Use and abuse of topical corticosteroids in infections of the skin and related structures

Journal of Drugs in Dermatology, June, 2003 by Vicky Kwan Wong, Christine Della Croce, Sara Schonfeld, Anthony M. Mastrangelo, Mark Lebwohl

Abstract

Topical corticosteroids have improved the management of many inflammatory skin diseases, such as psoriasis and atopic dermatitis. However, these medications are associated with certain adverse effects that are potentially serious. The potent anti-inflammatory actions of these drugs increase susceptibility to bacterial and fungal infections, and therefore may preclude them from use when infection is the known cause of the disease. In addition, children may be more vulnerable than adults to systemic effects of topical corticosteroids because percutaneous absorption is proportionately greater. These are important considerations, and physicians need to weigh and compare the risks and benefits associated with these medications before initiating treatment. This involves an appreciation of which patient populations are at high risk, which skin conditions are incompatible with topical corticosteroid therapy, and which alternative nonsteroidal medications are effective in treating inflammatory skin diseases.

Introduction

Corticosteroids are potent anti-inflammatory agents that were originally thought of as 'wonder drugs'. They are now used empirically for nearly every condition that has an inflammatory symptom. These drugs were initially used systemically to treat rheumatic diseases, and were shortly thereafter developed into topical medications that are remarkably efficacious in the treatment of a wide range of dermatologic conditions. While topical corticosteroids are effective at reducing the symptoms associated with inflammation, they often are not curative and do not address the underlying cause of the disease.

Generally, a short course of therapy (1 week) with even the most potent corticosteroid is usually well tolerated in the absence of contraindications. But because of their inhibitory effects on the immune system and inflammation, the use of oral and in some instances topical corticosteroids is associated with increased susceptibility to infection(1,2). The decision to institute therapy, therefore, requires careful consideration of the risks and benefits of treatment. Accordingly, physicians need to be familiar with certain characteristics of corticosteroid usage. For example, physicians need to become familiar with identifying high-risk patient populations and the possible adverse effects associated with treatment. Physicians should also be able to recognize clinical conditions that are incompatible with corticosteroid treatment, such as some bacterial and fungal infections. When the use of corticosteroids is not appropriate, the administration of effective alternative medications should be considered. Finally, adverse effects associated with treatment can be minimized by conducting routine patient follow-up visits.

Topical corticosteroids

Corticosteroids can be divided into 2 groups based on preferential activity: glucocorticoids and mineralocorticoids (3). Glucocorticoids preferentially regulate carbohydrate metabolism, while mineralocorticoids regulate electrolyte balance. In humans, the main glucocorticoid is cortisol, which is also called hydrocortisone. The majority of topical corticosteroids that are used therapeutically are synthetic derivatives of hydrocortisone (Figure 1). The desire to enhance the therapeutic potential of corticosteroids through the chemical modification of hydrocortisone has led to the generation of a large variety of drugs with different pharmacologic characteristics (Table 1). By changing the chemical structure of hydrocortisone, chemists have been able to alter the potency and sometimes the specificity of the drug. For example, introduction of an additional double bond in the A ring between carbons 1 and 2, as in betamethasone and triamcinolone, slows the metabolism of the drug and selectively increases glucocorticoid activity by approximately 4-fold over hydrocortisone (3).

Immunosuppression and the inhibition of inflammation are the major pharmacologic activities of topical corticosteroids. These drugs have the ability to inhibit inflammation induced by a variety of inciting events, including radiant, allergen, and chemical stimuli (4-6). The mechanisms involved in these anti-inflammatory effects are generally known. Corticosteroids bind to glucocorticoid receptors that directly interact with DNA to modulate gene transcription (7). The overall result is a reduction in the expression of factors involved in initiating and maintaining inflammation, including cytokines, matrix metalloproteinases, adhesion molecules, and histamine (8-11).

Because of their immunosuppressive effects, topical corticosteroids are mainly used clinically to treat inflammatory skin conditions. Although their use is largely empiric, they are effective and therefore widely prescribed. In fact, topical corticosteroids were prescribed or recommended at approximately 14 million visits per year to office-based health practitioners between 1989 to 1991 (12). The great demand for topical corticosteroids has led to the development of various vehicle formulations, including foams, ointments, creams, gels, sprays, and solutions, that have increased the efficiency of drug application to various skin structures.