Dermatomyositis Case File

Dermatomyositis Case File

Eugene C. Toy, MD, Ericka Simpson, MD, Pedro Mancias, MD, Erin E. Furr-Stimming, MD

CASE 40

A 31-year-old woman presents with a 3-month history of muscle soreness, cramps, and muscle fatigue with climbing stairs and carrying objects. The patient has recently noted a rash on her cheeks, necks, chest, and back and swelling around her eyes. Her review of symptoms is significant for recent sensitivity of her fingers to cold temperatures, difficulty swallowing certain foods and pills, and some shortness of breath with exertion. The physical examination is significant for an erythematous rash across her cheeks, neck, chest, and back and mild lid edema. The cardiac examination is significant for occasional skipped beats. The neurologic examination shows proximal muscle weakness of the patient’s deltoids, biceps, hip flexors, and knee flexors. The sensory and coordination examination is normal. Laboratory studies are normal except for elevated serum creatine kinase (CK) of 770 IU/L (normal 50-200). Electromyography (EMG) and nerve conduction studies (NCSs) reveal an irritative myopathy and normal nerve conductions.

▶ What is the most likely diagnosis?

▶ What is the next diagnostic step?

▶ What is the next step in therapy?

ANSWERS TO CASE 40:

Dermatomyositis                                                      

Summary: A young woman complains of a subacute onset of proximal muscle weakness and myalgias, skin rash, and a clinical history of Raynaud phenomena, dysphagia, and cardiac arrhythmia. Diagnostic studies reveal an irritative and damaging myopathy that is likely inflammatory in etiology.

• Most likely diagnosis: Dermatomyositis
• Next diagnostic step: Skeletal muscle biopsy
• Next step in therapy: Immunomodulatory therapy; cardiac and respiratory evaluation

ANALYSIS

Objectives

1. Describe the most common types of inflammatory myopathies.
2. Be familiar with the diagnostic workup of inflammatory myopathies.
3. Be familiar with the treatment and management of dermatomyositis.

Considerations

The patient presented in this case has a subacute onset of proximal muscle pain and weakness, swallowing difficulties, and rash. This clinical presentation is consistent with dermatomyositis. The two most common idiopathic inflammatory myopathies are dermatomyositis and polymyositis. Both diseases share the common symptom of proximal muscle weakness. Dermatomyositis differs from polymyositis not only by its immune pathogenesis but also by the involvement of skin, with rash, discoloration, and tissue calcification. Inclusion body myositis (IBM) is another inflammatory myopathy that shares some features with polymyositis and dermatomyositis. However, IBM occurs in older patients, usually age greater than 50, and affects men more than women. It tends to present with a more gradual onset of weakness, which can date back several years by the time of diagnosis. It generally follows a more indolent course and can be refractory to therapy.

APPROACH TO:

Dermatomyositis                                                     

DEFINITIONS

HELIOTROPE RASH: Bluish-purple discolorations on the face, lids, neck, shoulders, upper chest, elbows, knees, knuckles, and back of patients with dermatomyositis.

GOTTRON NODULES: Flat-topped raised nonpruritic lesions found over the dorsum of the metacarpophalangeal (MCP), proximal interphalangeal (PIP), and distal interphalangeal (DIP) joints.

ANTI-JO-1 ANTIBODY: Antibody that recognizes a cytoplasmic histidyl transfer RNA synthetase.

CREATINE KINASE (CK): An enzyme found primarily in the heart and skeletal muscles, and to a lesser extent in the brain. Significant injury to any of these structures will lead to a measurable increase in CK levels.

RAYNAUD PHENOMENON: A condition resulting from poor circulation in the extremities (ie, fingers and toes). In a person with Raynaud phenomenon, when his or her skin is exposed to cold temperatures or the person becomes upset, the blood vessels under the skin spasm, resulting in decreased blood flow in fingers and toes. This is called vasospasm and can cause these areas to be cyanotic and cold.

