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Sarcoid myopathy

Sarcoid myopathy
Literature review current through: Jan 2024.
This topic last updated: Jan 05, 2024.

INTRODUCTION — Sarcoidosis is a multisystem disorder of unknown etiology. It commonly presents in young adults with bilateral hilar adenopathy, pulmonary infiltrates, skin and/or eye lesions, although any organ can be affected.

Musculoskeletal disease affects 4 to 38 percent of patients and may lead to clinically significant disease affecting the muscles, bones, and joints [1,2].

The pathogenesis of sarcoid myopathy is unclear. However, the histopathologic findings of sarcoidosis in the muscles are the same as in other tissues. In sarcoid myopathy, granulomatous inflammation in muscle appears to lead to muscle fibrosis and tissue injury.

Sarcoid involvement of the muscle will be reviewed here. Sarcoid arthropathy and bone disease, other extrapulmonary manifestations of sarcoidosis, pulmonary sarcoidosis, and general issues related to sarcoidosis and its pathogenesis are discussed separately:

(See "Sarcoid arthropathy".)

(See "Overview of extrapulmonary manifestations of sarcoidosis".)

(See "Sarcoidosis of bone".)

(See "Clinical manifestations and diagnosis of sarcoidosis".)

(See "Pathology and pathogenesis of sarcoidosis".)

CLINICAL MANIFESTATIONS

Clinical features

Asymptomatic disease — The majority of patients with sarcoid myopathy are asymptomatic. Symptomatic myopathy is rare, with only 4 cases in a series of >1000 patients with sarcoidosis [3]. Skeletal muscle involvement is estimated to occur subclinically in as many as 50 to 80 percent of individuals with sarcoidosis. However, it is very infrequently (0.5 to 2.5 percent) symptomatic [4-6].

Patients with asymptomatic sarcoid myopathy may have elevation of muscle enzymes or noncaseating granulomas on muscle biopsy.

Symptomatic disease — In symptomatic patients, sarcoid myopathy is associated with fever, myalgias, arthralgias, and erythema nodosum.

Patients with sarcoidosis rarely present initially with myopathy. Features of other organ involvement are usually present when sarcoid myopathy is diagnosed [6,7].

Muscle group involvement – Although sarcoid myopathy most commonly affects the muscles of the proximal extremities, it may also affect the diaphragm, heart, and extraocular muscles [4,8-13].

Respiratory failure may be an early sign of sarcoid myopathy. Respiratory insufficiency and failure may rarely be caused by weakness of the intercostal muscles, diaphragm, and pharyngeal muscles [14].

Cardiac sarcoidosis may present with syncope, heart failure, and sudden death and is considered as a separate entity from sarcoid myopathy. (See "Clinical manifestations and diagnosis of cardiac sarcoidosis".)

Extraocular muscle sarcoidosis may present with painful or painless proptosis, periorbital edema, or diplopia [10,15,16].

Symptomatic disease patterns – Three clinical patterns of symptomatic myopathy have been described; these include chronic myopathy, acute myositis, and nodular myopathy [6,17]:

Chronic myopathy – Chronic myopathy is the most common form of sarcoid myopathy. It is characterized by the insidious onset of progressive symmetric proximal muscle weakness with normal or mildly elevated muscle enzymes. Chronic myopathy can lead to early muscle atrophy, contractures, pseudohypertrophy, and dysphagia and responds poorly to glucocorticoids. It can mimic chronic polymyositis, muscular dystrophy, and glucocorticoid-induced myopathy. (See "Glucocorticoid-induced myopathy".)

Acute myositis – An acute myositis is typically seen in younger patients (<40 years) and is more common in female patients. It is characterized by diffuse muscle swelling and pain in proximal (more than distal) muscles bilaterally that may progress to muscle contractures, hardening, and hypertrophy. It is associated with elevated muscle enzymes and muscle weakness. This presentation typically mimics acute polymyositis, given that both may present with fatigue, muscle weakness, arthralgias, myalgias, and fever.

Nodular myopathy – The least frequent pattern is nodular myopathy, which can present with single or multiple, bilateral, tender nodules and normal muscle enzymes. These nodules may occur in any muscle, but the lower limbs are more commonly affected. The nodules are usually palpable and painful and are not associated with muscle weakness or limitation of movement. Occasionally, contractures and myalgias are present. Nodules may be any size, and larger lesions can resemble a tumor [5,18].

Serologies – Serum angiotensin-converting enzyme (ACE) and soluble interleukin 2 (IL-2) receptor (sIL-2R) may be elevated in patients with sarcoid myopathy, although data supporting their use are limited [8].

