Polymyositis, Dermatomyositis, and Autoimmune Necrotizing Myopathy: Clinical Features




Idiopathic inflammatory myopathies are a heterogeneous group of autoimmune disorders predominantly affecting skeletal muscles, resulting in muscle inflammation and weakness. The 3 most common inflammatory myopathies are polymyositis (PM), dermatomyositis (DM), and inclusion body myositis. This review details the clinical findings noted in PM, DM, and the emerging entity of autoimmune necrotizing myopathy.


Idiopathic inflammatory myopathies (IIMs) are a heterogeneous group of autoimmune disorders predominantly affecting skeletal muscles, resulting in muscle inflammation and weakness. Along with the musculoskeletal manifestations, involvement of other organ systems is seen, including the skin, cardiac, gastrointestinal, and pulmonary systems. The 3 most common inflammatory myopathies are polymyositis (PM), dermatomyositis (DM), and inclusion body myositis (IBM). Several much rarer syndromes are also described under the broad spectrum of inflammatory myopathies.


This review details the clinical findings noted in PM, DM, and the emerging entity of autoimmune necrotizing myopathy.


The Bohan and Peter criteria have been traditionally used to define and diagnose PM and DM. IBM was not part of the original classification but has been included over time. The Bohan and Peter criteria combine clinical, laboratory, and pathologic features to define PM and DM. More recently, newer criteria have been proposed for the classification of myositis but are not yet widely accepted.


Epidemiology


There is a variation in the age at which PM and DM occur. Although DM has a bimodal incidence pattern, peaking during childhood and then again between 50 and 70 years of age, PM is rare in childhood and occurs mainly after the second decade of life. Both conditions are more common in women. The reported incidence of both PM and DM is 4 to 10 cases per million population per year.




Definition


The most commonly used criteria for the diagnosis and classification of PM and DM are those defined by Bohan and Peter: (1) symmetric proximal muscle weakness; (2) elevation of serum skeletal muscle enzyme levels, including creatine kinase and aldolase; (3) electromyographic (EMG) evidence of the classic pattern of muscular impairment, with polyphasic, short, small motor unit potentials, fibrillation, positive sharp waves, increased insertional irritability, and repetitive high-frequency discharges; (4) muscle biopsy specimens with typical histopathologic findings of degeneration, regeneration, necrosis, and interstitial mononuclear infiltrates; and (5) characteristic cutaneous manifestation of DM, including heliotrope rash or Gottron sign ( Box 1 ). As mentioned earlier, over time, IBM has been included in these criteria as its own entity.



Box 1




  • 1.

    Symmetric proximal muscle weakness


  • 2.

    Elevation of skeletal muscle enzyme levels


  • 3.

    Abnormal EMG results a


  • 4.

    Muscle biopsy abnormalities b


  • 5.

    Typical skin rash of DM c



a Polyphasic, short, small motor unit potentials; fibrillation; positive sharp waves; insertional irritability; and bizarre, high-frequency, repetitive discharges.


b Degeneration/regeneration, perifascicular atrophy, necrosis, phagocytosis, fiber size variation, and mononuclear inflammatory infiltrate.


c Gottron sign and heliotrope rash.


The Bohan and Peter classification criteria




Definition


The most commonly used criteria for the diagnosis and classification of PM and DM are those defined by Bohan and Peter: (1) symmetric proximal muscle weakness; (2) elevation of serum skeletal muscle enzyme levels, including creatine kinase and aldolase; (3) electromyographic (EMG) evidence of the classic pattern of muscular impairment, with polyphasic, short, small motor unit potentials, fibrillation, positive sharp waves, increased insertional irritability, and repetitive high-frequency discharges; (4) muscle biopsy specimens with typical histopathologic findings of degeneration, regeneration, necrosis, and interstitial mononuclear infiltrates; and (5) characteristic cutaneous manifestation of DM, including heliotrope rash or Gottron sign ( Box 1 ). As mentioned earlier, over time, IBM has been included in these criteria as its own entity.



Box 1




  • 1.

    Symmetric proximal muscle weakness


  • 2.

    Elevation of skeletal muscle enzyme levels


  • 3.

    Abnormal EMG results a


  • 4.

    Muscle biopsy abnormalities b


  • 5.

