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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 Tcell clones reactive to Type II collagen • Lysosomal enzyme release eventually results in destruction of the cartilage Diagnostic Criteria Presence of 3 or more: • Recurrent chondritis both auricles • Non-erosive inflammatory polyarthritis • Nasal chondritis • Ocular inflammation • Respiratory tract chondritis • Cochlear &/or vestibular dysfunction 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% Treatment ? Methotrexate, Colchicine, Dapsone, Hydroxychloroquine Treat inflammation-Prednisone Treat pain-NSAIDS Diagnosis 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 Mrs. MJ • PMHx: Transposition of ureters 1983Recurrent UTI’s (prior to surgery 89/year, after surgery 1-2/year) • Allergies: Lactose (hives & difficulty breathing) 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 • Graves disease • Pain • RP Review of Systems System CNS Findings •Pain interferes with sleep Medications •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 HEENT •Cauliflower ears & occasional tinnitus •Flat nose (RP presentation), swollen & painful •Difficulty swallowing Resp •Unremarkable Cardio •Unremarkable Medications 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 Endo Findings •Graves Disease- Tremor Heme •Unremarkable Fluids & •Unremarkable Lytes Medications •Methimazole 5mg od •Propranolol 20mg bid Review of Systems System Findings MSK Bone Scan June 2009 Medications •Methotrexate •Mild arthropathies elbows, •Dapsone •Colchicine shoulders, hips, knees, wrists •Hydroxy•Mild active enthesopathies chloroquine •Prednisone shoulders, hips Review of Systems System Findings Medications MSK BMD 2009 Osteopenic: •Zoledronic acid 5mg March 2009 (annually x 3) •Vit D 1000 units od •Calcium 500mg elemental tid •-2.1 L spine, -2.1 L hip, -1.7 femoral neck •Risks: family hx, steroid use, no weight bearing exercise, Graves disease 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 Pain History 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 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 DRPs • MJ has a prolonged flare of polychondritis and could potentially benefit from re-evaluation of her disease modifying agents Question • 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? Therapeutic Options •No change in therapy •Infliximab •Rituximab •Azathioprine •Cyclophosphamide Clinical Question P 40 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 I C O •6 females & 3 males •Rituximab of varying doses and regimens (1000mg 2 wks apart) •None •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 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 Marie et al. Rheumatology 2009 Design Case Report P I C •38 year-old female with RP and an aortic aneurysm in the abdominal aorta & thickening of the abdominal aortic wall •Infliximab 5mg/kg at weeks 0, 2, 6 and 8, then 5mg/kg every 8 weeks •None •Resolution of ocular inflammation Results •Improved aortic impairment •Asymptomatic at 3 years Buonuomo et al. Rheumatol Int 2009 Design Case Report •14 year-old female with RP- exacerbation of P episcleritis, ear involvement, throat pain, dysphonia (laryngotracheal involvement) I •Infliximab 5mg/kg at weeks 0, 2 and 8 C •None •After 3rd infusion- acute respiratory distress requiring intubation, mechanical ventilation & Results 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 •Chondritis, skin rash, dyspnea, episcleritis resolved over 4 days Results •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 Recommendation • Improve pain control – Discontinue Codeine Contin – Start Morphine 30mg long acting q 12h – Start Morphine IR 5mg prn for breakthrough pain 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 > 400 steps a day ↓ night time awakening due to pain & OH use Patient & Pharmacist Patient & Pharmacist Patient & Pharmacist Daily & at refills Daily & at refills Daily & at refills Duration of therapy Duration of therapy 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 Follow Up- Feb 2010 • 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 Questions? References 1. 2. 3. 4. 5. 6. 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. 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. 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. 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]. RichezC, Dumoulin X, Schaeverbeke T. Successful treatment of relapsing polychondritis with infliximab. Clinical and Experimental Rheumatology 2004;22:629-31. 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.