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