    Typical skin rash of DM c



a Polyphasic, short, small motor unit potentials; fibrillation; positive sharp waves; insertional irritability; and bizarre, high-frequency, repetitive discharges.


b Degeneration/regeneration, perifascicular atrophy, necrosis, phagocytosis, fiber size variation, and mononuclear inflammatory infiltrate.


c Gottron sign and heliotrope rash.


The Bohan and Peter classification criteria




Muscular manifestations


The classic clinical finding of both PM and DM is the progressive development of symmetric proximal muscle and truncal weakness that develops relatively slowly, over the course of weeks to months. Patients usually report progressive difficulty with everyday tasks requiring the use of proximal muscles, such as rising from a chair, climbing steps, lifting objects, or combing their hair. Fine motor movements that require the use of distal muscles, such as buttoning shirts and writing, are affected only late in the course of the disease, and when found early in the illness, these affected movements should prompt a search for another neuromuscular disorder. Facial muscles remain unaffected; however, pharyngeal and respiratory muscles can become affected, resulting in complications that are discussed in detail later in this review. Often erroneously thought to be painless diseases, both PM and DM may have associated myalgias and muscle tenderness early in the disease course, more often seen in DM.


The exception to this pattern of muscle involvement is amyopathic DM (ADM), in which patients have the classic dermatologic findings of DM without the accompanying muscular findings.




Extramuscular manifestations


The joints, skin, cardiac and pulmonary systems, and the gastrointestinal tract are affected. Extramuscular organ involvement, such as interstitial lung disease (ILD) and cardiac involvement, is associated with worse prognosis.




Joint manifestations


Joint involvement can occur in those with PM and DM and is characterized by arthralgias and arthritis. It is usually noted early in the course of disease, involving wrists, knees, and the small joints of the hands. Joint involvement is classically nonerosive and frequently responsive to the treatment of the underlying inflammatory myopathy.




Dermatologic manifestations


Of the IIMs, 5 have cutaneous manifestations: adult DM, juvenile DM (JDM), DM associated with malignancy, DM with overlap syndrome, and ADM.


Bohan and Peter proposed 5 diagnostic criteria for DM, 4 of which focus on clinical, histopathologic, EMG, and chemical evaluation of muscle inflammation. The presence of cutaneous manifestations is the fifth criterion.


Cutaneous manifestations of DM can precede the onset of myositis by several months, and for up to 2 years. However, it is uncommon for myositis to occur before the onset of cutaneous manifestations. Skin involvement can be the most active component of DM and can be recalcitrant to therapy that is otherwise adequate for treatment of muscle symptoms.


The hallmark cutaneous manifestations of DM can be divided into 5 categories: pathognomonic, highly characteristic, characteristic, more common in JDM, and rare in DM.


Gottron papules, observed in more than 80% of patients with DM, are considered pathognomonic for DM. They are violaceous flat-topped papules and plaques located over the dorsal aspect of interphalangeal or metacarpophalangeal joints ( Fig. 1 E). Over time, these papules may evolve and develop atrophic, depressed, white centers with prominent telangiectasias.




Fig. 1


Examples of dermatologic manifestations of DM. ( A ) Heliotrope rash is a very common sign of DM. It can become more confluent and involve the entire face. ( B ) Gottron papules, another characteristic manifestation, are symmetric macular violaceous erythema with or without edema overlying the dorsal aspect of the interphalangeal or metacarpophalangeal joints, olecranon process, patella, and medial malleoli. ( C ) Other characteristic manifestations include the V sign that can occur on the neck and upper chest. ( D ) Image showing cuticular erythema and hypertrophy. Other characteristic findings include nail fold telangiectasias, cuticular overgrowth, and prominent periungual erythema, which are frequently seen in patients with DM. ( E ) Gottron sign, also called Gottron papules, is observed in more than 80% of patients with DM. Gottron papules are violaceous flat-topped papules and plaques located over the dorsal aspect of the interphalangeal or metacarpophalangeal joints. ( F ) Shawl sign, another characteristic manifestation, occurs on the nape of the neck, shoulders, and upper back. ( G ) Raynaud phenomenon occurs in approximately 25% of patients with DM.


The heliotrope rash, considered highly characteristic of DM, is a periorbital violaceous erythema with or without associated edema of the eyelids and periorbital tissue (see Fig. 1 A). The rash can become more confluent and involve the entire face.


