D2.283 - Beyond the skin. A rare case of contact angioedema due to Methylisothiazolinone

Methylisothiazolinone (MI), a derivative of isothiazolinones is a wide cause of occupational contact dermatitis and it's still present in many non-cosmetic products, such as paints, cleaning agents, and others industrial products. It was widely used as a preservative in cosmetics, until the European Union ban in leave-on products since April 2013 with a maximum concentration of 0.0015% (15ppm) in rinse-off cosmetics that has led to a sharp decline in sensitization, previously estimated at around 9%. Currently only one case of angioedema-like contact dermatitis and a case of pemphigoid-like reaction after the use of mouthwash containing MI were already described. 

A 50-year-old woman experienced tingling of the upper lip and tongue, after 8 hours following the use of a mouthwash (CURASEPT® biosmalto), which lasted for about 2 days and resolved spontaneously with the interruption of the mouthwash. Approximately one week later the patient experimented a more severe episode (lip angioedema, burning oral ulcers) after using the same mouthwash 8 hours before. Treatment with antihistamines and topical corticosteroids led to resolution of the edema within 2 days, while the oral symptoms (burning and tingling) subsided in 10 days. The patient denied any history of urticaria or adverse reactions to foods.  Physical examination revealed flat red dermographism. Open patch test with CURASEPT® was performed on the right antecubital fossae with a negative 30-minute lecture.  Therefore, patch tests were performed using the SIDAPA baseline series, dental screening series and the mouthwash itself on the patient back.  

At 48 hours, the results showed positive reaction to Kathon CG (+), mercaptobenzothiazole (++), p-phenylenediamine (++), thiuram mix (+++), methylisothiazolinone (+++).  

The CURASEPT patch showed a positive reaction (++) after 96h.  

These findings show a rare case of cell-mediated allergy (delayed angioedema) due to MI. Given the patient's response and test results, strict avoidance of methylisothiazolinone was recommended to prevent recurrence of symptoms. Notably, the marked cell-mediated sensitization to thiuram mix and mercaptobenzothiazole was not considered clinically relevant. 

Since no safety threshold exists for leave-on products, especially for the ones formulated with oral mucosa contact, it would be desirable for international authorities making a statement on this matter to minimize the risk of allergy reaction