and anorexiadizziness, dyspnea, and anorexia

Her joint pain and stiffness are mild and unchangedHer joint pain and stiffness are mild and unchanged

Managed with Managed with ibuprofenibuprofen and hydroxychloroquine until 4 and hydroxychloroquine until 4 months ago, when a flare caused a switch to months ago, when a flare caused a switch to diclofenacdiclofenac and and prednisoloneprednisolone

Past history: Peptic ulcer 10 years ago and Past history: Peptic ulcer 10 years ago and mild hypertensionmild hypertension

Exam shows a thin, pale apathetic woman Exam shows a thin, pale apathetic woman with Temp 98.4ºF, BP 110/65, pulse 110 bpmwith Temp 98.4ºF, BP 110/65, pulse 110 bpm

Symmetrical 1+ synovitis of the wrist, MCP, Symmetrical 1+ synovitis of the wrist, MCP, PIP, and MTP jointsPIP, and MTP joints

Exam of the heart, lungs, and abdomen is Exam of the heart, lungs, and abdomen is unremarkableunremarkable

Rheumatoid Arthritis: Treatment dilemma 2 contd

What system must you investigate more What system must you investigate more ??A. CardiovascularA. Cardiovascular

B. NeuropsychologicalB. Neuropsychological

C. EndocrineC. Endocrine

D. GastrointestinalD. Gastrointestinal

Clues of impending disasterClues of impending disaster High risk for NSAID gastropathyHigh risk for NSAID gastropathy Presentation suggestive of blood lossPresentation suggestive of blood loss

Pale, dizzy, weakPale, dizzy, weakTachycardia, low blood pressureTachycardia, low blood pressure

No evidence of flare in RA to explain No evidence of flare in RA to explain recent symptoms of increased fatiguerecent symptoms of increased fatigue

Rheumatoid Arthritis:Rheumatoid Arthritis:Treatment dilemma 2 contdTreatment dilemma 2 contd

Medications for RAMedications for RA

Nonsteroidal anti-inflammatory drugs Nonsteroidal anti-inflammatory drugs (NSAIDs)(NSAIDs)

Corticosteroids (steroids)Corticosteroids (steroids)

Disease-modifying antirheumatic drugs Disease-modifying antirheumatic drugs (DMARDs)(DMARDs)

BiologicsBiologics Combination of any of the above therapiesCombination of any of the above therapies

NSAIDsNSAIDs NSAIDs can help relieve not only pain but NSAIDs can help relieve not only pain but

inflammation as wellinflammation as well NSAIDs have not been shown to slow the joint NSAIDs have not been shown to slow the joint

destruction of RAdestruction of RA Side effects Side effects Recent controversies involving Cox-II therapyRecent controversies involving Cox-II therapy

FDA Advisory panel view of gradient of CVS riskFDA Advisory panel view of gradient of CVS riskRofecoxib > Valdecoxib > Celecoxib (ACR Rofecoxib > Valdecoxib > Celecoxib (ACR

2005)2005)Concomitant aspirin use negates GIT protective Concomitant aspirin use negates GIT protective

benefits of COX 2 inhibitorsbenefits of COX 2 inhibitorsJury still out on lots of COX2 inhibitors issuesJury still out on lots of COX2 inhibitors issues

Combination or monotherapy Combination or monotherapy with DMARDs?with DMARDs?

Many trials don’t show superiority of traditional Many trials don’t show superiority of traditional combination DMARD therapy over monotherapycombination DMARD therapy over monotherapy

Some don’t control for glucocorticoid useSome don’t control for glucocorticoid use

A review of studies between A review of studies between 1992-19971992-1997 did not show any did not show any benefit of most combinations over monotherapy – benefit of most combinations over monotherapy – exceptions being MTX and CSA vs MTX alone (ACR exceptions being MTX and CSA vs MTX alone (ACR

20 48% vs. 16%) 20 48% vs. 16%) ((Tugwell et alTugwell et al)) HCQ and MTX vs. MTX alone (Ferraz et al)HCQ and MTX vs. MTX alone (Ferraz et al) MTX+SSZ+HCQ vs. SSZ+HCQ vs. MTX alone (O Dell)MTX+SSZ+HCQ vs. SSZ+HCQ vs. MTX alone (O Dell)

Studies Studies 1999-20001999-2000 showed only two where combination showed only two where combination therapy was therapy was superiorsuperior MTX+SSZ+HCQ+PRED vs. MTX or other DMARD MTX+SSZ+HCQ+PRED vs. MTX or other DMARD

with or without steroid (Mottonen)with or without steroid (Mottonen) MTX+SSZ+HCQ vs. double or mono of these drugs MTX+SSZ+HCQ vs. double or mono of these drugs

(Calguneri). Study biased in favour of combo as (Calguneri). Study biased in favour of combo as inferior mono used in one third of pts.inferior mono used in one third of pts.

