ORIGINAL ARTICLE Year : 2022  |  Volume : 26  |  Issue : 2  |  Page : 61-66

Allergens in corticosteroid vehicles in Saudi Arabia

Mana Alharbi1, Seba Almutairi2, Maisa Alfalah3
1 Department of Dermatology, Imam Muhammad Ibn Saud Islamic University, Riyadh, Saudi Arabia
2 College of Medicine, King Saud Bin Abdulaziz University for Health Sciences, Riyadh; Department of Dermatology, King Fahad University Hospital, Al Khobar, Saudi Arabia
3 Department of Dermatology, King Abdulaziz Medical City, Riyadh, Saudi Arabia

Date of Submission25-Mar-2022Date of Acceptance05-Jul-2022Date of Web Publication30-Dec-2022

Correspondence Address:
Dr. Seba Almutairi
Department of Dermatology, King Fahad University Hospital, P. O. Box: 3660, Riyadh 11481
Saudi Arabia

Source of Support: None, Conflict of Interest: None

DOI: 10.4103/jdds.jdds_26_22

Background: Both the active steroid compounds and vehicle ingredients of the topical corticosteroid products can cause allergic contact dermatitis. Purpose: The objective of the current study was to assess the presence of allergens in topical corticosteroid vehicles used in Saudi Arabia. Methods: Package inserts of topical corticosteroid products available through February 2022 were reviewed independently by two dermatologists. Topical corticosteroids were excluded if they were not approved by the Saudi Food and Drug Authority. Results: Out of 79 products examined, 49 (62%) were included in the study. Out of the 49 products, 29 (59%) had one or more allergens (a total of 38 allergens). Three topical corticosteroids were responsible for more than 80% of all allergens. These included mometasone furoate (n = 12), clobetasol propionate (n = 7), and betamethasone valerate (n = 5). The most frequent allergens were propylene glycol (66%), parabens (16%), sorbitan (13%), and lanolin (5%). Formaldehyde(s), methylchloro-isothiazolinone, and methyl-isothiazolinone were not detected in any product. Approximately 48% of the products with allergens were creams, 41% were ointments, and 10% were lotions. With two exceptions, there were no statistically significant differences in the overall presence of allergens by the type, formulation, and concentration of topical corticosteroid products. Conclusion: Almost 60% of topical corticosteroid products widely used in dermatologic clinics in Saudi Arabia had one or more vehicle allergens. Since the best treatment for contact allergy is avoidance, dermatologists should be aware of vehicle allergens in topical corticosteroids and consider the use of allergen-free products.

Keywords: Allergic contact dermatitis, parabens, propylene glycol, Saudi Arabia, topical corticosteroid

How to cite this article:
Alharbi M, Almutairi S, Alfalah M. Allergens in corticosteroid vehicles in Saudi Arabia. J Dermatol Dermatol Surg 2022;26:61-6
  Introduction 

Allergic contact dermatitis (ACD) is a common inflammatory skin disease induced by repeated skin contact with low-molecular-weight chemicals.[1] A large number of chemicals, medications, and environmental agents are implicated.[2],[3] These agents work as allergens that produce delayed T-cell-mediated (type IV) hypersensitivity reaction.[1],[4] Initial skin lesions include redness, papules, and vesicles which can later progress to scaling and dryness.[5],[6] ACD can be differentiated from irritant contact dermatitis by a positive patch test.[5],[6] ACD is very common affecting at least 20% of the general population, with higher susceptibility in women.[3] ACD affecting exposed parts such as face and hands can negatively impact the quality of life, especially at the emotional domain.[7]

Topical corticosteroids are frequently used to treat several skin conditions such as dermatitis, eczema, psoriasis, and vitiligo.[8] Topical corticosteroids can cause ACD in 1%–4% of the patients depending on the patch test used.[9],[10],[11] Both the active steroid compounds and vehicle ingredients of the topical corticosteroid products can cause ACD.[11],[12] Vehicles and preservatives are especially important, as they vary between different branded topical corticosteroid products.[13],[14],[15] This variation together with different corticosteroid potency and formulations may cofound the diagnosis or complicate the efforts to predict the responsible allergen.[16]

At least six vehicle allergen groups have been described in topical corticosteroid products; propylene glycol and sorbitan sesquioleate are the most frequent.[13] Propylene glycol has been described in topical corticosteroids in Saudi Arabia.[17] Other allergens may also be present. The frequency of allergens in products of different corticosteroid potency and formulations is not well characterized. The objective of the current study was to assess what allergens are in the vehicles of topical corticosteroids used in Saudi Arabia. In addition, we examined the associations of these allergens with the type, formulation, and concentration of topical corticosteroid products.

