Lung transplant recipients receiving voriconazole and skin squamous cell carcinoma risk in Australia

Neoh, Chin Fen; Snell, Gregory I; Levvey, Bronwyn; Kotsimbos, Tom; Morrissey, Orla; Slavin, Monica A; Stewart, Kay; Kong, David Chee Ming

doi:10.5694/mja13.00214

Cited by 15 publications

(8 citation statements)

References 11 publications

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“…Thus, it has been speculated that prolonged voriconazole therapy results in chronic phototoxicity, which then contributes to the development of skin SCC in transplant patients . However, erythema of photo‐exposed surfaces was observed in only one patient in our cohort, which preceded the first skin SCC diagnosis by 2 months . Given the retrospective nature of the present study, it is possible that the incidence of voriconazole‐induced photosensitivity prior to SCC was not reported in the medical history or by the patients during routine review.…”

Section: Discussionmentioning

confidence: 79%

“…4 However, erythema of photo-exposed surfaces was observed in only one patient in our cohort, which preceded the first skin SCC diagnosis by 2 months. 10 Given the retrospective nature of the present study, it is possible that the incidence of voriconazole-induced photosensitivity prior to SCC was not reported in the medical history or by the patients during routine review. Although Singer et al 8 reported that high cumulative voriconazole dose was an independent risk factor for skin SCC in LTx patients, Vadnerker et al 6 revealed that the occurrence of skin SCC among LTx patients was related to the duration of voriconazole therapy, 6 consistent with the findings of Feist et al 9 and Zwald et al 11 A recent study revealed that LTx recipients had a 73% increased risk of developing skin SCC post-voriconazole exposure; the risk was increased by 3% for each additional 30-day exposure at standard voriconazole dose.…”

Section: Discussionmentioning

confidence: 95%

“…Contributing factors may include the nine fold increased duration of voriconazole exposure, the 10‐fold increased total cumulative dose of voriconazole or the two fold longer duration of immunosuppressive therapy among the Group 2 patients. More importantly, prolonged use of voriconazole prophylaxis may indicate a more compromised immune system, which could have affected the risk of developing skin SCC in LTx patients . As such, clinicians should consider discontinuing voriconazole and switching to alternatives such as posaconazole or itraconazole if prolonged antifungal prophylaxis is required, given the low incidence of skin adverse events associated with these two azoles …”

Section: Discussionmentioning

confidence: 99%

“…2 Several risk factors for developing skin carcinoma among SOT recipients have been identified, including: high-level immunosuppression; increased exposure to ultraviolet (UV) radiation; Fitzpatrick skin types I, II, III; advanced age; history of non-melanoma skin cancer or melanoma; and an increased number of keratotic skin lesions. 3 The emerging evidence for causal associations between long-term voriconazole exposure and skin SCC [4][5][6][7][8][9][10][11] is of concern given the frequent use of voriconazole prophylaxis, which is commonly administered for months in the LTx setting. 12 Also, residing in geographical locations with high-level sun exposure has been identified as an independent risk factor for LTx patients developing skin SCC.…”

Section: Introductionmentioning

confidence: 99%

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Squamous cell carcinoma of the skin and voriconazole therapy in lung transplant recipients: a case series

Neoh

Snell

Levvey

et al. 2017

Pharmacy Practice and Res

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Background Prolonged voriconazole therapy may be associated with skin squamous cell carcinoma (SCC) in lung transplant (LTx) patients. This is of concern given the frequent use of voriconazole in the LTx setting. The impact of voriconazole therapy on the risk of developing skin SCC in an Australian LTx cohort with additional risk due to high levels of sun exposure remains unclear. Aim This study described the extent and outcomes of new or recurrent skin SCC among LTx patients receiving voriconazole. Methods The present retrospective cohort study was undertaken at The Alfred Hospital, Australia. Adult LTx recipients with skin SCC who had received voriconazole between 1 July 2003 and 30 June 2010 were included. Medical records and histopathology reports were reviewed. Demographics, clinical characteristics, voriconazole exposure (dose and duration), potential risk factors for skin SCC and manifestations of the skin SCC were recorded. The Naranjo algorithm was used to determine the likelihood of skin SCC being due to voriconazole exposure. Results Of the 102 LTx patients receiving voriconazole, 14 (13.7%) had at least one episode of skin SCC: seven (Group 1) had skin SCC during or after voriconazole exposure; three (Group 2) had skin SCC before commencing voriconazole therapy, which recurred or worsened subsequently; three (Group 3) had a history of skin SCC prior to voriconazole being prescribed but no skin SCC was noted during or after voriconazole exposure; and one (Group 4) had multiple skin SCCs before LTx and voriconazole use, and developed further skin SCC post voriconazole. The median (interquartile range) of voriconazole exposure in Group 1, 2 and 3 patients was 119 days (79.5, 693), 1127 days (665.5, 1129) and 173 days (135.5, 341), respectively. The Naranjo score indicated a probable association between voriconazole use and skin SCC in three patients and a possible relationship in eight. Conclusions Prolonged voriconazole exposure may contribute to the development, recurrence and progression of skin SCC in LTx patients.

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Section: Discussionmentioning

confidence: 79%

Section: Discussionmentioning

confidence: 95%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Squamous cell carcinoma of the skin and voriconazole therapy in lung transplant recipients: a case series

Neoh

Snell

Levvey

et al. 2017

Pharmacy Practice and Res

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“…A 45-year-old woman who had necrotizing Aspergillus tracheobronchitis after lung transplantation was given two prolonged courses of voriconazole and developed squamous cell carcinomas on the face and the backs of her hands; she then received two prolonged courses of posaconazole and died of metastatic squamous cell carcinoma 7 years after the first course of voriconazole. 46 …”

Section: Skin Tumoursmentioning

confidence: 97%

Photosensitivity reactions and skin tumours associated with voriconazole

Aronson¹

2015

Adverse Drug Reaction Bulletin

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Use of voriconazole, a triazole antifungal drug, has often been associated with photosensitivity, and this adverse reaction has been linked to a risk of tumours in light-exposed areas, especially squamous cell carcinomas, but also melanomas. The mechanisms by which voriconazole causes these effects are not clear, but susceptibility factors for a predisposition to skin cancers include duration of use, immunosuppression, ultraviolet (UV) exposure, advanced age, and skin type. Voriconazole should be used carefully, particularly in patients with susceptibility factors for skin cancer. If prolonged voriconazole therapy is required, it is advisable to have frequent diligent skin examinations, to avoid excess sunlight, and to use UV protectants liberally.

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