Review of studies since Review of studies since 2000 2000 have shown that step-up have shown that step-up therapy of Leflunomide +MTX is superior but, with therapy of Leflunomide +MTX is superior but, with significant toxicity.significant toxicity.

A caveat is that some of the studies have weaker A caveat is that some of the studies have weaker DMARD and more active pts in monotherapy armDMARD and more active pts in monotherapy arm..

TICORA trial oTICORA trial of conventional f conventional combination treatmentcombination treatment

Tight control was better with intensive Tight control was better with intensive monitoringmonitoring

50% needed to be on MTX+SSP+HCQ50% needed to be on MTX+SSP+HCQ Also, MTX and IA steroids were needed in Also, MTX and IA steroids were needed in

the tight control groupthe tight control group 2/3’s needed dose escalation2/3’s needed dose escalation

New BiologicsNew Biologics

Infliximab ( chimeric monoclonal antibody Infliximab ( chimeric monoclonal antibody to TNF)to TNF)

Etanercept (soluble TNF receptor)Etanercept (soluble TNF receptor) Adalimumab (humanised monoclonal Adalimumab (humanised monoclonal

antibody to TNF)antibody to TNF) Rituximab (anti-CD 20 )Rituximab (anti-CD 20 ) AbataceptAbatacept

Rozman. J Rheumatol. 1998;53:27–32. Moreland. Rheum Dis Clin North Am. 1998;24:579–591.

Optimising treatmentOptimising treatment

Early use of biologics and use as monotherapy Early use of biologics and use as monotherapy or combinationor combination

Combination TNF and MTX in established Combination TNF and MTX in established diseasedisease

TNF blockers in moderate versus severe TNF blockers in moderate versus severe diseasedisease

Tight control of disease activityTight control of disease activity Induction and MaintenanceInduction and Maintenance Switching between biologicsSwitching between biologics

Early diseaseEarly disease

Studies have shown that MTX and TNF blockers Studies have shown that MTX and TNF blockers are clinically similar but, x-ray progression is are clinically similar but, x-ray progression is less in the TNF groupless in the TNF group

This has been shown with both Etanercept and This has been shown with both Etanercept and AdalimumabAdalimumab

TNF InhibitorsTNF Inhibitors

ATTRACTATTRACT BESTBEST TEMPOTEMPO Some of the studies done in Early RA Some of the studies done in Early RA Some studies done in late disease (DMARD Some studies done in late disease (DMARD

refractory ptsrefractory pts Evidence now for giving TNF blockers early Evidence now for giving TNF blockers early

and inducing remission and then using MTX and inducing remission and then using MTX as maintenanceas maintenance

Moderate versus Severe Moderate versus Severe diseasedisease

ADA +MTX for 4 years showed that clinical ADA +MTX for 4 years showed that clinical remission (DAS-28 <2.6) is achieved after 6 remission (DAS-28 <2.6) is achieved after 6 months in those with moderate disease (DAS-28 months in those with moderate disease (DAS-28 <5.1), and 9 months in those with severe <5.1), and 9 months in those with severe disease (DAS-28 >5.1)disease (DAS-28 >5.1)

This was also shown in 4 Etanercept trials and This was also shown in 4 Etanercept trials and was independent of disease durationwas independent of disease duration

Induction RegimesInduction Regimes

ACR -70 responses of 80% in Inflix + MTX in ACR -70 responses of 80% in Inflix + MTX in ERA at 1 yearERA at 1 year

HAQ and QOL better tooHAQ and QOL better too Should we be inducing remission with anti-TNF Should we be inducing remission with anti-TNF

and at 2 years MTX maintenance continuedand at 2 years MTX maintenance continued Larger studies neededLarger studies needed Makes economic senseMakes economic sense

