Dermatomyositis 

Updated: Sep 26, 2018
Author: Alisa N Femia, MD; Chief Editor: Herbert S Diamond, MD 

Overview

Practice Essentials

Dermatomyositis is an idiopathic inflammatory myopathy with characteristic cutaneous findings that occur in children and adults (see the image below). This systemic disorder most frequently affects the skin and muscles but may also affect the joints; the esophagus; the lungs; and, less commonly, the heart.[1, 2] Dystrophic calcinosis may complicate dermatomyositis and is most often observed in children and adolescents.

These lesions on dorsal hands demonstrate photodis These lesions on dorsal hands demonstrate photodistribution of dermatomyositis. Note sparing of interdigital web spaces.

Signs and symptoms

Persons with dermatomyositis often present with skin disease as one of the initial manifestations, and it may be the sole manifestation at onset in perhaps as many as 40% of individuals with this condition. Cutaneous involvement may manifest as follows:

  • Eruption predominantly on photo-exposed surfaces

  • Pruritus of skin lesions, sometimes intense enough to disturb sleep

  • Erythema of the mid-face

  • Eruption along the eyelid margins, with or without periorbital edema

  • Eruption on the dorsal hands, particularly over the knuckles

  • Changes in the nailfolds of the fingers

  • Eruption of the upper outer thighs

  • Scaly scalp or diffuse hair loss[3]

Muscle disease may occur concurrently, may precede the skin disease, or may follow the skin disease by weeks to years. Muscle involvement manifests as the following:

  • Proximal muscle weakness

  • Muscle fatigue/weakness when climbing stairs, walking, rising from a seated position, combing hair, or reaching for items above shoulders

  • Muscle tenderness: May occur, but not a typical feature of dermatomyositis

Systemic manifestations that may occur include the following:

  • General systemic disturbances, fever, arthralgia, malaise, weight loss, Raynaud phenomenon

  • Dysphagia due to esophageal skeletal muscle involvement

  • Gastroesophageal reflux due to esophageal smooth muscle involvement

  • Dysphonia

  • Atrioventricular defects, tachyarrhythmias, dilated cardiomyopathies

  • Gastrointestinal ulcers and infections, more common in children

  • Pulmonary involvement due to weakness of thoracic muscles, interstitial lung disease

  • Subcutaneous calcification,[4] which may result in contracture of joints; more common in children

  • Children may also develop a tiptoe gait secondary to flexion contracture of the ankles in early childhood

  • Malignancy in adult patients

See Clinical Presentation for more detail.

Diagnosis

Examination for cutaneous dermatomyositis may reveal the following findings:

  • Characteristic, possibly pathognomonic cutaneous features: Heliotrope, Gottron papules

  • Characteristic but not pathognomonic features: Malar erythema, violaceous erythema or poikiloderma in a photosensitive distribution, violaceous erythema on the extensor surfaces, and periungual and cuticular changes

    • Violaceous erythema or poikiloderma involving the anterior chest is referred to as the “V-neck sign” whereas involvement of the upper back and shoulders is referred to as the “shawl sign”

  • Rare cutaneous manifestations include vesiculobullous erosive lesions and an exfoliative erythroderma, which may be more common in patients with an associated malignancy than in those without a malignancy; biopsy samples of these manifestations reveal an interface dermatitis similar to that seen in biopsy samples of heliotrope rash, Gottron papules, poikiloderma, or scalp lesions

Examination for muscle disease in dermatomyositis may demonstrate the following:

  • Quadriparesis involving proximal musculature

  • Difficulty rising from a seated or supine position without support

  • Extensor muscles often more affected than the flexor muscles

  • Neck flexor muscle weakness

  • Distal strength, sensation, and tendon reflexes maintained (unless the patient has severely weak and atrophic muscle)

Testing

Laboratory and other studies that may be helpful include the following:

  • Muscle enzyme levels (eg, creatine kinase, aldolase, aspartate aminotransferase, lactic dehydrogenase)

  • Myositis-specific antibodies

  • Antinuclear antibody levels

  • Pulmonary function studies with diffusion capacity

  • Electrocardiography

  • Esophageal manometry

  • Colonoscopy to screen for underlying malignancy

  • Papanicolaou smear in women for malignancy screening

  • CA-125 and CA-19-9 for malignancy screening

Imaging studies

The following imaging studies may be used in the evaluation of dermatomyositis:

  • MRI or ultrasonography of the muscles

  • Chest radiography

  • Barium swallow

  • Electromyography

  • Imaging to screen for underlying malignancy, including CT scanning of the chest, abdomen, and pelvis, as well as transvaginal ultrasound and mammography for women

Procedures

The following procedures may be helpful in the evaluation of dermatomyositis:

  • Skin biopsy

  • Muscle biopsy (open or via a needle): Findings can be diagnostic (perivascular and interfascicular inflammatory infiltrates with adjoining groups of muscle fiber degeneration/regeneration)

See Workup for more detail.

Management

Therapy for the muscle component of dermatomyositis involves the use of corticosteroids, typically with an immunosuppressive agent. Therapy for the skin disease includes the following, among other options:

  • Sun avoidance

  • Sunscreens and photoprotective clothing

  • Topical corticosteroids

  • Antimalarial agents

  • Methotrexate

  • Mycophenolate mofetil

  • Immune globulins

Pharmacotherapy

Medications used in the management of dermatomyositis include the following:

  • Corticosteroids (eg, prednisone): Prednisone is a first-line therapy for muscle involvement in dermatomyositis

  • Immunosuppressive agents (eg, methotrexate, mycophenolate mofetil, azathioprine, rituximab, sirolimus)

  • Immune globulins (eg, intravenous or subcutaneous immunoglobulin)

  • Antimalarial agents (eg, hydroxychloroquine, chloroquine)

In addition to the medications listed above, diltiazem, colchicine, alendronate, and warfarin are among the medications that have shown potential benefit in treating calcinosis. Surgical excision of focal, tender calcinotic lesions is also considered a therapeutic option.

Nonpharmacotherapy

General therapeutic measures may include the following:

  • Physical therapy and rehabilitative measures

  • Sun avoidance

  • Sun-protection (eg, broad-spectrum sunscreens, sun protective clothing)

  • Elevation of head of bed

  • Avoidance of eating before bedtime

Surgery

Surgical care is usually unnecessary in the management of dermatomyositis. However, some patients may benefit from surgical removal of localized areas of calcinosis, particularly those that are painful.

See Treatment and Medication for more detail.

Background

Dermatomyositis is an idiopathic inflammatory myopathy (IIM) with characteristic cutaneous findings. It is a systemic disorder that most frequently affects the skin and muscles, but may also affect the joints; the esophagus; the lungs; and, less commonly, the heart.[1, 2] Calcinosis is a complication of dermatomyositis that is observed most often in children and adolescents. An association between dermatomyositis and cancer has long been recognized in adult patients.[5, 6, 7, 8, 9, 10]

In 1975, Bohan and Peter first suggested a set of five criteria to aid in the diagnosis and classification of dermatomyositis.[11, 12] Four of the five criteria are related to the muscle disease, as follows:

  • Progressive proximal symmetrical weakness

  • Elevated levels of muscle enzymes

  • An abnormal finding on electromyography

  • An abnormal finding on muscle biopsy

The fifth criterion is compatible cutaneous disease.

In addition to dermatomyositis, Bohan and Peter suggested the following four subsets of myositis[12] :

  • Polymyositis

  • Myositis with malignancy

  • Childhood dermatomyositis/polymyositis

  • Myositis overlapping with another collagen-vascular disorder

In a subsequent publication, Bohan et al noted that cutaneous disease may precede the development of the myopathy in patients with dermatomyositis.[11] In addition, the existence of another subset of patients with dermatomyositis that affects only the skin (ie, amyopathic dermatomyositis [ADM], or dermatomyositis sine myositis) has been recognized. Finally, another subset of patients with dermatomyositis are those with controlled myopathy who continue to have severe and sometimes debilitating skin disease (ie, postmyopathic dermatomyositis).

