In 1997, the Food and Drug Administration gave indication to the Thin-layer Rapid Use Epicutaneous (T.R.U.E.) Test for use as a valuable, first-line screening tool in the diagnosis of allergic contact dermatitis (ACD). Many dermatologists and allergists use this standard tool in their practices and refer to contact dermatitis referral centers when the T.R.U.E test fails to identify a relevant allergen. Specifically, the T.R.U.E. test screens for 46 distinct allergens in addition to the Balsam of Peru mixture, and is thought to adequately identify an allergen in approximately 24.5% of patients.1 This being said, many relevant allergens are not detected by use of this screening tool alone and, for this reason, “Allergen Focus” has been expanded to cover the notorious allergens of the year. This article focuses on sorbitans. Contact Dermatides The contact dermatides include ACD, irritant contact dermatitis (ICD) and contact urticaria (CU). ICD is the most common form, accounting for approximately 80% of environmental-occupational based dermatoses, and can be further divided into acute toxic and cumulative insult types. Acute toxic reactions result from a one-time exposure to a strong external irritant. Cumulative insult reactions occur after chronic exposure to a weak external irritant such as soaps. CU (wheal and flare reaction) represents an IgE and mast cell-mediated immediate-type hypersensitivity reaction that can lead to anaphylaxis. The foremost example of this would be latex protein hypersensitivity. While this is beyond the scope of this section, we acknowledge this form of hypersensitivity and direct the reader to key resources.2,3 ACD is a T-cell dependent delayed-type (Type IV) hypersensitivity reaction, which has a high impact both in terms of patient morbidity and economics. This type of hypersensitivity reaction is primarily instigated by small lipophilic chemicals (haptens) with a molecular weight less than 500 Daltons. These chemical allergens trigger a complex immunologic cascade in the skin, which leads to the clinical picture of ACD. The condition ranges from acute vesicles to chronic erythematous scaling patches and plaques. It can cause significant debilitation for patients. Patch testing remains the gold standard for differentiating irritant and allergic forms of contact dermatitis. Furthermore, by allowing practitioners to recognize inciting agents, patch testing is a powerful tool for treating the root cause of allergic contact dermatitis.4 Case Illustration A 56-year-old Caucasian female presented to Tufts Medical Center Department of Dermatology with severe, pruritic pretibial dermatitis for 4 years. Minimal to moderate stasis dermatitis was present. She also had facial dermatitis and intermittent dermatitis on her upper and lower extremities. Of note, her condition was worsening despite treatment with clobetasol ointment. Her past medical history was notable for mild asthma. An Overview of Sorbitans A recent column in Skin & Aging focused on the potential for corticosteroids to induce contact sensitization.5 This paradoxical phenomenon has become a well recognized side-effect of these dermatological agents.5,6 Evidence has shown that additional ingredients in corticosteroid preparations may also induce ACD. Various studies have found that preservatives and emulsifiers within topical steroid formulations can also be sensitizers in susceptible patients.7 Exposing inflamed skin to ingredients in topical steroids has likely accelerated sensitization.8-10 In this column we will highlight the emerging potential for sorbitans, one such family of emulsifiers, to induce ACD. Sorbitans are a group of compounds derived from sorbitol, a sugar alcohol.8 Joseph Boussin, a French chemist, first isolated sorbitol from berries in 1872.11 Notable sorbitan derivatives include sorbitan sesquioleate (SSO), sorbitan monooleate (SMO), sorbitan monostearate (SMS) and polysorbate.8 SSO is fatty acid ester formed from mono- and diesters of oleic acid and hexitol anhydrides of sorbitol.12 SMO is also a fatty acid ester, but formed from monoesters of oleic acid and hexitol anhydrides of sorbitol.13 SMS is derived from esters of stearic acid and sorbitol. Polysorbates are fatty acid esters of polyoxyethylene sorbitan.9 They are all non-ionic, oil-soluble, water-dispersible compounds that function as emulsifiers in numerous cosmetic products and medicaments.12,14 According to the Contact Allergen Replacement Database (CARD), these substances can all potentially cross-react. Sorbitans in Corticosteroids Topical steroids are classified according