704 Br J Ophthalmol 1998;82:704–708 PERSPECTIVE Br J Ophthalmol: first published as 10.1136/bjo.82.6.704 on 1 June 1998. Downloaded from Systemic corticosteroid therapy—side eVects and their management Rosalyn M Stanbury, Elizabeth M Graham Corticosteroids have been used in ophthalmology for Haematological almost 50 years. Hench, in 1949,1 was the first to report on Polycythaemia is a feature of Cushing’s syndrome but does the beneficial eVects of ACTH and cortisone. His work not appear to be a feature of corticosteroid therapy. was with rheumatoid arthritis and since 1929 he had The total white blood count is increased in patients on noticed that rheumatoid arthritis improved in pregnancy corticosteroids. The various classes of white blood cells are and jaundice. He conjectured that an adrenal hormone aVected in the following ways: might be the common agent causing this improvement. In + Polymorphonuclear leucocytes increased 1948 he managed to acquire the necessary hormones and + Lymphocytes decreased; T cells are reduced to a greater found clinical improvement in the rheumatoid arthritis and extent than B cells although immunoglobulin synthesis a reduction of the erythrocyte sedimentation rate on treat- is also decreased4 ment with the hormones and relapse when they were + Monocytes decreased stopped. His article concluded that theoretically these + Eosinophils decreased agents may be of benefit in other conditions which can be Corticosteroid use promotes blood coagulation and relieved by pregnancy and jaundice. Very soon after this alters the patient’s response to anticoagulants and hence steroids were used, both systemically and topically, to treat frequent checks on the extent of anticoagulation are neces- inflammation of the eye. sary especially if the steroid dose is varying. Within ophthalmology there are many indications for the use of corticosteroids. The decision to institute steroid Fluid and electrolyte balance therapy always requires careful consideration of the relative Corticosteroid use is associated with sodium and water risks and benefits in each patient. In uveitis, for example, retention; this can be reduced by recommending a low salt the use of corticosteroids may often be in high doses for diet. 2 long periods of time. Before starting systemic steroids the Potassium loss occurs and a hypokalaemic alkalosis may http://bjo.bmj.com/ ophthalmologist must consider: develop. A diet rich in potassium (most fruits, vegetables, + the reasons for initiating steroid treatment especially broccoli and carrots, fish, and poultry) is usually + the expected visual outcome suYcient to make good this loss but occasionally + how the patient will be assessed potassium supplements are required. + the impact on any associated systemic disease. The blood pressure should be checked at each If a beneficial eVect is not seen within the expected time outpatient visit and antihypertensive treatment may be scale the corticosteroids should be reduced and stopped. necessary. If a thiazide diuretic is chosen as the antihyper- on September 27, 2021 by guest. Protected copyright. This review considers some of the non-ocular problems tensive agent the serum potassium should be carefully and dilemmas encountered when systemic steroids are monitored. Thiazides also have a beneficial eVect on osteo- used, with practical suggestions to minimise their side porosis by reducing calcium loss in the urine. eVects. In particular, the new recommendations by the Corticosteroids should be used with extreme caution in Department of Health on the indications for intervention patients with limited cardiac reserve as cardiac failure can following exposure to chickenpox or shingles will be develop. discussed and recent publications on the management of corticosteroid osteoporosis will be reviewed. Endocrine and metabolic The patient should be warned about the development of a cushingoid habitus (moon facies, buValo hump, central Dermatological obesity). The appearance of these features is extremely + Thin, fragile skin is a feature of corticosteroid use and variable; some patients seem able to tolerate prednisolone the photograph in the Minerva section of the BMJ from 30 mg/day while others become cushingoid on less than 19 October 19963 vividly illustrates this; it shows a flap one half of this. The reason for this change in appearance of chest skin avulsed as the cardiac monitor is removed is not clearly understood but one hypothesis is that truncal from a patient who had been on long term steroids and peripheral adipocytes vary in sensitivity to the + Mild hirsutism glucocorticoid facilitated lipolytic eVect—that is, the + Bruising peripheral adipocytes are more sensitive to this eVect than + Facial erythema the central adipocytes. + Increased