INFLAMMATORY MYOPTHIES
Dr. M. A. SOFI MD; FRCP; (London);FRCPEdin;FRCSEdin INFLMMATORYMYOPATHIES
Are a group of disorderssharing the common featureof immune-mediatedmuscle injury. Clinical & histopathologicaldistinctions between theseconditions suggest thatdifferent pathogenicprocesses underlie each ofthe inflammatorymyopathies. The most common of thesedisorders include: Dermatomyositis (DM) Inclusion body myositis (IBM) Polymyositis (PM) Overlap syndromes (withanother systemic rheumaticdisease) Neither environmental factorsnor infectious causes haveknown roles in these disorders. All are thought to be due toimmune system abnormalitiesleading to the development ofinflammation in muscle andother tissues. Clinical manifestations
The main symptom commonto the all IM is muscleweakness. Other symptoms that indicateinvolvement of body systemsother than muscle can occur. Muscle weaknessTypicallypatients develop painlessweakness of the proximalin a symmetric pattern affectingboth sides of the body. The smaller distal muscles ofthe hands, wrists, feet, andankles are usually not affected. Difficulty rising from a chair,climbing stairs, or performingtasks such as reaching up to ahigh shelf Grip strength remains normal. At times there may be mildmuscle soreness. The weakness usually developsover several weeks to months. Some patients will developdifficulty swallowing or mayaspirate food into the lungs,which can lead to pneumonia. DM often develop skin rash or other changes in the skin.
Clinical manifestations Skin changes DM often develop skinrash or other changes inthe skin. Rash may occur withoutany muscle weakness . Gottrons sign is a flat redrash over the back of thefingers, elbows or knees. Gottrons papules are red,often scaly, bumpsoverlying the knuckles ofthe fingers. Gottrons sign: Erythematous to violaceous macules, patches, or papules on the extensor surfaces of joints Clinical manifestations
Heliotrope rash Theheliotrope rash islocated on the uppereyelids and is oftenaccompanied by eyelidswelling. Nail abnormalities The nailfolds (the skinaround the fingernails)may become reddenedand may developchanges in the bloodvessels. Heliotrope eruption : Periungual erythema in a patient with dermatomyositis Clinical manifestations
Skin changes Shawl sign The shawlsign is a widespread, flat,reddened area thatappears on the upperback, shoulders, and backof the neck. It can worsenwith exposure toultraviolet light. V sign The V sign has anappearance similar to that ofthe shawl sign, but appearson the front of the chest inthe area of skin exposed by aV-necked sweater. Shawl sign V sign Clinical manifestations
Mechanic's hands Peoplewith dermatomyositis orpolymyositis may developmechanic's hands, aroughening and cracking ofthe skin of the tips andsides of the fingers,resulting in irregular, dirty- appearing lines thatresemble those of a manuallaborer. Scalp Changes in thescalp resembling psoriasisoften occur in people withdermatomyositis. Mechanic's hands in a patient with dermatomyositis Clinical manifestations
Holster sign Generalized Erythederma An erythematous and violaceous rash over the lateral hip, called the "Holster sign," Antisynthetase syndrome
Clinical manifestations Lung diseaseILD occursmost commonly in patientswith anti-synthetaseantibodies in their blood. These patients may developa cough and SOB withexertion that ranges frommild symptoms to severe,progressive respiratorydistress. Antisynthetasesyndrome This subgroup of patientsall have anti-synthetaseantibodies. Anti-Jo-1 antibody isfound in about 20 percentof DM patients. This subgroup ischaracterized by rashes: Mechanics hands interstitial lung disease fever, arthritis, andRaynauds phenomenon. They develop painful calcium deposits on the skin and fascia.