to potency and class. Potency, determined by vasoconstrictive assays, is directly related to the type and vehicle of the corticosteroid. Many classification systems are available, but we find it most useful to subdivide according to super, high, mid and low potency. Class is determined by the molecular structure of the steroid. Currently, classes A, B, C, D1 and D2 have been identified. Separating these agents according to class can be helpful in avoiding use of structurally related steroids in sensitized individuals. However, cross reactions can also occur between different corticosteroid classes.5,15 Sorbitans can function as emulsifiers in class A, B, C, D1 and D2 steroids. They can also be found in super-, high-, mid- and low-potency steroids. Thus, patients have ample opportunity for exposure to these chemicals. Avoiding exposure to these chemicals can often be difficult. In a recent review, 28% of corticosteroid preparations were found to contain sorbitan derivatives.7 SSO, in particular, can be found in numerous types of corticosteroid ointments including first-line therapies such as clobetasol and halobetasol.16 Interestingly, creams are often found to contain causative allergens, but sometimes even ointments can contain the culprit. One should always consider contact allergy when a dermatitis does not respond to usual treatments. Table 1, previously published by Coloe and Zirwas in Dermatitis, provides a summary of contact sensitization by common ingredients used in different vehicles.7 Sorbitans in Other Products Sorbitan derivatives can be present in a wide-range of additional, non-steroid products. In a recent report, we found sorbitol and sorbitan derivatives in topical antibiotics, topical antifungals, lotions, lipsticks, topical vitamin A analogues and toothpaste.8 Sorbitol is found in many foods such as apples, cherries, berries, plums, pears, seaweed, and sucrose-free cakes and cookies.17 Sorbitol may also be used as a sweetener in oral medications.18 Hence, topical steroids are not the only pathway for sorbitan exposure and subsequent sensitization in chronically dermatitic skin (see Table 2).8 Sorbitans in Patch Testing SSO is present as an emulsifier in a number of patch test reagents. Most notably among these are fragrance mix (FM) I, ethyleneurea/melamine formaldehyde (Chemotechnique Diagnostics, Vellinge, Sweden), and the eight individual components of FM I (Hermal, Reinbek, Germany). Recognizing its use in these compounds may be important in avoiding false positives in a patient who is also allergic to sorbitan sesquioleate.19 Allergic Contact Dermatitis to Sorbitans Testing for sensitization to sorbitan sesquioleate and other sorbitan products is not routinely carried out in most dermatological centers. It is currently not tested by the NACDG. Previous studies showed relatively low yield for sorbitan testing, but these studies were performed decades ago.20-23 Recent data suggests that sorbitan sensitization is becoming more prevalent. A number of case reports and case series have demonstrated clinically relevant contact sensitivity to sorbitan derivatives. In these cases, sorbitans were found in diaper dermatitis products,12 wound dressings,24 and topical corticosteroids.12,25 Three separate reports also described contact sensitivity to sorbitan sesquioleate and sorbitan monooleate in patients with leg ulcers.9,26,27 We recently reported 13 patients who demonstrated contact allergy to SSO or SMO in a cohort of 112 dermatitis patients presenting to our department for patch test evaluation over a 6-month period.16 The patient presented in this report was previously included in this cohort. All patients were using products that contained sorbitol or sorbitol derivatives. Three-fourths of the patients were using topical corticosteroids that contained these derivatives. Of the patients who were available for follow-up, 90% showed improvement with our recommendations post patch testing, which included avoidance of sorbitan-containing products and sorbitan-containing topical steroids.16 Testing for Sorbitan Sensitivity At Tufts Medical Center, Ohio State University and University of California San Diego, SSO and SMO are routinely tested for at 20% in petrolatum and 5% in petrolatum, respectively (Chemotechnique Diagnostics, Vellinge, Sweden). Value of the Case Our patient underwent patch testing in order to determine whether any contact allergens were responsible for her debilitating dermatitis. She was tested to the Tufts Standard Screening Tray (a modified NACDG standard series), a cosmetic/preservative series, and