Life-threatening complications following multidose methotrexate for medical management of ectopic pregnancy

Abstract

SummaryA 25-year-old primigravida was diagnosed to be suffering from unruptured ectopic pregnancy. The serum β-human chorionic gonadotropin levels were 2851 mIU/l and the ectopic gestational sac was 2.7×2.7 cm without any fetal pole. It was decided to manage her by expectant therapy. But she received medical therapy with multidose methotrexate because of misinterpretation of expectant therapy as medical therapy. She suffered from methotrexate toxicity, which manifested as high-grade fever, vomiting, melena, oral ulcerations, pneumonitis, subconjunctival haemorrhages and skin pigmentation. She developed severe third space fluid collection and shock, which was mistaken for rupture ectopic gestation. Her haematological picture showed severe neutropaenia and thrombocytopaenia which confirmed the clinical picture to be due to methotrexate toxicity. She also developed septicaemia and candidal infection secondary to immunosuppression. She was managed in intensive care unit with ventilatory support, high-dose leucovorin and injection filgastrim. She responded well to the therapy with dramatic recovery in 4 days. BACKGROUND

Nonallergic cutaneous pigmentation is commonly observed after methotrexate administration

“…MTX is a folic acid antagonist that is used as the firstline therapy against ALL/lymphoma. 7 Although only a few reports have examined cutaneous reactions associated with MTX administration, 8 according to our data, 8 of 24 ALL/lymphoma patients administered MTX developed erythema following pigmentation, suggesting that cutaneous reactions are not rare. Clinicians might be unaware of such pigmentation because of the mildness of change (Figure 1(a) to (g)).…”

“…7 Various side effects of MTX administration have been reported, including stomatitis and leukoencephalopathy, but few cutaneous-related side effects have been described. 8,9 In this paper, we report eight cases of pediatric acute lymphoblastic leukemia (ALL)/lymphoma in which cutaneous pigmentation developed after MTX administration, among 24 cases of lymphoblastic neoplasm treated in the last five years in our institutes ( Table 1).…”

Severe bone marrow suppression following single-dose methotrexate treatment for ectopic pregnancy

“…The underlying mechanism of toxicity may be methylenetetrahydrofolate reductase (MTHFR) 2 mutations resulting in hypersensitivity of MTX, gene polymorphism in the folate metabolic pathway, decreased renal excretion due to any reason such as dehydration, ingestion of cola containing drinks and coincidental use of some drugs [9][10][11].…”

The management of heterotopic pregnancy with transvaginal ultrasound-guided local injection of absolute ethanol

“…[8] Furthermore, life-threatening neutropenia and febrile morbidity had been reported following MTX treatment to EP. [9]…”