ADM is diagnosed in patients with typical cutaneous disease who show no evidence of muscle weakness and in whom serum muscle enzyme levels are repeatedly normal over a 2-year period in the absence of the use of disease-modifying therapies such as corticosteroids, immunosuppressive agents, or both for 2 months or longer.

When studied, some ADM patients may have abnormal findings on ultrasonography, electromyography, magnetic resonance imaging (MRI), magnetic resonance spectroscopy, or muscle biopsy. These patients are better classified as having hypomyopathic dermatomyositis. ADM or hypomyopathic DM may also be related to an underlying malignancy.

The term clinically amyopathic dermatomyositis (CADM) is often used to encompass patients with both amyopathic and hypomyopathic dermatomyositis.[13] CADM is estimated to account for about 20% of patients with dermatomyositis,[14] and one large review suggests that CADM is associated with malignancy and lung disease as frequently as classic dermatomyositis.[15] In addition, some patients with CADM develop severe pulmonary disease, particularly persons from Asian countries.[16]

Patients exist in whom myositis resolves after therapy but skin disease remains an active and important feature of the disorder. These patients are not classified as having ADM, even though by this point the skin lesions are the major and often only manifestation of the disease. Germani and colleagues have suggested the term postmyopathic dermatomyositis for these patients.[17]

Therapy for the muscle component of dermatomyositis involves the use of systemic corticosteroids, with or without an immunomodulatory agent. The skin disease is treated with sun avoidance, sunscreens, photoprotective clothing, topical corticosteroids, antimalarial agents, methotrexate, mycophenolate mofetil, or intravenous immunoglobulin (IVIG). Systemic corticosteroids are generally not administered for cutaneous involvement. Rituximab may be useful in the treatment of muscle disease in dermatomyositis, and has had mixed results in treatment of skin disease.[18, 19, 20]

Physical therapy and rehabilitative measures are necessary in selected patients. Sun protective measures are necessary for patients with skin disease. Patients may visit The Myositis Association Web site for more information.

The prognosis of dermatomyositis depends on the severity of the myopathy, the presence of malignancy, and/or the presence of esophageal and/or cardiopulmonary involvement. Residual weakness is common, even in patients who fully recover.

For discussion of dermatomyositis in pediatric patients, see Juvenile Dermatomyositis.

Pathophysiology

Dermatomyositis is considered to be the result of a humoral attack against the muscle capillaries and small arterioles (endothelium of the endomysial blood vessels). Since 1966, there has been evidence supporting an ongoing microangiopathy.[21]

The disease starts when putative antibodies or other factors activate C3, forming C3b and C4b fragments that lead to formation of C3bNEO and membrane attack complex (MAC), which are deposited in the endomysial vasculature. Complement C5b-9 MAC is deposited and is needed in preparing the cell for destruction in antibody-mediated disease. B cells and CD4 (helper) cells are also present in abundance in the inflammatory reaction associated with the blood vessels.

As the disease progresses, the capillaries are destroyed, and the muscles undergo microinfarction. Perifascicular atrophy occurs in the beginning; however, as the disease advances, necrotic and degenerative fibers are present throughout the muscle.

The pathogenesis of the cutaneous component of dermatomyositis is poorly understood, but is thought to be similar to that of muscle involvement.

Studies on the pathogenesis of the muscle component have been controversial. Some suggest that the myopathy in dermatomyositis is pathogenetically different from that in polymyositis. The former is probably caused by complement-mediated (terminal attack complex) vascular inflammation, the latter by the direct cytotoxic effect of CD8+ lymphocytes on muscle. However, other cytokine studies suggest that some of the inflammatory processes may be similar. One report has linked tumor necrosis factor (TNF) abnormalities with dermatomyositis.[22]

Etiology

The cause of dermatomyositis is unknown. However, genetic, immunologic, infectious, and environmental factors have been implicated.

A genetic component may predispose to dermatomyositis. Dermatomyositis rarely occurs in multiple family members, but a link to certain human leukocyte antigen (HLA) types (eg, DR3, DR5, DR7) may exist.

Polymorphisms of tumor necrosis factor (TNF) may be involved; specifically, the presence of the -308A allele is linked to photosensitivity in adults and calcinosis in children.[22, 23, 24] A meta-analysis demonstrated that the TNF-α-308A/G polymorphism might contribute to dermatomyositis susceptibility, especially in a European population.[25]

Immunologic abnormalities are common in patients with dermatomyositis. Patients frequently have circulating autoantibodies. Abnormal T-cell activity may be involved in the pathogenesis of both the skin disease and the muscle disease. In addition, family members may manifest other diseases associated with autoimmunity.

Antinuclear antibodies (ANAs) and antibodies to cytoplasmic antigens (ie, antitransfer RNA synthetases) may be present. Although their presence may help to define subtypes of dermatomyositis and polymyositis, their role in pathogenesis is uncertain.

Infectious agents have been suggested as possible triggers of dermatomyositis. These include the following:

Cases of drug-induced dermatomyositis have been reported. Dermatomyositis-like skin changes have been reported with hydroxyurea in patients with chronic myelogenous leukemia or essential thrombocytosis.[26, 27] Other agents that may trigger the disease include the following:

  • Statins
  • Penicillamine
  • Anti–tumor necrosis factor drugs
  • Anti–programmed cell death drugs [28]
  • Interferon
  • Cyclophosphamide
  • Bacillus Calmette-Guérin (BCG) vaccine
  • Quinidine
  • Phenylbutazone (no longer approved or marketed for human use in the United States)

Dermatomyositis may be initiated or exacerbated by silicone breast implants or collagen injections, but the evidence for this is anecdotal and has not been verified in case-control studies. One report detailed HLA differences among women in whom inflammatory myopathy developed after silicone implants.[29]

Epidemiology

The estimated incidence of dermatomyositis is 9.63 cases per million population. The estimated incidence of AMD is 2.08 cases per million.[14]

Dermatomyositis can occur in people of any age. Two peak ages of onset exist: in adults, the peak age of onset is approximately 50 years, whereas in children, the peak age is approximately 5-10 years. Dermatomyositis and polymyositis are twice as common in women as in men. Neither condition shows any racial predilection.

Prognosis

Dermatomyositis may spontaneously remit in as many as 20% of affected patients. About 5% of patients have a fulminant progressive course with eventual death. However, patients who survive the disease may experience residual weakness and disability. Children with severe dermatomyositis may develop contractures. Therefore, many patients require long-term therapy.

Risk factors for a poorer prognosis in patients with dermatomyositis include the following:

  • An associated malignancy
  • Cardiac, pulmonary, or esophageal involvement
  • Older age (ie, >60 years)

Dermatomyositis may cause death because of muscle weakness or cardiopulmonary involvement. Patients with an associated cancer may die of the malignancy.

The association between malignancy and dermatomyositis has long been recognized. An estimated 25% of patients with dermatomyositis have or will develop an associated malignancy, and the risk appears to remain elevated for 3-5 years.[30, 31, 32] Strong data from Scandinavia, Australia, North America, and Asia continue to confirm this association with malignancy, and existing data supports that patients with CADM have a similar malignancy risk to those with classic dermatomyositis.[17, 31, 32, 33, 34, 35, 36]

Ovarian cancer is clearly over-represented in patients with dermatomyositis; however, any malignancy may occur. Reported maligancies include lung, colon, prostate, breast, pancreatic, cervical, and hematologic malignancies.[37] Predilection for certain types of malignancy may be more common in specific populations. For example, nasopharyngeal carcinoma appears to be over-represented in certain Asian populations.[38, 39, 40]

In an approximately 10-year retrospective study from southern China, 60 of 246 dermatomyositis patients developed malignancies. The risk of malignancy was highest in the first year after diagnosis of dermatomyositis, and nasopharyngeal carcinoma and ovarian carcinoma were the most common malignancies. Male gender, dysphagia and elevated erythrocyte sedimentation rate were risk factors for malignancy, whereas the presence of interstitial lung disease appeared to reduce the risk of malignancy.[41] Older age appears to be the strongest predictor of malignancy in patients with dermatomyositis.

