Inflammatory Diseases of MuscleInflammatory Diseases of Muscle

-- Polymyositis & Dermatomyositis-- Polymyositis & Dermatomyositis

魏正宗魏正宗

中山醫學大學附設醫院中山醫學大學附設醫院過敏免疫風濕科主任過敏免疫風濕科主任、、中藥臨床試驗中心主任中藥臨床試驗中心主任

Tel: 04 24729595 ext 34314; Email: wei3228@gmail.com

醫學系「免疫與感染學醫學系「免疫與感染學 VV 」模組 」模組

學習目標

Inflammatory Diseases of MuscleInflammatory Diseases of Muscle DefinitionDefinition PathophysiologyPathophysiology Clinical manifestationsClinical manifestations DiagnosisDiagnosis TreatmentTreatment PrognosisPrognosis

Weakness, etiologies:Weakness, etiologies:

1.1. NerveNerve

2.2. Neuromuscular junctionNeuromuscular junction

3.3. MuscleMuscle

4.4. PsychogenicPsychogenic

5 subsets of inflammatory myopathies5 subsets of inflammatory myopathies

Proximal muscle weaknessProximal muscle weakness

Shoulders, thighs, trunk and pelvic girdle Shoulders, thighs, trunk and pelvic girdle muscles are most affected.muscles are most affected.

Never facial and ocular musclesNever facial and ocular muscles Esophagus, pharynx and respiratory Esophagus, pharynx and respiratory

muscles may involved.muscles may involved. May arthralgia and myalgiaMay arthralgia and myalgia

Heliotrope signHeliotrope sign

Heliotrope sign:Heliotrope sign:

皮肌炎 Dermatomyositis

V-sign: rash over anterior neck and upper chest

Gottron’s signGottron’s sign

Gottron’s signGottron’s sign

Gottron’s sign and periungual erythemaGottron’s sign and periungual erythema

Periungual erythemaPeriungual erythema

Vasodilatation in capillary microscope

Mechanist hand

Lab Lab

Muscle enzyme– Muscle enzyme– Creatine KinaseCreatine Kinase Indicator of disease activity and severityIndicator of disease activity and severity May be normal in very early, remission or May be normal in very early, remission or

atrophy pts. atrophy pts. CK rise weeks preceding clinical evidence of CK rise weeks preceding clinical evidence of

muscle weaknessmuscle weakness Other muscle enzymes: ALT, AST, LDH, Other muscle enzymes: ALT, AST, LDH,

aldolasealdolase

AutoantibodiesAutoantibodies ANA,ANA, anti-nuclear antibody ~80% anti-nuclear antibody ~80% Anti-ENA,Anti-ENA, extractable nuclear antigen extractable nuclear antigen

Anti-Jo-1Anti-Jo-1• most common myositis-specific autoantibody ~30%. most common myositis-specific autoantibody ~30%. • anti–anti–tRNA synthetasetRNA synthetase syndrome syndrome: Lung iinvolvement, Raynaud's : Lung iinvolvement, Raynaud's

phenomenonphenomenon Anti-SRP antibodiesAnti-SRP antibodies

• signal recognition particle (SRP) : translocation of newly signal recognition particle (SRP) : translocation of newly synthesized proteins into the endoplasmic reticulum. synthesized proteins into the endoplasmic reticulum.

• only in only in polymyositispolymyositis with with severesevere myopathy and aggressive myopathy and aggressive disease disease

Anti-Mi-2 antibodies Anti-Mi-2 antibodies • directed against a helicase involved in transcriptional activationdirected against a helicase involved in transcriptional activation• associated with the relatively acute onset of classic associated with the relatively acute onset of classic

dermatomyositisdermatomyositis with erythroderma and the shawl sign with erythroderma and the shawl sign

EMG of PM/DMEMG of PM/DM

• Triads in 40% of pts: polyphasic, small polyphasic, small amplitude, short amplitude, short durationduration

• Chracteristic but not Chracteristic but not diagnosticdiagnostic

• 15% of pts may be 15% of pts may be normal EMGnormal EMG

Muscle biopsy of polymyositisMuscle biopsy of polymyositis

•Focal and endomysial infiltration of T cell, esp. CD8, with small number of macrophage

•Muscle fiber degeneration and atrophy

Muscle biopsy of dermatomyositisMuscle biopsy of dermatomyositis

Peri-vascular Peri-vascular infiltration of infiltration of inflammatory cells, inflammatory cells, composed of composed of higher percentage higher percentage of of B cell and CD4B cell and CD4 T cells.T cells.

