Bakri H. Elsheikh, MBBS, FRCP
DESCRIPTION
- Dermatomyositis (DM) is an idiopathic inflammatory myopathy characterized by proximal muscle weakness and characteristic cutaneous findings.
- DM is clinically, histologically, and pathogenically unique compared to the other subtypes of idiopathic inflammatory myopathies: Polymyositis (PM), inclusion body myositis (IBM), and immune-mediated necrotizing myopathy (NM).
EPIDEMIOLOGY
Incidence
- Estimated to be less than 1 per 100,000.
- DM can occur at any age, but there is a peak in adults between 40 and 60 and children between 5 and 15 years of age.
- Incidence is higher in females than in males.
- There is no known racial predilection.
Prevalence
Estimated in a small US population-based study to be 21 per 100,000 persons.
RISK FACTORS
DM can occur in isolation or in association with connective tissue diseases (overlap syndromes) or malignancy.
Genetics
Association with specific HLA alleles is known to occur in some patients.
GENERAL PREVENTION
Exposure to the sun might lead to rash emergence or worsening.
PATHOPHYSIOLOGY
- DM was considered a humorally mediated microangiopathy with evidence of early immunoglobulins and C5b-9 membrane attack complex (MAC) deposition in the perifascicular capillaries causing ischemic damage to perifascicular muscle fibers with subsequent recruitment of CD4+ T helper cells, B cells, and macrophages. This secondary perimysial and perivascular infiltration by inflammatory cells causes further muscle damage.
- Recent evidence, however, suggests the majority of the reported CD4+ cells are actually plasmacytoid dendritic cells (PDC) rather than T helper cells. The PDC cells are part of the innate immune system. They secrete type 1 interferon (IFN) and act as antigen-presenting cells.
- Studies using gene microarray revealed increased expression of type 1 IFN inducible genes and proteins in the perivascular and perimysial regions. This precedes MAC deposition suggesting it is likely a secondary phenomenon.
- These findings led to the hypothesis that overproduction of type 1 IFN by dendritic cells might be toxic to the capillaries and the perifascicular muscle fibers.
ETIOLOGY
Autoimmune etiology as detailed under “Pathophysiology.”
COMMONLY ASSOCIATED CONDITIONS
- Connective tissue disorders including systemic lupus erythematosus (SLE), rheumatoid arthritis, scleroderma, mixed connective tissue disease, and Sjögren's syndrome.
- Malignancy including ovarian, lung, breast, non-Hodgkin's lymphoma, pancreatic, stomach, colorectal, and melanoma. The risk is greatest after the age of 50. Most are identified within 2 years but the risk remains elevated up to 5 years after the diagnosis.
HISTORY
- DM presents with subacute (over weeks) proximal leg and arm weakness and characteristic skin rash. Both insidious (over months) and fulminant (days) course can occur.
- The rash usually precedes or accompanies the weakness. Some patients develop the rash but never develop weakness “DM sine myositis.”
- Dysphagia is reported in up to 30% of patients due to oropharyngeal and esophageal muscle involvement. Chewing can be affected.
- Extramuscular manifestations include:
- Joints: Arthralgia and joint contractures
- Cardiac: Myocarditis, pericarditis, andcongestive heart failure may occur but the majority of patients do not have cardiac symptoms.
- Pulmonary: Aspiration pneumonia and interstitial lung disease (ILD) (10–20%)
- Necrotizing vasculitis: Skin, muscle, retina, GI tract, and kidney especially in juvenile DM
PHYSICAL EXAM
- Symmetric weakness predominantly involves the neck flexors, hip flexors/extensors, and trunk and shoulder girdle muscles.
- Rash
- Heliotrope rash refers to purplish eyelids often associated with periorbital edema. It is the most specific rash for DM.
- Macular erythematous rash can be seen on
- Face, scalp, and anterior chest (V-sign)
- Back and shoulders (shawl sign)
- Knees, elbows, and knuckles (Gottron sign). This can evolve into scaly, papular erythematous lesions over the knuckles (Gottron papules).
- Periungual erythema and dilated capillaries at the base of the fingernails.
- Subcutaneous nodular calcifications over pressure points is more common in juvenile DM.
DIAGNOSTIC TESTS AND INTERPRETATION
Lab
Initial Lab Tests
- Serum creatine kinase is the most sensitive marker for muscle destruction but it can be normal in up to 10% of the patients.
- Alanine transaminase and aspartate transaminase may also be elevated. This might lead to unnecessary liver biopsy. Measurement of gamma-glutamyltransferase can be helpful.
- Antinuclear antibodies are detected in 24–60%, mostly in those with overlap syndrome.
- ESR is usually normal or mildly elevated.
- Some patients have myositis-specific antibodies including anti-Jo-1 and anti-Mi2. Anti-Jo-1 is found in approximately 20% of the cases of PM and DM. Patients usually have ILD, Raynaud phenomena, and/or arthritic complications (anti-synthetase syndrome). Anti-Mi2 found in 15–20% of DM patients is associated with acute onset, florid rash, and good prognosis.
- CBC, blood chemistries, urinalysis, and stool for occult blood may also be checked as part of underlying malignancy work-up.
Follow-Up & Special Considerations
Breast and pelvic examination for women and testicular and prostate examination for men are performed for cancer screening.
Imaging
Initial Approach
- Muscle MRI usually shows signal abnormalities in the affected muscles secondary to edema and inflammation and in chronic cases fatty replacement. Its current use is limited to identifying biopsy site in some patients.
