Corticosteroids Systemic (Oral and Injectable)Corticosteroids are man-made drugs that closely resemble cortisol, a hormone that your adrenal glands produce naturally. Corticosteroids are often referred to by the shortened term "steroids. Some corticosteroid medicines include cortisone, prednisone, and methylprednisolone. Prednisone is the most commonly used type of steroid to treat certain rheumatologic diseases. Steroid medications are available in several forms that vary in how easily they dissolve or how long they stay in the body.
Prednisone and other corticosteroids: Balance the risks and benefits - Mayo Clinic
Corticosteroids have been used in ophthalmology for almost 50 years. Hench, in , 1 was the first to report on the beneficial effects of ACTH and cortisone. His work was with rheumatoid arthritis and since he had noticed that rheumatoid arthritis improved in pregnancy and jaundice. He conjectured that an adrenal hormone might be the common agent causing this improvement.
In he managed to acquire the necessary hormones and found clinical improvement in the rheumatoid arthritis and a reduction of the erythrocyte sedimentation rate on treatment with the hormones and relapse when they were stopped. His article concluded that theoretically these agents may be of benefit in other conditions which can be relieved by pregnancy and jaundice.
Very soon after this steroids were used, both systemically and topically, to treat inflammation of the eye. Within ophthalmology there are many indications for the use of corticosteroids. The decision to institute steroid therapy always requires careful consideration of the relative risks and benefits in each patient. In uveitis, for example, the use of corticosteroids may often be in high doses for long periods of time.
If a beneficial effect is not seen within the expected time scale the corticosteroids should be reduced and stopped. This review considers some of the non-ocular problems and dilemmas encountered when systemic steroids are used, with practical suggestions to minimise their side effects.
In particular, the new recommendations by the Department of Health on the indications for intervention following exposure to chickenpox or shingles will be discussed and recent publications on the management of corticosteroid osteoporosis will be reviewed. Thin, fragile skin is a feature of corticosteroid use and the photograph in the Minerva section of the BMJ from 19 October 3 vividly illustrates this; it shows a flap of chest skin avulsed as the cardiac monitor is removed from a patient who had been on long term steroids.
Impaired wound healing, patients should be advised to take particular care to avoid injury. The total white blood count is increased in patients on corticosteroids. The various classes of white blood cells are affected in the following ways:. Lymphocytes decreased; T cells are reduced to a greater extent than B cells although immunoglobulin synthesis is also decreased 4. Corticosteroid use is associated with sodium and water retention; this can be reduced by recommending a low salt diet. Potassium loss occurs and a hypokalaemic alkalosis may develop.
A diet rich in potassium most fruits, vegetables, especially broccoli and carrots, fish, and poultry is usually sufficient to make good this loss but occasionally potassium supplements are required. The blood pressure should be checked at each outpatient visit and antihypertensive treatment may be necessary. If a thiazide diuretic is chosen as the antihypertensive agent the serum potassium should be carefully monitored.
Thiazides also have a beneficial effect on osteoporosis by reducing calcium loss in the urine. Corticosteroids should be used with extreme caution in patients with limited cardiac reserve as cardiac failure can develop. The patient should be warned about the development of a cushingoid habitus moon facies, buffalo hump, central obesity.
The reason for this change in appearance is not clearly understood but one hypothesis is that truncal and peripheral adipocytes vary in sensitivity to the glucocorticoid facilitated lipolytic effect—that is, the peripheral adipocytes are more sensitive to this effect than the central adipocytes.
Weight gain, which can be enormous in some patients, can be minimised by the early use of a calorie controlled diet. Reduced carbohydrate tolerance accompanies corticosteroid use. Glucose tolerance and sensitivity to insulin is decreased but if pancreatic function is normal no diabetes should develop.
The initial management is dietary modification with the addition of hypoglycaemic agents if necessary. This particular form of diabetes has a low sensitivity to insulin but does not tend to ketosis. When the steroids are stopped the diabetes normally disappears. The use of corticosteroids is not contraindicated in a known diabetic but patients should be aware that their blood glucose control is likely to deteriorate and that they will need increased treatment. Suppression of the hypophyseal pituitary adrenal axis occurs with surprisingly little corticosteroid.
A 1 week course has no significant effect but 2 weeks of supraphysiological doses that is, greater than prednisolone 7. Patients with suppressed adrenals require the reintroduction of corticosteroids at the time of a surgical procedure, trauma, or intercurrent illness and those on long term steroids may need an increased dose.
Sex hormones, both testosterone and oestrogen, are reduced by the administration of corticosteroids. Hormone replacement therapy has been shown to have a beneficial effect on osteoporosis in post-menopausal and amenorrhoeic women on corticosteroids 8 see below.
The supplementation of testosterone in men on corticosteroids is not common practice but may provide an additional means of preventing osteoporosis in this group. Serum lipids, both triglycerides and cholesterol, may be increased during corticosteroid therapy.
The teratogenic effect of cleft lip and palate that has been seen in animal studies has not been confirmed in the children of corticosteroid treated women. There appears to be no teratogenic contraindication to using corticosteroids in pregnancy.