Calcinosis may also complicate dermatomyositis. It is rare in adults but is more common in children and has been linked to delay in diagnosis and to less-aggressive therapy.[42] Contractures can occur if the patient is immobile.

Population-based studies from British Columbia concluded that patients with dermatomyositis (or polymyositis) are at increased risk for venous thromboembolism (deep venous thrombosis or pulmonary embolism)[43] and myocardial infarction,[43] especially in the first year after diagnosis. However, dermatomyositis was not associated with an increased risk of ischemic stroke.[43]

A study from Taiwan reported that the risk of osteoporosis in persons with dermatomyositis (or polymyositis) was 2.99 times higher than in those without these disorders. This risk was independent of treatment with corticosteroids and immunosuppressant drugs.[44]

In a study of patients with dermatomyositis with cutaneous involvement, 28 of 74 achieved clinical remission of the skin disease during a 3-year follow-up period. Clinical remission of skin disease was more likely to occur in older patients (odds ratio [OR], 1.07; 95% CI, 1.02-1.12; P = 0.01), those with a dermatomyositis-associated malignancy (OR, 14.46; 95% CI, 2.18-96.07; P =0 .01), and those treated with mycophenolate mofetil (OR, 6.00; 95% CI, 1.66-21.78; P = 0.01). Patients with antimelanoma differentiation–associated protein 5 antibodies had a significantly lower probability of achieving clinical remission.[45]

African Americans and patients in lower socioeconomic groups are more likely to experience a delay in diagnosis. The prognosis in children with dermatomyositis is worse in those in whom diagnosis is delayed.

Overall, data suggest that the mortality rate in persons with dermatomyositis is higher than that in the general population. Population-based data from Sweden demonstrate that mortality in idiopathic inflammatory myopathies is increased within 1 year of diagnosis and plateaus around 10 years after diagnosis, with the increase in mortality largely attributed to malignancy, as well as to diseases of the respiratory and vascular systems.[46]

 

Presentation

History

Persons with dermatomyositis often present with skin disease as one of the initial manifestations. In perhaps as many as 40% of individuals with dermatomyositis, the skin disease is the sole manifestation at onset. Muscle disease may occur concurrently, may precede the skin disease, or may follow the skin disease by weeks to years.

Muscle involvement manifests as proximal muscle weakness. Affected patients often begin to note muscle fatigue or weakness when climbing stairs, walking, rising from a sitting position, combing their hair, or reaching for items in cabinets that are above their shoulders. Muscle tenderness may occur but is not a regular feature of dermatomyositis.

Systemic manifestations may occur; therefore, the review of systems should assess for the presence of arthralgia, arthritis, dyspnea, dysphagia, arrhythmia, and dysphonia.

Malignancy is possible in any adult patient with dermatomyositis, but it is more common in adults older than 60 years. Only a handful of children with dermatomyositis and malignancy have been reported, and malignancy does not appear to be over-represented in the pediatric (ie, < 16 years) population.

A thorough history, review of systems, and assessment for previous malignancy should be performed in all patients with dermatomyositis to aid in evaluation for an associated malignancy. In the pediatric population, no further screening is recommended, whereas in the adult population, most experts support a thorough search for malignancy with age-related malignancy screening as well as blind imaging to rule out underlying malignancy.

Dermatomyositis in children is characterized by muscle weakness and resembles the adult form of the disease. Children commonly develop a tiptoe gait secondary to flexion contracture of the ankles in early childhood. Children tend to have extramuscular manifestations, especially gastrointestinal (GI) ulcers and infections, more frequently than adults. Extramuscular manifestations of the disease may include the following:

  • General systemic disturbances, fever, arthralgia, malaise, weight loss, Raynaud phenomenon

  • Dysphagia

  • Gastroesophageal reflux

  • Atrioventricular defects, tachyarrhythmias, dilated cardiomyopathies

  • GI ulcers and infections

  • Contracture of joints

  • Pulmonary involvement due to weakness of thoracic muscles, interstitial lung disease

Na et al found the frequency of subcutaneous calcifications to be significantly higher in juvenile dermatomyositis than adult dermatomyositis.[4]

Several reports describe drug-induced dermatomyositis or existing dermatomyositis exacerbated by certain drugs, including statins and interferon therapy. Consequently, a medication history should be elicited in all patients.[47]

Physical Examination

Dermatomyositis is a disease that primarily affects the skin and the muscles, but may also affect other organ systems. The possibly pathognomonic cutaneous features of dermatomyositis are a heliotrope rash and Gottron papules.

The heliotrope rash consists of a violaceous to erythematous rash, with or without edema, in a symmetrical distribution involving the periorbital skin (see the image below). Sometimes this sign is subtle and may consist of only a mild discoloration along the eyelid margin. Similar to other areas, scale may be present on the eyelids. A heliotrope rash is rarely observed in other disorders; therefore, its presence is highly suggestive of dermatomyositis.

Heliotrope rash in a woman with dermatomyositis. Heliotrope rash in a woman with dermatomyositis.

Gottron papules are flat-topped, erythematous to violaceous papules and plaques found over bony prominences, particularly the metacarpophalangeal joints, the proximal interphalangeal joints, and/or the distal interphalangeal joints. See the image below. They may also be found overlying the elbows, the knees, and/or the feet. A slight scale overlying the papules may be present, and, occasionally, a thick psoriasiform scale is observed. Gottron papules may clinically resemble lesions of lupus erythematosus; lichen planus; or, particularly in the event of psoriasiform scaling, psoriasis.

Gottron papules and nailfold telangiectasia are pr Gottron papules and nailfold telangiectasia are present in this patient with dermatomyositis.

Characteristic but not pathognomonic features include the following:

  • Malar erythema

  • Poikiloderma in a photosensitive distribution

  • Violaceous erythema on the extensor surfaces

  • Periungual and cuticular changes

Poikiloderma, which consists of erythema, hypopigmentation, hyperpigmentation, and telangiectasias, may occur on photoexposed skin, such as the extensor surfaces of the arm; the upper chest, in a "V-neck" configuration (see the image below); the upper back (shawl sign); or the lateral thighs (holster sign).

Dermatomyositis is often associated with a poikilo Dermatomyositis is often associated with a poikiloderma in a photodistribution.

Patients often notice an eruption on photoexposed surfaces. The disease is often pruritic, and, sometimes, intense pruritus may disturb sleep patterns. Patients may also complain of a scaly scalp or diffuse hair loss (see the image below).[3]

Diffuse alopecia with scaly scalp dermatosis is co Diffuse alopecia with scaly scalp dermatosis is common in patients with dermatomyositis.

Dilated capillary loops at the base of the fingernail are characteristic of dermatomyositis. Dropout of nailfold capillaries is also seen, along with cuticular hypertrophy and ragged cuticles. In patients with mechanic's hands, the palmar and lateral surfaces of the fingers may become rough and cracked. Mechanic's hands are linked to an increased risk of pulmonary disease as part of the anti-synthetase syndrome.

The above-mentioned pathognomonic and characteristic cutaneous lesions typically demonstrate interface dermatitis on histopathology. Other cutaneous lesions have been described in patients with dermatomyositis that do not reflect these interface changes. These include panniculitis (see the following image) and urticaria, as well as hyperkeratosis of the lateral palms and digits known as mechanic's hands, which has been associated with anti-synthetase antibodies.[48]

Calcifying panniculitis in patient with dermatomyo Calcifying panniculitis in patient with dermatomyositis.