SwitchingSwitching

Anecdoctal evidence shown that TNF switching Anecdoctal evidence shown that TNF switching worksworks

Inflix changing to Ada works in secondary non-Inflix changing to Ada works in secondary non-respondersresponders

Inflix changing to Enb works in primary non-Inflix changing to Enb works in primary non-respondersresponders

Larger RCTS neededLarger RCTS needed

RA Dilemma 3RA Dilemma 3

MS is 38MS is 38 She has tried MTX, and Combination She has tried MTX, and Combination

treatment with MTX and TNF Inhibitorstreatment with MTX and TNF Inhibitors Despite 18 months of treatment her joints Despite 18 months of treatment her joints

are swollen, she has EMS of 1 hour and are swollen, she has EMS of 1 hour and her DAS-28 is 5.2her DAS-28 is 5.2

What do you do?What do you do?

Beyond TNF InhibitorsBeyond TNF Inhibitors AbataceptAbatacept RituximabRituximab Tocilizumab – anti IL-6Tocilizumab – anti IL-6

HuMax – Selective CD-20 B cell depletionHuMax – Selective CD-20 B cell depletion Fully humanised version of RituximabFully humanised version of Rituximab ACR-20 of 50% in pts who have failed one or more DMARDs ACR-20 of 50% in pts who have failed one or more DMARDs

including TNF blockersincluding TNF blockers

Belimumab – Inhibitor of B LymphocyteBelimumab – Inhibitor of B Lymphocyte ACR 20 of 35% in those who have failed one or more DMARDs ACR 20 of 35% in those who have failed one or more DMARDs

including TNF blockersincluding TNF blockers This cohort had disease for 11 years on avgThis cohort had disease for 11 years on avg

Atacicept– Inhibitor of B LymphocyteAtacicept– Inhibitor of B Lymphocyte Only at trial stageOnly at trial stage

Certolizumab – PEGylated anti-TNFCertolizumab – PEGylated anti-TNF Enhanced pharmacokinetics with decreased clearance Enhanced pharmacokinetics with decreased clearance

and enhanced half-lifeand enhanced half-life Trials underwayTrials underway

Golimumab – human anti-TNFGolimumab – human anti-TNF Can be given sc or IVCan be given sc or IV 27% remission rate in refractory disease27% remission rate in refractory disease DAS-28, CDAI, SDAI etc for monitoring response DAS-28, CDAI, SDAI etc for monitoring response

aswell as HAQ aswell as HAQ

Abatacept Abatacept AIM and ATTAIN studiesAIM and ATTAIN studies

This drug blocks the second signal This drug blocks the second signal transduction between the APC and the T transduction between the APC and the T cell, leading to a decrease of downstream cell, leading to a decrease of downstream signal transductionsignal transduction

IV over 30mins, 2 weeks, 4 weeks and IV over 30mins, 2 weeks, 4 weeks and monthly thereaftermonthly thereafter

AIM – ABA+MTX vs Placebo + MTXAIM – ABA+MTX vs Placebo + MTX 29% ACR 70 at 1yr, less x ray progression29% ACR 70 at 1yr, less x ray progression 2 year data similar2 year data similar

ATTAIN – Studied TNF failuresATTAIN – Studied TNF failures ABA+DMARD vs. Placebo+ DMARDABA+DMARD vs. Placebo+ DMARD 391 pts, ACR 20 of 50% at 6 months with ACR 70 of 391 pts, ACR 20 of 50% at 6 months with ACR 70 of

10%10% Open label showed similar resultsOpen label showed similar results

ATTEST – Efficacy and safety trialATTEST – Efficacy and safety trial This compared ABA+MTX and Inflix +MTXThis compared ABA+MTX and Inflix +MTX Equal efficacyEqual efficacy Fewer serious SAEs, serious infections and infusions Fewer serious SAEs, serious infections and infusions

rxns and discontinuations in ABA grprxns and discontinuations in ABA grp

RituximabRituximab

Anti-CD 20Anti-CD 20 2 iv infusions two weeks apart2 iv infusions two weeks apart DANCER trial investigated Ritux in MTX DANCER trial investigated Ritux in MTX

failuresfailures ACR-70 of 20%ACR-70 of 20% A recent meta analysis of RCTs didn’t A recent meta analysis of RCTs didn’t

show increased risk of SAEs with show increased risk of SAEs with rituximab or abatacept but, did with rituximab or abatacept but, did with anakinra in high doses in pts with co-anakinra in high doses in pts with co-morbiditiesmorbidities