Imaging — Magnetic resonance imaging (MRI) is the imaging modality of choice for sarcoid myopathy. Computed tomography (CT) is used when MRI is not feasible. Positron emission tomography (PET) and gallium scanning can detect active sarcoid myopathy but are not commonly used because of expense and limited sensitivity.

MRI – MRI can detect specific patterns of disease that may help distinguish between different types of myopathy:

Acute myositis – Acute myositis is associated with diffuse increased signal intensity on T2-weighted images. Some cases may reveal a “tiger man” sign (ie, multiple linear regions of muscle edema) [8].

Chronic myositis – T1-weighted images can be used to quantify muscle fatty degeneration and atrophy associated with chronic myositis.

Nodular myopathy – Nodular myopathy produces a “dark star” pattern (ie, star-shaped area of low signal intensity centered within the nodule, surrounded by areas of high intensity on T1-weighted images with contrast and on T2-weighted axial images) [19-21]. Notably, this finding may persist even after treatment with glucocorticoids [22].

In a patient with known sarcoid myopathy, MRI can be used to determine the extent of disease and to track response to therapy.

MRI is more sensitive than other imaging methods, including gallium scanning and CT [23]. However, MRI may fail to demonstrate evidence of myopathy in up to half of patients, particularly when the muscle involvement is hyperacute or mild [7].

PET scanning18F-fluorodeoxyglucose PET (FDG-PET) scans can identify active sarcoid, which is characterized by the “tiger man sign” (ie, multiple linear and patchy hypermetabolic lesions in the skeletal muscle) [24].

PET scans have also been used to identify asymptomatic sarcoid skeletal muscle disease and assess treatment response [25,26]. However, the intensity of the FDG-PET signal does not correlate with serum ACE or muscle enzyme levels [26].

Gallium scanning – Gallium scans can identify active sarcoid, which is characterized by the “leopard man sign” (ie, multiple hot spots representing increased uptake of radionuclide throughout the affected muscle) [21,27,28]. This nodular pattern may help differentiate sarcoid myopathy from other inflammatory myopathies [29]. However, gallium uptake can also be diffuse [30].

CT scanning – Skeletal muscle CT scans can help delineate areas of muscle atrophy, which is commonly seen in chronic myopathy. Common areas of atrophy are the paraspinal, hip adductor, knee flexor, and ankle plantar flexor muscles [7].

Electrodiagnostic studies

Nodular myopathy – Electromyographic (EMG) studies in patients with nodular myopathy are normal.

Acute or chronic sarcoid myopathy – EMG studies in patients with acute or chronic sarcoid myopathy typically show low-amplitude, short-duration, polyphasic motor unit potential in proximal more than distal muscles with spontaneous fibrillations and positive sharp waves. This pattern is indistinguishable from the EMG findings of the inflammatory myopathies. (See "Diagnosis and differential diagnosis of dermatomyositis and polymyositis in adults", section on 'Electromyography'.)

Histopathology — Biopsy of affected muscle in patients with sarcoid myopathy typically reveals multiple noncaseating granulomas in perimysial connective tissue, generally with a diffuse cellular distribution with macrophages and CD4-positive T lymphocytes [31].

In addition, CD8-positive T lymphocytes are irregularly distributed within the granulomatous cellular infiltrate in early lesions and surrounding the granulomas seen in more mature lesions [31,32].

Perifascicular atrophy is seen in half of the cases. Immunohistochemistry studies reveal increased CD4 lymphocytes and a high CD4:CD8 T-lymphocyte ratio, in contrast to the low ratio seen in polymyositis and inclusion body myositis (IBM) [33].

In general, granulomatous myositis is rarely seen on muscle biopsies performed for various reasons. In one study of 2985 skeletal muscle biopsy specimens obtained at a single center over 12 years, only 12 specimens demonstrated granulomatous inflammation [34].

The pathologic features of sarcoidosis are discussed in greater detail elsewhere. (See "Pathology and pathogenesis of sarcoidosis", section on 'Pathology'.)

DIAGNOSIS

In whom to suspect — Sarcoid myopathy should be suspected in two scenarios:

With known sarcoidosis – Patients with known or suspected sarcoidosis who exhibit the insidious development of progressive proximal weakness, acute myalgia, elevated muscle enzymes, or nodular painful abnormality of muscle.

Without known sarcoidosis – Patients without known sarcoidosis but with proximal muscle weakness in the setting of an unidentified systemic illness. In such patients, sarcoid myopathy is likely one of many diagnoses under consideration.

Diagnostic evaluation

In patients with known sarcoidosis

Acute myositis – In patients with established sarcoidosis presenting with muscular symptoms, we obtain muscle enzyme testing (serum creatine kinase [CK] and aldolase) and perform electromyographic (EMG) studies.

