Background/Objectives: Eyelid dermatitis is an inflammatory disease affecting the palpebral skin characterized by itching, edema, and scaling of the periorbital area. This entity can be a manifestation of various underlying dermatological diseases, but allergic contact dermatitis (ACD) is the predominant etiology of eyelid dermatitis among patients, being diagnosed in 43.4% of cases. The thin and highly permeable nature of eyelid skin increases its susceptibility to allergens, making it a distinct clinical entity. This study aimed to identify the primary haptens associated with eyelid ACD and compare these findings with the allergens implicated in non-eyelid ACD over a 25-year period in a large cohort of patients. Methods: We conducted a monocentric, retrospective study on a dataset of 7955 patients patch-tested for ACD at the Outpatient Allergy Dermatology Clinic of the Azienda Ospedaliera Universitaria Senese (AOUS) from 1997 to 2021. Eyelid ACD cases were identified based on clinical features and positive patch test results. Data on demographics, occupation, and personal history of atopy were collected. The statistical analyses assessed the associations between allergens and eyelid ACD. The trends in the sensitization rates for the most prevalent allergens were also evaluated. Results: Eyelid ACD was identified in 4.6% of the study population, predominantly affecting women (88.6%). Patients with eyelid ACD were more likely to exhibit single-hapten positivity (54.6%) and an atopic phenotype (52.3%) compared to non-eyelid ACD cases. Nickel sulfate (54%), cobalt chloride (13.4%), and thimerosal (12.6%) were the most common allergens associated with eyelid ACD. While thimerosal sensitization decreased significantly following its removal from topical products, nickel sensitization increased, likely due to exposure from electronic devices and hand-eye contact. Conclusions: The haptens identified in eyelid ACD largely overlap with those found in other body regions, including metals, fragrances, and preservatives. However, the unique characteristics of eyelid skin and hand-eye contact patterns play a significant role in sensitization. This study highlights the need for further investigation into the pathophysiology of eyelid allergic contact dermatitis, with particular emphasis on elucidating the mechanisms of hapten sensitization. Such insights could contribute to the development of effective strategies aimed at reducing allergen exposure.
