Experimental and Clinical Pharmacology
The role of corticosteroids in rheumatology
- Anna Dorai-Raj, Leslie Schrieber
- Aust Prescr 1998;21:11-4
- 1 January 1998
- DOI: 10.18773/austprescr.1998.011
Corticosteroids can improve the symptoms of patients with rheumatic diseases. They may also have a disease-modifying effect in rheumatoid arthritis, but they are not first-line treatment. Adverse effects are related to the dose and duration of treatment. Patients taking long-term treatment should be advised of these and prescribed the lowest effective dose. They should not stop treatment abruptly.
The substantial anti-inflammatory activity of corticosteroids was recognised soon after their introduction in the 1950s. They were hailed as a 'cure' for rheumatoid arthritis (RA), based on uncontrolled observations. However, it subsequently became obvious that unacceptable adverse effects occurred with prolonged use of high-dose corticosteroids. They fell out of favour until recently. Corticosteroids have been reintroduced for the treatment of several rheumatological conditions. There is now a more rational approach to their use and a concerted effort to minimise adverse effects.
Oral preparations are the most commonly used, often as adjunctive therapy. Intravenous preparations have a more restricted role. Intra-articular/intralesional preparations are also commonly used in rheumatology for inflammatory rheumatic diseases and regional pain syndromes e.g. tennis elbow (lateral epicondylitis). Different corticosteroids vary with respect to their duration of action and relative glucocorticoid and mineralocorticoid activity. Corticosteroids are divided into short-, intermediate- and long-acting groups (Table 1). Short- and intermediate-acting preparations are more commonly used in practice as there is less inhibition of the hypothalamic-pituitary-adrenal (HPA) axis.
Corticosteroids have a wide range of biological activities including anti-inflammatory and immunosuppressive effects. They have major effects on leucocyte movement and, to a lesser extent, on leucocyte function. In general, they have greater effects on cellular than humoral processes. They inhibit the production of arachidonic acid metabolites, e.g. prostaglandins and leukotrienes, as well as that of certain cytokines e.g. interleukin 1.1
Low-dose daily oral therapy
Non-steroidal anti-inflammatory drugs (NSAIDs) provide rapid symptomatic relief in RA. However, they do not prevent the development of bony erosions. When the diagnosis of RA is established, a disease-modifying anti-rheumatic drug (DMARD) should be introduced to try to prevent the development of bony erosions and to induce disease remission. However, most of these drugs, e.g. sulfasalazine, take a minimum of 6 weeks, and in some cases up to 6 months, to take effect. Patients may require oral corticosteroids for symptomatic relief if NSAIDs produce an inadequate response. This may bridge the gap until DMARDs take effect. The corticosteroid dose can then be tapered off.
In patients who cannot tolerate NSAIDs or in whom the use of DMARDs has proven to be problematic, e.g. adverse effects, monitoring difficulties or poor compliance, the use of a low-dose corticosteroid e.g. prednisolone 5-10 mg/day, may provide good control of symptoms and improved function.
Importantly, with regard to the use of low-dose corticosteroids, a recent placebo controlled trial has shown that prednisolone 7.5 mg/day has a disease-modifying effect by preventing the development of bony erosions.2
Pulse intravenous methylprednisolone can be used in major organ-threatening diseases e.g. scleritis, pneumonitis and mononeuritis multiplex complicating RA. Oral prednisolone (up to 1 g) or intravenous methylprednisolone is given as a single dose to settle a severe flare of disease. The clinical effect may last from weeks to months. This may avoid the need to introduce oral daily therapy. More controversial has been whether or not high-dose boluses of corticosteroids used in conjunction with a DMARD, such as a gold compound, result in improved efficacy and less toxicity of the DMARD. Overall, pulse therapy is well tolerated with little toxicity reported.3
Both polymyalgia rheumatica and giant cell arteritis are treated with oral corticosteroids. Lower doses (15-20 mg) are used initially in polymyalgia, whereas higher doses, e.g. 40-50 mg/day are used in giant cell arteritis. The drugs are continued for a few weeks and then, depending on the symptoms and laboratory indices, e.g. ESR or C-reactive protein, the dose can be reduced to the lowest maintenance dose possible e.g. 5-10 mg/day. Both conditions require treatment with steroids for a period of about two years. Unfortunately, in older patients, the dramatic early relief of symptoms is complicated by a high frequency of adverse effects after prolonged corticosteroid use.