In patients with evidence of active sarcoidosis in other organ systems, the combination of proximal muscle weakness, elevated muscle enzymes, and myopathic EMG findings is adequate to establish a diagnosis of sarcoid myopathy. (See 'Clinical features' above and 'Electrodiagnostic studies' above and "Diagnosis and differential diagnosis of dermatomyositis and polymyositis in adults", section on 'Diagnostic approach'.)

MRI is not necessary to confirm the diagnosis in these cases, but a baseline MRI may be useful to track response to therapy.

Chronic and nodular myopathy – Chronic and nodular sarcoid myopathy may be diagnosed based on appropriate findings on MRI. These forms of sarcoid myopathy may not be accompanied by muscle enzyme elevation, and nodular myopathy is not accompanied by EMG abnormalities. Therefore, imaging is crucial to establishing these diagnoses.

In patients without known sarcoidosis – We evaluate patients without a prior diagnosis of sarcoidosis who are suspected of having a sarcoid myopathy using the same approach we use to evaluate any patient presenting with muscle weakness. (See "Approach to the patient with muscle weakness".)

An evaluation for other manifestations of sarcoidosis is also required. The evaluation of suspected pulmonary and extrapulmonary sarcoidosis is described in detail separately. (See "Clinical manifestations and diagnosis of sarcoidosis" and "Overview of extrapulmonary manifestations of sarcoidosis", section on 'Extrapulmonary disease in initial diagnosis'.)

Use of alternate imaging studies – In patients unable to undergo MRI, we perform 18F-fluorodeoxyglucose positron emission tomography (FDG-PET). Although expensive, it may still be useful when used selectively to evaluate the distribution of muscle changes, potentially reducing the need for repeat exploratory muscle biopsies in patients with biopsy-proven sarcoidosis and clinical evidence of sarcoid myopathy.

FDG-PET is also useful in patients with sarcoid myopathy who are not responding to therapy and to distinguish active muscle disease from chronic but inactive muscle disease and nonmuscular causes of weakness and fatigue. (See 'Imaging' above.)

Other imaging techniques, such as CT and gallium scanning, are less useful for diagnosis due to low sensitivity and specificity [23].

Muscle biopsy — In patients who are suspected of having sarcoid myopathy but do not have a known diagnosis of sarcoid, we suggest biopsy of an affected muscle group.

Biopsy approaches

Open surgical muscle biopsies or large-bore needle biopsies have typically been used to assess muscle disease in patients with suspected sarcoid myopathy.

A targeted fine-needle aspiration demonstrating cytologic evidence of granulomatous inflammation may be adequate to establish the presence of sarcoid myopathy in a patient previously diagnosed with sarcoidosis [35,36].

Diagnostic criteria – The diagnosis of sarcoid myopathy may be demonstrated by the presence of noncaseating granulomas and the exclusion of other causes of granulomatous histopathology (eg, idiopathic or infectious granulomatous myositis) with special stains for mycobacteria and fungi.

A biopsy showing granuloma is highly suggestive of sarcoidosis but is not diagnostic. Associated signs and symptoms of sarcoidosis should, therefore, be present before a definite diagnosis is made. (See "Clinical manifestations and diagnosis of sarcoidosis", section on 'Initial evaluation'.)

Evaluation to exclude mimics of sarcoid myopathy — When the diagnosis of sarcoid myopathy is not clear (and cannot be confirmed by muscle biopsy), we would consider additional testing, including the following:

Complete blood count and differential white blood cell count, erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP), and liver chemistries (which may be elevated due to direct involvement of the liver by sarcoid).

Autoantibody testing for granulomatous vasculitis, including antineutrophil cytoplasmic antibodies, and, if indicated clinically, for systemic lupus erythematosus, including antinuclear, anti-double-stranded deoxyribonucleic acid (dsDNA), anti-Smith, anti-ribonucleoprotein, and myositis-specific antibodies.

Urinalysis.

Testing for latent tuberculosis by tuberculin skin testing or an interferon-gamma release assay. (See "Tuberculosis infection (latent tuberculosis) in adults: Approach to diagnosis (screening)".)

CT of the chest and abdomen to identify neoplasm.

Special staining of the muscle tissue for mycobacteria and fungi.

DIFFERENTIAL DIAGNOSIS — The differential diagnosis of myopathy in patients with sarcoidosis includes conditions related and unrelated to the primary disorder. For example:

Muscle weakness can be caused by glucocorticoids

Generalized fatigue and weakness may be features of active sarcoidosis

Reduced walking capacity and dyspnea may be caused by impaired inspiratory muscle strength not due to myositis [37]

Multiple conditions can cause proximal weakness, soft tissue nodules, or a granulomatous myositis

The specific disorders that should be considered depend upon the patient's clinical and laboratory manifestations.

