The suggested clinical assessment is included along with the need for a multi-disciplinary (MDT) management approach.
The document contains more medical jargon than the style of most of this resource. Families should ask their Paediatric Oncology Outreach Nurse Specialist / Key Worker for further simplified information. This page is aimed more at GPs who may have patients presenting with symptoms.
What is myopathy?
Myopathy is an umbrella term used to describe any type of muscle disease resulting in muscle weakness. A number of different disease processes cause different types of myopathies, such as inflammatory myopathies, endocrine myopathies, hereditary myopathy and drug- induced myopathy [1]. This resource will focus on drug-induced myopathy, in particular myopathy caused by the use of steroids.
What is steroid-induced myopathy?
Steroids are the most common cause of drug-induced myopathy [1] Dexamethasone has recently been identified as the steroid of choice in Acute Lymphoblastic Leukaemia (A.L.L.) treatment as it is more effective in reducing isolated CNS relapse compared to prednisolone. Dexamethasone is a fluorinated glucocorticoid steroid and has a higher incidence of myopathy and behavioural changes compared to prednisolone, a non-fluorinated glucocorticoid [2] [3] [4]
Steroid-induced myopathy can be described as acute or chronic due to the onset of symptoms either at the beginning of steroid treatment or during ongoing maintenance treatment such as in ALL [8].
Who is at risk of developing drug-induced myopathy?
- Patients with ALL, CNS tumours, Lymphoma, Non-Hodgkin Lymphomas, HLH, LCH
- People who lead a sedentary lifestyle and have inactive muscles, such as patients undergoing treatment for cancer
- In an adult population, females tend to be more affected compared to males [9]
- Patients with respiratory conditions are also more susceptible to myopathy, such as patients on mechanical ventilation [8]
Pathophysiology
Muscle biopsy tests of patients with steroid-induced myopathy are found to have less myosin. In more chronic myopathy, muscle biopsy is shown to have less type II b muscle fibres [1]. There is no clear mechanism of pathology for myopathy but it has been suggested that increased protein degradation, reduced protein synthesis, altered carbohydrate metabolism, altered mitochondria, electrolyte disturbance and decreased sarcolemma excitability may all be affected [5].
Signs and symptoms of steroid myopathy
Acute generalised weakness that may or may not affect respiratory muscles tends to occur five-seven days after starting high-dose steroid treatment. [5]
Muscle bulk may be normal despite muscle weakness and a pattern of muscle weakness is often observed. This is a symmetrical pattern from the trunk and neck muscles in the middle of the body, sometimes described as proximally, to the muscles further away, sometimes described as distally. Certain muscle groups are more susceptible to weakness than others. These are gluteals (bottom muscles), quadriceps (thigh muscles) and gastrocnemius (calf muscles). [6]
In chronic steroid myopathy, proximal muscle weakness is more pronounced than distal muscle weakness, however, severe weakness of anterior tibialis muscle (ankle dorsiflexor muscle), can be found. Pelvic girdle muscles are usually more affected and earlier than shoulder girdle muscles. [7].
Truncal obesity, secondary to the cushingoid effects of the steroids, is also a common feature. Patients may report muscle cramp, muscle pain and stiffness, alongside muscle weakness. [1]
The cranial muscles can be involved with signs and symptoms including ptosis (dropping eye lid), facial weakness, dyarthria (motor disorder causing speech difficulties) and dysphagia (swallowing difficulties). [5].
Clinical presentation
Patients may describe difficulty with stairs, difficulty in transferring from sitting to standing, legs giving way, being unable to touch the back of their head, e.g. washing or brushing their own hair and difficulty reaching above their head, e.g. taking something out of a high cupboard [1].
As previously discussed, it is often the proximal muscles that are affected first in acute steroid induced myopathy, however the distal muscles may become involved in severe cases. If this is the case, patients may report difficulties with opening jars, manipulating small objects such as buttons or laces and being unable to clear the floor when walking; this is known as a foot drop [1].
