Myositis Mimics

Abstract

Patients with autoimmune myositis typically present with muscle weakness, elevated serum levels of muscle enzymes, and abnormal muscle biopsies. However, patients with other acquired myopathies or genetic muscle diseases may have remarkably similar presentations. Making the correct diagnosis of another muscle disease can prevent these patients from being exposed to the risks of immunosuppressive medications, which benefit those with myositis, but not those with other types of muscle disease. Here, we review some of the most common acquired and inherited muscle diseases that can mimic autoimmune myositis, including inclusion body myositis, limb girdle muscular dystrophies, metabolic myopathies, mitochondrial myopathies, and endocrine myopathies. We emphasize aspects of the medical history, physical exam, laboratory evaluation, and muscle biopsy analysis that can help clinicians distinguish myositis mimics from true autoimmune myositis.

Introduction

The autoimmune myopathies include dermatomyositis (DM), polymyositis (PM), immune-mediated necrotizing myopathy (IIM), and various overlap syndromes associated with other autoimmune diseases. These disorders are characterized clinically by subacute onset of generalized, symmetric proximal muscle weakness. If distal weakness occurs, it is usually a late feature and almost never as severe as proximal weakness. Although dysphagia may occur, especially in severe cases, facial weakness is exceptionally rare. Pain and muscle discomfort are not uncommon. DM is usually associated with skin rash and carries an increased risk of underlying malignancy. Both DM and PM are often associated with other manifestations of systemic autoimmunity, such as interstitial lung disease, arthritis, and Raynaud’s phenomenon [1].

Although well-recognized entities, the autoimmune myopathies are relatively rare causes of myopathy. Annual incidence in the USA has been reported between 4.2 and 7.9 cases per 100,000 person years and annual prevalence between 14 and 25.3 per 100,000 individuals [2, 3]. By comparison, the prevalence for inherited muscular dystrophies ranges from 19.8 to 25.1 per 100,000 person years [4-6]. Thus, for a patient presenting with proximal muscle weakness, genetic and other causes of myopathy must also be considered. Many of these alternative etiologies share some clinical and/or histopathological features with the autoimmune inflammatory myopathies and can be mistaken for autoimmune conditions. As misdiagnosis can lead to inappropriate and potentially harmful therapy, accurate diagnosis is essential. This review will focus on the clinical characteristics and diagnosis of those myopathies most commonly misdiagnosed as autoimmune inflammatory myopathies.

Inclusion Body Myositis

Inclusion body myositis (IBM) is probably the muscle disorder most frequently mistaken for autoimmune inflammatory myositis. Indeed as many as 50 % of IBM patients are initially misdiagnosed with PM [7, 8•, 9]. As the name suggests, the pathogenesis of IBM is thought to involve inflammation; however, there is also significant evidence for a degenerative process. It remains debated which of these processes is the primary driver of disease [10].

IBM is primarily a disorder of older men with a male to female ratio of about 2:1. Onset before age 50 is rare [7, 8•, 9]. Patients often present with slowly progressive weakness manifesting as falls and difficulty climbing stairs. Examination reveals weakness of the quadriceps, with relative, albeit not always complete sparing of the hamstrings. In contrast to autoimmune myopathies, IBM patients typically have weakness of the wrist flexors and deep finger flexors with relative sparing of wrist and finger extensors. The majority of patients have asymmetric weakness with the nondominant side most affected. Ankle dorsiflexion weakness, facial weakness, and dysphagia can also be seen at early or late stages of the disease, although a small percentage may have dysphagia as the sole presenting symptom [7, 8•, 9, 11, 12]. IBM is rarely associated with malignancy or extra-muscular symptoms, although a high prevalence of autoimmune disorders has been demonstrated in IBM populations [1, 9]. Additionally supporting its distinction from PM/DM is the fact that IBM exhibits little response to immunosuppressive therapy [8•, 13-17]. Although there is some modest evidence of the benefit of exercise, IBM is an inexorably progressive disease [7, 18, 19]. The majority of patients require some type of assistive device for ambulation within 10 years of symptom onset, and many patients eventually require a wheelchair for mobility. Dysphagia can lead to significant quality of life impairment [8•, 9]. Despite this significant morbidity, IBM is not associated with a decreased life expectancy although a higher percentage of deaths are due to respiratory issues compared to an age-matched population [11].

