Methotrexate hypersensitivity- maintenance of desensitized state with daily low oral dose after rapid IV desensitization. 
Saturday, March 3, 2018
South Hall A2 (Convention Center)
Johnson T. Wong, MD FAAAAI

Methotrexate has been useful in treating central nervous system (CNS) lymphoma and other malignancies in high doses (10-20gm) with Leukovorin rescue and in treating autoimmune diseases in relatively low dose (5-20mg). Hypersensitivity reactions may complicate their treatment and limit their usage.


We developed a management plan using a rapid continuous IV desensitization protocol followed by maintenance of the desensitized state using a low daily oral dose.


We were consulted on 3 cases of patients who developed angioedema and urticaria with high IV doses of Methotrexate for treatment of CNS lymphoma. All 3 patients were successfully managed by using a continuous IV desensitization protocol using 2-3 bags (8-12 steps) achieving final infusion rates of 2.5-5.0 gm/hr. All 3 patients were discharged on daily oral Methotrexate 2.5mg and Fexofenadine 180mg per day to maintain their desensitized state. Patients 1 and 3 tolerated restart of high dose infusion rate of Methotrexate (4-5 gm/hr) subsequently on multiple infusions without undergoing further desensitization. Patient 2 tolerated the restart rate of 2.5 gm/hr for 2 hr without problem. She developed moderate peri-orbital edema 1 hr after the infusion rate was increased to 5.0 gm/hr. Plasma histamine was elevated. She tolerated reinitiation at 1.0 gm/hr advancing to 2.5 gm/hr, a protocol that she tolerated for subsequent infusions.


High dose Methotrexate treatment may be complicated by hypersensitivity reactions. This can be managed by using a protocol of rapid continuous IV desensitization with the desensitized state maintained by a low daily oral dose between subsequent infusions.