Clinical manifestations Other systemic rheumaticdiseasesWhen myositisaccompanies scleroderma orsystemic lupus, the myositisdoes not always causesymptoms. May have mild muscleweakness, others have onlyabnormal blood muscleenzymes. Cancer Inflammatorymyopathies, especially adultswith dermatomyositis who donot have anti-synthetaseantibodies, have an increasedrisk of cancer. Juveniledermatomyositis Children with inflammatorymyopathy usually but notalways have a DM rash. They develop painfulcalcium deposits on the skinandfascia. Laboratory findings Elevated muscle enzyme:CK, LDH, AST, ALT are allmuscle enzymes that may beelevated Autoantibodies, includingantinuclear antibodies, in upto 80 percent of patients withDM and PM Elevated levels of serum andurine myoglobin The erythrocytesedimentation rate (ESR) isoften normal or is onlymildly elevated, even inpatients with active muscledisease Specific autoantibodies: Myositis-specificautoantibodies are detectedprimarily in patients withinflammatory myositis andwhich may offer informationregarding prognosis andpotential patterns of organinvolvement Myositis-associatedautoantibodies are foundwith other autoimmunerheumatic diseases that maybe associated with myositisespecially in patients withoverlap syndromes Laboratory findings HISTOPATHOLOGY:
Dermatomyositis (DM) and polymyositis (PM)can be distinguished from each other and fromother forms of myopathy by their histopathologicfindings. In patients with dermatomyositis, characteristicfindings may also be seen on skin biopsy, althoughthese findings are very similar on light microscopyto changes that can be seen in systemic lupuserythematosus Differential diagnosis: Inflammatory myopathies
Hypothyroidism (usuallysevere cases). Drug induced: Drugs thatcan cause myopathy include: Statins used fordyslipidemia Prednisone in high andprolonged doses Colchicine used on a dailybasis in patients with kidneydisease. Muscular dystrophies -specific patterns of weaknessand may be familial. Metabolic myopathies (Rare) due to abnormalitiesin enzymes involved in themetabolism of carbohydratesor fats. Electrolyte abnormalities -such as severe potassiumdepletion. Infections - (most commonlyviral). Inclusion body myositis Diagnosis: Inflammatory myopathies
The diagnosis involves acareful history, a thoroughphysical exam, and someblood tests. Nearly all patients withmyositis will have elevationof creatine kinase (CK)levels. Many will have antinuclearantibodies (ANA) or one ofthe anti-synthetaseantibodies in their blood. Some patients will beserologically silent,meaning they have noantibody markers. Magnetic resonance imaging(MRI) scan of the musclescan demonstrateinflammation of muscles. Electromyogram (EMG) candemonstrate abnormalelectrical activity in muscles,also indicating muscleinjury. Muscle biopsy is the mostaccurate test to definitivediagnosis. May not be necessary incases with typicalpresentations andcharacteristic rash. Management: Inflammatory myopathies
Osteoporosis prevention Calcium supplement withvitamin D to preventosteoporosis. Bisphosphonates, are oftenrecommended in patientstreated with prednisone. Exercise Physical therapy andrehabilitation should begin soonafter the diagnosis of DM or PMto prevent contractures Avoidance of sunlight: People with DM should protectthemselves from the sun by usingsunscreen Aspiration prevention Patients who have troubleswallowing must take care to avoidinhaling (aspirating) foods anddrinks. Initial therapy The goals of treatment are toimprove muscle strength and toavoid the development of extra- muscular complications. In patients with dermatomyositis(DM), resolution of cutaneousdisease manifestations is anadditional goal. Management: Inflammatory myopathies
Glucocorticoid regimen: Treatment with high dosesfor the first several monthsto establish disease control Taper to the lowest effectivedose for a total duration of 9to 12 months First 4 6 week at1mg/kgper day withongoing assessment of theclinical response. After weeks at theinitial dose,prednisonetapering should begin by 10mg each week until a dose of40 mg/day is reached. 80% of patients withinflammatory myopathiesimprove withglucocorticoids alone. 50 % of patients with PM donot respond to steroidsalone Glucocorticoid sparing agent: Patients treated withcombination therapy(Predisone + Azothioprin)had better functionaloutcomes and required lessprednisone as maintenancetherapy (1.6 mg/day versus8.7 mg/day) Management: Inflammatory myopathies
Apparent glucocorticoidfailuresThreepossibilities should bereviewed beforeintensifyingimmunosuppression: Alternative diagnoses : Inclusion body myositis Muscular dystrophy Hypothyroidism Glucocorticoid-inducedmyopathy should beconsidered. Unrecognized malignancy associated with myositis may be a cause of failed response to glucocorticoids. Most myositis-associated malignancies are diagnosed within the two-year period before and after the development of myositis. Management: Inflammatory myopathies
