Your Child and Prednisone: Answers to parents’ questions about prednisone.
by Jeffrey D. Punch, MD
This FAQ was written to provide parents and caregivers with current, practical information about the anti-rejection medication prednisone. Check with your doctor regarding specific concerns you may have and report all side effects promptly. Most importantly, never make a change in your child’s medication without your doctor’s prior approval.
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What is prednisone?
Prednisone is one of the most universally prescribed immunosuppressant drugs. It is used not only to prevent rejection after organ transplantation, but also to treat numerous “autoimmune diseases,” such as rheumatoid arthritis, systemic lupus erythematosus (SLE), polymyositis, and others.
Prednisone is a synthetic steroid hormone. The body manufactures natural steroid hormones to control numerous bodily functions, such as metabolism, sexual function and development, and blood pressure. Prednisone has similar effects to the natural steroid called “cortisol” which is made in the adrenal glands. (Adrenal glands are about the size of a golf ball and are located just above the top of each kidney.)
Normally, the body makes approximately 25 mg of cortisol per day. When “stressed” the body may make over 100 mg. (Stress in this sense means trauma, such as major surgery, broken bones, or a major illness.) Prednisone has roughly five times the potency of cortisol, so 5 mg of prednisone is like 25 mg of cortisol.
Why is prednisone prescribed?
Early in the days of transplantation, it was discovered that large doses of prednisone can suppress many parts of the immune system. During animal experiments, researchers found that prednisone allowed grafts from one animal to another to function longer than if prednisone was not given. However, it was found that the immune suppressive effects of prednisone wore off several days after being discontinued; meaning, if the drug was stopped, the animals rejected their grafts.
How does prednisone work?
Prednisone seems to work by doing many things to the immune cells that fight infection and cause rejection. It inhibits immune cells that kill other cells, and it inhibits the secretion of substances (cytokines) which tend to “rev up” the immune system. The result is that all inflammatory processes are slowed and weakened.
Inflammation is how the body kills what it perceives as foreign. A bacteria is foreign, so the body kills it with inflammation. An organ transplant is foreign, so the body tries to kill it with inflammation as well. By turning down the body’s ability to produce inflammation an organ transplant can survive longer. Unfortunately, this also leaves the body more susceptible to infection by bacteria, protozoa, fungi, or viruses.
If prednisone suppresses the immune system, why doesn’t it prevent rejection?
Prednisone is said to be “non-specific” because it suppresses so many different immune processes. However, it does not completely inhibit all immune functions; the body can still fight against foreign tissue and cause rejection at a slow rate. Furthermore, patients cannot tolerate being on very high doses of prednisone for long periods of time because they are too susceptible to infection.
If new drugs are better than prednisone, why is it still used?
Although new drugs like cyclosporine and tacrolimus are more “specific” for the type of inflammation that causes organ transplant rejection, these drugs are not able to prevent rejection initially after a transplant when given by themselves. Without some prednisone, these drugs do not seem to work as well. However, the advent of these new drugs has allowed prednisone dosages to be lowered to a point where side effects are more tolerable than in the past.
How is prednisone given?
There are many different forms of corticosteroid preparations. Prednisone is an oral agent that is commonly used. Medrol (prednisolone) is an alternative to prednisone that can be given orally or by IV. Medrol has never been shown to be different from prednisone in terms of side effects. Another common form of corticosteroid is Solu-Medrol Injection (methylprednisolone) which is given by IV.
The dosages of prednisone vary widely from transplant center to transplant center. Typically, the dose is very high for several days after a transplant, and then the dose is gradually decreased to a lower “maintenance dose.” The time frame for reaching maintenance dosage also varies greatly, from a few weeks to several months.
What is a “pulse”?
Prednisone is sometimes used to treat rejection. When rejection has been diagnosed, the dose of prednisone is increased by 10 to 200 times and called a “pulse”. In many situations, pulses will cause the rejection to go away.