Other rare skin findings include the following:

  • Cutaneous mucinosis

  • Follicular hyperkeratosis

  • Hyperpigmentation

  • Ichthyosis

  • White plaques on the buccal mucosa

  • Cutaneous vasculitis

  • Flagellate erythema

  • Diffuse subcutaneous edema

  • Vesiculobullous or erosive lesions

  • Exfoliative erythroderma

Children with dermatomyositis may have an insidious onset that hides the true diagnosis until the dermatologic disease is clearly observed and diagnosed. Calcinosis is a complication of juvenile dermatomyositis (see the image below), but it is rarely observed at the onset of disease. The prognosis in children with dermatomyositis is worse in those in whom diagnosis is delayed.

Calcinosis caused by dermatomyositis in childhood Calcinosis caused by dermatomyositis in childhood can be observed in patient who had active dermatomyositis 15 years before time of this photograph.

Muscle disease commonly manifests as a proximal symmetrical muscle weakness. The degree of weakness may range from mild to moderate to severe; sometimes, quadriparesis is observed. Patients may have difficulty rising from a chair or squatting and then raising themselves from this position. Sometimes, in an effort to rise, patients use other muscles that are not as affected.

Testing of muscle strength is part of each patient assessment. Often, the extensor muscles of the arms are more affected than the flexor muscles. Distal strength is almost always maintained. Neck flexor weakness may also be seen.

Muscle pain and tenderness may be observed early in the course of the disease; muscle tenderness is a variable finding. Sensation is normal, and tendon reflexes are preserved unless the muscle is severely weak and atrophic.

Other systemic features include joint swelling, changes associated with Raynaud phenomenon, and abnormal findings on cardiopulmonary examination. When joint swelling occurs, the small joints of the hands are the most frequently involved. The arthritis associated with dermatomyositis is non-deforming. Patients with pulmonary disease may have abnormal breath sounds. Patients with an associated malignancy may have physical findings relevant to the affected organs.

 

DDx

 

Workup

Approach Considerations

The workup for dermatomyositis may include selected laboratory tests and diagnostic imaging (eg, magnetic resonance imaging [MRI], chest radiography, ultrasonography, electromyography [EMG], or computed tomography [CT]), as well as muscle and skin biopsy and other tests as appropriate.

In adult patients with dermatomyositis, assessment for malignancy should be performed upon initial diagnosis and repeated at least annually for 3 years. The risk of malignancy increases with age. The exact testing order should be based on the patient's sex, age, and race; however, testing beyond age-appropriate screening is most often recommended.

Laboratory Studies

Muscle enzyme levels are often abnormal during the course of dermatomyositis, except in patients with amyopathic dermatomyositis (ADM). The most sensitive/specific enzyme abnormality is elevated creatine kinase (CK), but aldolase studies and other tests (eg, for aspartate aminotransferase [AST] or lactic dehydrogenase [LDH]) may also yield abnormal results.

At times, the elevation of the enzymes precedes the appearance of clinical evidence of myositis. Thus, if a patient who is presumably stable develops an elevation of an enzyme that was previously within the reference range, the clinician should assess the possibility of a flare of the muscle disease.

Several serologic abnormalities have been identified and may be helpful in the classification of subtypes for prognosis, but they are not used for routine diagnosis. As a group, these antibodies have been termed myositis-specific antibodies (MSAs). These autoantibodies occur in about 30% of all patients with dermatomyositis or polymyositis.

A positive antinuclear antibody (ANA) finding is common in patients with dermatomyositis, but is not necessary for diagnosis.

Anti–Mi-2 antibodies are highly specific for dermatomyositis, but sensitivity is low; only 25% of patients with dermatomyositis demonstrate these antibodies. These autoantibodies are associated with acute-onset classic dermatomyositis, including the V-neck sign and shawl rash (poikiloderma), as well as a relatively good prognosis.

Anti–Jo-1 (antihistidyl transfer RNA [t-RNA] synthetase) antibodies are more common in patients with polymyositis, but may occur in patients with dermatomyositis. They are associated with pulmonary involvement (interstitial lung disease), Raynaud phenomenon, arthritis, and mechanic's hands in the setting of the anti-synthetase syndrome.

Other MSAs include anti-signal recognition protein (anti-SRP), which is associated with severe myositis; anti–PM-Scl and anti-Ku, which are associated with overlapping features of myositis and scleroderma; and anti-NXP-2, which is associated with calcinosis in the juvenile population, and more recently, in the adult population as well.[42]

An autoantibody directed against a 155-kd protein known as anti-p155/140 or antitranscription intermediary factor (TIF)-1γ, has been associated with malignancy in dermatomyositis.[49, 50, 51] Subsequently, the presence of anti-p155/140 antibodies targeting TIF-1α in addition to TIF-1γ, rather than TIF-1γ alone, was shown to be associated with malignancy.[52] Although these findings may be used to help prognosticate patients with dermatomyositis in the future, these antibodies may be found in patients without cancer,[52] and serology is not currently used routinely to help diagnose cancer-associated dermatomyositis.

A 140-kd polypeptide autoantibody, known as anti-CADM140 or antimelanoma differentiation antigen (MDA)–5, has been associated with clinically amyopathic dermatomyositis (CADM) and rapidly progressive interstitial lung disease, especially, but not exclusively, in the Asian population.[53, 54, 55, 56, 57, 58] In the United States population, skin and mucosal ulcerations and/or tender palmar papules (which are likely due to vasculopathy), along with hair loss, hand swelling, and arthritis/arthralgias, have been associated with circulating anti-MDA5 antibodies.[59]

A study of 11 patients with CADM suggests that levels of anti-MDA5 antibodies may fluctuate over time and may correlate with disease activity.[60] In addition, in the juvenile dermatomyositis population, anti-(MDA)-5 antibodies were recently found to be associated with skin and oral ulceration, arthritis, and milder muscle involvement in a cohort of United Kingdom patients.[61]

Imaging Studies

MRI may be useful in assessing for the presence of an inflammatory myopathy in patients without weakness. It can assist in differentiating steroid myopathy from continued inflammation and may serve as a guide in selecting a muscle biopsy site. Ultrasonography of the muscles has also been suggested for evaluation but has not been widely accepted.

Electromyography (EMG) is a means of detecting muscle inflammation and damage and has, at times, been useful in selecting a muscle biopsy site. Since the introduction of muscle MRI, EMG has been obtained less commonly in this setting.

A barium swallow allows evaluation of esophageal dysmotility.

CT scanning of the chest, abdomen, and pelvis is useful in the evaluation of potential malignancy that might be associated with dermatomyositis.

Transvaginal ultrasonography of the pelvis is particularly important for malignancy screening in women, given the strong association between ovarian cancer and dermatomyositis. Mammography is also useful in women for the evaluation of a potential malignancy.

Other Studies

Other tests may include the following:

  • Muscle biopsy

  • Pulmonary function studies with diffusion capacity

  • Electrocardiography (ECG)

  • Esophageal manometry (in selected patients)

  • Age-related colonoscopy and fecal-occult blood testing for malignancy screening

  • Papanicolaou smear in women for malignancy screening

  • Cancer antigen 125 (CA-125) and CA-19-9 for malignancy screening

Muscle biopsy, either open or via needle, may enhance the clinician's ability to diagnose dermatomyositis. The biopsy results may be useful in differentiating steroid myopathy from active inflammatory myopathy when patients have been on corticosteroid therapy but are still weak.

Histologic Findings

Skin biopsy reveals an interface dermatitis that is difficult to differentiate from lupus erythematosus (see the image below).[62] Vacuolar changes of the columnar epithelium and lymphocytic inflammatory infiltrates at the dermal-epidermal junction basement membrane can occur. Mucin deposition in the dermis is also characteristic.

Histopathology of dermatomyositis is interface der Histopathology of dermatomyositis is interface dermatitis.

Findings on muscle biopsy can be diagnostic. Muscle biopsy in patients with dermatomyositis reveals perivascular and interfascicular inflammatory infiltrates with adjoining groups of muscle fiber degeneration/regeneration (see the image below). This contrasts with polymyositis infiltrates, which are mainly intrafascicular (endomysial inflammation) with scattered individual muscle fiber necrosis.