a fragrance series supplied by Chemotechnique Diagnostics, Vellinge, Sweden. One exception was that the individual fragrance mix I (FM I) components on our fragrance series were supplied by Hermal, Reinbek, Germany. She tested positive to a number of contact allergens including formaldehyde, ethylene urea melamine formaldehyde (a textile formaldehyde resin screening mixture, lanolin, balsam of Peru, and fragrance mix). Of particular note, she demonstrated a 3+ (spreading or bullous) reaction to SSO and a 2+ (papules plus edema or vesiculation) reaction to SMO. When we examined her products to assign clinical relevance, we found that SSO was used as an emulsifier in her clobetasol ointment. Thus, the agent used to treat her dermatitis was likely exacerbating it. A provocative use test was not done with clobetasol as the patient improved significantly after stopping the steroid. Her moisturizer, shampoo and body wash contained the formaldehyde-releasing preservative, DMDM hydantoin. Her shampoo and body wash also contained fragrance. These all could have been contributing significantly to her eruption. Additionally, wash and wear permanent press fabrics, even if 100% cotton, can be finished with formaldehyde. The same is true of blended fabrics such as cotton/polyester or cotton/rayon. Therefore, she could have difficulty with certain fabrics, too. Interestingly, in terms of her textile formaldehyde allergy, the pants of her uniform were previously bothering her. Changing to 100% non-wrinkle-resistant cotton helped to improve her symptoms. She was advised to avoid all sorbitan-containing steroids in the future. We further counseled her to read labels of topical products and avoid sorbitol or sorbitan derivatives in lotions, topical antifungals and topical antibiotics. Her dermatitis improved significantly when she switched to a non-sorbitan containing topical steroid, suggesting that this was a key contributing factor in her dermatitis. She was further advised to use products that were free of lanolin, formaldehyde, formaldehyde releasing preservatives and fragrance. Collectively, these recommendations helped to significantly improve her condition. Contact allergy to sorbitan derivatives appears to be increasingly problematic. Many topical corticosteroids, the primary agents for combating dermatitis, contain these emulsifiers. Applying even weak sensitizers to chronically dermatitic skin can cause sensitization.10,28 Testing for SSO and SMO can be useful in avoiding certain topical corticosteroids and products that may exacerbate contact dermatitis.16 This case illustrates the benefit of testing for sorbitan sensitization in addition to other allergen series based on history and physical exam. By discovering SSO and SMO allergies, in addition to her other contact allergens, we were able to effectively treat her chronic and debilitating dermatitis. Adam Asarch is with Tufts University School of Medicine in Boston, MA. Dr. Scheinman is with the Tufts Medical Center, Department of Dermatology in Boston, MA.
Focus on the Non-T.R.U.E. Test Allergen: Sorbitans
In 1997, the Food and Drug Administration gave indication to the Thin-layer Rapid Use Epicutaneous (T.R.U.E.) Test for use as a valuable, first-line screening tool in the diagnosis of allergic contact dermatitis (ACD). Many dermatologists and allergists use this standard tool in their practices and refer to contact dermatitis referral centers when the T.R.U.E test fails to identify a relevant allergen. Specifically, the T.R.U.E. test screens for 46 distinct allergens in addition to the Balsam of Peru mixture, and is thought to adequately identify an allergen in approximately 24.5% of patients.1 This being said, many relevant allergens are not detected by use of this screening tool alone and, for this reason, “Allergen Focus” has been expanded to cover the notorious allergens of the year. This article focuses on sorbitans. Contact Dermatides The contact dermatides include ACD, irritant contact dermatitis (ICD) and contact urticaria (CU). ICD is the most common form, accounting for approximately 80% of environmental-occupational based dermatoses, and can be further divided into acute toxic and cumulative insult types. Acute toxic reactions result from a one-time exposure to a strong external irritant. Cumulative insult reactions occur after chronic exposure to a weak external irritant such as soaps. CU (wheal and flare reaction) represents an IgE and mast cell-mediated immediate-type hypersensitivity reaction that can lead to anaphylaxis. The foremost example of this would be latex