Search

Allergic contact dermatitis (ACD) is a delayed-type hypersensitivity (DTH) reaction induced by repeated contact with sensitizers. The ability of a chemical to act as a sensitizer has most frequently been tested in animals. As the use of animals for these purposes is gradually and globally being phased out, there is a need for reliable in vitro surrogate assays. Currently proposed in vitro assays are designed to test four key events of the adverse outcome pathway (AOP) involving covalent modification of self-proteins by sensitizers (haptenation) and presentation of new antigens (hapten/carrier complexes) to the immune system. There appears to be imperfect alignment of in vitro assays with clinical and/or animal data, suggesting possibly additional mechanisms of ACD development. Indeed, studies on allergies to small drugs, small chemical-induced HLA-peptide exchange for vaccination purposes and cosmetic ingredient-induced exposure of autoantigens suggest a possibility of DTH response promotion by hapten/carrier-independent mechanisms. Therefore, there is a need for additional appropriate in vitro assays, in order to achieve maximal concordance between clinical and/or animal data and in vitro assays. In this paper, we will review evidence supporting the idea of diverse mechanisms of ACD development. We will also discuss the impact of these multiple mechanisms, on the AOP and on the in vitro assays that should be used for allergen detection. We will propose alloreactivity-like reactions, aided by computer modeling and biochemical tests of compound-HLA binding, as additional tools for better prediction of DTH reactions, resulting from exposure to ingredients in cosmetic products. The combination of the proposed tests, along with the existing assays, should further enhance animal-free assessment of sensitizing potential of individual chemicals. [ABSTRACT FROM AUTHOR]

Background: Toxicity is rarely considered in the differential diagnosis of conjunctivitis, but we present here a new form of toxic conjunctivitis with unusual clinical features. Between 2010 and 2013, a new clinical presentation of chronic conjunctivitis unresponsive to normal treatment was noted within a Primary Care Ophthalmology Service.Methods: Retrospective review of case records and histopathology results.Results: A total of 55 adult patients, all females, presented with epiphora and stickiness. They did not complain of itch and had had symptoms for an average of 9 months. Clinical examination showed bilateral moderate to severe upper and lower tarsal conjunctival papillary reaction, without corneal or eyelid changes and mild bulbar conjunctival hyperaemia in a third of cases. Biopsies were taken in 15 cases to exclude an atypical infection or lymphoma. Histologically, there was a variable superficial stromal lymphocytic infiltrate, involving the epithelium in more severe cases. The majority of the cells were CD3 positive T-lymphocytes and follicle formation was not noted. The clinical history in all cases included prolonged use of eye make- up and other facial cosmetic products. Clinical symptoms of epiphora settled with topical steroid drops, but the clinical signs of chronic tarsal inflammation persisted until withdrawal of the facial wipes thought to contain the inciting agent, though the exact nature of this remains unclear.Conclusion: The presentation, appearances, histological features are consistent with a contact allergen-driven chronic conjunctivitis. Steroid treatment provided good relief of symptoms and patients were advised to avoid potential contact allergens. Management remains difficult. Further research into contact allergies of mucous membranes and identification of its allergens is required. [ABSTRACT FROM AUTHOR]