Histopathology of dermatomyositis showing inflamma Histopathology of dermatomyositis showing inflammatory myopathic changes with a predominantly perivascular chronic inflammatory infiltrate.

Although inflammation is the histologic hallmark of dermatomyositis, polymyositis, and inclusion-body myositis, dermatomyositis is the only 1 of the 3 that shows perifascicular atrophy. In addition, many fibers undergo degeneration and necrosis that cause them to lose their staining ability; therefore, they are termed ghost fibers. When these changes are associated with collections of inflammatory cells around the blood vessels, the diagnosis of dermatomyositis is certain (see the images below).

Hematoxylin and eosin paraffin shows dermatomyosit Hematoxylin and eosin paraffin shows dermatomyositis. In dermatomyositis, inflammation is characteristically perivascular and perimysial. Vessel oriented approximately vertically in center has mild perivascular chronic inflammatory infiltrate. Endothelium is plump; wall is not necrotic. A few lymphocytes in wall of vessel are probably in transit from lumen to external aspect of vessel. Some observers may interpret this finding as vasculitis, but it is certainly neither necrotizing vasculitis nor arteritis. Image courtesy of Roberta J. Seidman, MD.
Hematoxylin and eosin frozen section shows perifas Hematoxylin and eosin frozen section shows perifascicular atrophy in dermatomyositis. Fascicles in this sample show atrophy, predominantly at periphery, along connective-tissue border. Ischemia is considered to cause perifascicular atrophy. This finding is characteristic of dermatomyositis, mostly associated with juvenile form but also observed in adult form. Image courtesy of Roberta J Seidman, MD.
Immunofluorescence for membrane attack complex of Immunofluorescence for membrane attack complex of complement (MAC) in dermatomyositis. Bright ring of yellow-green fluorescence at center represents MAC in wall of microvessel. Finding was not present after treatment with steroids. Image courtesy of Roberta J Seidman, MD.

Other Tests

The Cutaneous Dermatomyositis Disease Area and Severity Index (CDASI) is a clinical tool used to assess disease activity in cutaneous dermatomyositis. The CDASI has been validated for use by dermatologists, and more recently has also been shown to be a reliable measure when used by rheumatologists.[63]

 

Treatment

Approach Considerations

Therapy for dermatomyositis involves both general measures and specific measures to control the muscle disease and the skin disease. In addition, some patients with dermatomyositis need treatment for other systemic manifestations or complications.

The muscle component is treated by administering corticosteroids, typically with an immunosuppressive agent. The skin disease is treated by avoiding sun exposure and by using sunscreens and photoprotective clothing, as well as with topical corticosteroids, antimalarial agents,[64] and immunomodulatory medications such as methotrexate, mycophenolate mofetil, or intravenous immunoglobulin.

Surgical care is usually unnecessary in the management of dermatomyositis. Some patients may benefit from surgical removal of focal areas of calcinosis, particularly those that are painful. Inpatient care is needed for patients with fulminant dermatomyositis with muscle and/or internal organ involvement.

Children and adolescents are much more prone to the development of calcinosis. Aggressive and early treatment may prevent this complication.

General Measures

Several general measures are helpful in the care of patients with dermatomyositis. Bed rest is often valuable for those with severe inflammation of the muscles.

In patients with muscle weakness, especially children, a program of physical therapy is useful to help prevent the contractures that can complicate the disease when patients do not fully move their joints. Rehabilitative exercise is also recommended for both adult and pediatric patients in order to maintain muscle strength, even during the course of active muscle disease.

For patients with dysphagia and/or gastroesophageal reflux, elevation of the head of their bed and avoidance of eating prior to bedtime are helpful. These simple maneuvers may prevent aspiration pneumonitis. Occasionally, nasogastric tube feeding is needed to increase caloric input.

Treatment of Muscle Disease

The mainstay of therapy for the muscle disease is systemically administered corticosteroids.[65, 66, 67] Traditionally, prednisone (0.5-2 mg/kg/d) up to a dose of 60 mg/d is given as initial therapy. The drug should be slowly tapered to avoid relapse of the disease. Because most patients develop steroid-related toxic effects, most authorities administer a steroid-sparing immunosuppressive or cytotoxic agent early in the course.[68] Drugs reported to be steroid-sparing in some patients or in small open-label studies have included the following[69, 70, 71, 72] :

  • Methotrexate
  • Azathioprine
  • Cyclophosphamide
  • Cyclosporine
  • Mycophenolate mofetil
  • Leflunomide
  • Chlorambucil
  • Tacrolimus

Generally, methotrexate, mycophenolate mofetil, or azathioprine are used first line as glucocorticoid-sparing agents for muscle involvement. Response rates to methotrexate have been reported to be approximately 70-80%.[73] In addition, one small, randomized trial supported the long-term benefits of azathioprine as compared with prednisone monotherapy.[74] Results with cyclophosphamide in severe cases have been disappointing.

For refractory cases, the use of monthly high-dose intravenous immune globulin (IVIG) for 6 months has proved beneficial in the short term.[75, 76] In addition to its positive effects on refractory muscle and skin disease, IVIG has been reported to be beneficial for other systemic manifestations, including severe esophageal dysfunction.[77]

Rituximab, a chimeric antibody directed against CD20+ B cells, may be effective, but results have been mixed.[18, 78] In a multicenter, randomized, double-blind placebo-controlled trial of 44 weeks of rituximab therapy in patients with dermatomyositis and polymyositis, most patients experienced improvement in muscle disease activity; however, no significant differences were noted between groups based on muscle parameters. The study had a delayed-start design, with rituximab started immediately in one arm and after 8 weeks in the second arm, which is speculated to have influenced the results.[78]

An analysis of 195 patients with polymyositis and dermatomyositis looked to determine predictors of response to rituximab, and found that antisynthetase and anti-Mi2 autoantibodies, as well as lower disease damage and juvenile-onset disease, were predictors of clinical improvement with rituximab.[79]

The calcineurin inhibitor tacrolimus appears to be effective, safe, and well tolerated in patients with dermatomyositis that is refractory to other treatments. In addition to improvement in muscle strength and physical function, amelioration of skin lesions and interstitial lung disease have been reported. However, randomized, controlled trials have yet to be conducted.[80]

Treatment of Skin Disease

Therapy of cutaneous disease of dermatomyositis is often difficult. Some patients with dermatomyositis present primarily with skin disease (ie, amyopathic dermatomyositis [ADM]), whereas others present with a muscle component that is controlled but with significant ongoing skin disease.

First-line therapy is to recognize that the patient is photosensitive and to prescribe sun avoidance and sun protection measures, including broad-spectrum sunscreens and photoprotective clothing. The cutaneous component of dermatomyositis is exacerbated by sunlight and other sources of ultraviolet light; in addition, the muscle component may be exacerbated.

Hydroxychloroquine and chloroquine have been beneficial in small, open-label case studies;[81, 82] however, roughly 25-30% of patients with dermatomyositis who are treated with hydroxychloroquine develop a drug eruption, and patients should be counseled regarding this potential side effect.[81] Some patients who develop a drug eruption to hydroxychoroquine may go on to tolerate chloroquine.[81]  

In a study of 111 patients with dermatomyositis who were treated with hydroxychloroquine, Wolstencroft et al found a link between risk of skin eruptions and autoantibody subsets. Skin eruptions occurred in 7 of 14 patients with antibodies against small ubiquitinlike modifier 1 activating enzyme (SAE-1/2) but in only 16 of 97 patients without anti-SAE-1/2 autoantibodies (50.0% versus 16.5%, respectively). None of 15 patients with autoantibodies against melanoma differentiation-associated gene 5 (MDA-5) had a skin eruption, versus 23 of 96 (24.0%) of those without anti-MDA-5 autoantibodies.[83]

Methotrexate is often considered first-line systemic therapy if antimalarials fail or are contraindicated.[84] Mycophenolate mofetil has been reported to be useful as well.[69, 85, 86, 87, 88]