  Methods 

Setting and design

The current study was done at the Dermatology Department of the King Abdulaziz Medical City (KAMC), Riyadh, Saudi Arabia. It was an investigational cross-sectional study that was conducted during 2022. Ethical approval was obtained from the local ethical committee.

Study subjects

The study examined the official package inserts of all generic and branded topical corticosteroid products used in the daily dermatology clinical practice that is approved by the Saudi Food and Drug Authority (SFDA).[18] Different trade names containing the same active corticosteroid compounds were examined separately. Similarly, different formulations (cream, ointment, and lotion) and concentrations were included separately. Topical corticosteroids were excluded from the study if they were not listed on SFDA website, withdrawn by the appropriate marketing authorization or license holder, or present in any formulations other than cream, ointment, and lotion.

Allergens

A list of allergens previously reported in the literature in relation to corticosteroid vehicles has been predefined for data collection. The list included (1) propylene glycol or propylene glycol stearate; (2) propyl paraben or methyl paraben; (3) sorbitan sesquioleate, sorbitan monostearate, polysorbate 80, or polysorbate 60; (4) lanolin anhydrous or liquid anhydrous lanolin; (5) formaldehyde(s); and (6) methylchloro-isothiazolinone or methyl-isothiazolinone (MCI/MI).

Data collection

Package inserts of the included topical corticosteroid products available through February 2022 were reviewed independently by two dermatologists. Each recorded data on eligibility, reason of exclusion, product name (generic and trade names), formulation, concentration, and types of allergens. Data by the two dermatologists were compared, and any unmatched findings were re-evaluated.

Statistical analysis

Categorical variables were presented as frequencies and percentages. The associations of allergens with the type, formulation, and concentration of topical corticosteroid products were examined using Chi-square or Fisher's exact tests, as appropriate. The Statistical Package for the Social Sciences software (SPSS Version 25.0. Armonk, NY, USA: IBM Corp) was used for all statistical analyses.

  Results 

Out of 79 topical corticosteroid products examined, 49 (62%) were included in the study. Thirty products were excluded: 26 products not listed on SFDA website, 3 products withdrawn by the appropriate marketing authorization or license holder, and 1 product in the form of shampoo [Table 1]. In addition, this resulted in exclusion of generic flumethasone pivalate and alclometasone. Out of the 49 topical corticosteroid products included, nine generic corticosteroid types were examined: mometasone furoate (n = 17, 35%), betamethasone valerate (n = 11, 22%), clobetasol propionate (n = 8, 16%), betamethasone dipropionate (n = 3, 6%), hydrocortisone (n = 3, 6%), hydrocortisone butyrate (n = 3, 6%), fluticasone propionate (n = 2, 4%), clobetasone butyrate (n = 1, 2%), and hydrocortisone acetate (n = 1, 2%). The formulations were cream (n = 14, 45%), ointment (n = 12, 43%), and lotion (n = 3, 12%). The concentrations were 0.01% (n = 1, 2%), 0.05% (n = 13, 27%), 0.1% (n = 31, 63%), and 1% (n = 4, 8%).

Table 1: Presence of allergens in individual topical corticosteroid products of different names, formulations, and concentrations

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Of the 49 products examined, 29 (59%) examined had one or more allergens [a total of 38 allergens, [Figure 1]]. The most frequent allergen was propylene glycol (66%), parabens (16%), sorbitan (13%), and lanolin (5%). Formaldehyde(s) and MCI/MI were not detected in any of the examined products. Nine (18%) products had two different allergens [Table 1]. Eight topical corticosteroids (containing mometasone furoate, clobetasol propionate, or fluticasone propionate) had propylene glycol and either parabens or sorbitan allergens. The last one (hydrocortisone) had sorbitan and lanolin allergens. Approximately 48% of the products with allergens were in the form of creams, 41% were ointments, and 10% were lotions.