Glucocorticoid- and other drug-induced myopathies – A number of drugs, including glucocorticoids, may induce a myopathy. These myopathies can usually be distinguished from sarcoid myopathy by MRI and by the patient's medical history. (See "Glucocorticoid-induced myopathy" and "Drug-induced myopathies".)

Glucocorticoid-related myopathy is common in patients being treated with moderate to high doses of glucocorticoids (eg, >20 mg daily) for other organ manifestations of sarcoidosis.

Like sarcoid myopathy, it usually affects proximal strength in the lower extremities, with relative sparing of other muscles. It is often accompanied by other side effects of glucocorticoids (eg, Cushingoid features) and improves with a reduction in the glucocorticoid dose.

Granulomatous myopathy from non-sarcoid causes – In patients with a muscle biopsy that reveals multiple noncaseating granulomas, the most common diagnosis is sarcoidosis; however, other granulomatous diseases must also be considered depending upon the clinical context. Examples include:

Infectious diseases (eg, tuberculosis, fungal infection, syphilis, brucellosis, human T-lymphotropic virus type I, and Pneumocystis jirovecii)

Noninfectious disorders (eg, granulomatosis with polyangiitis; inflammatory bowel diseases)

Neoplasms (eg, lymphoma)

Foreign body reaction [12,38]

Specific testing to differentiate between sarcoidosis and one of these conditions is individualized, depending upon the findings that are present in a given patient (see appropriate topic reviews).

Inflammatory myopathy – Polymyositis and inclusion body myositis (IBM) can both cause muscle weakness that can be similar to the symptoms and findings in sarcoidosis.

A prior diagnosis of sarcoidosis or a finding consistent with other organ involvement of sarcoidosis is usually helpful to establish a diagnosis of sarcoid myopathy. The muscle biopsy finding of granulomatous inflammation with a high CD4:CD8 T-lymphocyte ratio is diagnostic of sarcoid myopathy. When the pathology is equivocal, myositis-specific antibodies or myositis-associated antibodies may help establish the diagnosis of an inflammatory myopathy. (See "Clinical manifestations of dermatomyositis and polymyositis in adults".)

Acute sarcoid myositis can mimic acute polymyositis, given that both may present with muscle weakness, myalgia, muscle enzyme elevation, and fever. Electromyographic (EMG) studies, muscle enzymes, and MRI findings may not be able to distinguish the two entities.

IBM and sarcoid myopathy can have overlapping clinical and pathologic features (eg, granulomas) [39,40]. Moreover, IBM and sarcoid myopathy have been reported to occur in the same patients. In one series of 27 patients with IBM, two (7 percent) also had sarcoid myopathy [33]. Patients with features of both diseases are less likely to respond to therapy than patients with sarcoid myopathy alone [39,40]. (See "Clinical manifestations and diagnosis of inclusion body myositis" and "Clinical manifestations of dermatomyositis and polymyositis in adults".)

Soft tissue tumors – Nodular soft tissue tumors, such as giant cell tumor and sarcoma, may have a similar clinical appearance to nodular sarcoid myopathy. Patients with sarcoid myopathy are likely to have other features of systemic sarcoidosis that would be absent in patients with soft tissue tumors, and characteristic findings of nodular sarcoid on MRI may also strongly suggest the diagnosis of sarcoid myopathy rather than malignancy. A biopsy of the lesion can confirm the diagnosis. (See "Clinical presentation, histopathology, diagnostic evaluation, and staging of soft tissue sarcoma" and "Giant cell tumor of bone".)

TREATMENT — There have been no randomized trials of glucocorticoids or other agents for sarcoid myopathy. Therefore, our approach is based upon clinical experience and limited data. Our treatment strategy is also informed and supported by the use of these medications in patients with pulmonary and other manifestations of sarcoidosis and patients with inflammatory myopathies, such as dermatomyositis and polymyositis. (See "Initial treatment of dermatomyositis and polymyositis in adults" and "Treatment of recurrent and resistant dermatomyositis and polymyositis in adults".)

The treatment approach varies according to clinical manifestations, which are described above. (See 'Clinical features' above.)

Asymptomatic muscle disease — Asymptomatic muscle disease does not require specific pharmacotherapy.

Patients with sarcoidosis who lack symptomatic muscle disease should be encouraged to remain active and participate in light exercise.

Nodular myositis — A patient with only one or a few painful nodular sarcoid muscle lesions may respond to combined therapy consisting of a single intralesional injection of 40 mg of triamcinolone, rest, and a nonsteroidal antiinflammatory drug (NSAID) [11]. However, most patients will need to be treated as an acute myositis since the lesions may be inaccessible or too numerous to inject. (See 'Acute myositis' below.)