CTD -Case 1CTD -Case 1• A 68-year-old man presents with complaints of diffuse A 68-year-old man presents with complaints of diffuse

muscle pain, weakness, and total body fatigue. He muscle pain, weakness, and total body fatigue. He reports:reports:

• Gradual onset over past 6 monthsGradual onset over past 6 months• Morning stiffness lasting 2 to 3 hoursMorning stiffness lasting 2 to 3 hours• Difficulty with getting out of a chair and combing his Difficulty with getting out of a chair and combing his

hairhair• Recent onset of right-sided headacheRecent onset of right-sided headache• Recent onset of jaw pain when eatingRecent onset of jaw pain when eating

ANY IDEAS? FINDINGS ON EXAM?ANY IDEAS? FINDINGS ON EXAM?

Objective FindingsObjective Findings Proximal muscle Proximal muscle

tenderness without tenderness without objective weaknessobjective weakness

Tender right temporal Tender right temporal scalp regionscalp region

Normal visual acuityNormal visual acuity

HELPFUL HELPFUL INVESTIGATIONS?INVESTIGATIONS?

Case 1Case 1

Hb ↓, ESR↑( usually > 40)Hb ↓, ESR↑( usually > 40) CK normalCK normal

DIAGNOSIS?DIAGNOSIS?

Case 1Case 1

Diagnosis:Diagnosis:

Giant cell arteritis with polymyalgia rheumaticaGiant cell arteritis with polymyalgia rheumatica

Case 1Case 1 Based on the clinical findings, what is the most important Based on the clinical findings, what is the most important

next step?next step?

A.A. Treat now with prednisolone 5 mg bid, and observeTreat now with prednisolone 5 mg bid, and observe

B.B. Schedule a temporal artery biopsy for tomorrow Schedule a temporal artery biopsy for tomorrow morning and use the results to determine whether morning and use the results to determine whether prednisone will be usedprednisone will be used

C.C. Start an NSAID at maximal doseStart an NSAID at maximal dose

D.D. Treat now with prednisolone at 40 to 60 mg per day Treat now with prednisolone at 40 to 60 mg per day and schedule temporal artery biopsy in the next few and schedule temporal artery biopsy in the next few daysdays

AnswerAnswer• D. Treat now with prednisolone at 40 to D. Treat now with prednisolone at 40 to

60 mg per day and schedule temporal 60 mg per day and schedule temporal artery biopsy for next weekartery biopsy for next week

• Patients with symptoms of PMR may have Patients with symptoms of PMR may have temporal arteritis temporal arteritis

• Sudden visual loss may occur in TASudden visual loss may occur in TA• The visual loss is usually not reversible The visual loss is usually not reversible

Case 2Case 2 27 y.o female, non- smoker c/o 6 month h(x) of 27 y.o female, non- smoker c/o 6 month h(x) of

light headedness on hanging out the washinglight headedness on hanging out the washing 1 episode of R arm weakness and numbness1 episode of R arm weakness and numbness Generalised aches and pains, weight loss and Generalised aches and pains, weight loss and

night sweatsnight sweats Hypotensive at GP’s (80/50)Hypotensive at GP’s (80/50)

WHAT WOULD YOU LOOK FOR ON WHAT WOULD YOU LOOK FOR ON EXAMINATION?EXAMINATION?

Case 2Case 2

Sys BP 80mmHgSys BP 80mmHg Diastolic BP not recordableDiastolic BP not recordable Absent radial pulses bilat, ↓ R + L brachial Absent radial pulses bilat, ↓ R + L brachial

pulsespulses Absent R carotid pulseAbsent R carotid pulse Normal L carotid pulse and normal femoral Normal L carotid pulse and normal femoral

pulsespulses Normal neuro examNormal neuro exam

INVESTIGATIONS?INVESTIGATIONS?

Case 2Case 2

Hb↑ , WCC normal , ESR ↑Hb↑ , WCC normal , ESR ↑ U + E normalU + E normal ANA weakly positiveANA weakly positive Syphilis serology negativeSyphilis serology negative CXR normalCXR normal CT brain normalCT brain normal

DIAGNOSIS?DIAGNOSIS?

