ORIGINAL ARTICLE SKIN AND EYE DISEASES The role of Staphylococcal enterotoxin in atopic keratoconjunctivitis and corneal ulceration H. Fujishima 1,2 , N. Okada 2 , M. Dogru 2 , F. Baba 3 , M. Tomita 3 , J. Abe 4 , K. Matsumoto 4 & H. Saito 4 1 Department of Ophthalmology, Tsurumi University School of Dental Medicine, Yokohama, Japan; 2 Department of Ophthalmology, Keio University School of Medicine, Tokyo, Japan; 3 Institute for Advanced Biosciences, Keio University, Tsuruoka, Yamagata, Japan; 4 Department of Allergy & Immunology, National Research Institute for Child Health & Development, Tokyo, Japan To cite this article: Fujishima H, Okada N, Dogru M, Baba F, Tomita M, Abe J, Matsumoto K, Saito H. The role of Staphylococcal enterotoxin in atopic keratoconjunctivitis and corneal ulceration Allergy 2012; 67: 799–803. Keywords corneal; enterotoxin; keratoconjunctivitis; staphylococcus; ulcer. Correspondence Hiroshi Fujishima, Department of Ophthalmology, Tsurumi University School of Dental Medicine, 2-1-3 Tsurumi, Tsurumi-ku, Yokohama 230-8501, Japan. Tel.: +81 4 5581 1001 Fax: +81 4 5573 9599 E-mail: fujishima117@gmail.com Accepted for publication 27 February 2012 DOI:10.1111/j.1398-9995.2012.02818.x Edited by: Hans-Uwe Simon Abstract Background: Patients with atopic eczema frequently experience colonization with Staphylococcus aureus that is directly correlated with the eczema severity. We hypothesized that S. aureus-secreted enterotoxins (SE) are involved in the patho- physiology of atopic keratoconjunctivitis (AKC). Methods: A total of 45 subjects (18 with AKC, nine vernal keratoconjunctivitis (VKC), eight seasonal allergic conjunctivitis (SAC), and ten healthy volunteers) were enrolled. Slit lamp examinations, including fluorescein staining, were per- formed. Scraped samples were collected from the upper tarsal conjunctiva, lower conjunctival sacs, and the skin around the eyelid margins. Superantigen (SAg) genes were detected using polymerase chain reaction (PCR). Results: Among 45 cases, S. aureus was detected significantly more in AKC patients than VKC patients (P = 0.026), SAC patients (P = 0.0003), and healthy volunteers (P = 0.0001). SAg genes were detected in 11 patients. SEB (2/11), SEG (8/11), and SEI (8/11) were detected, but no other SE. There was a significant dif- ference in SE detection between AKC and SAC patients (P = 0.03). In severe types of ocular allergic disease such as AKC and VKC (N = 27), SE was detected in six of ten patients with corneal ulcers and two of 17 patients without corneal ulcers. SE was detected in significantly more patients with corneal ulcers (P = 0.025). Conclusions: In patients with AKC, S. aureus and SE were detected more fre- quently compared with other patients and healthy volunteers, especially in associ- ation with corneal ulceration suggesting a role of SE. So far, it is unknown whether SE leads to tissue damage of the cornea by initiating an immune response or has direct toxic effects. Atopic dermatitis (AD) is a chronic inflammatory skin dis- ease characterized by hypersensitivity reactions against com- mon environmental allergens. Patients with AD have a high incidence of colonization with Staphylococcus aureus (1–3). Atopic keratoconjunctivitis (AKC) can involve the cornea because of inflammatory substances released from the giant papillae, leading to corneal shield ulceration or corneal pla- que in some cases (4–6). In such cases, atopic eczema (AE) is frequently observed on the facial skin around the eyes. AE is a multifocal skin disease caused by a variety of factors, including genetic conditions, altered skin structure, immuno- logic disorders, and environmental factors. Atopic dermatitis is characterized by the development of specific and unspecific Th2 responses after exposure to com- mon environmental antigens (4–6). The incidence of S. aureus colonization on the skin of patients with AE is approximately 90%. Evidence from the literature implicates epidermal staphylococcal infection as a pathogenic factor in AD. Semic-Jusufagic et al. (7) reported that SE is a potential modulator of childhood wheezing and eczema. Mandron et al. (8) reported age-related differences in sensitivity of peripheral blood monocytes to lipopolysaccharide (LPS) and S. aureus enterotoxin B in AD. Even though risk factors associated with AD and atopic ocular surface disease appear Allergy 67 (2012) 799–803 © 2012 John Wiley & Sons A/S 799 Allergy