Acute myositis — In patients with acute myositis (or multiple nodular sarcoid lesions), we suggest treatment with prednisone 0.5 mg/kg daily; up to 1 mg/kg daily may be required for patients with significant pain or weakness.

Glucocorticoids should be gradually tapered over four to eight weeks as tolerated to below 7.5 mg daily; then patients should be gradually tapered off glucocorticoids over the next four to eight weeks, such that total duration of glucocorticoid therapy is less than three months. Inability to reduce the glucocorticoid dose to these targets due to recurrent symptoms is an indication for addition of MTX or AZA (see 'DMARD therapy' below). However, in our experience, most patients will respond to glucocorticoid monotherapy.

Chronic myositis

Indications for treatment — Immunosuppression is indicated only for patients with muscle weakness or myalgias due to active disease as demonstrated by recent elevation of muscle enzymes greater than 1.5 times the upper limit of normal, active inflammation on muscle biopsy findings, electromyographic (EMG) study abnormalities, a changing course of symptoms (eg, progressive weakness), or MRI or other imaging findings that are consistent with active myositis.

Glucocorticoid therapy — In patients with chronic myositis, we suggest initiating treatment with prednisone 1 mg/kg daily (to a maximum of 80 mg daily). We follow the same approach to treatment used in the management of polymyositis or dermatomyositis, with a gradual tapering of the glucocorticoids over 6 to 12 months.

Patients who fail to respond adequately to glucocorticoids should also receive treatment with a disease-modifying antirheumatic drug (DMARD) (see 'DMARD therapy' below). Chronic myositis is commonly refractory to glucocorticoids. Relapses are common after glucocorticoids are discontinued.

Responses to glucocorticoid therapy vary between case series, with benefit reported in 40 to 60 percent of patients [7,41]. In one study, only 7 of 26 patients (27 percent) had a complete response, while 6 (22 percent) were stabilized and 13 (50 percent) were nonresponsive. (See 'DMARD therapy' below.)

DMARD therapy — We suggest adding a DMARD (eg, azathioprine [AZA] 2 mg/kg orally daily or methotrexate [MTX] 20 to 25 mg weekly) in the following scenarios [42]:

Inadequate response to glucocorticoids after two to three months of therapy

Inability to taper prednisone below 10 mg after six months of therapy

Intolerance of glucocorticoids

In some scenarios, we suggest initiating a DMARD and prednisone simultaneously:

Increased risk of adverse effects from glucocorticoids (eg, due to diabetes mellitus or reduced bone mass, or with other severe adverse effects)

Severe muscle disease (eg, severe weakness leading to an inability to walk)

The presence of other organ involvement requiring DMARD therapy (eg, arthritis or pulmonary disease)

Earlier treatment has significantly better outcomes [7]. Therefore, early identification of glucocorticoid-resistant disease is crucial. The use and adverse effects of MTX and AZA are the same as for rheumatoid arthritis or inflammatory myositis and are discussed in detail separately. (See "Initial treatment of dermatomyositis and polymyositis in adults", section on 'Initial therapy'.)

In patients requiring DMARDS, we typically start a prednisone taper at three months and taper completely off over 6 to 12 months. We suggest continuing MTX or AZA for a total of two to three years before reducing and discontinuing the immunosuppressive medication.

Resistance to DMARDs — In patients with sarcoid myopathy who exhibit an inadequate response to a three-month trial of glucocorticoids combined with MTX or AZA, we suggest adding infliximab (titrated to 3 to 5 mg/kg administered by intravenous infusion at weeks 0, 2, 6, and subsequently every eight weeks) or adalimumab (40 mg by subcutaneous injection every other week).

These tumor necrosis factor (TNF) inhibitors have been shown in case reports to be effective in such patients [43,44]. Additional evidence suggesting potential benefit comes from various series and clinical trials in which the efficacy of TNF-alpha inhibitors (infliximab and adalimumab) has been shown for the treatment of pulmonary and other extraarticular manifestations of sarcoidosis. (See "Treatment of pulmonary sarcoidosis refractory to initial therapy", section on 'Tumor necrosis factor-alpha antagonists' and "Sarcoid arthropathy", section on 'Add a TNF inhibitor for persistent symptoms'.)

Similar regimens are used in pulmonary sarcoidosis and for other manifestations of extrapulmonary disease, such as sarcoid arthritis. We do not use etanercept, which has failed to show benefit in patients with progressive pulmonary sarcoidosis or chronic ocular disease.

Physical activity — All patients with sarcoidosis and muscle weakness should receive a physical therapy evaluation and instruction in a regular exercise program to maintain muscle strength and endurance and to prevent muscle fatigue.

Monitoring — Patients with chronic myositis require monitoring of their response to therapy and for drug safety:

Myopathy – Initially, patients are evaluated monthly, usually until they respond to therapy and are on a stable treatment regimen. Subsequently, patients can be seen every 8 to 12 weeks.