Case 2Case 2

Diagnosis: Takayasu’s arteritisDiagnosis: Takayasu’s arteritis Differential diagnosis of aortic arch Differential diagnosis of aortic arch

syndrome : relapsing polychondritis, syndrome : relapsing polychondritis, syphilitic aortitis syphilitic aortitis

Imaging to assist with diagnosis?Imaging to assist with diagnosis?

Case 3Case 3 A 56 year old man presented to A+E with a fever A 56 year old man presented to A+E with a fever

and difficulty lifting his right foot while walking for and difficulty lifting his right foot while walking for the past few days. He complained of diffuse the past few days. He complained of diffuse myalgia and arthralgia over the previous 4 myalgia and arthralgia over the previous 4 months. He had lost approximately 6kgs in months. He had lost approximately 6kgs in weight over this time. He also reported weight over this time. He also reported intermittent testicular pain.intermittent testicular pain.

His blood pressure was 178/100. He had a right His blood pressure was 178/100. He had a right sided foot drop and a purpuric rash on his legs.sided foot drop and a purpuric rash on his legs.

ANY IDEAS? USEFUL INVESTIGATIONS?ANY IDEAS? USEFUL INVESTIGATIONS?

Case 3Case 3 Investigations:Investigations: Hb 10.6g/dl Hb 10.6g/dl WCC 12*109/l WCC 12*109/l ANCA negativeANCA negative ANA negativeANA negative Plts 242*109/lPlts 242*109/l ESR 60ESR 60 CRP 72CRP 72 Albumin 30Albumin 30

What is the most likely diagnosis?What is the most likely diagnosis?

Case 3Case 3

Polyarteritis nodosa. PAN is a rare systemic Polyarteritis nodosa. PAN is a rare systemic vasculitis characterised by necrotizing vasculitis characterised by necrotizing inflammation of small and medium sized inflammation of small and medium sized arteries. It is a multisystem disease affecting arteries. It is a multisystem disease affecting kidneys, nervous system, gastrointestinal tract, kidneys, nervous system, gastrointestinal tract, cardiac and musculoskeletal systemscardiac and musculoskeletal systems

Case 3Case 3

How would you confirm the How would you confirm the diagnosis?diagnosis?

Is there any virus associated with this Is there any virus associated with this disease?disease?

Name 2 possible medical treatments.Name 2 possible medical treatments.

Case 3Case 3

Coeliac plexus angiogram or renal angiogram may Coeliac plexus angiogram or renal angiogram may reveal evidence of hepatic or renal artery aneurysm reveal evidence of hepatic or renal artery aneurysm and segmental narrowing. Biopsy of affected tissue and segmental narrowing. Biopsy of affected tissue shows PMN cells and granulocytes in the artery shows PMN cells and granulocytes in the artery wall, with necrotizing inflammation of small and wall, with necrotizing inflammation of small and medium muscular arteries.medium muscular arteries.

ANCA is typically negative.ANCA is typically negative.

25% of patients with PAN are Hep B surface 25% of patients with PAN are Hep B surface antigen positiveantigen positive

NAME 2 POSSIBLE MEDICAL TREATMENTSNAME 2 POSSIBLE MEDICAL TREATMENTS

Case 3Case 3

SteroidsSteroids

Cyclophosphamide (for organ specific Cyclophosphamide (for organ specific disease eg renal involvement)disease eg renal involvement)

Case 4Case 4 A 38 year old man was referred to the out- patients A 38 year old man was referred to the out- patients

department with symmetrical joint pain involving his department with symmetrical joint pain involving his knees and wrists for the last 6 months. He also knees and wrists for the last 6 months. He also complained of a sore mouth, malaise and weight loss of complained of a sore mouth, malaise and weight loss of 4kgs over the past 3 months. In his past history he had a 4kgs over the past 3 months. In his past history he had a DVT 2 years ago and reported recurrent episodes of DVT 2 years ago and reported recurrent episodes of painful, red eyes.painful, red eyes.

He was initially assessed by his GP, who performed the He was initially assessed by his GP, who performed the investigations below. He developed a red rash in his investigations below. He developed a red rash in his right antecubital fossa 2 days after this.right antecubital fossa 2 days after this.