Image studyImage study

MRIMRI Muscle scanMuscle scan

Other systemic features of idiopathic Other systemic features of idiopathic inflammatory myopathyinflammatory myopathy

EsophagealEsophageal Uncoordinated peristalsisUncoordinated peristalsis RefluxReflux DysphagiaDysphagia

GastrointestinalGastrointestinal Uncoordinated peristalsisUncoordinated peristalsis Delayed gastric emptyingDelayed gastric emptying Ischemic necrosisIschemic necrosis

EndocrineEndocrine Autoimmune thyroiditisAutoimmune thyroiditis ““euthyroid sick “syndromeeuthyroid sick “syndrome

Cardiopulmonary featuresCardiopulmonary features

Cardiovascular Cardiovascular manifestationsmanifestations Raynaud’s Raynaud’s

phenomenonphenomenon MyocarditisMyocarditis Conduction Conduction

abnormalitiesabnormalities Heart failureHeart failure

Pulmonary Pulmonary manifestationmanifestation Diffuse interstitial Diffuse interstitial

diseasedisease Pulmonary hypertensionPulmonary hypertension Bronchiolitis obliterans Bronchiolitis obliterans

organizing pneumoniaorganizing pneumonia

Raynaud’s phenomenonRaynaud’s phenomenon

Diagnostic criteria of Diagnostic criteria of Dermatomyositis/PolymyositisDermatomyositis/Polymyositis

1.1. Proximal muscle weaknessProximal muscle weakness

2.2. Increased muscle enzyme(CK)Increased muscle enzyme(CK)

3.3. EMG findingsEMG findings

4.4. Muscle biopsyMuscle biopsy

5.5. Skin lesion Skin lesion -- Gottron's sign, heliotrope sign-- Gottron's sign, heliotrope sign

Myositis in autoimmune diseasesMyositis in autoimmune diseases

Common in scleroderma, SLE, MCTD, Common in scleroderma, SLE, MCTD, Sjogren’s syndromeSjogren’s syndrome

Sometimes in RA, Adult Still’s disease, Sometimes in RA, Adult Still’s disease, Vasculitis syndrome. Esp. Wegner’s Vasculitis syndrome. Esp. Wegner’s granulomatosis and polyarteritis nodosa.granulomatosis and polyarteritis nodosa.

Myositis association with malignancyMyositis association with malignancy

Frequency of malignancy in myositis Frequency of malignancy in myositis derived fromderived from 5% 5%-35%-35%

Most common sites: NPC, Lung, GI, GynMost common sites: NPC, Lung, GI, Gyn Work-up: careful Work-up: careful historyhistory and and PEPE and and

routine laboratoryroutine laboratory, tumor markers, image , tumor markers, image studiesstudies

Approaching DM/PM

Management of PM/DMManagement of PM/DM

Corticosteroid alone (60-100 mg/day)Corticosteroid alone (60-100 mg/day) Immunosuppressive agents in Immunosuppressive agents in

conjunction with corticosteroid conjunction with corticosteroid therapytherapy Hydroxychloroquine (100-200 mg/day)Hydroxychloroquine (100-200 mg/day) AzathioprineAzathioprine (2 mg/kg/d-50 mg/d) (2 mg/kg/d-50 mg/d) MethotrexateMethotrexate (MTX 7.5-25 mg/wk) (MTX 7.5-25 mg/wk) Cyclphosphamide (50-200mg/d)Cyclphosphamide (50-200mg/d) Cyclosporin ACyclosporin A (7.5-10mg/kg/d) (7.5-10mg/kg/d)

Steroid in MyositisSteroid in Myositis

prednisolone1-2 mg/kg/day or prednisolone1-2 mg/kg/day or methylprednisolone pulse therapymethylprednisolone pulse therapy

90% 90% improved after steroid therapy in improved after steroid therapy in weeks to monthsweeks to months

50-75% had complete remission50-75% had complete remission Need slowly tapering of steroidNeed slowly tapering of steroid Tends to occur when taper steroidTends to occur when taper steroid

Resistant diseaseResistant disease

            -  Rituximab (anti-CD20)-  Rituximab (anti-CD20)            -  Intravenous immune globulin (IVIG) -  Intravenous immune globulin (IVIG)

            -  Mycophenolate mofetil-  Mycophenolate mofetil

            -  Tumor necrosis factor inhibitors -  Tumor necrosis factor inhibitors

Unfavorable OutcomeUnfavorable Outcome

MalignancyMalignancy Other collagen vascular diseaseOther collagen vascular disease Raynaud’s phenomenonRaynaud’s phenomenon DysphagiaDysphagia Older ageOlder age Severe or refractory muscle diseaseSevere or refractory muscle disease Cardiac involvementCardiac involvement Pneumonitis/Interstitial lung diseasePneumonitis/Interstitial lung disease

ConclusionsConclusions

Workup of muscle weaknessWorkup of muscle weakness Differential diagnosis of myopathyDifferential diagnosis of myopathy Classification and diagnostic criteria of Classification and diagnostic criteria of

dermatomyositis and polymyositisdermatomyositis and polymyositis Has specific autoantibodiesHas specific autoantibodies Can be controlled by steroid and steroid-Can be controlled by steroid and steroid-

sparing agentssparing agents

ReferencesReferences

eMedicine : Polymyositis/Dermatomyositis eMedicine : Polymyositis/Dermatomyositis http://www.emedicine.com/neuro/topic85.htm

UpToDate UpToDate : Polymyositis/Dermatomyositis : Polymyositis/Dermatomyositis http://www.lib.csmu.edu.tw/overlib/2305.php