In addition to the medical history (eg, symptoms of weakness, pain, dysphagia, aspiration, or tachypnea), testing of muscle strength should be performed, especially for the affected muscle groups. We obtain a complete blood count, liver enzymes, and creatine kinase (CK) at each visit. Monitoring of the clinical response of the muscle disease, including testing of muscle strength, is done in a similar fashion to that in patients with dermatomyositis or polymyositis and is described in detail separately. (See "Initial treatment of dermatomyositis and polymyositis in adults", section on 'Assessing treatment response'.)

Evaluation of the response to therapy can also be performed, if needed, by repeating the original imaging done at baseline; the most sensitive and specific imaging modality is MRI. In some cases, improvement of positron emission tomography (PET)/CT findings is also seen after treatment.

Progressive weakness in the absence of a rising CK should prompt an evaluation for glucocorticoid-related myopathy. (See "Glucocorticoid-induced myopathy".)

Drug safety – Glucocorticoids, MTX, AZA, and TNF inhibitors are monitored in a standard fashion, as in rheumatoid arthritis or idiopathic inflammatory myositis, depending upon the specific medication:

(See "Use of methotrexate in the treatment of rheumatoid arthritis".)

(See "Major side effects of low-dose methotrexate".)

(See "Pharmacology and side effects of azathioprine when used in rheumatic diseases".)

(See "General principles and overview of management of rheumatoid arthritis in adults", section on 'Drug monitoring and prevention of drug toxicity'.)

PROGNOSIS — The prognosis of the muscle disease is variable, but it generally does not affect mortality. Patients treated early in the course of their myopathy are more likely to benefit from therapy. In one case series of 11 patients with chronic, generalized sarcoid myopathy, the therapeutic response was poor in patients with chronic disease (greater than two years), while the best outcomes were seen with earlier diagnosis and treatment (from within a few months up to two years of disease) [7].

Chronic myopathy leads to atrophy of muscle, causing long-term functional decline. Mortality is likely not affected by the course of the myopathy in most patients, as survival usually depends upon the involvement of other organs and tissues (eg, lungs, kidneys, heart). (See "Treatment of pulmonary sarcoidosis: Initial approach", section on 'Long-term outcome'.)

SOCIETY GUIDELINE LINKS — Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Sarcoidosis".)

SUMMARY AND RECOMMENDATIONS

Clinical and laboratory features – Three types of clinical muscle disease are recognized:

Chronic myopathy characterized by insidious proximal muscle weakness

Acute myopathy with weakness and elevated muscle enzymes

Nodular myopathy, which is the least commonly seen

Muscle involvement is commonly subclinical. (See 'Clinical manifestations' above.)

Muscle enzymes such as creatine kinase (CK) are mostly elevated in acute myopathy, and in general muscle enzymes elevation is less frequent as well as not as high as seen in idiopathic inflammatory myopathies such as polymyositis, dermatomyositis, or nodular myositis.

Assessment of muscle disease – In a patient with sarcoidosis, the presence of muscle weakness, muscle pain, or muscle nodules is suggestive of sarcoid myopathy. MRI may help to identify and distinguish between the different types of myopathy but is normal in some patients with mild or acute disease. Electromyographic (EMG) studies may reveal a myopathic pattern, but EMGs are normal in patients with nodular involvement. Biopsy of affected muscle typically shows multiple characteristic noncaseating granulomas in perimysial connective tissue. (See 'Clinical features' above and 'Imaging' above and 'Electrodiagnostic studies' above and 'Histopathology' above.)

Diagnosis – A diagnosis of sarcoid myopathy can generally be made in patients with sarcoid in another site; elevated muscle enzymes; myopathic EMG studies; characteristic findings on MRI in patients with nodular myopathy; diffuse inflammatory myopathic MRI findings in acute or chronic myopathy; and/or biopsy evidence of noncaseating granulomas, usually with a high CD4:CD8 T-lymphocyte ratio. (See 'Diagnosis' above.)

In addition, other causes of similar symptoms and findings should be excluded. (See 'Evaluation to exclude mimics of sarcoid myopathy' above.)

Differential diagnosis – The differential diagnosis of sarcoid myopathy includes glucocorticoid- and other drug-induced myopathies, and in patients with a muscle biopsy that reveals multiple noncaseating granulomas, other granulomatous diseases, including infections and granulomatosis with polyangiitis, must also be considered. (See 'Differential diagnosis' above.)

Treatment – Early institution of therapy for symptomatic disease is critical, as glucocorticoids and other immunosuppressive agents cannot reverse muscle atrophy.