Azathioprine has been reported to be effective for muscle involvement, but there is a paucity of literature regarding cutaneous response. Azathioprine appears to be less effective for cutaneous disease. Sirolimus, tactrolimus, and dapsone inhibitors are among other immunomodulatory medications that may be of value in some patients.[89, 90, 91, 80] In addition, small case series or individual reports of successful management with leflunomide have also appeared in the literature.[72]

Intravenous immune globulin (IVIG) has benefited muscle involvement and cleared the skin lesions in the patients in whom it was used. A retrospective evaluation of 42 patients with dermatomyositis compared 24 patients treated with IVIG as an add-on to conventional immunosuppressive therapies to those treated with conventional immunosuppression alone. This study found that muscular and cutaneous involvement were significantly improved at 6 months in the IVIG-treated group, and modified Cutaneous Dermatomyositis Area and Severity Index (CDASI) scores were significantly improved over pretreatment scores during 4 years of follow-up, despite no significant difference in cutaneous remission rates and a high cutaneous relapse rate.[92]

Subcutaneous IgG has also been effective in dermatomyositis.[93] Rituximab has been used for skin disease, but the results are mixed.[19, 78] In a trial that included 72 adult patients DM, Aggarwal et al reported improvement in refractory skin rashs after the addition of rituximab to standard therapy. The most significant improvement occurred in erythroderma, erythematous rashes without secondary changes of ulceration or necrosis, heliotrope, Gottron sign, and papules. A trend for faster cutaneous response (20% relative improvement from baseline) was noted when rituximab was given early (week 0/1) rather than late (week 8/9).[20]

Management of Calcinosis

Calcinosis, a complication of dermatomyositis, is particularly likely to affect children and adolescents. Some experts believe that aggressive early treatment of the myositis may aid in preventing calcinosis. Once established, the process of calcinosis is debilitating in many patients. Although spontaneous remission is possible, it often takes many years to occur.

The use of the calcium channel blocker diltiazem (240 mg bid) is reportedly associated with gradual resolution of calcinosis in a small number of cases.[94] In addition, the use of an oral bisphosphonate might be helpful.[95] Intravenous (IV) pamidronate has been demonstrated in several cases to result in resolution of the calcinosis.[96] Colchicine, alendronate, and warfarin appear to be potentially beneficial for the resolution of calcinosis, although the data are not conclusive.

Some patients with localized areas of calcinosis may wish to have the calcinotic nodules surgically removed, particularly if they are tender. A retrospective study from the Mayo clinic of 78 patients with dystrophic calcinosis in the setting of autoimmune connective-tissue disease (of which dermatomyositis and systemic sclerosis were the most common underlying diseases) found that surgical excision and diltiazem produced the best results in diminishing calcinosis.[97]

Diet and Activity

A well-balanced diet is useful. Patients with severe muscle inflammation may need extra protein to balance their loss. Patients with dysphagia should avoid eating before bedtime; they may require a special diet, depending on the severity of the esophageal dysfunction.

Sun avoidance and sun protection measures are recommended in patients with skin lesions. Patients with dermatomyositis should maintain activity as much as possible. Although vigorous physical training should be avoided when the myositis is active, a rehabilitative exercise regimen is typically still recommended during the course of active muscle disease. Exercises to maintain the patient's range of motion are also advised.

Resistance training and aerobic exercise may also be beneficial for muscle involvement, especially if instituted early. In a randomized controlled trial, 12 weeks of endurance exercise yielded improvement in muscle performance, maximal oxygen consumption (VO2 max), and activities of daily living as compared with a non-exercising control group. In a 1-year open-label extension follow-up, improvement in muscle performance was sustained, but other assessments returned to baseline, emphasizing the need for a continued exercise program.[98]

Another randomized controlled trial of 19 patients compared patients with recent-onset polymyositis/dermatomyositis assigned to 12 weeks of resistive home exercise with telephone support, along with encouragement for another 12 weeks of home or gym exercise, with a control group assigned to 24 weeks of range-of-motion exercises. Both groups experienced improvement in muscle performance and aerobic capacity, but there were no significant differences between groups. In an open-label 2-year follow-up, the exercise group maintained significant improvement in muscle performance and aerobic capacity compared to baseline, suggesting that sustained exercise may be of some benefit.[99]

Consultations

Consultations with the following specialists may be indicated:

  • Rheumatologist
  • Dermatologist
  • Neurologist
  • Medical or surgical oncologist (for patients with cancer)
  • Internal medicine specialist or pediatrician (depending on patient age)
  • Pulmonologist
  • Cardiologist
  • Gastroenterologist

Patients with dermatomyositis may be served better by a physician or a team of physicians who have experience in managing this relatively rare disorder. Transfer to a tertiary center is often warranted for initial care and even for follow-up care.

Long-Term Monitoring

Disease activity must be closely monitored. Repeat measurements of muscle enzymes and clinical assessment of patients' strength may facilitate assessment of the activity of the myositis. Machines that can aid in the quantification of strength are available but are not used widely. The American College of Rheumatology and the European League Against Rheumatism have developed criteria for clinical response to treatment in patients with dermatomyositis; however, these are principally intended for use in clinical trials.[100]

The skin component of dermatomyositis is assessed by means physical examination in conjunction with history taking. The Cutaneous Dermatomyositis Disease Area and Severity Index (CDASI), the Dermatomyositis Skin Severity Index (DSSI), and the Cutaneous Assessment Tool (CAT) skin indices have been developed as outcome instruments. The CDASI has been found to be valid and responsive for characterizing cutaneous dermatomyositis severity and detecting improvement in disease activity.[101] Further testing to compare the responsiveness of all three measures is necessary.[102]

Annual physical examinations are useful to monitor for potential toxicity due to therapy or for the presence of a malignancy.

Malignancy evaluations, including imaging studies as noted above, should be conducted annually for at least the first 3 years after diagnosis. A report by Hill et al suggested that the risk of malignancy never returns to baseline, even after 3 years; thus, continued vigilance is warranted.[7]  However, most data suggests that the majority of dermatomyositis-associated malignancies occur within the first 3-5 years after diagnosis.

Selection of testing should be based on the patient's age, sex, race, and other symptoms or findings. Typically, a workup more extensive than age-appropriate screening is recommended. The principal malignancies associated with dermatomyositis are ovarian cancer and breast cancer in females and lung cancer in males.[103] After 3-5 years, patients should be monitored in the same manner as any other person of their same age, race, and sex.

Further Reading

The reader is referred to articles by Callen and Wortmann (2006), Iorizzo and Joizzo (2008), and Krathen et al (2008) for further reading.

 

Medication

Medication Summary

The goals of pharmacotherapy are to reduce morbidity and to prevent complications. In addition to the agents listed below, colchicine, alendronate, and warfarin, amongst other therapies, have been shown to be potentially beneficial for the treatment of calcinosis.

Prednisone is the first-line therapy for muscle involvement in dermatomyositis. The dose is altered according to the response of the patient’s condition.

Antimalarials, particularly hydroxychloroquine, may be useful for cutaneous disease; however, the majority of patients with cutaneous involvement require additional immunomodulatory medications for adequate control. Patients with dermatomyositis are at increased risk for drug eruptions with hydroxychloroquine.

Immunosuppressive/cytotoxic drugs are used as steroid-sparing agents for the muscle disease of dermatomyositis. Methotrexate has been demonstrated to be useful for skin disease, even in the absence of significant muscle disease, and is considered by many experts in the field to be first-line therapy for patients in whom antimalarials fail.[104, 105, 70, 37] Mycophenolate mofetil may also be useful for cutaneous disease. Intravenous immunoglobulin (IVIG) is also beneficial for both cutaneous and muscular involvement.

Biologic therapies have been investigated as potential therapeutic options for dermatomyositis. Existing data regarding anti–tumor necrosis factor alpha therapies have been mixed, and raise potential concerns for use in the dermatomyositis population. Therefore, their widespread use is discouraged until adequate, preferably controlled, studies demonstrate their efficacy and safety.

