Inflammatory Muscle Disease PDF

INFLAMMATORY MUSCLE DISEASE SHAINA GOUDIE, MA MD FRCPC SEPT 2024 OBJECTIVES Identify the presentation of myositis Dermatomyositis Polymyositis Inclusion body myositis Statin induced myopathy Rhabdomyolysis DERMATOMYOSITIS AND POLYMYOSITIS (DM/PM) These are th...

INFLAMMATORY MUSCLE DISEASE SHAINA GOUDIE, MA MD FRCPC SEPT 2024 OBJECTIVES Identify the presentation of myositis Dermatomyositis Polymyositis Inclusion body myositis Statin induced myopathy Rhabdomyolysis DERMATOMYOSITIS AND POLYMYOSITIS (DM/PM) These are the two that I consider to be truly “rheumatic” along with cases where myositis is part of another CTD/overlap syndrome They share some shared epidemiologic traits and clinical criteria Rheumatology These are immune mediated and the general principle of therapy is immunosuppression for that reason  Myositis is prettyrare Acheymuscles TCR common DM/PM EPIDEMIOLOGY These are rare – often queried, less often diagnosed 2-10 cases/million In adults most cases occur between ages 45-65 Middle Age In adults the sex ratio is 2-3:1 F:M Female predominance DM is more likely to overlap with other rheumatic disorders ie lupus  A lone Clinical features DM/PM CLINICAL FEATURES progressive Proximal muscle weakness – objective painless weakness (not aches, pains, stiffness, deconditioning etc) Progressive symptoms over weeks to months oppositeofpolymyalgia Affecting most commonly shoulder girdle, neck flexors, hip flexors proximalmuscles Pharyngeal/esophageal/diaphragmatic/cardiac involvement can occur notthemost common but Facial and ocular involvement is rare and should lead to work up for another disease very worrysome Pain is typically absent or minimal Anything above theneck neuro Other features can include fatigue, weight loss, low grade fever, Raynaud’s, arthritis, lung disease in certain subsets IILD  CLINICAL FEATURES UNIQUE TO DERMATOMYOSITIS mostinteresting Unlike polymyositis, dermatomyositis has extra-muscular features These include skin rashes, of m the muscle 1 other cutaneous features, ILD, and higher risk of malignancy in adult patients (every patient with DM needs careful screen for age appropriate cancers) Espforfits Cutaneous features are: calcinosis, nailfold capillary abnormality, mechanic’s hands 5 yearsof Rashes are: dry fissured thedise ClassicMasher potential Heliotrope (eyes, malar region + nasolabial folds, forehead) Adults Gottron’s papules (dorsum of the hand over the knuckles) only 9ham V-sign (anterior chest and neck) and Holster sign (lateral proximal thigh) carcinosis chiliumkdepiits.fi ndammation calcifmassicDM feature 0500 0 Heliotrope Rash V sign Dialated nail capillaries Holstersign DM/PM INVESTIGATION we want the objective clinical features Elevated serum creatinine kinase usually in the 1000s – would be atypical to have myositis without elevated CK (rare cases of amyopathic dermatomyositis) don'tneedtoknow this forexam Fetess Elevation of other muscle markers – aldolase, AST/ALT, LDH, myoglobinuria Abnormal EMG – specific myopathic changes can be identified (Sn 85%, Sp 33%) Myopathicdischarges Muscle Biopsy – traditional gold standard Muscle MRI – can show sequelae of inflammatory disease (Sn 96-100%) Verysensitive can lightup where the Skin biopsy in DM – shows interface dermatitis, same pathologically as cutaneous lupus muscle is this is whythe location rash is so important inflamme of Muckle vs in b w knuckle  OTHER LAB TESTS CRP and ESR will often be elevated in keeping with inflammatory process Nonspecific In DM we will expect a positive ANA and some myositis specific antibodies (MSAs) diagnostic prognostic MSAs have diagnostic and prognostic value (re: risk of malignancy, additional manifestations, value response to treatment) of ie risk PM tends to be more of a seronegative process malignancy Remember The ANA is like an umbrella and the other antibodies on extended panels fall under it, this is Nodiagnosis why the ANA is not sensitive enough to be diagnostic for anything on it’s own and has a high false positive rate (at least 15% of general population has a nonspecific ANA titre) on ANAalone MSAs include Anti-Jo-1, Anti-SRP, Anti-MI-2, Anti-MDA5 Tpfcantibdies  ANTI-SYNTHETASE SYNDROME Specific subset of a DM-like presentation Characterized by the anti-Jo-1 antibody MSApanel Clinical features include myositis, interstitial lung disease, Raynaud’s phenomenon, symmetric non-erosive small joint arthritis, mechanics hands, fever mechanicshands fissuring cracking of skin unwell PATHOLOGY MuscleBiopsy GoldStandard PM