Rheumatology Potpourri. Dr. Philip A. Baer Seacourses Asia CME December 2017

Transcription

1 Rheumatology Potpourri Dr. Philip A. Baer Seacourses Asia CME December 2017

2 Copyright 2017 by Sea Courses Inc. All rights reserved. No part of this document may be reproduced, copied, stored, or transmitted in any form or by any means graphic, electronic, or mechanical, including photocopying, recording, or information storage and retrieval systems without prior written permission of Sea Courses Inc. except where permitted by law. Sea Courses is not responsible for any speaker or participant s statements, materials, acts or omissions.

3 Learning Objectives Diagnose and treat polymyalgia rheumatica (PMR) and giant cell arteritis (GCA) while minimizing the adverse effects of steroid therapy. Distinguish CPPD arthritis from other forms of crystal-induced arthritis, and manage CPPD arthritis appropriately. Recognize different muscle problems associated with statin use, particularly necrotizing autoimmune myopathy (NAM).

4 Case 1 History 76 y.o. woman Controlled hypertension and angina Usually active 2 months history of aching pain in shoulders, upper arms, thighs Morning stiffness 1 hour Limited in daily activities Appetite down; weight loss 8 pounds

5 Case 1 Exam & Labs Exam: Vital signs normal OA hands Tender proximal muscles No weakness Labs: Hgb 106, MCV 88, ESR 65 CK normal, slightly low albumin

6 Musculoskeletal Pain in Older Patients Think polymyalgia rheumatica when Age >60 Proximal muscle myalgias and stiffness without specific muscle weakness High ESR Anemia

7 Polymyalgia Rheumatica (PMR) A clinical syndrome characterized by aching and stiffness of the shoulder and hip girdle muscles affecting older patients, associated with an elevated ESR, lasting over 1 month and responsive to low dose steroids First description in 1888 (Bruce) Barber suggested the present name in 1957

8 PMR: Epidemiology Incidence in Canada: Approximately 50/100,000 patients over age 50/year Predominant age: 60 or older. Incidence increases with age (rare under 50 years old) Predominant gender: Female > Male (2:1)

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10 PMR: Core Inclusion Criteria

11 PMR: Core Exclusion Criteria Active infection Active cancer Active giant cell arteritis (GCA)

12 PMR: Features Suggesting GCA Abrupt-onset headache (usually temporal) and temporal tenderness Visual disturbance, including diplopia Jaw or tongue claudication Prominence, beading or diminished pulse on examination of the temporal artery Upper cranial nerve palsies Limb claudication or other evidence of large-vessel involvement

13 PMR: Other Diseases to Exclude Other inflammatory rheumatic diseases Drug-induced myalgia Chronic pain syndromes Endocrine disease Neurological conditions, e.g. Parkinson s disease

14 PMR: General Principles

15 PMR: Lab Evaluation

16 PMR: Initial Steroid Dose

17 PMR: Initial Therapy and Follow-up A patient-reported global improvement of 70% within a week of commencing steroids is consistent with PMR, with normalization of inflammatory markers in 4 weeks A lesser response should prompt the search for an alternative condition The diagnosis of PMR should be confirmed on further follow-up. Follow-up visits should include vigilance for mimicking conditions Consider low-dose ASA, CV risk assessment, and osteoporosis prophylaxis during follow-up

18 PMR: High Dose Steroids?

19 PMR: NSAIDs?

20 PMR: Steroid Tapering

21 PMR: Steroid Tapering

22 PMR: Immunosuppressants?

23 PMR: Biologics?

24 PMR: Duration of Therapy Usually 1 3 years of treatment, although some will require small doses of steroids beyond this. Steroids may be stopped when the patient is asymptomatic from their inflammatory symptoms. Isolated raised ESR or CRP is not an indication for continuing steroid therapy but may require investigation and referral. Persistent pain may arise from co-existing OA and rotator cuff tears.

25 PMR: Therapy of Relapses Relapse is the recurrence of symptoms of PMR or onset of GCA, and not just unexplained raised ESR or CRP Treatment of relapse: Clinical features of GCA: treat as GCA (usually oral prednisone 40 60mg daily) Clinical features of PMR: increase prednisone to previous higher dose Single i.m. injection of methylprednisolone 120mg can also be used Further relapses: consider introducing DMARD therapy after two relapses

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30 ACR/EULAR PMR Algorithm

31 Relationship between PMR & GCA 10-15% of patients with PMR have GCA 40-60% of patients with GCA have PMR GCA PMR PMR GCA

32 Case 2: History A 68-year-old man presents with complaints of diffuse muscle pain, weakness, and total body fatigue. He reports: Gradual onset over past 6 months Morning stiffness lasting 2 to 3 hours Difficulty with getting out of a chair and combing his hair Recent onset of right-sided headache Recent onset of jaw pain when eating