CLINICAL APPROACH

Polymyositis and dermatomyositis are frequently considered together because they have similar clinical and laboratory features and because they progress at a similar rate. Although IBM shares some features with polymyositis and dermatomyositis, it generally follows a prolonged course and is more refractory to therapy.

Epidemiology and Clinical Features

Dermatomyositis affects 10 people out of every 1 million, with a female-to-male predominance of about 2:1. Although there is a juvenile form of this disease that begins between the ages of 5 and 15, the peak incidence in adults occurs between the ages of 40 and 50. Dermatomyositis has a subacute onset, usually worsening over a period of days or weeks; however, it might also last for months.

The distinguishing characteristic of dermatomyositis is a rash preceding or accompanying muscle weakness. The rash is described as patchy, bluish-purple discolorations on the face, neck, shoulders, upper chest, elbows, knees, knuckles, and back. Some patients might also develop hardened bumps of calcium deposits under the skin. Trouble with swallowing (dysphagia) might also occur. In approximately 25% to 50% of cases, mild myalgias and muscle tenderness occur.

Polymyositis also causes varying degrees of decreased muscle function. The disease has a more gradual onset compared to dermatomyositis and generally begins in the second decade of life yet rarely occurs in isolation of contributing conditions, such as Sjogren’s or Rheumatoid arthritis. Dysphagia is more common with polymyositis, which can affect nutrition and also increase the risk of aspiration pneumonia. Approximately one-third of patients with polymyositis or dermatomyositis experience muscle tenderness and cramps.

The chief clinical feature of polymyositis and dermatomyositis is progressive, painless, symmetrical proximal muscle weakness, with symptoms possibly dating back 3 to 6 months by the time of the diagnosis. Upper extremity muscle weakness manifests as difficulty in performing activities that require holding the arms up, such as hair washing, shaving, or reaching into overhead cupboards. Neck muscle weakness may lead to difficulty raising the head from a pillow or even holding it up while standing. Involvement of pharyngeal muscles may result in hoarseness, dysphonia, dysphagia, and nasal regurgitation after swallowing. Lower extremity proximal muscle weakness manifests as difficulty climbing stairs and rising from a seated or squatting position. Patients will often seek chairs with armrests to push off from or grab the sink or towel bar to rise from the toilet.

Other Clinical Features

Weakness is a major complaint, but proximal myalgias and constitutional symptoms such as fever, fatigue, and weight loss can also occur.

Interstitial pneumonitis occurs in approximately 10% of patients with polymyositis or dermatomyositis, usually developing gradually over the course of the illness. Myocardial involvement in polymyositis and dermatomyositis is well described. The reported frequency of congestive heart failure (with or without cardiomegaly) ranges from fewer than 5% of patients to 27% to 45%. Electrocardiographic (ECG) abnormalities are more common, with left anterior fascicular block and right bundle-branch block representing the most frequent conduction defects.

Both polymyositis and dermatomyositis were associated with an increased risk of malignancy, with a threefold risk demonstrated in patients with dermatomyositis and a 1.4-fold risk for patients with polymyositis. The types of malignancy generally reflected those expected for age and sex, although ovarian cancer was overrepresented in women with dermatomyositis, and both groups of patients displayed a greater-than-expected occurrence of non-Hodgkin lymphoma.

Cutaneous Features of Dermatomyositis

In dermatomyositis, patients can have an erythematous, often pruritic rash over the face, including the cheeks, nasolabial folds, chin, and forehead. Heliotrope (purplish) discoloration over the upper eyelids with periorbital edema is characteristic (Figure 40–1), as is the shawl sign, which describes the pattern of an erythematous rash in a “V” distribution on the chest and across the shoulders. Gottron papules—flat-topped raised nonpruritic lesions found over the dorsum of the MCP, PIP, and DIP joints—are virtually pathognomonic for dermatomyositis (Figure 40–2). Often pinkish to violaceous, sometimes with a slight scale, these are distinguished from cutaneous lupus in that lupus has a predilection for the dorsum of the fingers between the joints.