Case 4Case 4

Investigations:Investigations: Hb 10g/dl, ESR 40, CRP 67Hb 10g/dl, ESR 40, CRP 67 WCC 8 * 109/l, Plts 220 WCC 8 * 109/l, Plts 220 U + E normal U + E normal

Antiphospholipid, ANA, Rh factor all negativeAntiphospholipid, ANA, Rh factor all negative

What is the most likely diagnosis?What is the most likely diagnosis?

Case 4Case 4

Bechet’s diseaseBechet’s disease

Case 4Case 4

What are the recognised features of this What are the recognised features of this condition?condition?

What is the nature of the rash in his What is the nature of the rash in his antecubital fossa? antecubital fossa?

Case 4Case 4

Orogenital ulcerationOrogenital ulceration Recurrent uveitisRecurrent uveitis Arterial and venous thrombosisArterial and venous thrombosis Recurrent thrombophlebitisRecurrent thrombophlebitis Erythema nodosumErythema nodosum Non-erosive arthritis Non-erosive arthritis Neurological involvement such as TIA’s, seizures and Neurological involvement such as TIA’s, seizures and

meningeal irritationmeningeal irritation

The rash at the site of a needle prick is known as the Pathergy The rash at the site of a needle prick is known as the Pathergy reaction or test. It is due to hypersensitivity of the surrounding skin. An reaction or test. It is due to hypersensitivity of the surrounding skin. An erythematous area develops after 24-48hrs of taking a blood sample. erythematous area develops after 24-48hrs of taking a blood sample. It is more likely to be positive in active disease and certain populatins.It is more likely to be positive in active disease and certain populatins.

Case 5Case 5

A 26-year-old woman presents with small joint A 26-year-old woman presents with small joint arthritis, red rash across cheeks, Hgb 9.3 mg%, arthritis, red rash across cheeks, Hgb 9.3 mg%, ESR 82 mm/s and alopeciaESR 82 mm/s and alopecia

She is very tired with her symptoms and started She is very tired with her symptoms and started NSAIDS with some benefitNSAIDS with some benefit

What is the diagnosis and what drugs would you What is the diagnosis and what drugs would you use?use?

Case 5 contdCase 5 contd

SLESLE

Rx – NSAIDS, Steroids, anti-malarials, Rx – NSAIDS, Steroids, anti-malarials, MMF , CyclophosphamideMMF , Cyclophosphamide AZAAZA RituximabRituximab

Case 6Case 6

A 26-year-old woman presents with progressive A 26-year-old woman presents with progressive weight loss, fevers to 39°C, arthralgias, and weight loss, fevers to 39°C, arthralgias, and ischemic ulcers on the fingersischemic ulcers on the fingers

Physical examination reveals an enlarged spleen Physical examination reveals an enlarged spleen and a harsh midsystolic murmurand a harsh midsystolic murmur

Hgb 9.3 mg%, ESR 82 mm/sHgb 9.3 mg%, ESR 82 mm/s Urinalysis shows 15 to 20 RBCsUrinalysis shows 15 to 20 RBCs

Case 6Case 6

Which of the following would you do first?Which of the following would you do first?A. A. Echocardiogram and blood culturesEchocardiogram and blood cultures

B.B. Renal biopsyRenal biopsy

C.C. Anti-ds DNA antibody levelsAnti-ds DNA antibody levels

D.D. C-reactive protein levelC-reactive protein level

Case 6Case 6

• A. An echocardiogram and blood culturesA. An echocardiogram and blood cultures

• Echocardiogram showedEchocardiogram showedvegetations on the valvesvegetations on the valves

• Blood cultures were positiveBlood cultures were positivefor for Staph aureusStaph aureus

ALWAYS look for mimics of ALWAYS look for mimics of vasculitis that have specific vasculitis that have specific treatmentstreatments

Don’t GuessDon’t Guess

*

Case 7Case 7

A 43-year-old woman has a presumptive diagnosis of A 43-year-old woman has a presumptive diagnosis of Wegener’s granulomatosis based on sinusitis with bone Wegener’s granulomatosis based on sinusitis with bone destruction, abnormal chest x-ray, skin rash, and active destruction, abnormal chest x-ray, skin rash, and active urinary sediment. Which biopsy would provide the highest urinary sediment. Which biopsy would provide the highest diagnostic return?diagnostic return?