In most cases, the diagnosis of IBM relies predominately on recognition of the characteristic pattern of weakness, with several canonical histopathologic features on muscle biopsy providing supportive evidence for the diagnosis. The most prominent of these features is endomysial inflammation composed primarily of CD8+ T cells often with invasion of non-necrotic muscle fibers. Rimmed vacuoles are often present but may be absent in 15–20 % of cases. In these cases, it may be difficult to distinguish between PM and IBM on the basis of biopsy alone [20]. Tubulofilamentous inclusions are also described as a classical feature, although these are only visible on electron microscopy, which is not widely available [12]. More recently, studies have shown the presence of beta-amyloid and tau deposits, as well as accumulation of several other proteins known to be involved in other neurodegenerative diseases, such as TDP-43. Other studies have also shown accumulation of autophagy-related proteins, such as LC3 and p62 [21-23]. Although more research needs to be done, these proteins may prove useful both in diagnosing and understanding the pathology of IBM. Additional supportive diagnostic features include moderately elevated creatine kinase (CK) and irritative myopathy on electromyography (EMG). Both myopathic and neuropathic motor unit action potentials may be seen. About one third of patients will also exhibit a mild distal sensory axonal peripheral neuropathy [12, 24]. Muscle MRI may show inflammation and fatty infiltration in the quadriceps, medial gastrocnemius, and tibialis anterior, although the clinical role of muscle imaging in IBM remains to be fully defined [25, 26].

Various schemata have been proposed over the last several decades to assist in the diagnosis of IBM. Many of these initially relied heavily on the canonical biopsy features. However, in recent years, there has been greater emphasis on clinical features, largely related to concerns regarding the low sensitivity and poor feasibility of testing for many biopsy features [27-29, 30•]. Lloyd et al. recently undertook a systemic analysis of the sensitivity and specificity of these diagnostic criteria, concluding that while all were highly specific, there was a wide variability in sensitivity. Pathological criteria were among the lowest sensitivity features. Using only high-performing features, they constructed a set of criteria with a sensitivity of 90 % and specificity of 95 % when all three of the following are fulfilled: (a) finger flexor or quadriceps weakness, (b) biopsy showing endomysial inflammation, and (c) biopsy revealing either invasion of non-necrotic muscle fibers by lymphocytes or the presence of rimmed vacuoles [30•]. Given that deep finger flexor weakness can be reliably used to distinguish IBM from PM, learning to assess this muscle group is essential to prevent incorrect diagnoses. We note here that the deep finger flexors are muscles found in the anterior aspect of the forearm that mediate flexion at the distal interphalangeal joint. A common mistake is to test strength of the hand intrinsic muscles (i.e., grip strength); these are not affected in IBM. Prominent quadriceps weakness greater than or equal to hip flexor weakness is often noted as a specific finding in IBM. However, this feature appears to be less sensitive (60 %) than finger flexor weakness (100 %) in the diagnosis of IBM [30•].

Additional efforts to aid the diagnosis of IBM have focused primarily on the identification of other disease biomarkers. A recently discovered antibody to cytosolic 5′-nucleotidase 1a (c5N1A), an enzyme involved in nucleoside metabolism, has a high specificity for IBM (92–98 %) compared to PM and most other neuromuscular diseases; the presence of this antibody in a weak patient without a rash makes it much more likely the patient has IBM than PM. However, the sensitivity of the test is only 60–70 % and anti-NT5C1a may be found in up to 20 % of patients with dermatomyositis, lupus, and Sjogren’s syndrome [31, 32, 33••, 34••]. Several studies have shown major histocompatibility complex class I (MHC-I) upregulation in IBM, although this does not appear to distinguish it from PM/DM [35, 36]. MHC-II staining may perform better in this regard with 100 % of IBM cases demonstrating MHC- II positivity compared with 60–70 % of PM/DM cases in one study [37]. As described above, the identification of degenerative protein aggregates, markers of autophagy, and mitochondrial changes may also prove useful in the diagnosis of IBM, but further work is required to validate these findings and determine how they should be incorporated into clinical practice [38, 39].

Muscular Dystrophies

Of the many types of muscular dystrophy, several are often initially misdiagnosed as autoimmune inflammatory myopathies because they may present with proximal muscle weakness and inflammation on muscle biopsy. Although a family history of weakness can be helpful in distinguishing these conditions, due to de novo mutations and autosomal recessive inheritance patterns, this may not always be elicited. The most frequently troublesome of these are facioscapulohumeral muscular dystrophy (FSHD), dysferlinopathy, and calpainopathy, which will be the focus of this review.