Figure 40–1. Heliotrope rash. (Reproduced, with permission, from Wolff K, Johnson RA, Suurmond D. Fitzpatrick’s Color Atlas & Synopsis of Clinical Dermatology. 5th ed. New York, NY: McGraw-Hill; 2005:373.)

Figure 40–2. Gottron papules. (Reproduced, with permission, from Kasper DL, et al. Harrison’s Principles of Internal Medicine. 16th ed. New York, NY: McGraw-Hill; 2004:316.)

Calcinosis Cutis

Children with dermatomyositis are also particularly prone to calcinosis cutis, which is the development of dystrophic calcification in the soft tissues and muscles, leading to skin ulceration, secondary infection, and joint contracture. Calcinosis cutis occurs in up to 40% of children with dermatomyositis and less commonly in adults; there is no proven therapy to prevent this complication.

Inclusion Body Myositis

Inclusion body myositis (IBM) tends to present with a more gradual onset of weakness, which can date back several years by the time of diagnosis. Although the muscle weakness is proximal, distal muscle groups can also be affected, and asymmetry of involvement is characteristic. Atrophy of the deltoids and quadriceps is often present, and weakness of forearm muscles (especially finger flexors) and ankle dorsiflexors is typical. Peripheral neuropathy with loss of deep tendon reflexes can be present in some patients.

DIAGNOSIS

The diagnosis of polymyositis and dermatomyositis generally relies on the presence of characteristic clinical and laboratory findings, including symmetric proximal muscle weakness and elevated muscle enzymes. However, diagnosis can be complicated because of the similarity between these two diseases and other more commonly described disorders. Both polymyositis and dermatomyositis are often diagnosed by ruling out other conditions.

Laboratory studies include a CK serum level. The laboratory hallmark of polymyositis and dermatomyositis, although not specific to either of these, is a dramatic elevation of the serum CK, often in the range of 1000 to 10,000 IU/L. Early in the disease process milder elevations can be seen. In IBM, CK elevations tend to be less striking, often increasing only to the 600 to 800 IU/L range; 20% to 30% of patients with IBM can have a normal CK at presentation. With initiation of effective treatment in dermatomyositis and polymyositis, CK levels decrease rapidly, and periodic measurements are used to follow up disease activity over the course of the long term. Caution is advised when interpreting CK elevations, as levels can remain mildly elevated with clinically quiescent disease. Therefore, the degree of elevation does not necessarily correlate with the degree of muscle weakness, although disease exacerbation is often associated with increased levels. Elevated serum levels of aldolase, erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), aspartate aminotransferase (AST), and alanine aminotransferase (ALT) are less sensitive and specific for active myositis.

Autoantibodies can be present in polymyositis, dermatomyositis, and IBM. Autoantibodies present in polymyositis and dermatomyositis include the myositis-specific autoantibodies anti-Jo-1, seen in 20% of patients, and the less commonly encountered anti-PL-7, anti-PL-12, anti-OJ, and anti-EJ. These antibodies recognize cytoplasmic transfer RNA synthetases (for transfer RNA synthetase), and they are markers of the subset of polymyositis and dermatomyositis patients described as having antisynthetase syndrome, which is characterized by fever, inflammatory arthritis, Raynaud phenomenon, and interstitial lung disease and is associated with a reduction in survival compared with uncomplicated polymyositis and dermatomyositis.

The evaluation of the patient with suspected myositis should include EMG and NCSs that will show changes in muscle activity at rest and with contraction suggestive of an irritative or inflammatory myopathy. A muscle biopsy specimen demonstrating typical histologic features in the absence of markers of metabolic myopathy, infection, or drug effect establishes the diagnosis of polymyositis. Muscle biopsy may not be necessary in a patient presenting with proximal muscle weakness, CK elevation, and the classic cutaneous manifestations of dermatomyositis. When biopsy is performed, however, care must be taken not to select a muscle that is so weak or atrophic that the biopsy reveals end-stage disease. The common pathophysiologic features of polymyositis, dermatomyositis, and IBM are chronic inflammation, fibrosis, and a net loss of myofibrils.