protein hypersensitivity. While this is beyond the scope of this section, we acknowledge this form of hypersensitivity and direct the reader to key resources.2,3 ACD is a T-cell dependent delayed-type (Type IV) hypersensitivity reaction, which has a high impact both in terms of patient morbidity and economics. This type of hypersensitivity reaction is primarily instigated by small lipophilic chemicals (haptens) with a molecular weight less than 500 Daltons. These chemical allergens trigger a complex immunologic cascade in the skin, which leads to the clinical picture of ACD. The condition ranges from acute vesicles to chronic erythematous scaling patches and plaques. It can cause significant debilitation for patients. Patch testing remains the gold standard for differentiating irritant and allergic forms of contact dermatitis. Furthermore, by allowing practitioners to recognize inciting agents, patch testing is a powerful tool for treating the root cause of allergic contact dermatitis.4 Case Illustration A 56-year-old Caucasian female presented to Tufts Medical Center Department of Dermatology with severe, pruritic pretibial dermatitis for 4 years. Minimal to moderate stasis dermatitis was present. She also had facial dermatitis and intermittent dermatitis on her upper and lower extremities. Of note, her condition was worsening despite treatment with clobetasol ointment. Her past medical history was notable for mild asthma. An Overview of Sorbitans A recent column in Skin & Aging focused on the potential for corticosteroids to induce contact sensitization.5 This paradoxical phenomenon has become a well recognized side-effect of these dermatological agents.5,6 Evidence has shown that additional ingredients in corticosteroid preparations may also induce ACD. Various studies have found that preservatives and emulsifiers within topical steroid formulations can also be sensitizers in susceptible patients.7 Exposing inflamed skin to ingredients in topical steroids has likely accelerated sensitization.8-10 In this column we will highlight the emerging potential for sorbitans, one such family of emulsifiers, to induce ACD. Sorbitans are a group of compounds derived from sorbitol, a sugar alcohol.8 Joseph Boussin, a French chemist, first isolated sorbitol from berries in 1872.11 Notable sorbitan derivatives include sorbitan sesquioleate (SSO), sorbitan monooleate (SMO), sorbitan monostearate (SMS) and polysorbate.8 SSO is fatty acid ester formed from mono- and diesters of oleic acid and hexitol anhydrides of sorbitol.12 SMO is also a fatty acid ester, but formed from monoesters of oleic acid and hexitol anhydrides of sorbitol.13 SMS is derived from esters of stearic acid and sorbitol. Polysorbates are fatty acid esters of polyoxyethylene sorbitan.9 They are all non-ionic, oil-soluble, water-dispersible compounds that function as emulsifiers in numerous cosmetic products and medicaments.12,14 According to the Contact Allergen Replacement Database (CARD), these substances can all potentially cross-react. Sorbitans in Corticosteroids Topical steroids are classified according to potency and class. Potency, determined by vasoconstrictive assays, is directly related to the type and vehicle of the corticosteroid. Many classification systems are available, but we find it most useful to subdivide according to super, high, mid and low potency. Class is determined by the molecular structure of the steroid. Currently, classes A, B, C, D1 and D2 have been identified. Separating these agents according to class can be helpful in avoiding use of structurally related steroids in sensitized individuals. However, cross reactions can also occur between different corticosteroid classes.5,15 Sorbitans can function as emulsifiers in class A, B, C, D1 and D2 steroids. They can also be found in super-, high-, mid- and low-potency steroids. Thus, patients have ample opportunity for exposure to these chemicals. Avoiding exposure to these chemicals can often be difficult. In a recent review, 28% of corticosteroid preparations were found to contain sorbitan derivatives.7 SSO, in particular, can be found in numerous types of corticosteroid ointments including first-line therapies such as clobetasol and halobetasol.16 Interestingly, creams are often found to contain causative allergens, but sometimes even ointments can contain the culprit. One should always consider contact allergy when a dermatitis does not respond to usual treatments. Table 1, previously published by Coloe and Zirwas in Dermatitis, provides a summary of contact sensitization by common ingredients used in