Minimize the potential for side effects with topical corticosteroids

March 2004

Topical corticosteroids are among the most commonly used dermatologic medications for infants and children. Significant adverse effects are known to occur when corticosteroids are used systemically for long-term treatment. What is their adverse effect profile when applied topically?

Corticosteroid phobia?

Prior to addressing specific studies that assessed the adverse effects of topical corticosteroid therapy, it is interesting to describe the concerns that patients and caregivers have about their potential for adverse events. Charman administered a questionnaire to 200 patients (age range 4 months to 67.8 years) treated with topical corticosteroids for atopic dermatitis in England.

Patient and caregiver knowledge on topical corticosteroid potency, potential for adverse effects and compliance were evaluated. Of those surveyed, 72.5% had concerns about using the topical medication, and of these, 33% admitted to some degree of noncompliance with therapy because of these fears. Among the most commonly held concerns were “skin thinning” (34.5% of all patients) and “absorption/effects on growth and development” (9.5% of all patients).

Hydrocortisone was most commonly used, and of those using it, 31% classified its potency as very strong, strong, or they were not aware of its potency ranking. Although this study was conducted in England, and thus, may not be applicable to patients in the United States, it does reveal the potential for patient misunderstanding about topical corticosteroid use and compliance.

TCS potency and absorption

Several factors can affect topical corticosteroid potency and the risk for local and systemic adverse effects, including the innate potency of the corticosteroid, site of application, product vehicle (eg, ointment or cream), duration of use, and the size of the body surface area covered. Potency is ranked into seven groups, with Group 1 the most potent and Group 7 the least potent (see table 1 for examples). The site of application affects the risk for adverse effects because of the thickness of the stratum corneum and vascular supply.

Areas with a relatively thin stratum corneum have an increased potential for absorption and systemic effects. For example, penetration of the medication applied to the eyelid has a four-fold and 36-fold increase in the potential for absorption as compared to the forehead and palms/soles, respectively. Body sites with generally thinner stratum corneum layers and/or increased vascular supply include the face, mucous membranes, and intertriginous areas. High potency topical corticosteroids should be avoided in these areas. The use of occlusive devices (eg, occlusive dressing, tight fitting diaper) can also greatly increase the risk for systemic absorption.

Topical corticosteroids are available as ointments, creams, gels, lotions and other vehicles. Ointments and creams are most commonly used. Ointments are water-insoluble mixtures of oil and petrolatum and provide greater occlusiveness as compared to creams, and are best for dryer skin. This allows increased hydration of the stratum corneum and increased absorption. Creams and lotions are suspensions of oil in water and are not as occlusive as ointments, and thus are not as likely to potentiate absorption of the corticosteroid (see table for effect of vehicle formulation on potency ranking). Because creams and lotions are not as greasy as ointments, they are often more cosmetically acceptable.

Adverse effects

Topical corticosteroids have been associated with numerous adverse effects upon the skin and skin structures, with skin atrophy and striae the most common. Topical corticosteroids can decrease collagen synthesis, leading to skin atrophy, but this adverse effect is reversible upon discontinuance. Striae occur when skin, weakened by decreased collagen synthesis, is stretched, and is irreversible. Atrophy and striae usually do not develop until three to four weeks of therapy. It is generally believed that infants and children are at increased risk of systemic adverse effects from topical corticosteroids because of their increased body surface area to weight ratio, and because of the potential for decreased hepatic metabolism of absorbed drug in young infants.

The published literature contains numerous studies describing the potential for significant adverse effects of therapy, such as suppression of the hypothalamic-pituitary-adrenal (HPA) axis. Many of these studies are not easily comparable as different means of assessing HPA axis have been used, such as measuring plasma cortisol or the use of adrenocorticotrophic hormone (ACTH) testing.

