Report Is there a role of food additives in recurrent aphthous stomatitis? a prospective study with patch testing Duygu G € ulseren 1,2 , MD, Asli Hapa 1 , MD, Sibel Ersoy-Evans 1 , MD, Gonca Elc ß in 1 , MD, and Ays ß en Karaduman 1 , MD 1 Hacettepe University, School of Medicine, Department of Dermatology, Ankara, Turkey, and 2 University of Virginia Medical Center, Division of Dermatopathology, Charlottesville, VA, USA Correspondence Duygu G€ ulseren, MD Department of Dermatology School of Medicine Hacettepe University Ankara Turkey E-mail: duygu_gulsrn@hotmail.com Funding: None. Conflicts of interest: None. doi: 10.1111/ijd.13515 Abstract Background Recurrent aphthous stomatitis (RAS) is a common disease of the oral mucosa with an unknown etiology. This study aimed to determine if food additives play a role in the etiology of RAS as well as to determine if patch testing can be used to detect which allergens cause RAS. Methods This prospective study included 24 patients with RAS and 22 healthy controls. All the participants underwent patch testing for 23 food additives. Results In total, 21 (87.5%) RAS patients and 3 (13.6%) controls had positive patch test reactions to ≥1 allergens; the difference in the patch test positivity rate between groups was significant (P < 0.05). The most common allergen that elicited positive patch test results in the patient group was cochineal red (n = 15 [62.5%]), followed by azorubine (n = 11 [45.8%]) and amaranth (n = 6 [25%]). Conclusions The present findings show that food additives might play a role in the etiology of RAS and that patch testing could be a method for determining the etiology of RAS. Introduction Recurrent aphthous stomatitis (RAS) is characterized by ≥1 more painful, inflammatory ulcerative lesion of the nonkeratinized oral mucosa that can result in difficulty in eating, speaking, and swal- lowing. RAS affects approximately 20% of the general population at any time. 1 In general, RAS ulcers vary in size from pinhead to several centimeters and are covered by a pseudomembrane sur- rounded by an erythematous halo. A slightly higher predominance is observed in females and in individuals of higher socioeconomic status. 2 Although the etiology of RAS is not precisely known, ato- pic diathesis was reported to be associated with RAS. 3–7 The oral mucosa is exposed to a wide range of antigenic agents in foods, such as additives used to preserve flavor, or enhance the taste and appearance of food. Such food additives are suggested to likely function as allergens in various oral mucosal diseases, including orofacial granulomatosis, 8–10 oral lichen planus, 8–11 angioedema, 8 erythema multiforme, 8 burning mouth syndrome, 12,13 lichenoid tissue reaction, 13 cheilitis, 13,14 stomatitis, 13 gingivitis, 13 and perioral dermatitis. 13 Moreover, oral patch testing for allergens was reported to be useful for precisely detecting food additives that cause disease of the oral mucosa. 10,12,15 Although the role of food additives in the etiology of RAS has been studied, their etiological role remains unclear. 8,13 The pre- sent study aimed to determine if food additives play a role in the etiology of RAS, as well as to determine if patch testing can be used to detect which allergens cause RAS. Materials and methods Participants The study was conducted at Hacettepe University, School of Medicine, Dermatology Out-Patient Clinic, Ankara, Turkey, between September 2009 and March 2011. Data were collected from 24 RAS patients and 22 controls. Inclusion criteria for RAS patients were age ≥18 years, ≥1 active aphthous ulcers at the time RAS was diagnosed, and no associated systemic diseases that can cause oral ulcers, such as Behc ßet’s disease, coeliac disease, and inflammatory bowel disease. The control group included patients who underwent European standard patch testing because of allergic contact dermatitis on their hands. The study protocol was approved by the Hacettepe University School of Medicine Ethics Committee, and all the participants provided written informed consent. ª 2016 The International Society of Dermatology International Journal of Dermatology 2016 1