Asymptomatic – Asymptomatic muscle disease does not require immunosuppressive therapy. (See 'Asymptomatic muscle disease' above.)

Nodular myositis – For patients with only one or a few painful nodular sarcoid muscle lesions, we suggest intralesional injections of triamcinolone (Grade 2C). Systemic glucocorticoids are an alternative for patients with more diffuse disease. (See 'Nodular myositis' above.)

Acute myositis – In patients with acute myositis, we suggest treatment with prednisone (Grade 2C). We prescribe 0.5 to 1.0 mg/kg daily, which should be tapered over three months. Patients who are unable to tolerate prednisone taper should be treated with disease-modifying antirheumatic drug (DMARD) therapy. (See 'Acute myositis' above.)

Chronic myositis – In patients with chronic myositis, we suggest initial treatment with prednisone 1.0 mg/kg daily (Grade 2C).

Many patients require additional therapy; we suggest a DMARD such as azathioprine (AZA; 2 mg/kg daily) or methotrexate (MTX; 20 to 25 mg weekly) (Grade 2C). (See 'Chronic myositis' above.)

Resistant disease – In patients with chronic myositis who fail to have an adequate response to glucocorticoids combined with AZA or MTX, we suggest adding infliximab (titrated to 3 to 5 mg/kg every eight weeks) or adalimumab (40 mg subcutaneous every other week) (Grade 2C). (See 'Resistance to DMARDs' above.)

ACKNOWLEDGMENT — The UpToDate editorial staff acknowledges Winston Sequeira, MD, who contributed to an earlier version of this topic review.