Different hospitals use different systems for pulses. Some use intravenous pulses, others give them by mouth; some give them every day, some give them every other day; some give three, some give five pulses; dosages vary greatly.
What are the side effects of prednisone?
There are many possible side effects. Here is a partial list:
- Ulcers and abdominal pain
- High blood pressure
- Weight gain (especially around the mid-section, in the face, and behind the neck)
- Cataracts (clouded lenses in the eyes)
- Difficulty sleeping
- Brittle, easily broken bones
- High blood sugar, and a tendency to develop diabetes
- Muscular weakness
- Excess hair growth
- Mood swings/personality changes
- In children, growth may be slowed
Ulcers and abdominal pain
Prednisone is thought to be associated with ulcers in the stomach and the first portion of the intestine (duodenum). Also, some patients taking prednisone will have “heartburn” symptoms from the stomach area. For these reasons, some physicians commonly prescribe drugs that reduce acid in the stomach (antacids) to be taken along with prednisone. Examples of drugs that reduce stomach acid are Tagamet, Zantac, and Pepcid.
High blood pressure
The likelihood of developing high blood pressure while taking prednisone depends on the dose and duration of treatment. Prednisone can cause high blood pressure in normal adults and children. Cyclosporine and tacrolimus can also cause high blood pressure. The combination of prednisone and either tacrolimus or cyclosporine is even more likely to cause high blood pressure.
Many children will have high blood pressure early after transplantation that will resolve when prednisone is lowered to maintenance levels. In some cases, the high blood pressure persists.
The first step in treatment is to restrict dietary salt, and sometimes this is all that is needed. In other cases, a blood pressure medication or a diuretic may be required. Children tolerate these medications quite well and they are quite safe.
Some children will really gain weight while taking prednisone despite efforts to control their diets. Mostly we give common sense advice for controlling weight: Limit in-between meal snacks and avoid high calorie foods, especially fats (chips, fries, and other snack foods). Probably the most important thing for parents to do is to strongly encourage daily vigorous exercise.
Acne is related to the sex hormone testosterone-like effect of prednisone. Patients are sent to dermatologists for topical treatments.
Cataracts (clouded lenses in the eyes)
Cataracts are an uncommon problem in children, but about 1% of children on prednisone will get them. It is possible to detect the development of cataracts early in some cases and alter the prednisone dosage to prevent worsening. Ophthalmologists say that sight is rarely altered in the long term.
Cataracts are common in older adults whether they take prednisone or not. Cataracts are treatable by operation.
Insomnia is not usually a big problem on the lower maintenance dose of prednisone. Insomnia can be a problem initially, but it gets better as the dosage is gradually lowered. Once again, daily vigorous exercise is extremely helpful with this problem.
Brittle, easily broken bones
Children who have liver failure need careful monitoring of their calcium metabolism. These children are at risk for "rickets" due to vitamin D malabsorption. When children have successful, functioning transplants they generally are not susceptible to this problem.
Prednisone does have a tendency to cause bones to become thinner and easier to break than normal. However, broken bones are usually not a major problem for children on prednisone. Exercise has been shown to strengthen bones and should be strongly encouraged.
The major bone problem we worry about with prednisone is “avascular necrosis of the joint” (usually the hip). This is a terrible problem and usually requires prosthetic joint replacement. It is most often caused by high dose steroids, but it can occur in anyone on steroids, even for short periods of time. Fortunately, it is uncommon.
High blood sugar and a tendency to develop diabetes
Prednisone changes the way our bodies metabolize fat and carbohydrates (sugar and starch). This alteration results in a tendency to gain weight and a tendency to develop abnormally high blood sugar.
Normally when we eat, our blood sugar rises as carbohydrates are absorbed in the gut. The body responds by secreting insulin which lowers the blood sugar back to the resting level. Prednisone can make one’s body somewhat resistant to the effects of insulin, thus resulting in higher than normal blood sugar. This same problem (insulin resistance) is what causes “adult-onset diabetes,” the disease of high blood sugar. Adult-onset diabetes can occur in adults even if they are not on prednisone, especially if they are very overweight.