different vehicles.7 Sorbitans in Other Products Sorbitan derivatives can be present in a wide-range of additional, non-steroid products. In a recent report, we found sorbitol and sorbitan derivatives in topical antibiotics, topical antifungals, lotions, lipsticks, topical vitamin A analogues and toothpaste.8 Sorbitol is found in many foods such as apples, cherries, berries, plums, pears, seaweed, and sucrose-free cakes and cookies.17 Sorbitol may also be used as a sweetener in oral medications.18 Hence, topical steroids are not the only pathway for sorbitan exposure and subsequent sensitization in chronically dermatitic skin (see Table 2).8 Sorbitans in Patch Testing SSO is present as an emulsifier in a number of patch test reagents. Most notably among these are fragrance mix (FM) I, ethyleneurea/melamine formaldehyde (Chemotechnique Diagnostics, Vellinge, Sweden), and the eight individual components of FM I (Hermal, Reinbek, Germany). Recognizing its use in these compounds may be important in avoiding false positives in a patient who is also allergic to sorbitan sesquioleate.19 Allergic Contact Dermatitis to Sorbitans Testing for sensitization to sorbitan sesquioleate and other sorbitan products is not routinely carried out in most dermatological centers. It is currently not tested by the NACDG. Previous studies showed relatively low yield for sorbitan testing, but these studies were performed decades ago.20-23 Recent data suggests that sorbitan sensitization is becoming more prevalent. A number of case reports and case series have demonstrated clinically relevant contact sensitivity to sorbitan derivatives. In these cases, sorbitans were found in diaper dermatitis products,12 wound dressings,24 and topical corticosteroids.12,25 Three separate reports also described contact sensitivity to sorbitan sesquioleate and sorbitan monooleate in patients with leg ulcers.9,26,27 We recently reported 13 patients who demonstrated contact allergy to SSO or SMO in a cohort of 112 dermatitis patients presenting to our department for patch test evaluation over a 6-month period.16 The patient presented in this report was previously included in this cohort. All patients were using products that contained sorbitol or sorbitol derivatives. Three-fourths of the patients were using topical corticosteroids that contained these derivatives. Of the patients who were available for follow-up, 90% showed improvement with our recommendations post patch testing, which included avoidance of sorbitan-containing products and sorbitan-containing topical steroids.16 Testing for Sorbitan Sensitivity At Tufts Medical Center, Ohio State University and University of California San Diego, SSO and SMO are routinely tested for at 20% in petrolatum and 5% in petrolatum, respectively (Chemotechnique Diagnostics, Vellinge, Sweden). Value of the Case Our patient underwent patch testing in order to determine whether any contact allergens were responsible for her debilitating dermatitis. She was tested to the Tufts Standard Screening Tray (a modified NACDG standard series), a cosmetic/preservative series, and a fragrance series supplied by Chemotechnique Diagnostics, Vellinge, Sweden. One exception was that the individual fragrance mix I (FM I) components on our fragrance series were supplied by Hermal, Reinbek, Germany. She tested positive to a number of contact allergens including formaldehyde, ethylene urea melamine formaldehyde (a textile formaldehyde resin screening mixture, lanolin, balsam of Peru, and fragrance mix). Of particular note, she demonstrated a 3+ (spreading or bullous) reaction to SSO and a 2+ (papules plus edema or vesiculation) reaction to SMO. When we examined her products to assign clinical relevance, we found that SSO was used as an emulsifier in her clobetasol ointment. Thus, the agent used to treat her dermatitis was likely exacerbating it. A provocative use test was not done with clobetasol as the patient improved significantly after stopping the steroid. Her moisturizer, shampoo and body wash contained the formaldehyde-releasing preservative, DMDM hydantoin. Her shampoo and body wash also contained fragrance. These all could have been contributing significantly to her eruption. Additionally, wash and wear permanent press fabrics, even if 100% cotton, can be finished with formaldehyde. The same is true of blended fabrics such as cotton/polyester or cotton/rayon. Therefore, she could have difficulty with certain fabrics, too. Interestingly, in terms of her textile formaldehyde allergy, the pants of her uniform were previously bothering her. Changing to 