Mothers with pre-eclampsia and fluid retention require particularly close monitoring if placed on corticosteroids. Corticosteroids are excreted in small amounts into the breast milk and the infant is therefore at risk of adrenal suppression. Corticosteroids inhibit linear growth. The mechanism is unknown but may involve a combination of reduced growth hormone production and a direct inhibitory effect on bone and connective tissue.
There is some evidence that the administration of growth hormone can reverse these changes. Unlike the other side effects of steroids growth suppression is helped by alternate day treatment. Doses below prednisolone 10—15 mg on alternate days do not slow growth velocity significantly.
Within a few years of the introduction of steroids an increased tendency to osteoporosis and fracture were noticed. Many studies on the association of osteoporosis and steroid use have been performed on patients with rheumatoid arthritis where clearly additional factors for osteoporosis exist.
The greatest rate of bone loss occurs in the first 6 months and is thought to continue at a lower rate for as long as steroids are used.
Studies show a correlation between cumulative steroid dose and bone density; therefore, treating with the lowest possible steroid dose is important. There is no benefit in using alternate day therapy. Bone loss is greatest in trabecular cancellous bone, which is more metabolically active but also occurs in cortical bone. The mechanism of steroid induced bone loss is multifactorial There are no longitudinal studies specifically addressing the question of whether steroid induced bone loss reverses when steroids are stopped, but evidence exists that significant increases in bone mineral density occur with specific therapy for steroid induced osteoporosis.
Patients who are about to begin or are receiving long term steroid treatment should have their bone mineral density BMD measured using dual energy x ray absorptiometry DEXA.
This is usually performed on the lumbar spine and femoral neck. The result is expressed as a standard deviation from controls of the same race and sex.
A DEXA scan should be performed at the beginning of steroid treatment and annually thereafter. The following measures should be considered for a patient who is about to embark on steroid therapy or who is already on treatment:. Hormone replacement therapy may be considered for post-menopausal and amenorrhoeic women. Side effects, 12 in particular the recent reports of an increased risk of breast carcinoma, need discussing with the patient.
Corticosteroid induced bone loss is in part due to reduced calcium absorption from the gut and increased urinary loss. Recent studies have shown that calcium and vitamin D supplements are beneficial in preventing bone loss. The role of bisphosphonates as prophylactic agents in the prevention of steroid induced osteoporosis is not yet established.
The long term consequences of these drugs is unknown; concern arises because they are deposited in bone but their use as a treatment for osteoporosis is considered safe up to 7 years. No other action is necessary if the BMD is normal; this should be rechecked annually.
Patients should be warned if they are at increased risk of fractures and the presence of back pain should be investigated with a lateral spine x ray to exclude a vertebral fracture.
During corticosteroid use there is a reduction in muscle protein synthesis and protein catabolism; therefore, muscle weakness and loss of bulk can occur.
In its extreme form a steroid myopathy may develop, affecting the proximal muscles. This can be severe enough to affect mobility and is easily demonstrated by asking patients to stand from sitting without using their hands. Should a myopathy develop the steroid dose should be minimised and the use of steroid sparing agents considered. Recovery is slow and may be incomplete but can be helped by a programme to increase muscle strength. Muscle weakness can also occur as a result of hypokalaemia; electrolytes should therefore be checked in this situation.
The risk increases with both dose and duration of treatment but it is not possible to predict who will be affected. Steroid use is the commonest cause of osteonecrosis in the UK. Pathology shows segmental necrosis of subchondral bone associated with marrow fibrosis and reactive bone formation. Though the pathogenesis remains obscure, a number of theories have been proposed:.
In order to prevent the progression to joint destruction early diagnosis is essential. Early in the disease the plain x ray and computed tomography scan may be normal and a bone scan shows only non-specific changes. The magnetic resonance T2 weighted image shows a double ring sign representing a central low intensity area of fat necrosis surrounded by an increased signal of vascular proliferation; this is pathognomonic for osteonecrosis.
Treatment initially involves restricted weight bearing, physiotherapy to maintain the range of movement, and non-steroidal anti-inflammatory drugs; this gives relief of symptoms and may stabilise the condition. Some feel that surgical core decompression early in the disease decreases the rate of progression to joint destruction, others disagree.
Total joint replacement is the only long term definitive treatment. These patients are often young and so wear and loosening of the prosthesis can be problems. The management of osteonecrosis remains a considerable problem.
Existing psychiatric problems can be aggravated by corticosteroid treatment and so a full medical history is vital. Mood swings, euphoria, depression, and suicide attempts may all occur in previously stable personalities.
Symptoms respond to tapering of the corticosteroids, usually within 3 weeks. Reports in the Lancet draw attention to the unsatisfactory state of the law with respect to steroid induced psychosis as a defence for criminal activity. While clearly hypomanic, he was found guilty. Steroids act in multiple ways to inhibit the immune system and so their use is associated with an increased susceptibility to infection.
The clinical presentation may be atypical and the severity of the infection may be masked—for example, septicaemia; this allows the infection to become advanced before being recognised.
A predisposition to bacterial, viral, fungal, and candidal infections can all occur. When corticosteroids were first widely used the fear was expressed that reactivation of quiescent tuberculosis might occur. In isoniazid became available; it had a high activity against tuberculosis and a low toxicity rate compared with previously available treatments and was advocated for use as a prophylaxis in high risk patients.