Figure 1: Number of detected allergens (above) and frequent types of allergens (below) in examined topical corticosteroid products

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Three topical corticosteroids were responsible for more 83% of all allergens detected [Figure 1]. These included mometasone furoate (n = 12), clobetasol propionate (n = 7), and betamethasone valerate (n = 5). The products with the highest percentage of allergens were those containing fluticasone propionate (100%), clobetasol propionate (88%), mometasone furoate (71%), hydrocortisone (67%), betamethasone valerate (46%), and betamethasone dipropionate [33%, [Figure 2]]. There were no allergens in products containing hydrocortisone butyrate, hydrocortisone acetate, and clobetasone butyrate.

Figure 2: Percentage of allergens in topical corticosteroid products with different types

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With two exceptions, there were no statistically significant differences in the overall presence of allergens by the type, formulation, and concentration of topical corticosteroid products [Table 2]. Propylene glycol was more common (P = 0.02) in products containing fluticasone propionate, clobetasol propionate, or mometasone furoate and nonexistent in products containing hydrocortisone butyrate, hydrocortisone acetate, or clobetasone butyrate. Unlike other allergens, sorbitan was associated with generally lower concentration of topical corticosteroid products (P = 0.02).

Table 2: Presence of allergens in topical corticosteroid products by type, formulation, and concentration

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  Discussion 

Allergens are common in topical corticosteroid products widely used in dermatologic clinics in Saudi Arabia. Almost 60% of these products had one or more allergens. The current finding was within the range reported in previous studies.[13],[14],[15] For example, 77% of 166 topical corticosteroid products widely used in the USA had at least one vehicle allergen.[13] Similarly, 76% of 40 topical corticosteroid products widely used in Canada had at least one vehicle allergen.[15] The higher rate of allergens in the USA study may be related to the relatively older data which included some products that are no longer used.[13] The higher rate of allergens in the Canadian study may be related to extending the list of allergens reviewed to 11 different allergens, including 4 used in the current study.[15] On the other hand, only 38% of 78 topical corticosteroid products widely used in Poland in 2015 had at least one vehicle allergen. The lower rate of allergens in the Polish study may be related to the smaller number of vehicle allergen groups evaluated. Most importantly, common allergens such as propylene glycol and sorbitan were not evaluated.[14]

The most frequent allergen in the current study was propylene glycol which represented almost two-thirds of all allergens, followed by parabens and sorbitan. Propylene glycol is an emollient and emulsifier that has been named Allergen of the Year for 2018 by the American Contact Dermatitis Society.[19] It is an allergen and also an irritant.[20] From 0.9% to 3.5% of topical corticosteroid users had positive patch tests for propylene glycol.[20],[21] In Saudi Arabia, propylene glycol is an important allergen,[22] and a list of propylene glycol-free topical corticosteroids has been described.[17]

In the current study and previous studies, cream products were more likely to contain allergens compared with other formulations.[13],[14] However, we could detect any association between the type of vehicle allergen and formulation. Stratification of data and consequently smaller number of products in each group may explain (at least partially) the lack of association between most of the allergens and formulation, potency, and type. Three topical corticosteroids were responsible for more than 80% of all allergens, including propylene glycol. These included mometasone furoate, clobetasol propionate, and betamethasone valerate. The finding may encourage the dermatologist to prescribe allergen-free alternative products.[17] It may be helpful to consider potential vehicle allergens in patients who do not respond or have worsening of symptoms after the application of topical corticosteroids.[23]

  Conclusion 

Almost 60% of topical corticosteroid products widely used in dermatologic clinics in Saudi Arabia had one or more vehicle allergens. The most frequent allergen was propylene glycol which represented almost two-thirds of all allergens, followed by parabens and sorbitan. Regular review of widely used topical corticosteroid products may be required. Since the best treatment for contact dermatitis is avoidance, dermatologists should be aware of vehicle allergens in topical corticosteroids and consider using allergen-free alternatives.[17]

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.

 

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  [Table 1], [Table 2]