100% non-wrinkle-resistant cotton helped to improve her symptoms. She was advised to avoid all sorbitan-containing steroids in the future. We further counseled her to read labels of topical products and avoid sorbitol or sorbitan derivatives in lotions, topical antifungals and topical antibiotics. Her dermatitis improved significantly when she switched to a non-sorbitan containing topical steroid, suggesting that this was a key contributing factor in her dermatitis. She was further advised to use products that were free of lanolin, formaldehyde, formaldehyde releasing preservatives and fragrance. Collectively, these recommendations helped to significantly improve her condition. Contact allergy to sorbitan derivatives appears to be increasingly problematic. Many topical corticosteroids, the primary agents for combating dermatitis, contain these emulsifiers. Applying even weak sensitizers to chronically dermatitic skin can cause sensitization.10,28 Testing for SSO and SMO can be useful in avoiding certain topical corticosteroids and products that may exacerbate contact dermatitis.16 This case illustrates the benefit of testing for sorbitan sensitization in addition to other allergen series based on history and physical exam. By discovering SSO and SMO allergies, in addition to her other contact allergens, we were able to effectively treat her chronic and debilitating dermatitis. Adam Asarch is with Tufts University School of Medicine in Boston, MA. Dr. Scheinman is with the Tufts Medical Center, Department of Dermatology in Boston, MA.
In 1997, the Food and Drug Administration gave indication to the Thin-layer Rapid Use Epicutaneous (T.R.U.E.) Test for use as a valuable, first-line screening tool in the diagnosis of allergic contact dermatitis (ACD). Many dermatologists and allergists use this standard tool in their practices and refer to contact dermatitis referral centers when the T.R.U.E test fails to identify a relevant allergen. Specifically, the T.R.U.E. test screens for 46 distinct allergens in addition to the Balsam of Peru mixture, and is thought to adequately identify an allergen in approximately 24.5% of patients.1 This being said, many relevant allergens are not detected by use of this screening tool alone and, for this reason, “Allergen Focus” has been expanded to cover the notorious allergens of the year. This article focuses on sorbitans. Contact Dermatides The contact dermatides include ACD, irritant contact dermatitis (ICD) and contact urticaria (CU). ICD is the most common form, accounting for approximately 80% of environmental-occupational based dermatoses, and can be further divided into acute toxic and cumulative insult types. Acute toxic reactions result from a one-time exposure to a strong external irritant. Cumulative insult reactions occur after chronic exposure to a weak external irritant such as soaps. CU (wheal and flare reaction) represents an IgE and mast cell-mediated immediate-type hypersensitivity reaction that can lead to anaphylaxis. The foremost example of this would be latex protein hypersensitivity. While this is beyond the scope of this section, we acknowledge this form of hypersensitivity and direct the reader to key resources.2,3 ACD is a T-cell dependent delayed-type (Type IV) hypersensitivity reaction, which has a high impact both in terms of patient morbidity and economics. This type of hypersensitivity reaction is primarily instigated by small lipophilic chemicals (haptens) with a molecular weight less than 500 Daltons. These chemical allergens trigger a complex immunologic cascade in the skin, which leads to the clinical picture of ACD. The condition ranges from acute vesicles to chronic erythematous scaling patches and plaques. It can cause significant debilitation for patients. Patch testing remains the gold standard for differentiating irritant and allergic forms of contact dermatitis. Furthermore, by allowing practitioners to recognize inciting agents, patch testing is a powerful tool for treating the root cause of allergic contact dermatitis.4 Case Illustration A 56-year-old Caucasian female presented to Tufts Medical Center Department of Dermatology with severe, pruritic pretibial dermatitis for 4 years. Minimal to moderate stasis dermatitis was present. She also had facial dermatitis and intermittent dermatitis on her upper and lower extremities. Of note, her condition was worsening despite treatment with clobetasol ointment. Her past medical history was notable for mild asthma. An Overview of Sorbitans A recent column in Skin & Aging focused on the potential for corticosteroids to induce