Characteristic manifestations include Gottron sign, which is a symmetric macular violaceous erythema with or without edema overlying the dorsal aspect of the interphalangeal or metacarpophalangeal joints, olecranon process, patella, and medial malleoli (see Fig. 1 B). Other characteristic manifestations include macular violaceous erythema in symmetric distribution in classic areas; shawl sign on the nape of the neck, shoulders, and upper back (see Fig. 1 F); “V sign” on the V-shaped region of the neck and upper chest (see Fig. 1 C) ; and linear extensor erythema involving the extensor aspects of the legs, thighs, arms, fingers, hands, and feet.


Mechanic’s hands, also considered characteristic, present with hyperkeratosis, scaling, and horizontal fissuring of the palms and fingers bilaterally. Mechanic’s hands can be a manifestation of the antisynthetase syndrome, which is discussed later. This finding is frequently mistaken for contact dermatitis.


Other characteristic findings include nail fold telangiectasias, cuticular overgrowth, and prominent periungual erythema, which are frequently seen in patients with DM (see Fig. 1 D). Nail fold telangiectasias occur in 30% to 60% of patients early in the course of the illness. Pruritus is a common, but often underrecognized, complaint of patients with DM. The presence of pruritus can be helpful in differentiating from cutaneous changes of systemic lupus erythematosus in which pruritus is rare. When cutaneous changes become severe, patients may develop erythroderma, which is total body erythema.


Skin lesions are photosensitive and can be precipitated by both UVA and UVB radiations. A history of severe sunburn preceding the onset of DM has been reported.


Cutaneous calcinosis, although more common in JDM, occurring in 30% to 70% of JDM cases, is also seen in adult DM, occurring in 10% of cases. It is an often-disabling complication in which subcutaneous calcium deposition occurs in various patterns. Deep deposits occur with linear masses, superficial deposits can erupt through the skin, and reticular subcutaneous deposits can also occur. Cutaneous calcinosis frequently occurs at sites of compression, such as elbows and buttocks, and is associated with increased disease activity and duration. When occurring over the extensor surfaces, cutaneous calcinosis can be painful and can lead to chronic ulceration and infections.


Rare findings include nonscarring alopecia, erythroderma, vesiculobullous lesions, leukocytoclastic vasculitis, and livedo reticularis. Flagellate erythema has also been noted. It is characterized by erythematous linear lesions on the trunk, back, and proximal extremities and is associated with active disease.


Poikiloderma, a speckled pattern of hypopigmented and hyperpigmented macules interspersed with telangiectasia and cutaneous atrophy on a background of erythema, is a manifestation of disease chronicity that is most commonly found over photo-exposed areas. Severe atrophy of involved skin can lead to fragility, superficial erosions, and ulcerations.


A small subset of patients with DM develop hyperkeratotic follicular erythematous papules that occur in a linear distribution over the dorsal aspect of the hands and feet, frequently over the bony prominences. These papules are known as pityriasis rubra pilaris–like lesions or type Wong DM. The lesions clinically resemble pityriasis rubra pilaris, but they do not have the characteristic findings such as palmoplantar discoloration or desquamating hyperkeratosis. Some of these patients may have concomitant atopic dermatitis.


Cutaneous vasculitis may occur in severe acute forms of DM, with palpable purpura, urticaria-like lesions, livedo reticularis, and digital ulcerations. The presence of leukocytoclastic vasculitis is concerning for an underlying malignancy. Raynaud phenomenon occurs in approximately 25% of patients with DM (see Fig. 1 G).


ADM


ADM is characterized by the presence of the cutaneous manifestations of DM for 6 months or more in individuals who have normal muscle enzyme levels without evidence of muscle weakness. The term ADM was first coined in 1979 by Pearson, and ADM was eventually recognized as a subset of DM in the 1990s. ADM occurs at an incidence of 9.63 per million persons and represents about 10% to 20% of cases of DM.


Although previously thought less likely, some case studies have suggested that ADM may progress to frank myopathy for up to 10 years after the onset of cutaneous symptoms. One study of 16 patients noted that 18.75% of patients developed muscle weakness within 5 years of diagnosis of ADM.