Published case reports of topical corticosteroid-induced growth suppression, adrenal suppression, and even death from Addisonian crisis can be found. Published studies evaluating adrenal function with topical corticosteroid use are conflicting, as some report no adverse effects upon HPA function, while others report some degree of axis suppression. Review articles describe the potential for therapy to produce systemic adverse effects, although uncommonly.

Ellison evaluated the potential for resistance to topical corticosteroids in children with atopic dermatitis by assessing HPA axis function.

Thirty-five study patients (age range 0.7-18.7 years) with moderate-severe atopic dermatitis were evaluated. Patients had used topical medications of varying potency from infancy for a median duration of 6.9 years (0.5-17.7 years). Patients were placed into four categories based on potency, ranging from use of mild, moderate, or potent/very potent products (groups 1 to 3, respectively). Patients in group 4 had severe disease and required use of additional corticosteroid therapy given by non-topical routes. Low-dose ACTH testing was used to evaluate HPA axis function. The response to ACTH for groups 1 and 2 (mild-moderate potency) did not differ from control patients. However, group 3 patients (n=4, potent/very potent) had lower peak, increment, and area under curve cortisol responses as compared to controls (P<0.05). Eight patients failed low-dose ACTH testing (defined as peak cortisol <500 nmol/L, increment <200 nmol/L) – 1/17 group 2 patients (moderate potency), 4/4 group 3 patients (potent/very potent), and 3/7 group 4 patients (topicals + additional corticosteroid). Treatment score (potency, area treated, and duration) was significantly associated with lower peak and increment cortisol responses (P<0.05). Although small patient numbers limits this study, it does indicate the potential for systemic adverse effects from potent topical corticosteroids.

Patel similarly used low-dose ACTH testing to assess adrenal function in children using topical corticosteroids. Fourteen children (3.1 to 10.7 years of age) with moderate to severe atopic dermatitis, all using mild potency (median duration 6.5 years, range 3 to 10 years) were evaluated. Nine children had also intermittently used moderate potency medication (no additional information about duration of use was given).

Control patients included children of constitutional short stature without an identified endocrine disorder. There were no significant differences in the basal, peak, increment, or area under curve cortisol responses compared with control patients. The peak in plasma cortisol occurred earlier in children with atopic dermatitis (P<0.05), and a significant inverse relationship between time to peak and the extent of atopic dermatitis (P<0.05) was found. A significant relationship between topical corticosteroid dose or treatment score was not found, suggesting an effect upon adrenal function by the underlying disease and not therapy.

Conclusions

Although published studies assessing the potential of topical corticosteroids to result in systemic effects offer conflicting results, evidence does exist that they can produce systemic adverse effects, although uncommonly.

Clinicians prescribing topical corticosteroids and caring for patients receiving them can minimize the potential for systemic and local adverse effects by: using the lowest potency to control the disorder, avoiding higher potency on body site areas where absorption is more likely (eg, face), limiting duration of use for higher potency to two weeks, avoiding occlusive dressings, appreciating the differences among products with respect to potency and vehicle, and educating patients and caregivers on potency and adverse effects.

As symptoms of adrenal suppression may be nonspecific and difficult to recognize (eg, nausea, vomiting, fatigue), clinicians should consider assessing adrenal function (ACTH testing) in patients who are at higher risk of systemic effects (eg, use of higher potency topical corticosteroids, long duration or extent of application).

For more information:

• Charman CR. Topical corticosteroid phobia in patients with atopic eczema. Br J Dermatol. 2000;142:931-936.
• Eillison JA. Hypothalamic-pituitary-adrenal function and glucocorticoid sensitivity in atopic dermatitis. Pediatrics. 2000;105:794-799.
• Patel L. Adrenal function following topical steroid treatment in children with atopic dermatitis. Br J Dermatol. 1995;132:950-955.
• Leung DYM and the Joint Task Force on Practice Parameters. Disease management of atopic dermatitis: a practice parameter. Ann Allergy Asthma Immunol. 1997;79:197-211.