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A Case of Cauliflower Ears Hilary Rowe, BScPharm VIHA Pharmacy Resident 2009-10 Pain Clinic Rotation

A Case of Cauliflower Ears Hilary Rowe, BScPharm VIHA Pharmacy Resident 2009-10 Pain Clinic Rotation

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Outline

• Objectives

• Background

• Patient Case

• Clinical Question

• Review of Evidence

• Recommendation

• Monitoring

Objectives

• Describe 1 way inflammation destroys cartilage in relapsing polychondritis (RP)

• Name 3 risk factors for addiction in a pain patient

• Be familiar with the evidence of disease modifying agents in RP

Relapsing Polychondritis

• Destruction of cartilage and replacement with fibrous tissue

• Autoantibodies to type II, IX, XI collagen causes inflammatory infiltration

• Produce Th1 cytokines (TNF-α) by T-cell clones reactive to Type II collagen

• Lysosomal enzyme release eventually results in destruction of the cartilage

Presence of 3 or more:

• Recurrent chondritis both auricles

• Non-erosive inflammatory polyarthritis

• Nasal chondritis

• Ocular inflammation

• Respiratory tract chondritis

• Cochlear &/or vestibular dysfunction

Diagnostic Criteria

Symptoms

•Respiratory tract 56% •Audio-vestibular 46%

•Nasal chondritis 72% •Cardiac and vascular 24%

•Ocular inflammation 65% •Auricular chondritis 89 %

•Polyarthritis 81% •Skin lesions 17%

? Methotrexate, Colchicine,

Dapsone, Hydroxychloroquine

Treat inflammation-Prednisone

Treat pain-NSAIDS

Diagnosis

Treatment

Mrs. MJ

• ID: 40 yo female, ht 155cm, wt 62kg• CC: Acute decline in functioning with

widespread pain and stiffness in joints

• HPI Nov 2009: Current RP flare of longest duration; walking this summer and now in motorized wheel chair since September

• RP diagnosed Aug 2009, polyarthritis since 2005

• PMHx: Transposition of ureters 1983- Recurrent UTI’s (prior to surgery 8-9/year, after surgery 1-2/year)

• Allergies: Lactose (hives & difficulty breathing)

Mrs. MJ

Medications Prior to Assessment at Pain Clinic

Drug Schedule Indication

Tylenol #3 prn Pain

Morphine sulfate 5mg 2 tabs daily Pain

Codeine Contin 100mg SR 3 tabs bid Pain x 3 yrs

Meloxicam 15mg 1 tab daily Pain x 3 yrs

Colchicine 0.6mg 1 tab daily Polychondritis x 1mo

Dapsone 100mg 1 tab daily Polychondritis x 1 mo

Prednisone 5mg 8 tabs daily Polychondritis x 3 yrs

Methotrexate 25mg/mL 1.1 mL inj sc weekly Polychondritis x 3 yrs

Hydroxychloroquine 200mg bid Polychondritis x 3 yrs

Medications Prior to Assessment at Pain Clinic

Trazodone 50mg 4 tabs at hs Sleep

Duloxetine 60mg 1 cap daily Depression & Pain x 4 mo

Senokot prn Constipation

Propranolol 20mg 1 tab bid Graves Disease Tremor

Methimazole 5mg 1 tab daily Graves Disease x 3 yrs

Pantoprazole 40mg Daily Cytoprotection

Zoledronic Acid 5mg 1 inj yearly March 2009 Bone Health

Calcium/Magnesium 3 tabs daily Bone Health

Vit D 1000 units 1 tab daily Bone Health

Mrs. MJ

• Social & Family Hx:

– Lives with husband & two teenagers

– Prior to attack was running an event planning business

– Both parents were alcoholics

• Discharge Plan from Pain Clinic:

– Improve pain control & function

Medical Problem List

Active:• Prolonged flare of RP• Pain• Constipation

Chronic:• Depression • Osteopenia • RP• Graves disease • Pain

Review of Systems

System Findings Medications

CNS •Pain interferes with sleep •Trazodone 200mg at hs•1/4 -1/2 ounce of Vodka

Psych •Depression•Fear of addiction•Opioid Risk Tool : 5

•Duloxetine 60mg od

Score is 5:•3 points family history•1 point age•1 point depression

Other factors:•Drug seeking•Altering routes•Running out early•Rx forgery•Stealing•↑ dose with no change in disease state