Patients with ADM are at risk for developing the same disease complications as those with DM, such as lung disease and malignancy. The rate of diagnosis of malignancy occurring close to the diagnosis of ADM has been reported between 15% and 28%. There have been some reports of the possibility of increased malignancy in ADM compared with DM ; however, one study of 29 patients with ADM and DM did not find a statistically significant difference between the 2 groups.




Cardiac manifestations


Cardiac involvement in myositis was first described by Oppenheim in 1899. Historically, it was believed that myositis spared the heart. However, based on autopsy studies, it has become evident that cardiac involvement, although usually asymptomatic, is more common than previously believed. Cardiac involvement is a major cause of mortality in patients with myositis. In a long-term follow-up study, cardiovascular involvement was found to be the most common cause of death in patients with myositis.


The myocardium has been reported to be affected in patients with DM with varying frequencies. Up to 50% of patients with DM evaluated by noninvasive studies have asymptomatic cardiac manifestations. Noninvasive studies have shown that up to 85% of patients have abnormal findings on electrocardiography, 77% on ambulatory monitoring, 42% on echocardiography, and 15% on radionuclide ventriculography.


Cardiac manifestations included arrhythmia, conduction abnormalities, cardiac arrest, congestive heart failure (CHF), myocarditis, pericarditis, angina, and secondary fibrosis.


The frequency of cardiac involvement in myositis has been reported between 6% and 75%. Cardiac involvement as a cause of death in PM has been reported between 10% and 20%, although this number is uncertain because large studies are unavailable.


Conduction abnormalities are the most common asymptomatic cardiac manifestation, which are observed in 32% to 72% of patients. These abnormalities include ST-T changes, bundle branch block, atrioventricular blocks, PR prolongation, Q-wave abnormalities, and arrhythmias. In some cases, patients required pacemaker placement.


Arrhythmias and CHF secondary to myocarditis rarely occur in patients with acute disease. In chronic DM, heart failure is seen more frequently and is in fact the most common symptomatic manifestation. The frequency of CHF has been reported to be 3% to 45% in patients with myositis. In chronic DM, heart failure has been attributed to the effects of long-standing hypertension secondary to steroid use. It has also been theorized that the cause of CHF is secondary to myocarditis, leading to left ventricular dysfunction and restrictive cardiomyopathy, or possibly because of fibrosis, resulting in chamber stiffness. It is thought that myocardial involvement resulting in myocarditis occurs by the same mechanism that results in skeletal muscle involvement. Mononuclear inflammatory cells infiltrate into the endomysium and perivascular areas, resulting in degeneration of cardiac myocytes. Histopathologic changes similar to those in the myocardium were also observed in the conduction system, which could explain the cause of heart block.


Angina secondary to Raynaud phenomenon, Prinzmetal angina, and small vessel disease has also been reported in patients with DM.


Pericardial tamponade is very rare, with a frequency reported at about 10%. However, because tamponade can be fatal, electrocardiography of every case is recommended. Clinically symptomatic cardiac involvement is uncommon, and when present, it is associated with a poor prognosis.


There have also been reported associations between cardiac involvement and anti–signal recognition particle (SRP) antibodies. However, more recent evidence suggests that anti-SRP antibodies may not contribute to cardiac involvement to the degree that was once suspected.




Pulmonary manifestations


Pulmonary complications are a major cause of morbidity and mortality in patients with PM and DM. These complications occur primarily or secondarily due to muscle weakness. Three distinct pulmonary complications of PM and DM have been described: hypoventilation, aspiration pneumonia, and ILD.


Respiratory failure due to hypoventilation has been historically thought to be a rare complication reported in less than 5% of patients with myositis. However, a more recent, larger, retrospective study of patients with DM and PM reported a higher prevalence of 21.8%. Hypoventilation occurs in patients with severe muscle weakness and inflammation, involving respiratory muscles. As a result, restrictive lung function impairment is noted on pulmonary function tests (PFTs). Patients are noted to have reduced lung volumes and maximal inspiratory and expiratory pressures, along with increased residual volumes and normal forced expiratory volume in the first second of expiration (FEV 1 ) to forced vital capacity (FVC) ratio. Chest radiographs reveal small lung volumes and basal atelectasis.


Aspiration pneumonia is a frequent complication of PM and DM, occurring in approximately 17% of patients. Patients suffering from aspiration pneumonia also frequently complain of dysphagia, which results from disease involvement of the striated muscles of the pharynx and upper esophagus. Aspiration pneumonia is more likely to occur in patients with more extensive muscle and skin disease.


