A report describes a case of an 80-year-old woman who was assessed for cutaneous edema at the site of her intravenous (IV) access during an infusion of normal saline. She showed no associated symptoms and was otherwise well. The patient experienced the same reaction in the contralateral arm with dextrose 5%. She received IV diphenhydramine, and the reaction subsided.

The patient stayed on a research protocol including cyclophosphamide, pembrolizumab, and antisurvivin tumor vaccine to treat refractory diffuse large B-cell lymphoma. She described a history of chronic hepatitis B on tenofovir and hypothyroidism on levothyroxine. She also contained a more than 20-year history of cold intolerance, reporting local hives with exposure to subzero degree centigrade temperatures, throat tightness, and epigastric pain after consuming frozen foods. She managed her symptoms by cold avoidance. 

The patient described an increase in symptom severity after starting pembrolizumab. She was suspected of having Cold-induced urticaria (CIndU) based on history and hypothesized the same as the cause of her cutaneous reaction to room temperature saline.

She underwent skin testing to support the diagnosis of CIndU. Her Latex and chlorhexidine skin prick test (SPT) results came out negative, ruling out the possibility of contact urticaria. On the contrary, the ice cube test and SPT with room temperature saline results came positive (60 mm and 40 mm wheals, respectively), with histamine control of 4 mm; while the SPT result to saline warmed to 30°C came negative. 

The patient received pretreatment with 20 mg of cetirizine, and her repeat SPT result to room temperature saline came negative. She then tolerated the challenge of an IV infusion of 250 mL of 30°C saline.

Given her history and diagnostic testing, she received a diagnosis of CIndU triggered by room temperature IV fluid. The patient received daily oral antihistamine therapy (20 mg of bilastine). She received successful Subsequent IV infusions administered after heating the IV lines at the point of insertion to 30°C. She also received additional chemotherapy doses in this manner.

Polito V, Genest G. Cold-Induced Urticaria Exacerbated During Treatment With Pembrolizumab. The journal of Allergy and Clinical Immunology. 2023;11(1):322-323. DOI:https://doi.org/10.1016/j.jaip.2022.10.049