33 Case 2: Exam and Labs Proximal muscle tenderness without objective weakness Tender right temporal scalp region Normal visual acuity Hgb 98 g/l ESR 85 CK 32

34 Case 2: Question Based on the clinical findings, what is the most important next step? A. Treat now with prednisone 5 mg bid, and observe B. Schedule a temporal artery biopsy for tomorrow morning and use the results to determine whether prednisone will be used C. Start an NSAID at maximal dose D. Treat now with prednisone at 40 to 60 mg per day and schedule temporal artery biopsy in the next few days

35 Case 2: Answer D. Treat now with prednisone at 40 to 60 mg per day and schedule temporal artery biopsy for next week Sudden visual loss may occur in GCA Visual loss occurs in 1/3 of untreated patients The visual loss is usually not reversible Nordberg E, et al. Rheum Dis Clin North Am. 1995;21:

36 Don t Hesitate For probable temporal arteritis: TREAT NOW! BIOPSY LATER! Biopsy as soon as possible Hunder GC. Primer on Rheum Dis. 11th edition. 1997:

37 Elastic stain of temporal artery in GCA: Disruption of elastic lamina and narrowing of the lumen

38 GCA - granulomatous inflammation and multinucleated giant cells

39 DIAGNOSIS OF GCA Halo sign

40 GCA: Dilated Temporal Artery

41 GCA: Optic Atrophy

42 Giant Cell Aortitis Risk of Thoracic Aortic Aneurysm in GCA: 15%

43 GCA: Steroid Therapy GCA without visual symptoms: Prednisone mg daily for 8 weeks Reduce by 5 mg q3-4 weeks to 10 mg daily Then treat as PMR GCA with possible or definite visual symptoms: Prednisone mg daily for 8 weeks Reduce over 4 weeks to 20 mg daily Then treat as uncomplicated GCA

44 GCA: Other Therapies Methotrexate, azathioprine, and other immunosuppressive drugs have been used to limit dosage and duration of corticosteroid therapy. No clear-cut data suggest that any of these drugs is superior to corticosteroid therapy. Anti-TNF therapy with infliximab failed in GCA studies. Anti-IL6 therapy with tocilizumab is now approved for GCA (USA)

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48 Case 3: History 80 y.o. woman, independent, lives alone Occasional aches in knees, wrists Acute swelling of right knee with pain, local warmth and redness Prior episode in L wrist and hand No trauma Low grade fever, no recent infection

49 X-ray: Chondrocalcinosis

50 Aspiration: Bloody fluid

51 Case 3: Labs CBC: WBC 14,000 with left shift egfr 55, uric acid 200 Calcium/PO 4 /Alkaline Phosphatase normal Synovial fluid: WBC 15,000 Thin, bloody fluid Gram stain/culture negative

52 CPPD Disease: Crystals Calcium pyrophosphate crystals Ordinary, polarized, and compensated polarized light microscopy

53 CPPD Disease: Classification Chondrocalcinosis Acute Pseudogout Pyrophosphate Arthropathy

54 Chondrocalcinosis

55 Chondrocalcinosis: Epidemiology Elderly Radiographic evidence: 65-74yr 15% 75-84yr 36% >84yr 50% Male = Female No geographic or racial predisposition

56 CPPD Disease: Clinical Features Acute synovitis Monoarthritis Polyarticular: rare Any joint: commonest in knee : wrist, shoulder, ankle Rapid onset of pain, stiffness and swelling (6-24 hrs) Low-grade fever common

57 CPPD: Pathophysiology

58 CPPD Disease: Triggers

59 CPPD Disease: Diagnosis Observation of calcium pyrophosphate dihydrate crystals in synovial fluid leukocytes in a patient with acute synovitis CPPD crystals are Rhomboid Positively birefringent

60 Synovial Fluid Crystals

61 CPPD Disease: Treatment Principles No definitive therapy for prevention Goals in managing acute attacks reduce symptoms identify and treat any associated or triggering illnesses encourage mobility as inflammation subsides

62 Acute CPPD Disease: Treatment Options Joint aspiration NSAIDs Colchicine (not as effective as for gout) Steroids (not as effective as for gout) oral intra-articular Analgesics

63 Acute CPP Crystal Arthritis: Treatment Options

64 Chronic Pyrophosphate Arthropathy: Clinical Features Findings mimic any type of arthritis Terminology -Pseudo RA -Pseudo OA -Pseudo neuropathic joint disease Distinguishing points-pattern of involvement -Inflammation -Superimposed pseudogout

65 Chronic Pyrophosphate Arthropathy: Epidemiology and Distribution Elderly Female Large/medium joints Knees Wrists, shoulders, elbows Hips, midtarsal, MCPs (2+3)

66 Knee radiograph showing hypertrophic OA features. Note prominent patello-femoral involvement, typical of pyrophosphate arthropathy.