For IBM, the muscle cells exhibit a variety of abnormal inclusions, including eosinophilic cytoplasmic inclusions, vacuoles rimmed with basophilic granules, and foci that stain positively with Congo red, consistent with amyloid deposits. On electron microscopy, IBM is characterized by the presence of cytoplasmic helical filaments (tonofilaments), which contain beta-amyloid protein and a number of other proteins implicated in neurodegeneration.

Often, the clinical presentation is straightforward and can help distinguish between the most common types of myositis (polymyositis, dermatomyositis, IBM, see Table 40–1). However, other conditions can present with myalgia, weakness, or serum CK elevation or any combination of these features and need to be ruled out. Often, these conditions may or may not be associated with an infiltrate of inflammatory cells on muscle biopsy. Many drugs and toxins can induce a metabolic myopathy with weakness, serum CK elevation, and myalgia, such as statins (cholesterol-lowering medications). Penicillamine and zidovudine are associated with inflammatory infiltrates. Infection, endocrinopathy, metabolic myopathy, fibromyalgia, polymyalgia rheumatica, sarcoid, paraneoplastic phenomena, and some genetically acquired muscular dystrophies also require consideration. Therefore, a thorough history including family, past medical, medication use, and exposures should be obtained.

CK, creatine kinase; DM, dermatomyositis; IBM, inclusion body myositis; PM, polymyositis.

TREATMENT AND MANAGEMENT

There is no cure for the inflammatory myopathies, and data are limited for optimal treatment recommendations; however, the mainstay of management for polymyositis and dermatomyositis involves immunosuppressant agents. Current guidelines recommend initial therapy with prednisone for 4 to 6 weeks and then a 9- to 12-month taper at the lowest effective dose. Also recommended by some specialists is the initiation of glucocorticoid-sparing agent (ie, methotrexate, azathioprine) at the same time glucocorticoids are begun. However, other clinicians reserve the use of glucocorticoid-sparing agents for patients who fail treatment with glucocorticoids alone. In refractory or recurrent cases of disease, intravenous immunoglobulin (IVIg) is added to the regimen to decrease the cumulative dose of glucocorticoids administered in patients who become steroid resistant or dependent. IBM is considered to be refractory to any medical therapy, although a few case series have reported stabilization and even improvement in patients treated with prednisone alone or in combination with azathioprine or methotrexate. IVIg therapy has some reported benefit in patients with dysphagia, or swallowing difficulties.

Screening

Due to extra skeletal muscle involvement, patients also require evaluation of pulmonary and cardiac function with chest x-ray, formal pulmonary function testing, ECG, and referrals to cardiology and pulmonology. Dermatomyositis and polymyositis are often associated with underlying malignancy. If malignancy is suspected, a thorough primary screening is indicated, including relevant radiography, gynecologic evaluation, colonoscopy, and breast mammography. Even if an initial evaluation for malignancy at the time of presentation of myositis is unrevealing, the clinician should remain alert to signs and symptoms of new malignancy in the first several years of follow-up.

Physical Therapy

Physical therapy is important in helping patients manage the muscle weakness associated with inflammatory myopathies. A physical therapist will assist a patient in designing an appropriate exercise program and will help the patient make progress throughout the program. Some patients might require assistive devices such as a walker, and a physical therapist will assist in determining the most suitable device.

Speech Therapy

Some patients who have swallowing problems need the assistance of a speech therapist. A speech therapist can recommend exercises that might improve swallowing as well as provide general tips and guidance for overcoming swallowing difficulties. As with many other conditions, education about inflammatory myopathies and local support groups can be the greatest tools for managing the disorder and preventing complications.

CASE CORRELATION

• See also Case 38 (Chronic Inflammatory Demyelinating Polyneuropathy) and Case 39 (Guillain-Barré Syndrome)

COMPREHENSION QUESTIONS

40.1 A 48-year-old woman presents to your clinic with a 6-week history of fatigue, difficulty swallowing food, and difficulty climbing stairs and carrying groceries. She has also noticed a purplish discoloration over her eyelids that started 2 months before her other symptoms. Serum CK was taken and found to be 2000 IU/L. What conditions should this patient be screened for?