sweating Weight gain, which can be enormous in some patients, + Impaired wound healing, patients should be advised to can be minimised by the early use of a calorie controlled take particular care to avoid injury diet. + Striae Reduced carbohydrate tolerance accompanies cortico- + Acne steroid use. Glucocorticoids increase gluconeogenesis and Systemic corticosteroid therapy 705 blood glucose increases by 10–20%. Glucose tolerance and slow growth velocity significantly.9 However, in our sensitivity to insulin is decreased but if pancreatic function experience this mode of medication does not seem Br J Ophthalmol: first published as 10.1136/bjo.82.6.704 on 1 June 1998. Downloaded from is normal no diabetes should develop. However, hypergly- eVective in the control of inflammatory eye disease. caemia and glycosuria should be checked for as one fifth of patients may develop “steroid diabetes”. The initial Musculoskeletal management is dietary modification with the addition of OSTEOPOROSIS hypoglycaemic agents if necessary. This particular form of Within a few years of the introduction of steroids an diabetes has a low sensitivity to insulin but does not tend to increased tendency to osteoporosis and fracture were ketosis. When the steroids are stopped the diabetes noticed. Many studies on the association of osteoporosis normally disappears. The use of corticosteroids is not and steroid use have been performed on patients with contraindicated in a known diabetic but patients should rheumatoid arthritis where clearly additional factors for be aware that their blood glucose control is likely to osteoporosis exist. The greatest rate of bone loss occurs in deteriorate and that they will need increased treatment. the first 6 months and is thought to continue at a lower rate Suppression of the hypophyseal pituitary adrenal axis for as long as steroids are used. Studies show a correlation occurs with surprisingly little corticosteroid. A 1 week between cumulative steroid dose and bone density; course has no significant eVect but 2 weeks of supraphysi- therefore, treating with the lowest possible steroid dose is ological doses (that is, greater than prednisolone 7.5 important. There is no benefit in using alternate day mg/day) within 1 year causes a degree of impairment which therapy. Bone loss is greatest in trabecular (cancellous) could become manifest in acute stress.5 Patients must be bone, which is more metabolically active but also occurs in aware of the dangers of stopping steroid treatment cortical bone. The mechanism of steroid induced bone loss suddenly and of the need to inform any medical is multifactorial10: practitioner of their past or present steroid usage. Patients + Reduced osteoblast activity resulting in reduced bone with suppressed adrenals require the reintroduction of cor- formation ticosteroids at the time of a surgical procedure, trauma, or + Increased bone resorption due to increased osteoclast intercurrent illness and those on long term steroids may activity need an increased dose. + Reduced intestinal absorption of calcium and phos- Sex hormones, both testosterone and oestrogen, are phate reduced by the administration of corticosteroids.67Oestro- + Reduced renal reabsorption of calcium gen and testosterone play a part in the regulation of bone + Secondary hyperparathyroidism metabolism (hypogonadism in males and females is associ- + Reduced sex hormones. ated with osteoporosis) and are factors in the development The incidence of fracture in steroid treated individuals is of corticosteroid induced osteoporosis. Hormone replace- between 10% and 20% and those at particular risk are: ment therapy has been shown to have a beneficial eVect on + Under 15 years and over 50 years osteoporosis in post-menopausal and amenorrhoeic + Post-menopausal or amenorrhoeic women women on corticosteroids8 (see below). The supplementa- + Slim build tion of testosterone in men on corticosteroids is not com- + Limited mobility. mon practice but may provide an additional means of pre- Medications that increase the risk of osteoporosis venting osteoporosis in this group. include thyroxine and heparin. Menstrual irregularities and amenorrhoea can also Steroid bone loss appears to be reversible, as when http://bjo.bmj.com/ occur. Cushing’s syndrome is cured the bone mass returns to Serum lipids, both triglycerides and cholesterol, may be normal. There are no longitudinal studies specifically increased during corticosteroid therapy. addressing the question of whether steroid induced bone Patients on corticosteroids have a negative nitrogen and loss reverses when steroids are stopped, but evidence exists calcium balance. that significant increases in bone mineral density occur with specific therapy for steroid induced osteoporosis.11 Patients