Emily O. Jenkins MDAM Report

9.2.09

DermatomyositisInflammatory myopathy

Prevalence: 1:100,000 in general population

Female to male prevalence of 2:1

peak incidence ages 40-50Immune complex

deposition in the vessels considered to be part of a complement-mediated vasculopathy

Hematoxylin and eosin stain (20x) of a muscle biopsy from a patient with dermatomyositis showing perivascular and perimysial inflammation, as well as perifascicular necrosis.

Diagnostic CriteriaBohan and Peter Criteria:

Symmetric proximal muscle weakness most common symptom

typical rashelevated serum muscle enzymesmyopathic changes on EMGcharacteristic muscle biopsy abnormalities and

absence of histopathologic signs of other myopathies

Signs and SymptomsGrotton’s Sign:

An erythematous, scaly eruption over the extensor surfaces of the metacarpophalangeal joints and digits

can mimic psoriasis

Signs and SymptomsHeliotrope rash:

A reddish-purple eruption on the upper eyelid

accompanied by swelling of the eyelid

Most specific rash in DM

Only present in a minority of patients.

Generalized ErythrodermaFacial erythema

Shawl Sign

Flagellate ErythemaErythematous linear

streaks on the trunkprobably induced by

scratching pruritic skin

Skin biopsy usually demonstrates an interface dermatitis, typical of other skin lesions in dermatomyositis

“Mechanic’s Hands”roughened, cracked

skin at tips and lateral aspects of the fingers resulting in irregular, dirty-appearing lines

Nail ChangesCapillary Loop Dilatation

Nail ChangesPeriungual Erythema

Immunopathogenesis Humorally-mediated disorder with cellular infiltrate focused around blood vessels Proinflammatory cytokines contribute to muscle weakness IL-1 and TNF-alpha are increased in muscle tissue Upregulation of MHC class I molecules on myocytes lead to disturbed muscle function

Complications Interstitial lung disease

10% of cases respiratory failure may result from diaphragmatic and chest muscle weakness can result in rapid respiratory failure and death

  Esophageal disease

weakness of the striated muscle of the upper 1/3 of the esophagus and/or oropharyngeal muscles can lead to nasal regurgitation, dysphagia, aspiration More common in elderly patients leads to increased incidence of bacterial pneumonia

  Myocarditis Malignancy

Outcome PredictorsWorse outcomes if:

delay in initial treatment of >6 months after symptom onset

greater weakness at presentationpresence of dysphagiarespiratory muscle weaknessinterstitial lung diseaseassociated malignancycardiac involvementadvanced age

Malignancy in DM PatientsIncidence: of patients with DM, 48%  over age 65 v.

9% under age 65 were found to have a malignancyRisk factors:

Evidence of capillary damage on muscle biopsyDM complicated by cutaneous necrosis on the trunkCutaneous leukocytoclastic vasculitisOlder age at diagnosis

Pathophysiology: paraneoplastic processRegenerating cells in myositis muscle, but not in

normal muscle, express high levels of myositis-specific autoantigens. Same antigens are expressed at high levels in several cancers

Types of cancer: adenocarcinoma of the cervix, lung, ovaries, pancreas, bladder and stomach make up about 70% of associated cancers

Cancer Screening in DM PatientsThorough medical history and physical examAge appropriate cancer screening

(mammogram and colonoscopy)CT of chest, abdomen and pelvis

recommended only if significantly increased risk

Pelvic US and transvaginal US for womenSerum CA 125 and CA 19-9 PSA UA for blood

TreatmentImprove muscle strength and avoid development of

extramuscular complicationsGlucocorticoids are the cornerstone of initial therapyTypically initiate prednisone at 1 mg/kg to a maximum

dose of 80 mgInitial treatment with high doses for the first several

months to establish disease controlSlow taper to the lowest effective dose for total

duration of 9-12 monthsAssessing treatment response: muscle strength

generally a better predictor than serum muscle enzyme concentrations

More than 80% of patients will improve with glucocorticoids alone

Among those who do respond, the majority do not return to normal strength

Glucocorticoid Sparing AgentsStarting a sparing agent at the time prednisone is initiated is

recommendedFirst line agents include azothioprine or methotrexateAzothioprine is preferred if patients have ILD, underlying liver

disease, or are unwilling to abstain from alcohol A randomized trial compared prednisone + azothioprine to pred

alone; no difference in clinical outcomes at 3 months, but at 3 years combination group required less maintenance prednisone

Response to azothioprine may take as long as 4-6 monthsBefore beginning azothoprine, patients should be screened for

thiopurine methytransferase deficiency (TPMT); if heterogeneous for this allele, pts can tolerate azothioprine but require lower daily doses

Homozygous negative pts, occuring in 1:300 people, cannot metabolize the drug and should not receive under any circumstances can lead to disasterous BM toxicity

Initial dose of azothioprine is 50 mg/day