Corticosteroid preparations - half-life and potency
|Drugs||Anti-inflammatory potency||Equivalent doses (mg)||Sodium retaining||
|- cortisone acetate||1||20||2+||8-12|
Diseases such as systemic lupus erythematosus, vasculitis and polymyositis require systemic corticosteroid therapy for effective control. These diseases vary greatly in the extent and severity of organ system involvement so there is a need to individualise treatment. In severe flares, high-dose oral or intravenous corticosteroids are usually required. Management should be under the guidance of a consultant physician e.g. a rheumatologist experienced in treating these complex disorders.
Considerations before starting oral corticosteroids1
Local corticosteroid therapy4
An injection of a corticosteroid into the site of inflammation can avoid most of the problems caused by large oral doses. Intra-articular and intralesional corticosteroids are of use when a high concentration in a particular joint, tendon sheath or bursa is required. The indications for intra-articular/intralesional preparations are shown in Table 2. There are, however, situations where a local corticosteroid injection is contraindicated and these are:
Intra-articular and intralesional therapy
|Soft tissues e.g. bursa, tendon sheath, tenosynovium, entheses||Local - inflammation, injury, overuse
Systemic inflammatory disorders - e.g. rheumatoid arthritis, gout
|Nerve entrapment||e.g. carpal tunnel syndrome|
The use of epidural corticosteroids for back pain is controversial, with reports of arachnoiditis complicating this application. They are not recommended.
Corticosteroid therapy has many possible complications (Table 3).1 More common adverse effects with long-term use include:
Some of the adverse effects are more serious and may require monitoring:
Adverse effects of corticosteroids
|Metabolic||Obesity, electrolyte imbalance, glucose/protein/lipid metabolism|
|Predisposition to infection|
|Musculoskeletal||Osteoporosis, myopathy, osteonecrosis|
|Gastrointestinal||Peptic ulcer disease, pancreatitis|
|Central nervous system||Psychosis, depression, benign intracranial hypertension|
|Dermatological||Acne, striae, alopecia, bruising, skin atrophy, hirsutism|
|Growth retardation||In children|
|Hypothalamic-pituitary-adrenal axis suppression|
|Corticosteroid withdrawal syndrome|
The bone loss associated with long-term (>6 months) corticosteroid treatment mainly affects trabecular bone. To minimise this effect, reduce the dose to the lowest possible and withdraw corticosteroids if possible. If long-term corticosteroid therapy is planned, bone mineral density (BMD) should be measured. Consideration should be given to preventive strategies, especially in high-risk patients. Adequate calcium intake and hormone replacement therapy in postmenopausal women who have no contraindication are appropriate. Where a patient has had a previous fracture, or has a reduced BMD at baseline, a bisphosphonate, e.g. etidronate or alendronate or active vitamin D metabolite, calcitriol, is appropriate to prevent bone loss. Prevention may be most effective when given at the start of therapy since bone loss is most rapid when corticosteroids are first commenced.
A recent 12-month clinical trial reported that the use of intermittent etidronate at the start of corticosteroid therapy prevented bone loss and reduced the risk of new vertebral fractures. Long-term studies are required to determine if these effects will be sustained.5
Withdrawal of corticosteroids
Patients treated with long-term moderate or low doses of corticosteroids should have their corticosteroid dose reduced and withdrawn slowly. The reasons for this are to:
To avoid these problems with withdrawal of corticosteroids, the dose should be reduced gradually. A suggested rate of reduction for prednisolone is 2.5 mg every 4-8 weeks until a dose of 7.5 mg is reached. Subsequent reduction should be by 1 mg decrements over the same interval.
Inhibition of linear growth and delay in epiphysial closure occur in children on long-term corticosteroids. Alternate day administration of the same total dose may reduce this adverse effect and is now preferred in children where possible.6This regimen is also possible in adults when their disease is stable. The adverse effects associated with this form of therapy are less compared to daily administration. However, in symptomatic disorders, e.g. RA, patients often experience a flare in their symptoms on the day off treatment and may be unable to tolerate this regimen.
Corticosteroids have a clear role in the management of rheumatic disease. Their toxicity requires that they are used only when necessary, at the lowest dose possible and for the shortest duration of time. Consideration should be paid to the measures that can be taken to limit toxicity. No compound has yet been developed that dissociates the anti-inflammatory properties of corticosteroids from their adverse effects.
(See also Dental implications)
Rheumatology Registrar, Rheumatology Registrar
Associate Professor of Medicine, University of Sydney and Department of Rheumatology, Royal North Shore Hospital, Sydney