A small, double-blind, placebo-controlled study of etanercept demonstrated a steroid-sparing effect in five of 11 etanercept-treated patients versus treatment failure in all five placebo-treated patients. The effects were mostly on muscle disease, but some positive effects on skin disease were noted, utilizing the Cutaneous Dermatomyositis Area and Severity Index (CDASI) as a measure. However, two patients in the treated group developed rash, and two developed antinuclear antibodies. One patient in the placebo group developed ovarian cancer, but none in the etanercept group developed cancer during the year-long treatment period.[106]

In addition, one retrospective review of eight patients with dermatomyositis or polymyositis treated with etanercept reported improvement in muscle disease in six patients.[107] However, a case series of five patients with dermatomyositis treated with etancercept found exacerbation of myositis and no improvement in skin disease in any patient.[108]

Infliximab has also been investigated in patients with dermatomyositis; however, results have not been promising. In an open study of 13 patients with refractory myositis, no improvement with infliximab was noted.[109] In addition, one study of infliximab combined with methotrexate for patients with myositis was terminated early due to a high drop-out rate and low inclusion rate.[110]

For these reasons, and because there are several reports of dermatomyositis induced by anti-tumor necrosis factor,[111] anti–tumor necrosis factor therapies should be used only rarely and with caution in patients with severe refractory dermatomyositis.

Disease-Modifying Antirheumatic Drugs

Class Summary

Disease-modifying antirheumatic drugs (DMARDs) can retard or prevent disease progression and, thus, joint destruction and subsequent loss of function.

Leflunomide (Arava)

Immunomodulatory agent; inhibits pyrimidine synthesis, which in turn results in antiproliferative and aniti-inflammatory effects.

Corticosteroids

Class Summary

The mainstay of therapy for patients with dermatomyositis and muscle involvement is systemic corticosteroids. Cutaneous disease has a variable response to systemic corticosteroids. Disease with pulmonary or cardiac involvement may respond, whereas disease involving esophageal dysfunction usually does not respond. Glucocorticoids may be used topically for cutaneous disease.

Prednisone (Rayos)

Prednisone is first-line therapy for dermatomyositis. It may decrease inflammation by reversing increased capillary permeability and suppressing polymorphonuclear (PMN) leukocyte activity. It may be beneficial to use intravenous (IV) pulses; this may be associated with a lower frequency of calcinosis.

Prednisolone (Prelone, Flo-Pred, Millipred)

Corticosteroids may decrease inflammation by reversing increased capillary permeability and suppressing polymorphonuclear (PMN) leukocyte activity. Shown to improve patients with inflammatory myositis.

Immunosuppressive Agents

Class Summary

Immunosuppressive agents are used early in the treatment course as steroid-sparing agents. They decrease the risk of steroid-related complications.

Methotrexate (Trexall, Rheumatrex)

Methotrexate is used for managing constitutional symptoms. It blocks purine synthesis and 5-aminoimidazole-4-carboxamide ribonucleotide (AICAR), thus increasing anti-inflammatory adenosine concentration at sites of inflammation. Methotrexate ameliorates symptoms of inflammation.

Azathioprine (Imuran, Azasan)

Azathioprine is a purine analogue that inhibits purine synthesis, resulting in inhibition of DNA, RNA, and protein synthesis. It may decrease proliferation of immune cells, thereby leading to lower autoimmune activity. It has few, if any, effects on the skin.

Mycophenolate (CellCept, Myfortic)

Mycophenolate is useful for both skin and muscle disease. It inhibits purine synthesis and proliferation of human lymphocytes.

Sirolimus (Rapamune)

Sirolimus inhibits lymphocyte proliferation by interfering with signal transduction pathways. It binds to immunophilin FK506 binding protein (FKBP) to block the action of mammalian target of rapamycin (mTOR). It is approved by the US Food and Drug Administration (FDA) for prophylaxis against organ rejection in patients receiving allogeneic renal allografts.

A cyclosporine-sparing regimen has recently been FDA-approved for patients with low-to-moderate rejection risk at 2-4 months after transplantation. This regimen allows cyclosporine to be withdrawn, thus significantly decreasing renal toxicity while maintaining a similar antirejection effect.

Rituximab (Rituxan)

Rituximab is a third-line choice for the treatment of dermatomyositis. It is a genetically engineered chimeric murine/human monoclonal antibody directed against the CD20 antigen found on the surface of normal and malignant B lymphocytes. It is an IgG1-kappa immunoglobulin that contains murine light- and heavy-chain variable region sequences and human constant region sequences.

Cyclophosphamide

Cyclophosphamide is used for immunosuppression in cases of autoimmune disorders. This agent is chemically related to nitrogen mustards. As an alkylating agent, the mechanism of action of the active metabolites may involve cross-linking of DNA, which may interfere with growth of normal and neoplastic cells.

Cyclosporine (Gengraf, Neoral, Sandimmune)

Cyclosporine (Gengraf, Neoral, Sandimmune)

Cyclosporine is a cyclic polypeptide that suppresses some humoral immunity and, to a greater extent, cell-mediated immune reactions.

Chlorambucil (Leukeran)

Chlorambucil alkylates and cross-links strands of DNA, inhibiting DNA replication and RNA transcription.

Immune Globulins

Class Summary

High-dose IVIG has been reported to be useful in patients with recalcitrant dermatomyositis.

Immune globulin, intravenous (Gammagard, Carimune NF, Gammaplex, Octagam)

IVIG is useful for patients in whom corticosteroids and immunosuppressants have failed.

Calcium Channel Blockers

Class Summary

Calcium channel blockers may be useful for treating calcinosis.

Diltiazem (Cardizem, Cartia XT, Tiazac, Taztia XT)

During depolarization, diltiazem inhibits calcium ions from entering the slow channels and voltage-sensitive areas of vascular smooth muscle and myocardium. Treatment of calcinosis is an off-label use (the mechanism of action is unknown). It appears that other calcium channel blockers are not effective in this setting.

Calcium Metabolism Modifiers

Class Summary

Bisphosphonates are used to treat hypercalcemia and to decrease calcium loss from bone.

Pamidronate

Pamidronate inhibits bone resorption via actions on osteoclasts or on osteoclast precursors, without significant effects on renal tubular calcium handling. It is indicated for treatment of hypercalcemia. Intravenous (IV) pamidronate has been demonstrated in several cases to result in resolution of the calcinosis.

Alendronate (Fosamax, Binosto)

Alendronate has been successful in treating the pain of PFD; it may have some benefit in increasing bone mineral density as well. It offers the additional benefit of oral administration. Inhibits bone resorption via actions on osteoclasts or on osteoclast precursors. Has been shown to be potentially beneficial for the treatment of calcinosis

Antimalarials

Class Summary

Antimalarial agents may be used as steroid-sparing agents to treat skin disease. Hydroxychloroquine is preferred; chloroquine and quinacrine (100 mg/day) are second-line agents. Quinacrine may suppress bone marrow and is distributed by the Centers for Disease Control and Prevention (CDC); blood cell counts should be obtained regularly.

Hydroxychloroquine (Plaquenil)

Hydroxychloroquine may allow partial or complete control of the disease. Anecdotal evidence has suggested that morbilliform drug reactions are more common in patients with dermatomyositis than in those with other collagen vascular diseases. Hydroxychloroquine inhibits chemotaxis of eosinophils and locomotion of neutrophils and impairs complement-dependent antigen-antibody reactions.

Chloroquine phosphate (Aralen)

Chloroquine phosphate inhibits chemotaxis of eosinophils and locomotion of neutrophils and impairs complement-dependent antigen-antibody reactions.

 

Questions & Answers

Overview

What is dermatomyositis?

What are the cutaneous signs and symptoms of dermatomyositis?

What are the muscular signs and symptoms of dermatomyositis?

What are the systemic manifestations of dermatomyositis?

Which physical findings are characteristic of cutaneous dermatomyositis?

Which physical findings suggest muscle disease in dermatomyositis?