Facioscapulohumeral Muscular Dystrophy

FSHD is the third most common form of muscular dystrophy with a prevalence of about 1:20,000. The majority of cases— about 95 %—are caused by an autosomal dominant mutation on chromosome 4 leading to contraction of a repeat sequence. This contraction results in failure to suppress expression of DUX4, a putative transcription factor that is normally only active early in development. It is thought that DUX4 expression leads to the transcription of a myriad of proteins with various downstream effects, although exactly how this leads to muscle destruction is not known [40].

Patients typically present in the second decade with weakness of the shoulder girdle muscles that is often quite asymmetric. However, it should be noted that some patients with mild disease may not notice weakness until much later in life. Scapular winging, which may be asymmetric, is often prominent. Relative sparing of the deltoid is a unique feature found in few other myopathies. Although facial weakness may be pronounced on exam, this may go unnoticed by the patient. Progression is variable but usually quite slow. About one third will have only facial and shoulder girdle weakness, whereas the remaining two thirds will also develop varying degrees of weakness involving the anterior arm, abdominal and pelvic girdle muscles. Dysphagia and respiratory insufficiency are rare but can occur late in the disease. Extra-muscular manifestations may occur, most commonly asymptomatic retinal telangiectasia and sensorineural hearing loss; cardiomyopathy is rare. The majority of patients will retain the ability to ambulate throughout their lifetime; only 10–20 % will require a wheelchair. Life expectancy is not altered [40, 41].

Although a definitive diagnosis can be made via genetic testing, many patients undergo additional evaluation prior to this, especially if typical features are not present. CK is mildly elevated; values greater than 1500 IU/L should suggest an alternative diagnosis. EMG shows mild myopathic changes. Muscle biopsy typically demonstrates nonspecific myopathic changes, including fiber size variability, internalized nuclei, and fibrosis. Up to one third of patients have an inflammatory infiltrate composed of both CD4+ and CD8+ T cells that can lead to misdiagnosis as PM [42, 43]. The infiltrate, which may be most prevalent in the early stages of the disease, appears patchy and varies widely in intensity between biopsy samples [44]. Its role in muscle destruction is unclear, as unlike with IBM and PM, there is no evidence of normal myofiber invasion. Despite the strong inflammatory component, several trials of steroids in FSHD have failed to demonstrate significant improvement in weakness [41].

Dysferlinopathy

Dysferlinopathy is an autosomal recessive disease caused by mutations in the dysferlin genes on chromosome 2. Although the function of the dysferlin protein is only partially understood, it is thought to play a role in membrane trafficking, stability, and repair [45]. Patients with this disease typically have no dysferlin on immunohistochemical staining of muscle tissue and consequently are unable to effectively repair injury to the muscle fiber membrane.

There are two primary phenotypes resulting from loss of dysferlin: limb girdle muscular dystrophy type 2B (LGMD 2B) and Miyoshi myopathy (MM) with the primary difference being proximal verses distal onset, respectively. LGMD 2B is characterized by slowly progressive proximal weakness involving both the shoulder and pelvic girdles with onset in late adolescence to mid-adulthood. Subclinical weakness of distal musculature may also be evident on examination. CK is often quite elevated with values up to 20–150 times normal. MM is characterized by predominately distal weakness with early involvement of the calf muscles. Weakness eventually also involves proximal leg muscles, and there may also be mild atrophy of the forearm muscles with sparing of the intrinsic muscles of the hands. Onset is younger than LGMD 2B, usually in mid-childhood to early adulthood. CK may also be significantly elevated. Less common phenotypes are also described, including scapuloperoneal syndrome, distal myopathy with anterior tibial onset, and asymptomatic hyperCKemia [46].

Although genetic testing is also available for definitive diagnosis of dysferlinopathy, many patients undergo additional evaluation with muscle biopsy if the correct diagnosis is not suspected. While biopsy typically reveals nonspecific myopathic changes (e.g., a necrotizing myopathy), up to one third demonstrate a marked inflammatory infiltrate [47]. Both T cells and macrophages may predominate [45, 47, 48]. This can lead to an erroneous diagnosis of PM, especially given the pronounced CK elevation and proximal weakness seen in LGMD 2B patients. However, immunohistochemical staining reveals an absence of dysferlin on both frozen and paraffin-embedded muscle samples. This in addition to the gradual progression of weakness and lack of response to immunosuppressive agents should ultimately lead to the correct diagnosis, which can be verified by genetic testing.