Review of Systems

System Findings Medications

HEENT •Cauliflower ears & occasional tinnitus•Flat nose (RP presentation), swollen & painful•Difficulty swallowing

Resp •Unremarkable

Cardio •Unremarkable

Review of Systems

System Findings Medications

GI •Constipation- BM up to 1 week apart

•Senokot •Pantoprazole 40mg od

GU Bone Scan June 2009•Right kidney 50% smaller then left, could be related to scarring •Labs unknown

Liver •Unremarkable

Review of Systems

System Findings Medications

Endo •Graves Disease- Tremor •Methimazole 5mg od•Propranolol 20mg bid

Heme •Unremarkable

Fluids & Lytes

•Unremarkable

Review of Systems

System Findings Medications

MSK Bone Scan June 2009

•Mild arthropathies elbows, shoulders, hips, knees, wrists

•Mild active enthesopathies shoulders, hips

•Methotrexate•Dapsone•Colchicine•Hydroxy-chloroquine•Prednisone

Review of Systems

System Findings Medications

MSK BMD 2009 Osteopenic:

•-2.1 L spine, -2.1 L hip, -1.7 femoral neck

•Risks: family hx, steroid use, no weight bearing exercise, Graves disease

•Zoledronic acid 5mg March 2009 (annually x 3)•Vit D 1000 units od•Calcium 500mg elemental tid

Pain History

Paroxysmal attacks: • Left side more affected then right • Described: red-hot poker stabbing and

digging into her• 20/10 causing her to sob, occurs with

flares • What makes it better-? more medication• What makes it worse- Nothing

Baseline aches: • Widespread: Nose, chest, sternum, jaw,

elbows, back, shoulders, wrists, hands, hips, ankles

• Described: ache• What makes it better-baths, medication• What makes it worse- > 300-400 steps

per a day

Pain History

DRPs

• MJ has a prolonged polychondritis flare and is experiencing additional pain not controlled by her current therapies

• MJ is experiencing constipation secondary to narcotics and immobility and could benefit from a regular bowel routine

• MJ has a prolonged flare of polychondritis and could potentially benefit from re-evaluation of her disease modifying agents

DRPs

• Are there any disease-modifying therapies that might be helpful for Mrs. MJ’s prolonged flare of relapsing polychondritis, taking into consideration the medications she has already tried?

Question

Therapeutic Options

•No change in therapy

•Infliximab

•Rituximab

•Azathioprine

•Cyclophosphamide

Clinical Question

P40 yo female with relapsing polychondritis, with an acute flare causing marked disability

I Disease modifying agent

C Placebo or current therapy

O

Reduce pain

Increase mobility

Slow progression of disease

Reduce morbidity and mortality

Decrease hospitalization

Search Strategy

• PubMed, Embase, Google

• Search terms:

– Relapsing polychondritis

– Disease modifying agents

– Autoimmune diseases

• Found

– 3 case reports, 1 retrospective review

Leroux et al. Arthritis & Rheumatism 2009

Design Retrospective review- 9 patients with RP

P •6 females & 3 males

I•Rituximab of varying doses and regimens (1000mg 2 wks apart)

C •None

O

•CRP & B cell levels•Changes to steroids or immunosuppressant's •CT thorax and inspiratory & expiratory flow volumes•Clinical evaluation

Leroux et al. Arthritis & Rheumatism 2009

Results:

•2 partial remissions

•4 stable

•3 worsened

–2 added new immunosuppressants

–2 increased steroid dose

•6 benefitted- at 12 months 2 remained stable & 4 were worse

Leroux et al. Arthritis & Rheumatism 2009

Limits:

•Retrospective chart review

•No standardized dose or regimen

•Small sample size

•No validated tool

•? 2nd course for partial remission at 6 mo

•1 patient died of sepsis at 7 months

Leroux et al. Arthritis & Rheumatism 2009

Marie et al. Rheumatology 2009

Design Case Report

P•38 year-old female with RP and an aortic aneurysm in the abdominal aorta & thickening of the abdominal aortic wall

