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.