Characterized by vascular sparing, focal endomysial infiltrates, CD 8+ T cell predominant infiltrate DM rashes nail changes makessense to bevascular Characterized by peri-vascular infiltrate, perifasicular fibre atrophy, CD 4+ T cell predominant infiltrate Different location of inflammation well doesn'trespond as notwidespread PMI my vocalizing Helpful DM/PM TREATMENT Immunosuppression! Autoimmune inflammatory process Neck, pharyngeal, esophageal, diaphragmatic, cardiac involvement can be dangerous HighRisk If you pickthis up Steroids: oral up to 1mg/kg with taper or if any of the above trouble spots are involved outside the or there is respiratory compromise admission for IV steroid pulse should be arranged hospitalthey should be Steroid therapy is not sustainable long term at higher doses because of marked side admitted for effect profile Steroids are treatment onlygood shortterm Muscle Atrophy longterm SE foralmosteverything Resp Involvement We offer steroid sparing therapies: case Methotrexate, Azathioprine, Rituximab, IVIg, nappy Mycophenolate (lung and skin disease), Hydroxychloroquine (skin disease) notstrong enoughforActive myositis Adjunctonly INCLUSION BODY MYOSITIS (IBM) thesetendto go to neuro not Rheim Predominantly affect Caucasian males over ages 50 Older whitemales Can be very slow to present, symptoms accruing over months to years Inflammatory weeks months Not DM Characterized by involvement of distal muscles (finger is flexors), more marked thigh involvement (DM/PM more marked usually in proximal arms), more muscle atrophy, more asymmetry vs DM PM symmetric Notasmuchinflammation in themuscles Tbeause itgoes onforsoLon CK can be normal in almost 1/3 of patients with IBM and when elevated tends to be in the Atrophywith 100s, not 1000s Notaselevated as DMPM DM probablywhythey go to neuro Can have some neuropathic changes (loss of deep tendon reflexes) but otherwise extra- Affffy muscular features rare IBM CONTINUED More likely to be seronegative Notacute Inflammatory infiltrate Biopsy will show some chronic inflammatory cells with characteristic red rimmed vacuoles IBM patients do not respond well to immunosuppression and often have no response to prednisone However since a small percentage may respond we do offer 3-6 months of steroids + steroid sparing just in case steroids upfront but practicetooffer a trialof probably wonthelp STATIN MYOPATHY most common drug Induced myopathy canhappen in the short or longterm Occurs in patients on a HMG-CoA reductase inhibitor Mild presentations are common including myalgias, cramps, and on occasion a mildly elevated CK (but may be normal) symptomaticwithmuscle cramps More common on higher doses, generally resolves with medication discontinuation sometimesevenwhen you Small percentage of patients on statin can develop a PM type presentation that is more switch from severe one statin to skin features 0 Extra muscular features The severe type may persist after medication discontinuation and may require treatment as another per DM/PM 5ᵗʰ characteristic inflammation in muscles Characterized by the anti200/100 antibody and a biopsy that shows muscle necrosis without inflammatory infiltrate RHABOMYOLYSIS Rapidbreakdown of skeletalmuscle An acute event leading to rapid break down of skeletal muscle Typically from an injury, over-exertion (Tely 10!), or a toxin crushinjury CK can be in the 10, 000s and can lead to organ failure SuperhighCK This is a problem for your kidneys These pts need to Notseen in inflammatorymyositis Can present with severe myalgias, muscle swelling, weakness be admitted Treatment is hydration, temporary dialysis if needed cutely injured Not mediated by antibodies Immunosuppression needed Nochronic Rnabdo Resolved once treated SUMMARY A variety of processes can affect the muscle Dermatomyositis and polymyositis are the characteristic immune mediated muscle diseases: Painless, Progressive, Objective Weakness clinical A hallmark DM is differentiated by skin and vasculature involvement and strong malignancy risk in adult patients MSAs are useful tests for diagnosis and prognosis (ie, Antisynthetase Syndrome) Treatment is immunosuppression IBM does not respond to immunosuppression and has distal involvement Statin myopathy can rarely be intense but generally improves by stopping the drug Rhabo is an acute injury/insult to muscle causing rapid breakdown of fibres, treat with hydration and renal protection THE END Level appropriate reading includes UpToDate, RheumInfo.com and Rheumatology Secrets [email protected] Office 221-7500