26th January 2024

Inflammatory Myopathy – Myositis

Background 

Inflammatory myopathies can take many forms. Those relevant to the MRCP examination include mainly polymyositis, dermatomyositis and inclusion body myositis. It is chronic progressive inflammation of muscles, and each form of myositis presents differently. Thus, the management is tailored accordingly. 

Epidemiology 

Inflammatory myopathies are rare- estimated to occur in 1 in 100,000 persons. While dermatomyositis and polymyositis occur more commonly in females, inclusion body myositis is more prevalent in males. The average age of those affected ranges from 40-60 years, with inclusion body myositis mainly affecting those above 50 years of age. 

Pathophysiology 

In polymyositis, lymphocytes such as CD 8+ cytotoxic T cells invade myofibers in the muscle. Triggers for this include viruses such as HIV and parvovirus and drugs such as Phenytoin and Penicillamine. A small percentage (8%) may occur due to malignancies. 

Dermatomyositis results from an exposure to a type 1 interferon, causing capillary, myofiber and keratinocyte injury. It is a humorally mediated process driven by CD4 + T cells, causing capillary damage and ischaemic muscle injury. 

Inclusion body myositis is primarily a degenerative disorder with a likely secondary cytotoxic inflammatory component. The muscles are infiltrated by T cells, myeloid dendritic cells, macrophages and plasma cells, which aggregate in clusters in the perimysial spaces and cause myofiber necrosis. 

Presentation 

Dermatomyositis presents with proximal, symmetrical muscle weakness, elevated muscle enzymes and distinctive cutaneous findings. Myalgia is common during the active phase and respiratory muscle, and there may sometimes be myocardial and respiratory muscle involvement and signs of dysphasia. 

Characteristic cutaneous findings include a heliotrope rash, a violaceous, oedematous rash affecting the eyelids and Gottron’s papules over the MCP and PIP joints and extensor surfaces. Other less common skin presentations include calcinosis cutis, poikiloderma, periungual telangiectasias and cuticular hypertrophy. 

Polymyositis presents with similar muscle weakness as dermatomyositis. However, there are no characteristic skin changes, making it more difficult to diagnose clinically. The hip extensors are often a severely affected muscle group, causing difficulty in climbing stairs and standing from a seated position. It is defined by the presence of anti-synthetase autoantibodies and features such as interstitial lung disease, inflammatory myopathy and small joint symmetrical polyarthritis. 

Inclusion body myositis tends to have a more insidious onset, with the average onset of symptoms 5 years prior to diagnosis. There is asymmetric, distal muscle involvement, such as finger flexors and forearm flexors and as such, these patients may complain of weakness in grip strength and difficulty in doing tasks such as opening jars. Myalgia, muscle atrophy and dysphagia can occur but not as commonly.

Image Source: Wikimedia Commons (2022). Dermatomyositis10, Licensed under a creative commons licence. Available for free at: https://upload.wikimedia.org/wikipedia/commons/a/a1/Dermatomyositis10.jpg (Accessed: 10 July  2022).

Image Source: Wikimedia Commons (2022). Dermatomyositis2, Licensed under a creative commons licence. Available for free at: https://upload.wikimedia.org/wikipedia/commons/7/7b/Dermatomyositis2.jpg (Accessed: 10 July  2022).

Diagnosis 

Dermatomyositis

Most patients with myositis will have one or more muscle enzymes elevated, such as creatinine kinase, lactate dehydrogenase, aldolase, aspartate aminotransferase or alanine aminotransferase. 

Blood Tests: In dermatomyositis, there are specific autoantibodies that may be found, such as Anti Mi-2, which is associated with cutaneous disease but seems to have a lower risk of associated malignancy. Anti-melanocyte differentiation-associated protein 5 (anti-MDA5) is associated with rapidly progressive interstitial lung disease and characteristic skin changes, including ulcerations, Gottron’s papules, painful palmar and macular papules and non-scarring alopecia. 

The diagnostic criterion generally used is the 2017 EULAR/ACR classification criteria. To make a diagnosis of dermatomyositis, there needs to be features such as the previously mentioned skin changes (heliotrope rash and Gottron’s papules or Gottron’s sign) AND symmetrical, progressive muscle weakness (usually the proximal upper extensors and/or lower extensors or neck flexors relatively weaker than extensors. 

Muscle Biopsy: If this is required, the histopathological changes would show inflammation in the perimysial region (around the muscle bundles) and include CD4+ cells. 

Polymyositis

Polymyositis is seen in patients with muscle weakness without characteristic skin changes. 

Laboratory Tests: These may reveal similar results to that of other inflammatory myopathies, and as such, a muscle biopsy is frequently required for diagnosis. 

Muscle Biopsy: Histopathology, in this case, would show predominantly cellular infiltrates in the endomysial and inflammatory cells invading individual muscle fibres. Myocyte injury is mediated by CD8+ cytotoxic T lymphocytes that surround and invade the myofibers. 

Inclusion Body Myositis 

Inclusion body myositis also presents without any skin changes, and thus, diagnosis is dependent upon laboratory investigations, electromyography and muscle biopsy. 

Blood Tests: Autoantibodies against cytoplasmic 5′-nucleotidase 1A (cN1A) may help distinguish IBM from other forms of myositis. 

Neurophysiology studies: Changes in electromyography include fibrillation potentials, bizarre high-frequency repetitive discharges and short, small, low-amplitude polyphasic motor unit potentials. 

Muscle biopsy: This is likely to be diagnostic in many cases and histologically has characteristic features of sarcoplasmic ‘rimmed’ vacuoles that are red-rimmed on modified trichrome stain and blue-rimmed on H&E stain. 

