Methotrexate ultraviolet reactivation reaction in the setting of voriconazole‐induced phototoxicity

Holahan, Heather M.; Ferguson, Nkanyezi N.; Farah, Ronda S.; Liu, Vincent

doi:10.1111/ijd.12913

Cited by 2 publications

(7 citation statements)

References 4 publications

(10 reference statements)

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“…In contrast to the previously published patients, the phototoxic lesions became more severe upon readministration of HD‐MTX, and the total healing time was markedly longer (Table 1). 8,9 Furthermore, this patient showed toxic MTX levels, whereas the previous cases did not. Because prolonged high MTX levels are known to increase systemic toxicity, it is likely that this contributed to the severity and duration of the phototoxicity 7 .…”

Section: Clinical Features Patient 12 Published Cases89mentioning

confidence: 56%

“…Voriconazole levels were also elevated (6 mg/L; range, 2.0‐5.5 mg/L). Skin biopsy indicated phototoxicity, and MTX‐voriconazole involvement was suspected based on previous reports 8,9 . Voriconazole was switched to daily i.v.…”

Section: Clinical Features Patient 12 Published Cases89mentioning

confidence: 99%

“…Although concomitant treatment with MTX and voriconazole is not uncommon in oncology patients, the enhanced risk of phototoxic reactions is not that well known. So far, only two publications on MTX/voriconazole‐associated phototoxicity exist: a case series and a single case report 8,9 . In the case series, 11 of 23 (48%) patients on concomitant MTX and voriconazole developed phototoxic lesions, suggesting this phenomenon may be underreported 8 .…”

Section: Clinical Features Patient 12 Published Cases89mentioning

confidence: 99%

“…Although only limited data are available, such chemotherapy reductions did not seem to be required in the previously published cases (Table 1). 8,9 …”

Section: Clinical Features Patient 12 Published Cases89mentioning

confidence: 99%

“…Skin biopsy indicated phototoxicity, and MTX-voriconazole involvement was suspected based on previous reports. 8,9 Voriconazole was switched to daily i.v. caspofungin, and the last HD-MTX cycle was cancelled.…”

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confidence: 99%

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Severe phototoxicity associated with concomitant use of methotrexate and voriconazole, an overlooked drug‐drug interaction

Bogaert

Verlinden

Vandecruys

et al. 2020

Pediatric Blood & Cancer

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Voriconazole-induced photosensitivity is described in 5% to 46% of pediatric patients depending on the setting and duration of use. 1,2 In contrast, methotrexate (MTX) has been rarely associated with UV reactivation, an inflammatory skin reaction in which the recurrence of previous sunburn is triggered in the absence of UV light exposure. [3][4][5] Here, we describe a patient under antifungal prophylaxis with voriconazole, who developed severe phototoxic lip and skin lesions after administration of high-dose (HD) MTX. This drugdrug interaction is not widely known and was initially misdiagnosed.Delayed recognition resulted in more extensive lesions requiring substantial reduction of his chemotherapy protocol.Written informed consent was obtained from the patient and his parents.The patient is a 17-year-old Caucasian male with T-cell lymphoblastic lymphoma treated according to the EORTC-CLG 58081 protocol. The first interval phase of this protocol consists of daily oral 6-mercaptopurine and four cycles of intravenous (i.v.) HD-MTX (5000 mg/m 2 ) combined with intrathecal (i.t.) triple therapy (12 mg MTX, 30 mg cytarabine, 3 mg methylprednisolon). The patient also received secondary prophylaxis with voriconazole following pulmonary aspergillosis, low-molecular-weight heparins for a superior sagittal sinus thrombosis, and ranitidine for stomach pains. During the interval phase, trimethoprim/sulfamethoxazole prophylaxis is routinely stopped in our center, because of the potential increase of MTX toxicity. 6 Seven days after the second HD-MTX cycle, he developed erythema, swelling and yellow-black crusting of the lips. These lesions were clinically diagnosed as herpes simplex infection (PCR was negative); therefore, chemotherapy was interrupted and acyclovir started.Three weeks later, he was sunburned and the lip lesions recurred. As the lips gradually healed, chemotherapy was resumed. Two days after the third HD-MTX administration, he developed a severe skin eruption distributed at sun-exposed areas (Supporting Information Figure S1).There was severe erythema of the face and swelling with yellow-black crusting of the lips. Sharply demarcated erythema was seen on forearms, dorsum of the hands, legs, and neckline. A few nummular blisters appeared on arms and legs. There were no ocular, oral, or genital lesions. Furthermore, the MTX level at 48 hours was found to be Abbreviations: HD, high dose; i.t., intrathecal; i.v., intravenous; MTX, methotrexate; UV, ultraviolet.

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Section: Clinical Features Patient 12 Published Cases89mentioning

confidence: 56%

Section: Clinical Features Patient 12 Published Cases89mentioning

confidence: 99%

Section: Clinical Features Patient 12 Published Cases89mentioning

confidence: 99%

“…Although only limited data are available, such chemotherapy reductions did not seem to be required in the previously published cases (Table 1). 8,9 …”

Section: Clinical Features Patient 12 Published Cases89mentioning

confidence: 99%

mentioning

confidence: 99%

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Severe phototoxicity associated with concomitant use of methotrexate and voriconazole, an overlooked drug‐drug interaction

Bogaert

Verlinden

Vandecruys

et al. 2020

Pediatric Blood & Cancer

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Methotrexate/voriconazole

2015

Reactions Weekly

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An 18-year-old man developed ultraviolet reactivation and phototoxicity [durations of treatments to reactions onsets and outcomes not stated] during treatment with methotrexate and voriconazole [dosages and routes not stated] respectively.The man was admitted for a haematopoietic progenitor cell transplant. He had been receiving voriconazole as an antifungal prophylaxis for pulmonary histoplasmosis. His graft-versus-host disease prophylactic regimen included methotrexate which was administered on day 1, 3, 6 and 11. After 2 days of transplantation, he noticed significant erythema and pain over the arms, dorsal hands, neck, and face. His physical examination showed symmetric, confluent erythema in sun-exposed areas, sharply demarcated at the mid biceps and neck. Five weeks earlier, he had suffered sunburn. A diagnosis of ultraviolet reactivation most likely secondary to methotrexate in the setting of voriconazole-induced phototoxicity was made.Author comment: "Methotrexate is commonly cited as a causative medication and is the most likely precipitating drug in our patient given the timing of symptom onset and subsequent improvement after completion of treatment"."Voriconazole is a broad-spectrum triazole antifungal agent known to induce phototoxicity characterized by erythema, pain, and oedema, within 30 min-2 h of sunlight exposure and likely played a role in our patient's preadmission sunburn".Holahan HM, et al. Methotrexate ultraviolet reactivation reaction in the setting of voriconazole-induced phototoxicity.

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Methotrexate ultraviolet reactivation reaction in the setting of voriconazole‐induced phototoxicity

Cited by 2 publications

References 4 publications

Severe phototoxicity associated with concomitant use of methotrexate and voriconazole, an overlooked drug‐drug interaction

Severe phototoxicity associated with concomitant use of methotrexate and voriconazole, an overlooked drug‐drug interaction

Methotrexate/voriconazole

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