Calpainopathy

Calpainopathy is an autosomal recessive disease caused by mutations of the calpain-3 gene, which encodes a calcium protease involved in sarcomere remodeling. Patients often present with weakness of the hip girdle muscles beginning in childhood. Shoulder girdle weakness may become evident later in the course, as can more distal extremity weakness. As in FSHD, calpainopathy patients may have prominent scapular winging. However, the facial, extraocular, and pharyngeal muscles are spared. Weakness is slowly progressive with loss of ambulation usually occurring in mid-adolescence to early adulthood. CK is mildly to moderately elevated. Muscle biopsy typically shows nonspecific myopathic changes with type I fiber predominance in later stages. Immunohistochemical staining for calpain-3 is reduced or absent [49]. A small number of patients may have eosinophilic infiltrates on muscle biopsy, although this is not a specific feature of calpainopathy [50].

Role of MHC Staining

MHC immunostaining has been proposed as a method to distinguish dystrophies with inflammatory biopsies from autoimmune myopathies. MHC-I is expressed but normally undetectable by immunostaining in healthy muscle fibers. It is upregulated under conditions of inflammation and its expression is necessary for the antigen-specific T cell-mediated cytotoxic response. Multiple studies have shown that MHC-I positivity is sensitive for autoimmune myopathy; however, specificity is limited; for example, MHC-I upregulation also occurs frequently in IBM (100 %), muscular dystrophies (95–100 %), and metabolic myopathies (60–70 %) [35-37, 51]. Greater success has been seen with the addition of MHC-II immuno-staining. Like MHC-I, MHC-II is not detectable by immunostaining in healthy muscle fibers. Its expression is required for the activation of T helper cells, and it also may enable myofibers to act as antigen-presenting cells. In one study, MHC-II staining was found to be positive in 60–70 % of DM/PM cases but only in 17–20 % of muscular dystrophy cases and in 10–15 % of metabolic myopathy cases. Thus, although MHC-II staining appears to have a relatively low sensitivity for autoimmune myositis (25–60 %), its specificity is relatively high (90–100 %) [35, 37]. The combination of MHC-I and MHC-II positivity may be helpful in distinguishing between inflammatory myositis and dystrophies with inflammatory biopsies. The exception is IBM, which also has a high frequency of MHC-II positivity but is not considered a typical, drug-responsive, autoimmune disease at this time.

Metabolic Myopathies

As a group, the metabolic myopathies are characterized by defects in muscle utilization of carbohydrate or fat, resulting in a decreased energy supply manifested as crises of cramping and weakness often associated with myoglobinuria. Some metabolic myopathies—most notably acid maltase deficiency and McArdle’s disease—can manifest with fixed as well as episodic proximal muscle weakness. This pattern of fixed weakness sometimes leads to confusion with autoimmune inflammatory myopathies, especially if a history of chronicity, fatigability, and myoglobinuria is not elicited. For this reason, this review will focus on these two entities, although it should be noted that many other metabolic myopathies can present with a proximal myopathy and should be considered in the appropriate clinical context.

Acid Maltase Deficiency (Pompe Disease)

Acid maltase deficiency is an autosomal recessive disorder caused by mutations of the GAA gene encoding the lysosomal enzyme acid alpha-glucosidase. Deficiency of this enzyme results in abnormal glycogen accumulation that disrupts muscle tissue architecture [52]. The severe infantile form of this disorder manifests as generalized hypotonia with muscle weakness, cardiomegaly, and respiratory failure. The milder and more clinically heterogenous adult onset form is typically characterized by progressive limb girdle and diaphragmatic weakness [52]. Respiratory insufficiency may progress to the need for mechanical ventilation [53]. Cardiac involvement is rare, but left ventricular hypertrophy and conduction defects have been reported [52, 54]. CK is usually mildly elevated with an average value of 800–900 IU/L in one study [52]. Muscle biopsies in patients with acid maltase deficiency should not be confused with those seen in the autoimmune myopathies. The histopathological hallmark of the disorder is PAS-positive vacuoles, although this feature is often not found in adult-onset disease. The finding of acid phosphatase-positive globular inclusions in a small percentage of late-onset cases may prove to be an additional diagnostic marker. Electron microscopy, if available, may also reveal the presence of cytoplasmic membrane-bound glycogen [55]. A blood-based GAA enzyme activity assay screens for enzyme deficiency, and confirmation can be achieved via GAA gene sequencing [52]. This testing is available at several laboratories in the USA, Australia, and Germany.