Antimalarials: Hydroxychloroquine (200 to 400 mg/day) is effective in up to 75 percent of patients in controlling skin disease but without any benefit to muscle disease. Treatmentcomplications: Side effects of therapyincluded: Cushingoid appearance(71 percent) Psychological orpsychiatric symptoms(35 percent) Osteoporosis (29percent) Infections (29 percent) INFLMMATORYMYOPATHIES
A form of DM, termed amyopathic DM, is acondition in which patients have characteristic skinfindings of DM without weakness or abnormalmuscle enzymes Epidemiology: Combined incidence of (DM) and (PM) has beenestimated at 2 per 100,000 annually . Female to male predominance of about two to one. Peak incidence in adults occurs between the ages of40 and 50. Estimates of prevalence range from 5 to 22 per100,000 . Inclusion Body Myosisits (IBM):
Sporadic inclusion bodymyositis (IBM) isclassified along withpolymyositis,dermatomyositis, andautoimmune necrotizingmyopathy as one of theidiopathic inflammatorymyopathies. However, despite somesimilarities, theclinicopathologicmanifestations of IBM areclearly distinct from theother two disorders EPIDEMIOLOGY IBM is a rare sporadicdisorder with a prevalence of cases per million adults; some estimates of prevalencehave been as high as 70 permillion population. It is the most commonacquired idiopathicinflammatory myopathy inindividuals over the age of 50. The disease affects men moreoften than women. The mean age at onset ofsymptoms is approximately60 years, with a range fromthe third to the ninth decade. Inclusion body myosisits: Clinical features
Muscle weakness is theusual presenting feature. Painless and insidious, andusually presents after theage of 50. Duration of symptoms is 6years before diagnosis. Weakness is asymmetricalin contrast to polymyositis. Fatigue and exerciseintolerance are common Respiratory muscles areusually spared. Dysphagia is problematic in % of patients. Examination Weakness of flexion andextension of the wrist andfingers is disproportionate. Extension of the knee is weakcompared with flexion of thehip. Facial muscle weakness mayoccur, but extra-ocularmuscles are not affected andptosis is not seen Tendon reflexes are usuallysuppressed in myopathy andin this condition it is mostmarked at the knee. Inclusion body myosisits: Investigations
Myositis-specificautoantibodies are typicallyabsent in patients with IBM Muscle biopsy should beperformed in all patientswith suspected IBM, Histopathologicalconfirmation is not alwayspossible Diagnosis may still be madebased on characteristicclinical findings. Muscle enzymes aretypically normal or mildlyelevated in IBM Creatine kinase (CK) levelsgenerally being less than 10times normal ESR or the C-reactiveprotein (CRP), are usuallynormal There is no association withantinuclear antibodies Laboratory findings ELECTROMYOGRAPHY
Characteristicelectromyography (EMG)are often seen ininflammatory myopathy. Such changes are notspecific for the diagnoses ofdermatomyositis orpolymyositis, EMG is normal in 10% ofpatients. Similar findings may occurin various infectious, toxic,or metabolic myopathies MR IMAGING: Magnetic resonance (MR)imaging of skeletal musclesis a noninvasive sensitivebut nonspecific modality fordetecting areas of muscleinflammation and edemawith active myositis,fibrosis, and calcification Inclusion body myosisits: Differential diagnosis
Sarcoidosis (chronicatrophic sarcoidmyopathy) Drug-inducedmyopathies Myotonic dystrophy, type1/2 Myofibrillar myopathies Acid maltase deficiency Hereditary inclusionbody myopathy Motor neuron disease Post polio syndrome Oculopharyngealmuscular dystrophy Late-onset distalmyopathies Overlap myositis Treatment Initial therapy:
The goals of treatment are toimprove muscle strengthand to avoid thedevelopment of extra- muscular complications. In patients with (DM),resolution of cutaneousdisease. Systemic glucocorticoids: Initiation with high dosesfor the first several monthsto establish disease control Start with 1 mg/kg per dayforfirst 6/52 Slowly taper to the lowesteffective dose for a totalduration of therapybetween 9 and 12 months Treatment GlucocorticoidtaperingAfter 4-6weeks tapering shouldbegin. Prednisone should betapered by 10 mg eachweek until a dose of 40mg/day is reached. After one week on 40mg/day, the dose shouldbe tapered by 5 mg eachweek until the 20mg/day. After one week on 20mg/day, the dose shouldbe tapered by 2.5 mgeach week until the 10mg/day After one week on 10mg/day dose should betapered by 1 mg everytwo weeks until thepatient reaches 5mg/day. If no improvement aglucocorticoid-sparingagent should be added Morbidity and mortality and prognosis
Poor prognostic factorsinclude the following: Advanced age Female sex Interstitial lung disease Presence of anti-Jo-1(lung disease) and anti- SRP antibodies (severemuscle disease, cardiacinvolvement) Associated malignancy Delayed or inadequatetreatment Dysphagia, dysphonia Cardiac and pulmonaryinvolvement Morbidity and mortality and prognosis
Complications ofpolymyositis mayinclude the following: Interstitial lung disease Aspiration pneumonia Heart block Arrhythmias Congestive heart failure Pericarditis Dysphagia Malabsorption Pneumonia Infection Myocardial infarction THANK YOU FOR YOUR ATTENTION