A. Psoriasis, dysphagia

B. Interstitial lung disease, heart failure, malignancy

C. Malignancy, cardiac arrhythmias, meningitis

D. Lupus, interstitial lung disease, kidney disease

40.2 Which of the following statements is true of inclusion body myositis (IBM)?

A. IBM differs from polymyositis only in regard to response to immune therapy.

B. IBM is the most commonly acquired myopathy in patients older than 50 years.

C. Inflammation must be present on muscle biopsy in order to confirm a diagnosis of IBM.

D. The presence of rimmed vacuoles on the muscle biopsy of IBM patients is caused by the effects of chronic immunosuppressant therapy.

40.3 A 35-year-old woman presents with a 2-month history of worsening muscle weakness. The patient complains that she has difficulty standing up from her couch and is no longer able to pick up her grandson. This morning she became very concerned because she was having difficulty brushing her hair. On physical examination, the patient is noted to have erythematous papules over the dorsal aspect of her MCP joints, as well as violaceous patches on her knees. Clinical picture and laboratory values suggest a diagnosis of dermatomyositis. Which of the following is the best therapy for this patient?

A. IVIg

B. Prednisone

C. Azathioprine

D. Methotrexate

ANSWERS

40.1 B. Dermatomyositis is associated with a greater risk of malignancy, although to varying degrees, and a 10% incidence of lung and cardiac involvement.

40.2 B. It is the most common acquired muscle disease occurring in persons older than 50 years, with a prevalence estimated at 4 to 9:1,000,000. It affects men more frequently than women, at a ratio greater than 2:1.

40.3 B. Current guidelines recommend initiating glucocorticoids in patients with dermatomyositis of polymyositis. Prednisone is the first-line glucocorticoid; however, in patients who are severely ill, intravenous methylprednisolone can be first used. Guidelines for when to initiate a glucocorticoid-sparing agent is still debated; however, many clinicians will implement methotrexate or azathioprine with treatment failure of glucocorticoids alone.

    CLINICAL PEARLS    

▶ Polymyositis is an autoimmune inflammatory myopathy of subacute onset with proximal muscle weakness and myalgia. ▶ The diagnosis of polymyositis is made based on clinical presentation, EMG findings, and elevated muscle enzymes, and it is confirmed by muscle biopsy. ▶ Dermatomyositis is rarer than polymyositis but is easier to diagnose because of the typical cutaneous findings. ▶ IBM is not a variant of polymyositis, but it is the most commonly acquired muscle disease occurring in persons older than 50 years. ▶ There are abnormal accumulations of proteins commonly seen in neurodegenerative disorders (Alzheimer disease, Parkinson disease, etc) in muscle fibers of IBM patients. ▶ Most patients with polymyositis have some distal weakness, although it is usually not as severe as the proximal weakness. ▶ The most common reason for a misdiagnosis of an inflammatory myopathy is erroneous pathologic interpretation of the biopsy.

REFERENCES

Dalakas MC. Review: an update on inflammatory and autoimmune myopathies. Neuropathol Appl Neurobiol. 2011;37:226-242. 

Kissel JT. Misunderstandings, misperceptions, and mistakes in the management of the inflammatory myopathies. Semin Neurol. 2002;22(1):41-51. 

Lam CG, Manlhiot C, Pullenayegum EM, Feldman BM. Efficacy of intravenous Ig therapy in juvenile dermatomyositis. Ann Rheum Dis. 2011;70:2089-2094. 

Metzger AL, Bohan A, Goldberg LS, et al. Polymyositis and dermatomyositis: combined methotrexate and corticosteroid therapy. Ann Intern Med. 1974;81:182-189. 

Neuromuscular Disease Center. Home page. http://www.neuro.wustl.edu/neuromuscular/. Accessed October 1, 2016. 

Rendt K. Inflammatory myopathies: narrowing the differential diagnosis. Cleve Clin J Med. 2001;68(6): 505, 509-514, 517-519.

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