Assessment
A full history, including specific questions related to signs of myopathy, should be taken. A neurological examination should be carried out where possible, with health care professionals being mindful of the common signs and symptoms and clinical presentation of steroid myopathy. Muscle stretch reflexes and sensory tests are typically normal [7].
There may be a role for Electromyography (EMG) testing if the patient has suffered complete paralysis. In this case EMG can be used to localise the disorder to particular muscle groups. However it has been suggested that EMG may demonstrate normal muscle function as it focuses on type I muscle fibre function opposed to type II muscle function, which are more commonly affected in steroid myopathy [1].
Certain blood tests may also be useful in testing for myopathy [8]. Creatinine Kinase (CK testing), which is a measure of the amount of a protein in your blood, may suggest muscle damage/severe inflammation. Elevated Aldolase in the blood can be a sign of muscle or liver damage. Lactate dehydrogenase (LDH) is an enzyme that is most often measured to check for tissue damage and is often elevated in haemolysis and also in tumours including haematological malignancies.
Treatment
Please discuss with the Principal Treatment Centre for Children’s Cancer’s. The most effective treatment of steroid-induced myopathy is to reduce the dose or, better still, stop the drug that is causing adverse effects [1] [5],[16]. However, in the treatment for childhood cancer this is often not possible due to the increased risk of relapse. For certain patients, replacing fluorinated prepared glucocorticoid such as dexamethasone with non-fluorinated steroid such as prednisolone, may be recommended.
A holistic management approach should be adopted to optimise the patient’s and family’s quality of life. Timely referrals should be made to other members of the MDT. For example, a referral may be made to the Occupational Therapists for transfer assessments, advice on fatigue management and the provision of adapted equipment to assist with activities of daily living.
The Physiotherapist may be able to provide advice and exercises to maintain joint range of movement, muscle length and strength, gait re-education and or walking aids to assist with mobility and chest physiotherapy techniques to optimise respiratory function.
The Speech and Language Therapists can provide swallowing assessments, communication aids and language techniques to enhance feeding and communication. Depending on the individual patient, there are many other members of the team who may be involved in managing the symptoms of steroid-induced myopathy. If you are unsure of the referral process within your area of work, please ask for advice from the MDT.
Long term
Recovery times vary for drug-induced myopathy, but usually there is improvement within three-four weeks after the dose is reduced, or stopped [8]. For most patients, improvement or complete recovery follows ALL treatment [9], although this is a significant, longer term side-effect of treatment for a small number of children and young people with cancer.
References
[1] Chawla J (2011) Stepwise approach to myopathy in systemic disease. Frontiers in Neurology 2:49 Published online Aug 5, 2011
[2] McNeer JL and Nachman JB (2010) The optimal use of steroids in paediatric acute lymphoblastic leukaemia: no easy answer. British Journal of Haematology 149(5) 638-652
[3] Childhood Acute Lymphoblastic Leukaemia Collaborative Group (CALLCG) (2010) Systematic review of the addition of vincristine plus steroid pulses in maintenance treatment for childhood acute lymphoblastic leukaemia: an individual patient data meta-analysis involving 5659 children British Journal of Hasematology 149 (5) 722-733
[4] Pereira, RM. and Freire de Carvalho, J. (2011) Glucocorticoid-induced myopathy: Joint Bone Spine 78(1) 41-44 [5] Foyle P, Campagnolo D, Rispoli L, Hwang GE, Lim S, Potter P, Talavera F, Kolaski K, Allen K (2012) http://emedicine.medscape.com/article
[6] Mitchell CD, Richards SM, Kinsey SE, Lilleyman J, Vora A, Eden TOB (2005) Benefit of Dexamethasone compared with prednisolone for childhood acute lymphoblastic leukaemia: results of the United Kingdom medical research council ALL 97 randomized trial. British Journal of Haematology 129 pp 734-745
[7] People Beating Cancerhttp://www.peoplebeatingcancer.org/
[8] Nozaki K, Prestronk A (2009) High aldolase with normal creatine kinase in serum predicts myopathy with perimydial pathology. Journal of Neurology, Neurosurgery and Psychiatry August 80(8) 904-8