Differential Diagnoses 

• Muscular dystrophies may present similarly to inflammatory myopathy. However, features such as calf hypertrophy, winging of the scapular would point more to a diagnosis of muscular dystrophy, which can be confirmed by muscle biopsy. 
• Myasthenia gravis may also have similar features, such as muscle weakness and dysphagia. However, symptoms in MG tend to be intermittent and physical examination findings would show muscle fatigability, whereas those of myositis would have a more progressive or insidious onset. Laboratory testing for autoantibodies and electrophysiology (EMG) studies may help distinguish between both. 
• Drug-induced myopathy can mimic inflammatory myopathies, and as such, a thorough history needs to be taken to determine whether the patient is on any drugs that may possibly trigger this, including glucocorticoids, statins, antimalarials, Penicillamine, anti-retroviral therapies, Colchicine, alcohol or cocaine. If the diagnosis remains unclear, then an EMG and/or muscle biopsy may aid in making a definitive diagnosis. 
• Inherited metabolic myopathies (disorders of carbohydrate and lipid metabolism) – patients tend to develop chronic muscle weakness. However, this would be preceded by years of acute episodes of intermittent muscle pain and tenderness induced by exertion followed by myoglobinuria, which is not a finding in inflammatory myopathies. 
• Motor Neuron disease (Amyotrophic Lateral Sclerosis) can present with muscle weakness but will also have features of hyperreflexia and muscle spasticity (long-tract signs), unlike myositis. Investigations such as EMG would not show myopathic changes, and muscle enzymes such as creatinine kinase will be normal or only mildly elevated. 

Management 

Dermatomyositis and Polymyositis 

Systemic glucocorticoids are the mainstay of acute treatment. Patients are started on a tapering dose usually for one year, which improves the strength and preservation of muscle function. 

A glucocorticoid-sparing agent is started simultaneously as the Prednisolone is weaned off. Azathioprine is frequently used and is usually started at a dose of 50mg/day. Prior to initiating Azathioprine, it is important to check for thiopurine methyltransferase deficiency (TPMT) deficiency, as these patients would be at significant risk of having myelosuppression and neutropenic sepsis on Azathioprine. Regular monitoring of liver function tests and complete blood count is done every three months. 

Methotrexate is also used as a steroid-sparing agent and is generally started at 15mg once weekly dosing and is titrated up. Folic acid is administered with Methotrexate to prevent folate deficiency, which can have symptoms such as mouth ulcers, paresthesia, fatigue, and muscle weakness. Methotrexate can have other adverse effects such as methotrexate pneumonitis and methotrexate toxicity. 

Antimalarials such as Hydroxychloroquine can be used to help to control skin disease. However, it is not beneficial for muscle disease. 

Inclusion body myositis 

The management of inclusion body myositis primarily aims to optimise muscle strength and function. Non-pharmacological interventions which have proven to be helpful include physiotherapy and speech therapy. Physiotherapy can provide a tailored exercise program, and with the assistance of occupational therapy, appropriate assistive devices can be sourced. 

It is not generally recommended to use immunosuppressive therapy in inclusion body myositis. However, in some cases, particularly where there is suspicion of overlap with another autoimmune disease, a trial of Prednisolone can be done, and if there is a response, consideration may be given to tapering prednisolone and commencing a steroid-sparing agent such as azathioprine or methotrexate. 

References 

• Greenberg S. UpToDate. Pathogenesis of inflammatory myopathies [Internet]. 2022 [cited 2022 April 20]. Available from https://www.uptodate.com/contents/pathogenesis-of-inflammatory-myopathies?search=myositis%20adult&source=search_result&selectedTitle=3~150&usage_type=default&display_rank=3
• Christopher-Stine L, Amato A, Vleugels R. UpToDate. Clinical manifestations of dermatomyositis and polymyositis in adults [Internet]. 2022 [cited 2022 April 20]. Available from https://www.uptodate.com/contents/clinical-manifestations-of-dermatomyositis-and-polymyositis-in-adults?source=history_widget
• Lloyd T, Christopher-Stine L. UpToDate. Clinical manifestations and diagnosis of inclusion body myositis [Internet]. 2022 [cited 2022 April 20]. Available from https://www.uptodate.com/contents/clinical-manifestations-and-diagnosis-of-inclusion-body-myositis?source=history_widget
• Leclair V, Lundberg I. New Myositis classification criteria – What we have learned since Bohan and Peter. Curr Rheumatol Rep. 2018; 20(4): 18. Available from: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5857275/
• Christopher-Stine L, Amato A, Vleugels R. UpToDate. Diagnosis and differential diagnosis of dermatomyositis and polymyositis in adults [Internet]. 2022 [cited 2022 April 23]. Available from: https://www.uptodate.com/contents/diagnosis-and-differential-diagnosis-of-dermatomyositis-and-polymyositis-in-adults?source=history_widget#H69088617
• Lloyd T, Christopher-Stine L. UpToDate. Clinical manifestations and diagnosis of inclusion body myositis [Internet]. 2022 [cited 2022 April 23]. Available from: https://www.uptodate.com/contents/clinical-manifestations-and-diagnosis-of-inclusion-body-myositis?source=history_widget#H10
• The Myositis Association. Types of Myositis[Internet]. 2022. [cited 2022 April 23]. Available from: https://www.myositis.org/about-myositis/types-of-myositis/
• Lloyd T. UpToDate. Management of inclusion body myositis. [Internet]. 2022 [cited 2022 May 7]. Available from: https://www.uptodate.com/contents/management-of-inclusion-body-myositis?source=history_widget
• Targoff I. UpToDate. Initial treatment of dermatomyositis and polymyositis in adults [Internet]. 2021 [cited 2022 May 7]. Available from: https://www.uptodate.com/contents/initial-treatment-of-dermatomyositis-and-polymyositis-in-adults?source=history_widget#H8