Accurate diagnosis is imperative for acid maltase deficiency as this is one of the only metabolic myopathies for which a specific therapy is available. Enzyme replacement therapy with recombinant human GAA was FDA-approved in 2006. Clinical experience thus far has demonstrated greater success in improving cardiac function than skeletal muscle function, as well as greater improvements in children than adults [52]. Further work remains to be done to address the optimal delivery of therapy in these patients.

McArdle’s Disease

McArdle’s disease is an autosomal recessive disorder caused by mutations in the PYGM gene that lead to a deficiency of myophosphorylase, a muscle-specific glycogen phosphorylase. Because cardiac and hepatic isoforms are not affected, McArdle’s disease is a ‘pure’ myopathy without other direct organ involvement. Myophosphorylase deficiency results in an inability to utilize glycogen stores for energy production, leading to glycogen accumulation within muscles [56]. Patients typically develop exercise-provoked muscle cramping and excessive fatigue within the first two decades of life. Basal CK can be quite elevated with 79 % of patients having levels >1000 IU/L in one study [57]. Muscle contractures and myoglobinuria are common after exercise; the latter can lead to renal failure if severe. Many patients will also describe a second-wind phenomenon, characterized by a sudden and significant improvement in exercise tolerance after about 10 min of sustained aerobic exercise. This feature is unique to McArdle’s disease and is due to the ability of muscle to utilize circulating glucose to bypass the dysfunction in glycogen breakdown [56]. Later in the disease course, about one third of patients will develop fixed proximal weakness and wasting predominately affecting the shoulder girdle [57]. Patients with this pattern of fixed proximal muscle weakness can be misdiagnosed with an autoimmune myopathy, particularly if a history of exercise intolerance and episodic weakness is not elicited.

There is no enzyme replacement therapy yet available for McArdle’s disease. Treatment revolves around dietary recommendations and promotion of low–moderate intensity aerobic exercise. Nevertheless, correct diagnosis remains imperative for optimal patient counseling and avoidance of inappropriate therapies, such as immunosuppression. Muscle biopsy reveals subsarcolemmal or intermyofibrillar glycogen deposits and the absence of myophosphorylase on immunohistochemical staining. However, when the diagnosis is suspected, a muscle biopsy may not be necessary. Instead, sequencing of the PYGM gene can be performed, which should reveal one of the more than 100 different mutations described to date [56].

Mitochondrial Myopathies

Mitochondria play a crucial role in oxidative phosphorylation and energy production. Their dysfunction can therefore affect multiple tissues, with muscle being preferentially affected due to high energy demands. Mitochondrial myopathy is a well- recognized and relatively common symptom of mitochondrial dysfunction, which is typically characterized as exercise intolerance with premature fatigue and varying degrees of muscle weakness. Although proximal muscle weakness can be seen, mitochondrial myopathies also commonly involve the extraocular muscles, which are virtually never affected in patients with autoimmune myopathy. Compared to the metabolic myopathies, mitochondrial myopathies are less commonly associated with rhabdomyolysis, myoglobinuria, and exercise-induced contractures. CK levels may be normal to mildly elevated. Muscle biopsy reveals the presence of ragged red fibers with Gomori trichrome stain, ragged blue fibers on succinate dehydrogenase stain, and the presence of cytochrome c oxidase-negative fibers. It should be noted, however, that while these findings are indicative of mitochondrial dysfunction, they can be seen with many disorders and are not specific for an inherited mitochondrial myopathy. For example, patients with DM and IBM may also have muscle biopsies showing evidence of mitochondrial dysfunction. However, patients with mitochondrial myopathy almost always lack the inflammatory infiltrates seen in patients with DM and PM.

The presence of certain extra-muscular manifestations may also suggest the possibility of a primary mitochondrial disorder. For example, patients with mitochondrial encephalomyopathy, lactic acidosis, and stroke-like syndrome (MELAS) and myoclonic epilepsy with ragged red fibers (MERRF) syndrome present with varying degrees of cognitive impairment, hearing loss, seizures, and neuropathy g[58, 59].

