Steroids

Steroids (also called corticosteroids) are naturally occurring hormones made in everyone’s body. Man-made/synthetic steroids, like prednisolone, are made to mimic the effects of the natural steroid, cortisol. This is different to the anabolic steroids used by some athletes/body-builders. Exactly how steroids like prednisolone work in DMD isn’t clear, but it is thought that due to their anti-inflammatory effects, they stop the damage that happens inside the muscles of people with DMD.

Prednisone, prednisolone and deflazacort are all steroids that have been used in DMD and are all as effective as each other. Prednisolone has the advantages of being inexpensive, available everywhere and having a liquid and tablet form. Deflazacort is not freely available in many countries including Australia, New Zealand and the USA. It may not cause as much weight gain in some people, but it does have an increased risk of cataracts and fractures.

Benefits of steroids

Steroids slow the progress of muscle weakness in DMD. By helping children with DMD maintain their strength, it delays the onset of many problems from DMD, including needing wheelchairs, scoliosis (curved spine), breathing problems and heart problems. All of these benefits help keep people with DMD healthy for longer and may prolong their lives. The exact benefit each child gains by using steroids will vary, but because of the marked improvement seen in studies, the use of steroid medication is recommended internationally for children with DMD.

When to start steroids

Steroids are started when people with DMD enter the “plateau phase” of the illness. This generally occurs between the ages of 4-6 years, when they stop gaining new skills, but before they start to slow down or lose skills. It is possible to start later, but once children have entered the “decline phase” of the illness, there may be fewer benefits from the steroids.

What are the side effects and how are they managed?

Long term use of steroid medication has many possible side effects. Not everyone gets them, but it’s important to know about them so they can be managed or the steroids can be changed.

The most common side effects are weight gain and changes in mood (irritability and mood swings). Weight gain can generally be managed by watching the diet with the help of a dietician. Often, the child's face will become round and puffy (called the “cushingoid or moon face”). Mood changes can be especially strong in the first six weeks of starting the medication, but generally settle down after this period. However, sometimes more support is needed.

Other possible steroid side effects include difficulty sleeping, stomach aches, slowed growth, delayed puberty and cataracts in the eyes. There can also be problems with bone health with an increased risk of fractures. Children with DMD should be actively monitored for this risk.

Rare side effects include raised blood pressure, glucose intolerance (diabetes), thinning of the skin, poor wound healing, increased infections, increased sweating, and dizziness.

Additionally, taking steroids by mouth suppresses the body’s ability to produce steroids, so children with DMD may need additional steroids in times of stress like severe illnesses or surgery.

If any of the side effects cannot be managed, then working with your treating doctor to test a lower dosage or a different medication regime may be considered, although it may lead to fewer benefits. If the side effects can’t be tolerated, then the steroids may need to be stopped.

For more information on the pros and cons of steroids, please click the button below.

The picture below, taken from the 2010 Busby et al. DMD Standards of Care, summarises the side effects of steroids. If the image appears too small, please click on the image to open it in a new tab.

Different Types of Steroids and Different Regimens

Prior to starting steroids, your neurologist will discuss the pros and cons of each steroid that is routinely used to treat DMD. The most common steroids that are used to treat DMD are Prednisolone and Deflazacort.

In Australia, these steroids will generally be prescribed for you to take daily, or, only on the weekends.

For a daily dosage regimen:

• Benefits: For most patients, there is an increase in strength and endurance as mentioned earlier.
• Downsides: there are often adverse effects on growth, weight gain, behaviour, and bone strength.

For a weekend-dosage regimen:

• Benefits: Avoids the unfavourable effect on growth and behaviour, and minimises the effect on weight gain. Continues to have a positive effect on strength and endurance.
• Downsides: There is less data supporting the benefits compared to daily dosing. It can be more difficult to predict the effect on the body's ability to produce its own steroids - this mean, theoretically, there may be an increased risk of having an adrenal crisis.

The benefits and downsides of the dosing regimen should be discussed with your neurologist prior to starting steroids.

Stopping Steroids

Even when people with DMD stop walking, the benefits of steroids to their heart, breathing, and spine continue, and the steroids can also help maintain use of their arms. There is no consensus as to when steroids should be stopped. This decision will need to be made on an individual basis with a discussion between the patient, their family, and their doctor. It is important to discuss the benefits of steroids versus the side effects.

It's very important not to stop taking steroids suddenly. As mentioned earlier, the body produces its own steroids, which are important for normal bodily functions. Taking steroids suppresses the body's ability to make its own steroids. Therefore, patients choosing to stop using steroids need to be slowly weaned off the steroids. This should be discussed with the patient's doctors.