contact sensitization.5 This paradoxical phenomenon has become a well recognized side-effect of these dermatological agents.5,6 Evidence has shown that additional ingredients in corticosteroid preparations may also induce ACD. Various studies have found that preservatives and emulsifiers within topical steroid formulations can also be sensitizers in susceptible patients.7 Exposing inflamed skin to ingredients in topical steroids has likely accelerated sensitization.8-10 In this column we will highlight the emerging potential for sorbitans, one such family of emulsifiers, to induce ACD. Sorbitans are a group of compounds derived from sorbitol, a sugar alcohol.8 Joseph Boussin, a French chemist, first isolated sorbitol from berries in 1872.11 Notable sorbitan derivatives include sorbitan sesquioleate (SSO), sorbitan monooleate (SMO), sorbitan monostearate (SMS) and polysorbate.8 SSO is fatty acid ester formed from mono- and diesters of oleic acid and hexitol anhydrides of sorbitol.12 SMO is also a fatty acid ester, but formed from monoesters of oleic acid and hexitol anhydrides of sorbitol.13 SMS is derived from esters of stearic acid and sorbitol. Polysorbates are fatty acid esters of polyoxyethylene sorbitan.9 They are all non-ionic, oil-soluble, water-dispersible compounds that function as emulsifiers in numerous cosmetic products and medicaments.12,14 According to the Contact Allergen Replacement Database (CARD), these substances can all potentially cross-react. Sorbitans in Corticosteroids Topical steroids are classified according to potency and class. Potency, determined by vasoconstrictive assays, is directly related to the type and vehicle of the corticosteroid. Many classification systems are available, but we find it most useful to subdivide according to super, high, mid and low potency. Class is determined by the molecular structure of the steroid. Currently, classes A, B, C, D1 and D2 have been identified. Separating these agents according to class can be helpful in avoiding use of structurally related steroids in sensitized individuals. However, cross reactions can also occur between different corticosteroid classes.5,15 Sorbitans can function as emulsifiers in class A, B, C, D1 and D2 steroids. They can also be found in super-, high-, mid- and low-potency steroids. Thus, patients have ample opportunity for exposure to these chemicals. Avoiding exposure to these chemicals can often be difficult. In a recent review, 28% of corticosteroid preparations were found to contain sorbitan derivatives.7 SSO, in particular, can be found in numerous types of corticosteroid ointments including first-line therapies such as clobetasol and halobetasol.16 Interestingly, creams are often found to contain causative allergens, but sometimes even ointments can contain the culprit. One should always consider contact allergy when a dermatitis does not respond to usual treatments. Table 1, previously published by Coloe and Zirwas in Dermatitis, provides a summary of contact sensitization by common ingredients used in different vehicles.7 Sorbitans in Other Products Sorbitan derivatives can be present in a wide-range of additional, non-steroid products. In a recent report, we found sorbitol and sorbitan derivatives in topical antibiotics, topical antifungals, lotions, lipsticks, topical vitamin A analogues and toothpaste.8 Sorbitol is found in many foods such as apples, cherries, berries, plums, pears, seaweed, and sucrose-free cakes and cookies.17 Sorbitol may also be used as a sweetener in oral medications.18 Hence, topical steroids are not the only pathway for sorbitan exposure and subsequent sensitization in chronically dermatitic skin (see Table 2).8 Sorbitans in Patch Testing SSO is present as an emulsifier in a number of patch test reagents. Most notably among these are fragrance mix (FM) I, ethyleneurea/melamine formaldehyde (Chemotechnique Diagnostics, Vellinge, Sweden), and the eight individual components of FM I (Hermal, Reinbek, Germany). Recognizing its use in these compounds may be important in avoiding false positives in a patient who is also allergic to sorbitan sesquioleate.19 Allergic Contact Dermatitis to Sorbitans Testing for sensitization to sorbitan sesquioleate and other sorbitan products is not routinely carried out in most dermatological centers. It is currently not tested by the NACDG. Previous studies showed relatively low yield for sorbitan testing, but these studies were performed decades ago.20-23 Recent data suggests that sorbitan sensitization is becoming more prevalent. A number of case reports and case series have