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Class C Steroids for Treatment of Dermatoses

Class C Steroids for Treatment of Dermatoses

Topical steroids are commonly prescribed for the treatment of skin diseases including psoriasis, atopic dermatitis and contact dermatitis. However, allergy to corticosteroids occur frequently in dermatitis patients, defined as allergy to either the steroid molecule itself or to an ingredient in the vehicle.1 Corticosteroids have been divided into 4 classes (A, B, C and D) based on their structure and cross-reactivity patterns.2 Class C steroids have a low potential for allergenic sensitization.2,3

Taro Pharmaceuticals U.S.A., Inc.’s Topicort Cream 0.05% and Ointment 0.05% (desoximetasone) are C16-methylated molecules, categorizing them class C steroids. Both products are indicated for the relief of the inflammatory and pruritic manifestations of corticosteroid-responsive dermatoses. The products are propylene glycol-free and paraben-free and have no age restriction. Each gram of desoximetasone cream 0.05% contains 0.5 mg of desoximetasone in an emollient cream base consisting of cetostearyl alcohol, edetate disodium, isopropyl myristate, lanolin alcohol, mineral oil, purified water and white petrolatum. Each gram of desoximetasone ointment 0.05% contains 0.5 mg of desoximetasone in an ointment base consisting of mineral oil and white petrolatum. A thin film of the cream or ointment should be applied to the affected skin areas twice daily and rubbed in gently, according to the products’ prescribing information. 

In a survey of 105 US dermatologists, 19% reported that they would prescribe desoximetasone to patients with a suspected allergy to a steroid molecule or vehicle.4

Because topical steroid allergy (TSA) is common, clinicians should have a high index of suspicion for TSA, especially in patients whose dermatitis does not improve with topical steroid, who get worse on a topical steroid or who have chronic dermatitis.1 Zirwas outlined 3 approaches to managing TSA. The first 2 approaches are reactive, and third approach is proactive.1 

The first reactive approach is for clinicians to initially prescribe topical steroids without considering the possibility of a TSA allergy. TSA is reactively considered after the patient potentially experiences an adverse event. Then, the patient is referred for comprehensive patch testing. The second reactive approach also starts with clinicians initially prescribing topical steroids without considering the possibility of TSA. In this approach, however, instead of referring the patient for comprehensive patch testing after a potentially adverse reaction, the clinician prescribes a class C steroid that does not contain any vehicle allergens. The proactive approach is for clinicians to initially prescribe topical steroids with the intent to avoid TSA. The goal in this approach is to avoid unnecessarily placing patients at risk for an adverse event. In this approach, class C steroids without vehicle allergens are prescribed as first-line agents in all instances in which there is a clinically appropriate product available. If no product is available, then either a class C steroid cream vehicle or a class D1 steroid in either an ointment or solution is recommended, as these products have the lowest risk of allergenicity.1

Because class C steroids have been shown to reduce allergenicity and recommended as a first-line agent to avoid TSA, The Dermatologist Product Spotlight provides a summary of a study that compared C16-methylated and and non-methylated corticosteroids. 

References

1. Zirwas M. Allergy to topical steroids. J Drugs Dermatol. 2012;11(suppl 12):S9-S11.

2. Scheuer E, Warshaw E. Allergy to corticosteroids: update and review of epidemiology, clinical characteristics, and structural cross-reactivity. Am J Contact Dermat. 2003;14(4):179-187.

3. Topical steroids potency chart. National Psoriasis Foundation website. https://www.psoriasis.org/page.aspx?pid=469. Accessed October 1, 2015.

4. Sandoval LF, Davis SA, Feldman SR. Dermatologist’s knowledge and preferences regarding topical steroids. J Drugs Dermatol. 2013;12(7):786-789.

Study: Methylated Versus Non-Methylated Corticosteroids

Baeck M, Chemelle JA, Rasse C, Terreux R, Goossens A. C(16)-methyl corticosteroids are far less allergenic than the non-methylated molecules. Contact Dermatitis. 2011;64(6):305-312.5

Study Objective

To analyze and compare the patch test results obtained with different esterified corticosteroids in order to confirm the greater reactivity/allergenicity of non- C16-methylated compounds in relation to their chemical structure and reactivity with proteins, as well as with regard to skin metabolism.5

Method

Researchers reviewed the results of patch testing with an extended corticosteroid series among a cohort of corticosteroid-allergic patients during an 18-year study period (January 1990-June 2008). Sixty-six corticosteroids, including those from the baseline series were tested. All corticosteroids (except for the 2 screening agents present in the European baseline series) were prepared by a laboratory technician. Ethanol was the vehicle used to test all corticosteroid molecules except for tixocortol pivalate and budesonide for which petrolatum worked well. Because of their weak trans-epidermal penetration, hydrocortisone, and cortisone acetate were diluted in an equal mixture of ethanol and dimethyl sulfoxide. Both vehicles were included as controls in the extended series. The patches were removed after 2 days, and the patch test reactions were evaluated at day 2, day 4 and, in many cases, also after 7 days in accordance with the International Contact Dermatitis Research Group criteria. The positive reactions obtained with the different molecules were collected, and the results were analyzed in relation to the structural characteristics of the molecule (methyl or halogen substitution), and the location of the ester. For each patient, the number of positive reactions to both the C16-methylated and non-methylated corticosteroids were computed. Statistical analysis was performed with the Wilkinson signed rank test.5 

Population

Patch testing with an extended corticosteroid series was performed on 315 individuals with a proven corticosteroid contact allergy.5    

Primary Endpoint

Comparison of the number of reactions to molecules with and without C16-methylated substitution.5

Results

Positive patch test reactions to corticosteroid molecules without C16-methylated substitution (groups A and D2) were, with statistical significance, much more frequently observed than to those that are halogenated and have a methyl group at C16 (groups D1 and C). Among the corticosteroids without C16-methylated substitution, frequent reactions were observed to molecules from the D2 esters, particularly to methylprednisolone aceponate (N=105) and hydrocortisone-17-butyrate (N=96), but also to hydrocortisone aceponate (N=86) and prednicarbate (N=111). Most patients reacted to more than 1 molecule from the group, and 37 patients reacted to all 4.5

“C16-methylated substitution, which interferes with protein binding, and also halogenation of corticosteroid molecules, which plays an important role in their stabilization, seem to protect them from being sensitizing,” concluded the researchers. “C16-methylated corticosteroids should be prescribed preferentially if a topical steroid is needed, while, of course, taking into account their potency.”5

Additional Resource

Product information for Topicort Cream 0.05%: www.taro.com/usa-rx-product-details/273/Desoximetasone-Cream-USP and Topicort Ointment 0.05%: www.taro.com/usa-rx-product-details/274/Desoximetasone-Ointment-USP.  

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