Which diagnostic tests are performed in the evaluation of dermatomyositis?

Which imaging studies may be used in the evaluation of dermatomyositis?

Which procedures may be performed in the evaluation of dermatomyositis?

What are the treatment options for dermatomyositis?

Which medications are used to manage dermatomyositis?

What are the general therapeutic measures used to manage dermatomyositis?

What is the role of surgery in the management of dermatomyositis?

What is dermatomyositis?

What are the Bohan and Peter diagnostic criteria for dermatomyositis?

What are the subsets of myositis?

What are amyopathic dermatomyositis (ADM) and postmyopathic dermatomyositis?

How is amyopathic dermatomyositis (ADM) diagnosed?

What is a possible underlying etiology for ADM or hypomyopathic dermatomyositis?

What is clinically amyopathic dermatomyositis (CADM)?

What is postmyopathic dermatomyositis?

What are the treatment options for dermatomyositis?

Which therapies for dermatomyositis are necessary in selected patients?

What is the prognosis of dermatomyositis?

What causes dermatomyositis?

What is the initial pathogenesis of dermatomyositis?

What is the pathogenic progression of dermatomyositis?

How does the pathogenesis of dermatomyositis differ from that of polymyositis?

What causes dermatomyositis?

What is the role of tumor necrosis factor (TNF) in the etiology of dermatomyositis?

What is the role of autoantibodies in the pathogenesis of dermatomyositis?

Which infectious agents may trigger dermatomyositis?

Which medications may induce dermatomyositis?

What is the role of silicone breast implants in the etiology of dermatomyositis?

What is the incidence of dermatomyositis?

How does the prevalence of dermatomyositis differ among age groups and between males and females?

How frequently does dermatomyositis remit?

What are risk factor for a poor prognosis in dermatomyositis?

What is the prevalence of comorbid malignancy with dermatomyositis?

What are the most common malignancies associated with dermatomyositis?

What are the risk factors for malignancy in dermatomyositis?

What are complications of dermatomyositis?

Which cardiovascular risks are increased with dermatomyositis?

What is the increased risk of osteoporosis with dermatomyositis?

Which patients are more likely to experience a delay in dermatomyositis diagnosis?

What is the rate of mortality with dermatomyositis?

Presentation

How common is a cutaneous presentation of dermatomyositis?

How does muscle involvement manifest in dermatomyositis?

What are systemic manifestations of dermatomyositis?

In what age group is malignancy with dermatomyositis most likely?

How does the initial assessment of suspected dermatomyositis differ between children and adults?

What are the signs and symptoms of dermatomyositis in children?

What are the pathognomonic cutaneous features of dermatomyositis?

How is the heliotrope rash of dermatomyositis characterized?

How are Gottron papules in dermatomyositis characterized?

What are non-pathognomonic cutaneous features of dermatomyositis?

How is poikiloderma in dermatomyositis characterized?

What can cause sleep disturbances in dermatomyositis?

Which physical findings of the hands are characteristic of dermatomyositis?

Which cutaneous lesions in dermatomyositis do not demonstrate interface dermatitis?

What are the less common cutaneous findings of dermatomyositis?

What is a possible complication of dermatomyositis seen in children?

Which muscular findings are characteristic of dermatomyositis?

How are muscles tested in suspected dermatomyositis?

How is muscle pain and tenderness characterized in dermatomyositis?

What are systemic findings characteristic of dermatomyositis?

DDX

What are the differential diagnoses for Dermatomyositis?

Workup

Which tests should be included in the initial evaluation of dermatomyositis?

When is assessment for malignancy indicated following a diagnosis of dermatomyositis?

How does a finding of anti-MI-2 antibodies affect the prognosis of dermatomyositis?

What is a finding of Anti–Jo-1 antibodies associated with in dermatomyositis?

What is the role of muscle enzyme measurement in the evaluation of dermatomyositis?

What is the role of antibody testing in the diagnosis and management of dermatomyositis?

Which MSAs are associated with specific features of dermatomyositis?

Which autoantibodies are associated with malignancy in dermatomyositis?

What autoantibodies are associated with clinically amyopathic dermatomyositis (CADM)?

What is a finding of anti-MDA-5 antibodies associated with in juvenile dermatomyositis?

What is the role of MRI in the evaluation of dermatomyositis?

What is the role of EMG in the evaluation of dermatomyositis?

What is the role of CT scanning in the evaluation of dermatomyositis?

What is the role of ultrasonography in the evaluations of dermatomyositis?

Which tests are performed in select patients to diagnose dermatomyositis?

What is the role of muscle biopsy in the evaluation of dermatomyositis?

What is the role of skin biopsy in the diagnosis of dermatomyositis?

Which muscle biopsy results are diagnostic of dermatomyositis?

What is the histologic hallmark of dermatomyositis?

What is the Cutaneous Dermatomyositis Disease Area and Severity Index (CDASI) tool and how is it used?

Treatment

What is the approach to treatment of dermatomyositis?

What are the treatment options for dermatomyositis?

When is surgery indicated in the treatment of dermatomyositis?

Which groups are at highest risk for calcinosis in dermatomyositis?

What is the role of physical therapy in the management of dermatomyositis?

How are the gastric manifestations of dermatomyositis managed?

Which medications are used to treat muscle disease in dermatomyositis?

What are the first line glucocorticoid-sparing agents for treatment of dermatomyositis?

Which medications are used to treat refractory dermatomyositis?

What is the role of rituximab in the treatment of dermatomyositis?

Which factors predict clinical improvement in dermatomyositis treated with rituximab?

What is the role of tacrolimus in the treatment of dermatomyositis?

What are the challenges in treating cutaneous disease of dermatomyositis?

What are the treatment options for photosensitivity in dermatomyositis?

What are possible adverse effects of antimalarial medications used to treat dermatomyositis?

What is first-line systemic therapy for dermatomyositis?

What is the role of immunosuppressive medications in the treatment of dermatomyositis?

What is the role of IV immune globulin (IVIG) in the treatment of dermatomyositis?

What is the efficacy of rituximab for the treatment of dermatomyositis?

What is calcinosis in dermatomyositis?

Which medications are used to treat calcinosis in dermatomyositis?

When is surgery indicated for treatment of calcinosis in dermatomyositis?

Which dietary modifications may be beneficial in the management of dermatomyositis?

What is the role of exercise in the management of dermatomyositis?

What types of exercise are beneficial for dermatomyositis?

What is the efficacy of sustained exercise for management of dermatomyositis?

Which specialist consultations may be useful in the diagnosis and management of dermatomyositis?

What long-term monitoring is needed for management of dermatomyositis?

How is dermatomyositis severity assessed?

How should the risk of malignancy be monitored in dermatomyositis?

What is the basis for testing selection for monitoring dermatomyositis?

Which articles are good references for information on dermatomyositis?

Medications

What are the goals of drug treatment for dermatomyositis?

What is the first-line therapy for muscle disease in dermatomyositis?

What medications may be useful in treating cutaneous disease of dermatomyositis?

What are the alternatives to steroids for the treatment of dermatomyositis?

What is the role of biologic therapies for treatment of dermatomyositis?

What is the efficacy of etanercept in the treatment of dermatomyositis?

What is the role of infliximab in the treatment of dermatomyositis?

What is the role of anti–tumor necrosis factor therapies in the treatment of dermatomyositis?

Which medications in the drug class Antimalarials are used in the treatment of Dermatomyositis?

Which medications in the drug class Calcium Metabolism Modifiers are used in the treatment of Dermatomyositis?

Which medications in the drug class Calcium Channel Blockers are used in the treatment of Dermatomyositis?

Which medications in the drug class Immune Globulins are used in the treatment of Dermatomyositis?

Which medications in the drug class Immunosuppressive Agents are used in the treatment of Dermatomyositis?

Which medications in the drug class Corticosteroids are used in the treatment of Dermatomyositis?

Which medications in the drug class Disease-Modifying Antirheumatic Drugs are used in the treatment of Dermatomyositis?