Endocrine Myopathies

Thyroid Myopathies

Hypothyroidism is a common cause of muscle dysfunction with up to 79 % of patients reporting symptoms such as weakness, fatiguability, muscle pain, cramps, or stiffness at the time of diagnosis [60]. The number of patients with a true hypothyroid myopathy is lower with only 37.5 % found to have proximal muscle weakness on manual muscle testing and only 7–33 % found to have myopathic changes on EMG testing [60-62]. Hypothyroid myopathy is typically characterized by subjective muscle discomfort with mild to moderate proximal muscle weakness and delayed contraction and relaxation of deep tendon reflexes. CK may be mildly to severely elevated. Rare patients may present with prominent muscle stiffness and pseudohypertrophy, a condition known as Hoffman’s syndrome [63]. There does not appear to be an association between the degree of weakness and the severity of hypothyroidism [60]. In less severe cases, muscle biopsies typically show type II fiber atrophy with occasional type I fiber hypertrophy [64]. Cases of necrotizing myopathy in the context of severe hypothyroidism have also been reported [65]. Although most cases are caused by primary hypothyroidism, a case associated with central hypothyroidism has also been reported; in this case, free T4 was undetectable in the context of a normal TSH [65]. With replacement of thyroid hormone, the majority of patients will improve over the course of about 6–8 months, although a small percentage have residual weakness even after 1 year of therapy [60].

Hyperthyroidism is also associated with myopathy, although this appears to be a less common occurrence than with hypothyroidism. In one study, 62 % of patients with newly diagnosed, untreated hyperthyroidism had clinical evidence of proximal muscle weakness but only 10 % actually exhibited myopathic changes on EMG. This finding, together with the lack of CK elevation, the rapidity of onset and resolution, and the positive correlation between severity of hyperthyroidism and degree of weakness, leads the authors to suggest that the weakness associated with hyperthyroidism may be one of functional muscle dysfunction than of true myopathy [60].

Other Endocrine Myopathies

Although thyroid disease causes the majority of endocrine-related myopathies, abnormalities of adrenal and parathyroid gland function can also cause myopathic weakness. Hyperadrenocorticism in Cushing’s syndrome causes a steroid-induced myopathy characterized by proximal weakness often with prominent muscle wasting. Other clinical features of Cushing’s syndrome, such as abnormal fat distribution, abdominal stria, and moon facies, are typically present. As with hypothyroid myopathy, muscle biopsy demonstrates type II fiber atrophy. Hyperparathyroidism can occasionally cause a syndrome of proximal muscle weakness and wasting with brisk reflexes. CK is normal to slightly elevated. Muscle biopsy shows varying degrees of atrophy with no alteration of fiber type arrangement. Lastly, diabetes mellitus can also cause an ischemic infarction of the thigh muscles that may mimic a myopathy; however, this is typically characterized by abrupt onset of pain, tenderness, and edema of one thigh at a time [63].

Conclusions

Although varied conditions can mimic one of the autoimmune myopathies, there are several key features that suggest an alternative etiology (Tables 1 and 2). These include a positive family history, prolonged evolution of weakness over the years, facial weakness, scapular winging, eye movement abnormalities, distal weakness equal to or greater than proximal weakness, and asymmetric weakness. The absence of myositis-specific autoantibodies (which are found in approximately 80 % of autoimmune myopathy patients) and systemic features of autoimmune processes should also raise one’s suspicion for an alternative diagnosis. As discussed above, an elevated CK is not specific for autoimmune myopathy and can be markedly elevated in multiple types of myopathies. Of note, the CK may also be elevated in acute denervating processes, including amyotrophic lateral sclerosis. Likewise, while T2-STIR hyper-intensities on muscle MRI can indicate areas of muscle inflammation, this is not specific and can be seen with denervating conditions as well. In summary, the differential diagnosis for proximal weakness is quite broad and a variety of conditions in addition to autoimmune entities must be considered. Correct diagnosis is achieved by consideration of both clinical and laboratory features, in conjunction with histopathological data from muscle biopsy.

Table 1.

Clinical features suggestive of a non-autoimmune myopathy

Positive family history of muscle weakness Slow progressive evolution of weakness over months to years Presence of facial or extraocular muscle weakness Scapular winging Presence of distal weakness greater than or equal to proximal weakness Presence of asymmetric weakness Lack of myositis autoantibodies Lack of systemic manifestations of autoimmune disorders

Table 2.

Tests to assist in identification of myositis mimics

Anti-c5N1A (positive in IBM) GAA enzyme activity assay (positive in Pompe disease) Thyroid function tests (TSH, free T4, free T3) Parathyroid hormone Cortisol level Genetic testing Muscle biopsy