- Chest, abdomen, and pelvis CT scans and mammography are obtained to screen for malignancy. Positron emission tomography scan can be considered if there is high clinical suspicion and the above are negative.
Follow-Up & Special Considerations
N/A
Diagnostic Procedures/Other
- Electromyography is usually abnormal in active disease; however, the findings are nonspecific. Increased insertional activity and abnormal spontaneous activity with fibrillation potentials, positive sharp waves, and occasionally complex repetitive discharges are found. The degree of abnormal spontaneous activity reflects disease activity. Motor unit potentials are polyphasic, of short duration, low amplitude with early recruitment.
Pathological Findings
- Muscle biopsy is invaluable for pathological confirmation of the disease and should be performed in all cases, preferably before starting treatment. The typical pathology is that of perifascicular muscle fiber atrophy. Inflammatory infiltrate composed of macrophages, B cells, and CD4+ cells is seen in the perimysial and perivascular regions. Increased expression of type 1 IFN inducible genes and protein and complement, C5b-9 (MAC) deposition are noted.
DIFFERENTIAL DIAGNOSIS
- Idiopathic inflammatory myopathies (PM, IBM, and NM)
- Connective tissue diseases, such as SLE, and mixed connective tissue disease
- Muscular dystrophies
- Drugs and toxins such as statins, hydroxychloroquine, colchicine, amiodarone, penicillamine, hydroxyurea, cocaine, and heroin
- Infectious myopathies related to viral, bacterial, fungal, and parasitic infections
- Endocrine disorders such as hypothyroidism, Cushing's syndrome, and hyperparathyroidism
MEDICATION
First Line
- Prednisone is the first drug of choice despite the absence of randomized control trials.
- Prednisone: 0.75–1.5 mg/kg/day (maximum dose 100 mg) PO qam for 2–4 weeks then switch directly to qod regimen. Consider daily dosing in diabetics to avoid blood glucose fluctuations. Treat until strength normalizes, plateaus, or 3–6 months have passed, then slowly taper.
- Methylprednisolone is used for patients with severe weakness or non-ambulatory: 1 g IV qd × 3–5 doses followed by oral regimen as above.
- Prescribers should be familiar with side effects, contraindications, and monitoring needed.
- Tuberculin skin test is performed to screen for tuberculosis (TB). Isoniazid treatment is initiated for those with positive PPD (purified protein derivative) or history of TB.
- Corticosteroid is associated with weight gain, hypertension, diabetes, infections, peptic ulcer disease, cataracts, glaucoma, hypokalemia, osteoporosis, and avascular necrosis.
- Concurrent management includes baseline Dexa scan treatment, bone prophylaxis with calcium (1 g/day), and vitamin D supplements (400–800 IU/day). Bisphosphonate is considered in postmenopausal women or those with abnormal Dexa. Bactrim DS 3 times weekly is given for PCP prophylaxis. H2 blockers are prescribed for patients with GI discomfort or history of peptic ulcer disease.
Second Line
- Generally initiated early in those with severe weakness, other organ involvement, unable to tolerate steroids, or failed the steroid taper.
- IVIG: 2 g/kg over 2 days monthly for 3 months. Subsequently decrease or spread out the dose to 1 g/kg monthly or 2 g/kg every 2 months.
- Methotrexate: 7.5–20 mg weekly
- Avoid in ILD because of risk of pulmonary fibrosis. Leucopenia, anemia, infection, and hepatotoxicity are other side effects. Folic acid supplements (1–2 mg/day) are given to all patients. Bactrim increases the risk of myelosuppression.
- Mycophenolate: 1–1.5 g twice daily
- Bone marrow suppression, infections, hypertension, and diarrhea are side effects.
- Azathioprine: 2–3 mg/kg/day
- Flu-like symptoms, hepatotoxicity, pancreatitis, leucopenia, and infections are side effects. Screening for thiopurine methyltransferase deficiency prior to starting the drug helps predict toxicity risk.
- Other used immunosuppressive drugs include cyclosporine, tacrolimus, rituximab, cyclophosphamide, and etanercept.
ADDITIONAL TREATMENT
General Measures
N/A
Issues for Referral
- Dermatology for skin rash
- Ophthalmology for periodic eye examination
Additional Therapies
- Physical therapy to help with range of motions and to maintain strength.
- Assistive devices, such as cane, walker, or wheelchair, might be needed.
- Aspiration precautions and speech therapy evaluation for patients with dysphagia.
COMPLEMENTARY AND ALTERNATIVE THERAPIES
N/A
SURGERY/OTHER PROCEDURES
Surgical excision is considered in some with cutaneous calcinosis as a last resort. Diltiazem, warfarin, colchicine, probenecid, and alendronate are used with variable success.
IN-PATIENT CONSIDERATIONS
Initial Stabilization
N/A
Admission Criteria
Patients are admitted for severe weakness or for treatment of complications (infections, organ failure, etc.).
IV Fluids
N/A
Nursing
N/A
Discharge Criteria
N/A
FOLLOW-UP RECOMMENDATIONS
While on high-dose prednisone patients are seen every 2–4 weeks.
Patient Monitoring
Patients are followed to monitor muscle strength, skin rash, extramuscular complications, and medication side effects.
DIET
- Low-salt, low-carbohydrate, and low-fat diet is recommended for patients on prednisone.
PATIENT EDUCATION
PROGNOSIS
- Generally favorable; however, a number of patients do not respond adequately and remain disabled. Delay in starting therapy, ILD, cardiac involvement, old age, and associated malignancy are associated with poorer prognosis.
COMPLICATIONS
- Are usually related to the side effects of the immunosuppressive medications.