67 Chronic CPPD Arthropathy: Treatment Options Steroid injection Colchicine NSAID + PPI Oral low dose steroids Hydroxychloroquine Methotrexate Surgery to preserve function

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71 June 30, 2016

72 Muscle Fibre: Normal Anatomy

73 Statin-induced Myopathy 1.5-3% of statin users in RCTs and 10-13% of participants enrolled in prospective clinical studies develop myalgias; rates of myositis lower (~ %) & dose-dependent Mean duration of statin therapy before onset of symptoms: 6 months Mean duration of myalgias after stopping statin therapy: 2 months

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75 Statin-induced Myopathy: Questions What if a patient develops a myopathy after several years of taking a statin? Not likely to be statin-induced. 2/3 develop symptoms within 6 months of starting therapy, however it is still possible to develop muscle symptoms at ANY time during treatment. Are some statins more likely to cause muscle damage? Which ones? Lipophilic statins (for example, simvastatin, atorvastatin, lovastatin) are more likely to produce muscular effects than are relatively hydrophilic agents (such as pravastatin, rosuvastatin, and fluvastatin). Lipophilic compounds are more likely to penetrate into muscle tissue, enhancing the potential for myotoxic effects.

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79 Statin-Induced Myopathy: Management Significant muscle symptoms: discontinue statin Asymptomatic but with CK>10x ULN: discontinue statin Rhabdomyolysis: no statins at any time due to risk of recurrence If patient requires a statin but muscle toxicity other than rhabdomyolysis: discontinue statin Once symptoms have resolved and the CK has returned to baseline, can try pravastatin or fluvastatin with careful monitoring

80 Statin-induced Myopathy: Questions When are EMG or muscle biopsy necessary in suspected statin myopathy? EMG and muscle biopsy are often done in atypical cases of statin induced myopathy. These would include those patients with persistent muscle pain after D/C of statin or with persistent, worsening weakness after D/C of statin, or persistently elevated CK long after D/C of statin (several months). Electromyography findings are commonly reported to show myopathic changes, usually in the proximal muscles, in agreement with clinical findings. Muscle pathology in statin induced myopathy is nonspecific, with necrosis, degeneration, and regeneration of fibres and phagocytic infiltration. Is Coenzyme Q10 helpful? Unclear. In one small RCT, 41 patients taking statins who had muscle pain received either coenzyme Q10 or vitamin E. After one month of treatment, 18 of 21 patients taking coenzyme Q10 reported improvement in muscle pain, compared with three of 20 taking vitamin E (P<0.001).

81 Statin-associated necrotizing myopathy Myopathy which persists or progresses after stopping statin Linked to autoantibodies against HMG-CoA reductase Distinct muscle biopsy findings: Macrophagocytic infiltrate engulfing necrotic muscle fibers Responds to immunosuppressant therapy

82 Necrotizing Autoimmune Myositis

83 Statin-associated necrotizing myopathy (NAM) Necrotic muscle fibre undergoing myophagia WITHOUT inflammatory infiltrate (no lymphocytes or neutrophils) & excessive variability of muscle fibre size. The absence of inflammation distinguishes this entity from the idiopathic inflammatory myopathies.

84 Statin-associated necrotizing myopathy (NAM)

85 EMG findings (All Inflammatory Myopathies) Fibrillation, PSWs, CRDs at rest Increased insertional activity

86 Myositis: Non-medical therapies Physiotherapy and Occupational Therapy Aerobic exercise programs after the acute phase Prevent contractures May help with steroid side effects (weight gain, osteoporosis, type 2 fibre atrophy) Speech therapy Especially if concomitant dysphagia

87 Pharmacologic Treatment of Myositis

88 Myositis: Resources

89 Myositis: Resources

90 Myositis: Resources

91 Myositis: Resources

92 Statin-Associated Autoimmune Myopathy: Approach

93 Statin-Associated Autoimmune Myopathy: Approach

94 PEARLs: Rheumatology Potpourri Think of PMR if over age 65 with proximal joint/muscle pain Start high dose steroids immediately if GCA suspected to prevent visual loss Think CPPD in older women with acute monoarthritis and aspirate joint if possible for crystal analysis Consider autoimmune statin-induced myopathy (NAM) in patients where myopathy persists after stopping statins

95 Barriers to Change: Rheum. Potpourri PMR/GCA: Difficulty distinguishing flares from OA and other comorbidities, leading to higher than required use of steroids CPPD: Confusion with gout and with cellulitis Statin-induced NAM: Difficulty recognizing this syndrome given so many patients on statins present with myalgias and high CKs

96 Questions?