In essence, prednisone can cause one to become diabetic. (The immunosuppressant drug tacrolimus may also be associated with a tendency to develop insulin resistance.) If this happens it may be necessary to take insulin shots. Although diabetes will occur in about 10-20% of adults taking prednisone, it is very uncommon in young children.
Blood sugar is normally part of the routine lab work done for follow-up after a transplant, along with liver chemistries, electrolytes, and kidney function tests.
Excess hair growth
Hypertrichosis, or excess hair growth, is a fairly common side effect of cyclosporine. It is somewhat variable, but most children on cyclosporine will experience it to some degree.
Hypertrichosis can also be caused by prednisone, but usually only with long term use of higher doses than are commonly used for maintenance immunosuppression. The hypertrichosis due to prednisone is caused by the sex steroid effect that high doses of corticosteroids can have, called an “androgen effect”. The androgen effect is variable, but it generally goes away when the dosage is lowered. No one knows what causes the hypertrichosis due to cyclosporine.
There are reports of fatigue and weakness due to prednisone. Again, usually these problems are seen at high, long term dosages.
Mood swings/personality changes
This is a very common side effect of prednisone. When prednisone patients feel down, they are really blue; and when they are happy, they are bouncing off the ceiling with joy. This side effect is definitely related to dose and tends not to be apparent on the lower maintenance dosages.
Outright psychosis is uncommon, but it can happen. Psychosis is a delusional state where the patient perceives things that are not there. They may have suspicions or beliefs that are unfounded and untrue. They may not recognize friends or family and may hear voices and have hallucinations. Psychosis usually happens only with very high doses of prednisone. Extremely vivid dreams and nightmares are much more common and can be terrifying.
In children, growth may be slowed
The problem with growth is that it is so variable. Growth rates are variable, growth problems are variable, and the effects of prednisone on growth are variable. Some children grow well despite prednisone, many others do not.
Mostly, we try to look at rates of growth. A five-year-old that has not grown at all for the past year has a compelling reason to try weaning from prednisone. A three-year-old that is the size of a normal 18-month-old, but is growing at a rate that translates to an eventual height of 5'4"; would have less of a reason to wean.
Generally, children that are not growing as fast as they should will return to a normal growth rate if prednisone is discontinued, and sometimes they will catch up to where they should be. However, sometimes they will remain smaller than they should be and never catch up. Children who require long term prednisone and are not growing should probably see a specialist in endocrinology (the study of hormones).
Does everyone get these side effects?
No. The side effects vary greatly from one person to another. In general, the side effects tend to be worse when the dosage is higher.
A steroid used in Europe, called deflazacort, is purported to have fewer side effects compared to prednisone. It is claimed to have less of an effect on calcium, growth, and sugar metabolism than prednisone. However, people have been concerned that the immunosuppressive action may not be as good. One recently published report concludes that deflazacort is actually more effective at suppressing antibody production compared to prednisone and is similarly effective as an immunosuppressant. However, the study was only on 14 patients. The study notes that additional and larger studies are necessary before widespread use of this corticosteroid after organ transplantation in children can be advocated.
Can patients be weaned from prednisone?
There is no easy answer to this question. The major concern is whether weaning from prednisone is safe—will stopping prednisone cause the transplanted organ to be rejected? This concern is offset by the potential benefits of stopping the prednisone (i.e., relief from side effects). The decision must be individualized. For a child who is having no side effects, is growing well, is not overweight, and appears normal, the benefit may be outweighed by the risk. Numerous other factors must be considered:
- The chances of developing rejection if prednisone is discontinued are different for liver recipients compared to heart recipients, compared to kidney recipients, etc.
- The consequences of developing rejection are also different depending on the organ.
- The ease of making the diagnosis of rejection is different with each organ.
- Some diseases which cause organ failure may recur if long term prednisone is not used (for example, autoimmune hepatitis). These patients have a special reason to continue prednisone.