A.A. Sinus mucosal biopsySinus mucosal biopsy

B.B. Renal biopsyRenal biopsy

C.C. Open lung biopsyOpen lung biopsy

D.D. Skin biopsySkin biopsy

Case 7Case 7

CC. Open lung biopsy. Open lung biopsy

Case 8Case 8

• A 32-year-old woman comes in Friday A 32-year-old woman comes in Friday morning with intermittent skin rash over morning with intermittent skin rash over the legs for 2 months. Lesions are not the legs for 2 months. Lesions are not painful and resolve with minimal painful and resolve with minimal discoloration discoloration • PMH is positive for chronic sinusitis requiring PMH is positive for chronic sinusitis requiring

antibiotics 3 to 4 times per year antibiotics 3 to 4 times per year • ROS is negative except for a 15-lb weight loss ROS is negative except for a 15-lb weight loss

over the past 2 monthsover the past 2 months

Nonulcerating Nonulcerating palpable purpura over palpable purpura over the lower extremitiesthe lower extremities

Remainder of the Remainder of the examination is examination is unremarkableunremarkable

You order a chest x-ray, CBC, urinalysis, ESR, and metabolic You order a chest x-ray, CBC, urinalysis, ESR, and metabolic screenscreen

She is scheduled to return next TuesdayShe is scheduled to return next Tuesday• You receive the following results inYou receive the following results in

the afternoon:the afternoon:

• Hgb 8.9; ESR 115; Hgb 8.9; ESR 115;

• creatinine 1.6creatinine 1.6

• UA = 20 to 30 RBC;UA = 20 to 30 RBC;

• 3+ protein; no casts3+ protein; no casts• Chest x-ray = Chest x-ray = • multiple infiltratesmultiple infiltrates

What should you do now?What should you do now?A.A. Order an ANA, ANCA, and anti-ds DNA Order an ANA, ANCA, and anti-ds DNA

to be drawn on Tuesdayto be drawn on TuesdayB.Have her seen immediately by your B.Have her seen immediately by your

rheumatology consultantrheumatology consultantC.C. Schedule a rheumatology consult forSchedule a rheumatology consult for

MondayMondayD.D. Call in a prescription for prednisolone atCall in a prescription for prednisolone at

40 mg bid until she is seen on Tuesday40 mg bid until she is seen on Tuesday

• B. Have her seen immediatelyB. Have her seen immediately

• DON’T HESITATEDON’T HESITATE

• For significant major organ dysfunction of For significant major organ dysfunction of unknown duration in suspected vasculitisunknown duration in suspected vasculitis

• Evaluate immediatelyEvaluate immediately• Therapy will depend on obtaining a specific diagnosisTherapy will depend on obtaining a specific diagnosis• Patients can clinically deteriorate suddenlyPatients can clinically deteriorate suddenly

Guidelines about treatmentGuidelines about treatment

Tissue damage with vasculitis requires early Tissue damage with vasculitis requires early diagnosis and treatmentdiagnosis and treatment

Combinations of high-dose steroids and Combinations of high-dose steroids and cytotoxic drugs are commonly usedcytotoxic drugs are commonly used

Effective treatment can improve outcomeEffective treatment can improve outcome There is a delicate balance between treatment There is a delicate balance between treatment

efficacy and toxicityefficacy and toxicity Well-defined clinical outcomes are needed to Well-defined clinical outcomes are needed to

guide the intensity and duration of treatmentguide the intensity and duration of treatment

Summary PointsSummary Points When a patient has a complex multisystem inflammatory When a patient has a complex multisystem inflammatory

picture—think vasculitispicture—think vasculitis If a vasculitic disorder is considered, search for its causeIf a vasculitic disorder is considered, search for its cause Employ tests and biopsies when indicated, but Employ tests and biopsies when indicated, but

remember to treat the patient, not the testremember to treat the patient, not the test Rapid diagnosis and treatment is often organ or Rapid diagnosis and treatment is often organ or

lifesavinglifesaving Consider viral associated rheumatic/vasculitis Consider viral associated rheumatic/vasculitis

syndromes when the autoantibody results are not typicalsyndromes when the autoantibody results are not typical

Treat RA early and appropriatelyTreat RA early and appropriately