ILD is an inflammatory lung disorder of unknown cause, characterized by infiltrates of monocytes, lymphocytes, and neutrophils, as well as interstitial fibrosis. ILD is a common complication in PM and DM. The incidence of ILD has been reported between 5% and 46% in cross-sectional studies. No significant difference in the prevalence of ILD exists between patients with PM and DM. ILD associated with myositis may occur before, concomitantly, or after the onset of skin or muscle symptoms. ILD associated with ADM is a distinct subset in which the lung disease is rapidly progressive.


Myositis-associated ILD occurs in 3 different patterns: (1) acute onset of symptoms, in which patients develop apparent progressive hypoxemia within a month of lung involvement; (2) chronic slowly progressive symptoms; and (3) asymptomatic progression, in which ILD is demonstrated only by abnormal results of chest imaging or PFTs.


Cough and dyspnea are the most frequently reported symptoms in ILD, although patients can be asymptomatic. In one study, 27% of patients with ILD were asymptomatic. PFTs demonstrate a restrictive ventilatory impairment and can show decreased total lung capacity, functional residual capacity, residual volume, FEV 1 , and FVC, with a normal or elevated FEV 1 /FVC ratio and reduced diffusing capacity of lung for carbon monoxide.


Although chest radiography is a useful screening test, high-resolution computed tomography (HRCT) of the lungs is the standard technique for detecting ILD. HRCT is thought to be useful in distinguishing fibrotic disease from active inflammation, with the former presenting as a reticular pattern and the latter as ground-glass pattern.


Bronchoalveolar lavage is not specific for the diagnosis of ILD, although it is useful in differentiating pulmonary symptoms, such as evaluating for infection, drug-induced reaction, and malignancy. However, similar to idiopathic pulmonary fibrosis, neutrophil-predominant alveolitis and increased eosinophil counts may indicate more progressive disease. Lung biopsy is not routinely performed for diagnosis because of the increased morbidity associated with the procedure.


Most frequently seen HRCT changes are those of idiopathic nonspecific interstitial pneumonia (NSIP), with irregular linear opacities and with areas of consolidation and ground-glass pattern. However, other patterns such as usual interstitial pneumonia, bronchiolitis obliterans with organizing pneumonia, and diffuse alveolar damage (DAD) are also seen.


The presence of antiaminoacyl–transfer RNA (tRNA) synthetase antibodies, of which antihistidyl-tRNA synthetase antibody (anti–Jo-1) is most frequently found, is the strongest predictive marker for ILD. The prevalence of ILD in patients with anti–Jo-1 antibodies is more than 70%. There are also other markers for ILD, including PM-Scl autoantibodies. Krebs von den Lungen 6, a glycoprotein expressed on type 2 alveolar pneumocytes and bronchiolar epithelial cells, and serum surfactant protein D have been suggested as useful markers for ILD in patients with myositis. However, these markers are not routinely used in clinical practice. Serum cytokeratin (CK) 19 fragment, a component of bronchoepithelial cells, is also associated with ILD in myositis. Patients with DAD have higher levels of CK-19 than patients with NSIP.


ILD is considered a major risk factor for premature death. It is unclear if the prognosis of ILD in patients with PM is different from those with DM. However, one study showed that patients with DM-associated ILD were less responsive to steroid therapy than those with PM-associated ILD.


Spontaneous pneumomediastinum has also been reported as a rare complication of myositis-associated ILD, occurring with a prevalence of 8.3% in patients with PM and DM. Pneumomediastinum usually results from rupture of subpleural or paracardial blebs in ILD. In a recent retrospective study, most cases of pneumomediastinum occurred in patients with DM or ADM. Poor survival was associated with an absence of muscle weakness and severe pulmonary involvement before the onset of pneumomediastinum.


Because of the concomitant use of immunosuppressive drugs in the treatment of inflammatory myopathies, infections are another complication to be considered, particularly opportunistic infections. Bronchoalveolar lavage is a useful tool in making the diagnosis.

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Oct 1, 2017 | Posted by in RHEUMATOLOGY | Comments Off on Polymyositis, Dermatomyositis, and Autoimmune Necrotizing Myopathy: Clinical Features
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