INFLAMMATORY MYOPTHIES
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Transcript of INFLAMMATORY MYOPTHIES
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