- One’s history of rejection may be important. Stopping prednisone may be safer if one has never had rejection.
- Finally, it may be that the risk of having rejection when prednisone is weaned is different depending on which other immunosuppressant drugs one is taking.
Unfortunately, there will be no definitive answers to some questions. Although there are studies that show, in some situations, weaning off prednisone looks to be safe in the short term (two to four years), we have no way of knowing if patients who stay on prednisone will experience better long term graft function (decades).
The bottom line is that this area is controversial and constantly changing. At one center patients are advised to do one thing, while at another center they are advised to do a completely different thing, even though both centers are completely up to date on all the pertinent scientific literature. It can be confusing and frustrating because there are very few right and wrong answers to this question.
Will the side effects go away if prednisone is discontinued?
Maybe. It is difficult to always know for sure which side effects are due to the prednisone and which are due to other medications, or other causes. For example, difficulty sleeping at night may be the prednisone, or it may be a social problem at school.
Why must prednisone be weaned slowly instead of just stopping abruptly?
The adrenal gland, which makes natural steroid hormones for the body, is suppressed by long term prednisone administration. Due to inactivity, it may atrophy (shrink). Since some steroid hormones are necessary for life, abruptly stopping prednisone may leave one without any steroids at all, a life-threatening condition known as "Addisonian crisis." The symptoms of this are low blood pressure, nausea and vomiting, and severe weakness.
Given time, if the adrenal is stimulated to produce steroids by gradually reducing the dosage of prednisone, it will usually begin to wake up and produce natural steroids in most cases.
It is thought that if one happens to become ill during the weaning process, more steroids are needed since the natural response to stress (such as trauma, an operation, an infection, etc.) is for the adrenal gland to pour out steroids. Until one’s adrenal gland is "up to par" though, this is not possible. Anyone on steroids or recently weaned off steroids needs to be aware of this.
Many patients will experience fatigue and some have joint pain and muscle aches during the time they are weaning from prednisone. This may represent a relative deficiency of steroids. The symptoms go away after a few weeks or if prednisone is resumed.
Is there a cut-off point for weaning off prednisone?
There is no cut-off, but people have written that after many years (three or more), some patients will not develop normal adrenal function. These patients are uncommon. Generally, it is probably more of a problem for patients who have been taking prednisone for 10 or more years, but even many of these patients can wean from prednisone if they go slowly with the wean.
Is it true that liver transplant patients have the best success weaning from prednisone?
Generally, the best results weaning from prednisone seem to be with liver transplant recipients, but the follow-up isn’t as long as for kidney transplant patients. So this may just show that liver recipients haven’t been followed long enough to know whether prednisone does or does not have benefits in terms of 10-year graft and patient survival.
With kidneys, there definitely is a body of evidence suggesting that kidneys will last longer if prednisone is used. The debate continues over whether it is worth the benefit, and whether the studies are biased by the manner patients are selected.
That same evidence has not been reported for livers, but that doesn’t mean prednisone has no beneficial long term effects for these patients; it just hasn’t been defined yet.
The consequences of losing any graft are that second grafts are not as successful as first grafts. Graft and patient survival rates tend to be at least 10% less for second grafts and at least 25% lower for third grafts. So one cannot just say "Well, if we stop the prednisone and you lose the graft, we can always do another graft." Also, the consequences of developing liver or heart failure are more severe than returning to dialysis in the case of a rejected kidney.
Are there alternatives to weaning from prednisone?
Although this too is a controversial area, changing from every day to every-other-day dosing (at a higher dose) may be safe in some situations and decrease side effects while preserving the immunosuppressive effects.
A Final Word
Mostly, children do okay on prednisone once the dose gets down. The main thing about prednisone is that it is extremely variable. Some patients have few side effects, while others have severe side effects.
Dr. Punch is a transplant surgeon and member of the C.L.A.S.S. Scientific Advisory Committee.