If a steroid cannot be taken because of a vomiting illness, seek medical attention.

Steroid use and stress dosing in boys with Duchenne Muscular Dystrophy (DMD)

People taking regular steroid medication require "stress doses".

The steroid doses commonly used in DMD change the body’s normal response to physical stress. When under stress, the body normally releases increased amounts of ‘stress’ hormones such as adrenaline. For people with DMD taking steroids, the body’s ability to do this is limited, so extra doses of steroid are required.

Causes of ‘stress’ include fever and vomiting, fractures, and surgery.

Causes of medical and surgical stress include illness such as fever and vomiting, procedures under general anaesthesia, and fractures. In these circumstances, people with DMD taking steroids should call their doctor. Healthcare providers should follow their local protocol for steroid stress dosing, or they can refer to the PJ Nicholoff Protocol here.

Steroids must not be stopped suddenly.

Stopping steroids suddenly does not allow the body time to begin making its own steroids again, and might cause a life-threatening medical emergency called an adrenal crisis. An adrenal crisis can happen if steroids are stopped suddenly – due to vomiting, or if doses are missed – or with medical or surgical stress.

If steroids cannot be taken orally, they should be given in hospital.

People who are unable to take their regular steroid doses due to sickness or vomiting should go to hospital, and doses should be given by injection.

If you develop signs of adrenal crisis, go to hospital immediately.

Signs of adrenal crises include weakness, fatigue, and nausea. People may also have low blood pressure or low blood sugar. If untreated, adrenal crisis can be life-threatening. Healthcare providers should follow their local protocol for adrenal crisis, or they can refer to the PJ Nicholoff Protocol here.

Steroids can lower the immune system.

Steroids can mask typical responses to infection, including fever. People with DMD taking steroids should go to the Emergency Department if they have a temperature over 38° Celsius. Healthcare providers should follow their local protocol for immune suppression.

PJ Nicholoff Steroid Protocol

This is an internationally agreed protocol for managing patients with DMD on regular steroids during periods of illness, trauma or stress including surgery. This protocol can be downloaded by clicking the button below.

Download PDF

Key points

• The evidence suggests that steroids should be part of the management of people with DMD, starting when their motor skills “plateau”.
• Steroids help people with DMD stay stronger for longer, and delay the complications of DMD such as needing a wheelchair, scoliosis and problems with the heart and breathing.
• Steroids can cause side effects, and patients on steroids need careful monitoring.
• If unwell while on the steroids, check with your doctor in case you need extra steroids.
• Never stop taking steroids suddenly.
• If steroids can’t be taken (for example, due to a vomiting illness), seek medical attention.

More Information

• Save Our Sons Duchenne Foundation                Tel: (02) 9554 6111             https://saveoursons.org.au/
• Muscular Dystrophy Australia (MDA)                   Tel (03) 9320 9555              www.mda.org.au
• Cochrane review of steroids for treating DMD:
  http://onlinelibrary.wiley.com/doi/10.1002/14651858.CD003725.pub3/abstract

References:

1. Bushby, K., et al., Diagnosis and management of Duchenne muscular dystrophy, part 1: diagnosis, and pharmacological and psychosocial management. Lancet Neurol, 2010. 9(1): p. 77-93.
2. Bushby, K., et al., Diagnosis and management of Duchenne muscular dystrophy, part 2: implementation of multidisciplinary care. Lancet Neurol, 2010. 9(2): p. 177-89.
3. Manzur, A.Y., et al., Glucocorticoid corticosteroids for Duchenne muscular dystrophy. Cochrane Database Syst Rev, 2008(1): p. CD003725.
4. Bonifati, M.D., et al., A multicenter, double-blind, randomized trial of deflazacort versus prednisone in Duchenne muscular dystrophy. Muscle Nerve, 2000. 23(9): p. 1344-7.
5. Ricotti, V., et al., Long-term benefits and adverse effects of intermittent versus daily glucocorticoids in boys with Duchenne muscular dystrophy. J Neurol Neurosurg Psychiatry, 2013. 84(6): p. 698-705.
6. Barber, B.J., et al., Oral corticosteroids and onset of cardiomyopathy in Duchenne muscular dystrophy. J Pediatr, 2013. 163(4): p. 1080-4 e1.
7. Biggar, W.D., et al., Long-term benefits of deflazacort treatment for boys with Duchenne muscular dystrophy in their second decade. Neuromuscul Disord, 2006. 16(4): p. 249-55.