demonstrated clinically relevant contact sensitivity to sorbitan derivatives. In these cases, sorbitans were found in diaper dermatitis products,12 wound dressings,24 and topical corticosteroids.12,25 Three separate reports also described contact sensitivity to sorbitan sesquioleate and sorbitan monooleate in patients with leg ulcers.9,26,27 We recently reported 13 patients who demonstrated contact allergy to SSO or SMO in a cohort of 112 dermatitis patients presenting to our department for patch test evaluation over a 6-month period.16 The patient presented in this report was previously included in this cohort. All patients were using products that contained sorbitol or sorbitol derivatives. Three-fourths of the patients were using topical corticosteroids that contained these derivatives. Of the patients who were available for follow-up, 90% showed improvement with our recommendations post patch testing, which included avoidance of sorbitan-containing products and sorbitan-containing topical steroids.16 Testing for Sorbitan Sensitivity At Tufts Medical Center, Ohio State University and University of California San Diego, SSO and SMO are routinely tested for at 20% in petrolatum and 5% in petrolatum, respectively (Chemotechnique Diagnostics, Vellinge, Sweden). Value of the Case Our patient underwent patch testing in order to determine whether any contact allergens were responsible for her debilitating dermatitis. She was tested to the Tufts Standard Screening Tray (a modified NACDG standard series), a cosmetic/preservative series, and a fragrance series supplied by Chemotechnique Diagnostics, Vellinge, Sweden. One exception was that the individual fragrance mix I (FM I) components on our fragrance series were supplied by Hermal, Reinbek, Germany. She tested positive to a number of contact allergens including formaldehyde, ethylene urea melamine formaldehyde (a textile formaldehyde resin screening mixture, lanolin, balsam of Peru, and fragrance mix). Of particular note, she demonstrated a 3+ (spreading or bullous) reaction to SSO and a 2+ (papules plus edema or vesiculation) reaction to SMO. When we examined her products to assign clinical relevance, we found that SSO was used as an emulsifier in her clobetasol ointment. Thus, the agent used to treat her dermatitis was likely exacerbating it. A provocative use test was not done with clobetasol as the patient improved significantly after stopping the steroid. Her moisturizer, shampoo and body wash contained the formaldehyde-releasing preservative, DMDM hydantoin. Her shampoo and body wash also contained fragrance. These all could have been contributing significantly to her eruption. Additionally, wash and wear permanent press fabrics, even if 100% cotton, can be finished with formaldehyde. The same is true of blended fabrics such as cotton/polyester or cotton/rayon. Therefore, she could have difficulty with certain fabrics, too. Interestingly, in terms of her textile formaldehyde allergy, the pants of her uniform were previously bothering her. Changing to 100% non-wrinkle-resistant cotton helped to improve her symptoms. She was advised to avoid all sorbitan-containing steroids in the future. We further counseled her to read labels of topical products and avoid sorbitol or sorbitan derivatives in lotions, topical antifungals and topical antibiotics. Her dermatitis improved significantly when she switched to a non-sorbitan containing topical steroid, suggesting that this was a key contributing factor in her dermatitis. She was further advised to use products that were free of lanolin, formaldehyde, formaldehyde releasing preservatives and fragrance. Collectively, these recommendations helped to significantly improve her condition. Contact allergy to sorbitan derivatives appears to be increasingly problematic. Many topical corticosteroids, the primary agents for combating dermatitis, contain these emulsifiers. Applying even weak sensitizers to chronically dermatitic skin can cause sensitization.10,28 Testing for SSO and SMO can be useful in avoiding certain topical corticosteroids and products that may exacerbate contact dermatitis.16 This case illustrates the benefit of testing for sorbitan sensitization in addition to other allergen series based on history and physical exam. By discovering SSO and SMO allergies, in addition to her other contact allergens, we were able to effectively treat her chronic and debilitating dermatitis. Adam Asarch is with Tufts University School of Medicine in Boston, MA. Dr. Scheinman is with the Tufts Medical Center, Department of Dermatology in Boston, MA.