I•Infliximab 5mg/kg at weeks 0, 2, 6 and 8, then 5mg/kg every 8 weeks

C •None

Results

•Resolution of ocular inflammation•Improved aortic impairment•Asymptomatic at 3 years

Buonuomo et al. Rheumatol Int 2009

Design Case Report

P•14 year-old female with RP- exacerbation of episcleritis, ear involvement, throat pain, dysphonia (laryngotracheal involvement)

I •Infliximab 5mg/kg at weeks 0, 2 and 8

C •None

Results

•After 3rd infusion- acute respiratory distress requiring intubation, mechanical ventilation & low tracheostomy•CT showed no difference in tracheal thickening

Richez et al. Rheumatol Int 2009

Design Case Report

P•41 year-old male with RP and auricular and vestibular relapse

I •Infliximab 5mg/kg at weeks 0, 6 then q 8 wks

C •None

Results

•Chondritis, skin rash, dyspnea, episcleritis resolved over 4 days•Vestibular dysfunction & deafness NO change•Before 5th infusion episcleritis returned•No new flares at 1 yr & prednisone dose ↓

Goals of Therapy

Patients Goals• Improve pain control• Increase mobility and ADL• Return to work

Team Goals• Improve pain control• Increase mobility and ADL• Slow progression of disease• Decrease morbidity & mortality• Minimize adverse drug events

Recommendation

• No definitive evidence to support suggesting a disease-modifying agent

• Risks and benefits of infliximab should be discussed with patient

• Patient should make an informed decision to start therapy

• Improve pain control

– Discontinue Codeine Contin

– Start Morphine 30mg long acting q 12h

– Start Morphine IR 5mg prn for breakthrough pain

Recommendation

Recommendation

• Codeine Contin ineffective pain 20/10, poor sleep, dose above ceiling effect of 400mg/day

• Morphine is effective for breakthrough pain

• Morphine less potential for abuse then hydromorphone and oxycodone

• SR formulation less potential for abuse

Monitoring

Efficacy

Monitor Who When How Long

Pain Scale rating < 20/10

Patient & Pharmacist

Daily & at refills

Duration of therapy

> 400 steps a day

Patient & Pharmacist

Daily & at refills

Duration of therapy

↓ night time awakening due to pain & OH use

Patient & Pharmacist

Daily & at refills

Duration of therapy

Monitoring

Adverse Events

Monitor Who When How Long

Constipation < 1 BM q 2 days

Patient & Pharmacist

Daily & at refills

While on narcotics

Day time drowsiness

Patient & Family

Daily While on narcotics

Drug seeking

behavior

Pharmacist & Doctor

At refills While on narcotics

• Patient switched from Codeine Contin to Morphine (↓ IR 2 daily to 2-3 nights/wk)

• Currently ↓ prednisone dose

• Patient wanted to trial dapsone & colchicine 1st (DMARD was not started)

• Patient now considering DMARD option

• Constipation improving

Follow Up- Feb 2010

Questions?

References

1. Kahan M, Srivastava A, Wilson L et al. Misuse of and dependence on opioids: study of chronic pain patients. Canadian Family Physician 2006;52:1081-87.

2. Marie I, Lahaxe L, Josse S, Levesque H. Sustained response to infliximab in a patient with relapsing polychondritis with aortic involvement. Rheumatology 2009 Oct;48(10):1328-33.

3. Leroux G, Costedoat-Chalumeau N, Brihaye B, et al. Treatment of relapsing polychondritis with rituximab: a retrospective study of nine patients. Arthritis Rheumatology 2009 May 15;61(5):577-82.

4. Buonuomo PS, Bracaglia C, Campana A, et al. Relapsing polychondritis: new therapeutic strategies with biological agents. Rheumatology International. 2009 Aug 15. [Epub ahead of print].

5. RichezC, Dumoulin X, Schaeverbeke T. Successful treatment of relapsing polychondritis with infliximab. Clinical and Experimental Rheumatology 2004;22:629-31.

6. Porro GB, Lazzaroni M, Imbesi V et al. Efficacy of pantoprazole in the prevention of peptic ulcers, induced by non-steroidal anti-inflammatory drugs: a prospective, placebo-controlled, double-blind, parallel-group study. Digestive and Liver Disease 2000 April; 32(3): 201-208.