  1. Spilberg I, Siltzbach LE, McEwen C. The arthritis of sarcoidosis. Arthritis Rheum 1969; 12:126.
  2. Abril A, Cohen MD. Rheumatologic manifestations of sarcoidosis. Curr Opin Rheumatol 2004; 16:51.
  3. Patil S, Hilliard CA, Arakane M, et al. Musculoskeletal sarcoidosis: A single center experience over 15 years. Int J Rheum Dis 2021; 24:533.
  4. Baydur A, Pandya K, Sharma OP, et al. Control of ventilation, respiratory muscle strength, and granulomatous involvement of skeletal muscle in patients with sarcoidosis. Chest 1993; 103:396.
  5. Zisman DA, Biermann JS, Martinez FJ, et al. Sarcoidosis presenting as a tumorlike muscular lesion. Case report and review of the literature. Medicine (Baltimore) 1999; 78:112.
  6. Fayad F, Lioté F, Berenbaum F, et al. Muscle involvement in sarcoidosis: a retrospective and followup studies. J Rheumatol 2006; 33:98.
  7. Maeshima S, Koike H, Noda S, et al. Clinicopathological features of sarcoidosis manifesting as generalized chronic myopathy. J Neurol 2015; 262:1035.
  8. Ten Dam L, Raaphorst J, van der Kooi AJ, et al. Clinical characteristics and outcome in muscular sarcoidosis: a retrospective cohort study and literature review. Neuromuscul Disord 2022; 32:557.
  9. Dewberry RG, Schneider BF, Cale WF, Phillips LH 2nd. Sarcoid myopathy presenting with diaphragm weakness. Muscle Nerve 1993; 16:832.
  10. Cornblath WT, Elner V, Rolfe M. Extraocular muscle involvement in sarcoidosis. Ophthalmology 1993; 100:501.
  11. Janssen M, Dijkmans BA, Eulderink F. Muscle cramps in the calf as presenting symptom of sarcoidosis. Ann Rheum Dis 1991; 50:51.
  12. Simmonds NJ, Hoffbrand BI. Contracturing granulomatous myositis: a separate entity. J Neurol Neurosurg Psychiatry 1990; 53:998.
  13. Gdynia HJ, Osterfeld N, Dorst J, et al. Granulomatous myositis mimicking slowly progressive lower motor neuron disease. Eur J Med Res 2008; 13:330.
  14. Pfeffer G, Povitz M, Gibson GJ, Chinnery PF. Diagnosis of muscle diseases presenting with early respiratory failure. J Neurol 2015; 262:1101.
  15. Kim JS, Scawn RL, Lee BW, et al. Masquerading Orbital Sarcoidosis with Isolated Extraocular Muscle Involvement. Open Ophthalmol J 2016; 10:140.
  16. Biesman BS. Extraocular muscle sarcoid. Ophthalmology 1994; 101:1.
  17. Mathur A, Kremer JM. Immunopathology, musculoskeletal features, and treatment of sarcoidosis. Curr Opin Rheumatol 1993; 5:90.
  18. Nemoto I, Shimizu T, Fujita Y, et al. Tumour-like muscular sarcoidosis. Clin Exp Dermatol 2007; 32:298.
  19. Otake S, Banno T, Ohba S, et al. Muscular sarcoidosis: findings at MR imaging. Radiology 1990; 176:145.
  20. Otake S. Sarcoidosis involving skeletal muscle: imaging findings and relative value of imaging procedures. AJR Am J Roentgenol 1994; 162:369.
  21. Otake S, Ishigaki T. Muscular sarcoidosis. Semin Musculoskelet Radiol 2001; 5:167.
  22. Otake S, Imagumbai N, Suzuki M, Ohba S. MR imaging of muscular sarcoidosis after steroid therapy. Eur Radiol 1998; 8:1651.
  23. Kurashima K, Shimizu H, Ogawa H, et al. MR and CT in the evaluation of sarcoid myopathy. J Comput Assist Tomogr 1991; 15:1004.
  24. Marie I, Josse S, Lahaxe L, et al. Clinical images: Muscle sarcoidosis demonstrated on positron emission tomography. Arthritis Rheum 2009; 60:2847.
  25. Kolilekas L, Triantafillidou C, Manali E, et al. The many faces of sarcoidosis: asymptomatic muscle mass mimicking giant-cell tumor. Rheumatol Int 2009; 29:1389.
  26. Milojevic IG, Sobic-Saranovic D, Milojevic B, Artiko VM. Muscular sarcoidosis in the eyes of 18 F-FDG PET/CT. J Clin Ultrasound 2022; 50:399.
  27. Patel N, Krasnow A, Sebastian JL, et al. Isolated muscular sarcoidosis causing fever of unknown origin: the value of gallium-67 imaging. J Nucl Med 1991; 32:319.
  28. Liem IH, Drent M, Antevska E, et al. Intense muscle uptake of gallium-67 in a patient with sarcoidosis. J Nucl Med 1998; 39:1605.
  29. Sohn HS, Kim EN, Park JM, Chung YA. Muscular sarcoidosis: Ga-67 scintigraphy and magnetic resonance imaging. Clin Nucl Med 2001; 26:29.
  30. Fayad F, Duet M, Orcel P, Lioté F. Systemic sarcoidosis: the "leopard-man" sign. Joint Bone Spine 2006; 73:109.
  31. Tews DS, Pongratz DE. Immunohistological analysis of sarcoid myopathy. J Neurol Neurosurg Psychiatry 1995; 59:322.
  32. Takanashi T, Suzuki Y, Yoshino Y, Nonaka I. Granulomatous myositis: pathologic re-evaluation by immunohistochemical analysis of infiltrating mononuclear cells. J Neurol Sci 1997; 145:41.
  33. Vattemi G, Tonin P, Marini M, et al. Sarcoidosis and inclusion body myositis. Rheumatology (Oxford) 2008; 47:1433.
  34. Prayson RA. Granulomatous myositis. Clinicopathologic study of 12 cases. Am J Clin Pathol 1999; 112:63.
  35. Guo M, Lemos L, Baliga M. Nodular sarcoid myositis of skeletal muscle diagnosed by fine needle aspiration biopsy. A case report. Acta Cytol 1999; 43:1171.
  36. Yamamoto T, Nagira K, Akisue T, et al. Aspiration biopsy of nodular sarcoidosis of the muscle. Diagn Cytopathol 2002; 26:109.
  37. Kabitz HJ, Lang F, Walterspacher S, et al. Impact of impaired inspiratory muscle strength on dyspnea and walking capacity in sarcoidosis. Chest 2006; 130:1496.
  38. Prieto-González S, Grau JM. Diagnosis and classification of granulomatous myositis. Autoimmun Rev 2014; 13:372.
  39. Alhammad RM, Liewluck T. Myopathies featuring non-caseating granulomas: Sarcoidosis, inclusion body myositis and an unfolding overlap. Neuromuscul Disord 2019; 29:39.
  40. Dieudonné Y, Allenbach Y, Benveniste O, et al. Granulomatosis-associated myositis: High prevalence of sporadic inclusion body myositis. Neurology 2020; 94:e910.
  41. Baughman RP, Costabel U, du Bois RM. Treatment of sarcoidosis. Clin Chest Med 2008; 29:533.
  42. Baughman RP, Lower EE. Steroid-sparing alternative treatments for sarcoidosis. Clin Chest Med 1997; 18:853.
  43. Baughman RP, Lower EE, Drent M. Inhibitors of tumor necrosis factor (TNF) in sarcoidosis: who, what, and how to use them. Sarcoidosis Vasc Diffuse Lung Dis 2008; 25:76.
  44. Marie I, Lahaxe L, Vera P, Edet-Samson A. Follow-up of muscular sarcoidosis using fluorodeoxyglucose positron emission tomography. QJM 2010; 103:1000.
Topic 5586 Version 21.0

References

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