Voriconazole‐induced periostitis post transplant: an illustrative review of thoracic computed tomography imaging manifestations

Abstract

Voriconazole, first commercially approved in 2002 as a second-generation antifungal agent, is commonly used in the immunocompromised setting as both a therapeutic and prophylactic agent. Since 2009, scattered case reports and small case series have detailed a secondary drug-related hyperfluorosis-induced painful periostitis that can occur in the treated patient population. We present a pictorial review of the thoracic imaging manifestations utilizing 3 illustrative cases in the setting of both solid organ and bone marrow transplantation. Knowledge of the relatively characteristic radiographic appearance and distribution, when coupled with the appropriate clinical context and associated laboratory findings, is important in narrowing an otherwise relatively broad differential diagnosis.

Voriconazole-associated periostitis: Pathophysiology, risk factors, clinical manifestations, diagnosis, and management

“…A total of 89 cases of voriconazole-induced periostitis were reviewed (Table 1 ), including 2 pediatric patients, one 14-year-old lung transplant patient and one 3-mo-old stem cell transplant recipient[ 5 - 53 ]. Cases were published in the format of case reports (limited 1 case in an article, 19 articles)[ 7 , 9 , 10 , 16 , 19 , 22 , 25 , 27 , 30 , 32 , 34 , 37 , 38 , 40 , 42 , 43 , 45 , 47 , 51 ], case series (> 1 case in an article, 9 articles)[ 5 , 8 , 11 , 15 , 18 , 23 , 35 , 39 , 48 ], image section (12 articles)[ 12 , 13 , 17 , 21 , 28 , 31 , 33 , 36 , 46 , 49 , 50 , 53 ], photo quiz (1 article)[ 20 ], conference abstracts (5 articles)[ 6 , 14 , 24 , 26 , 29 ], letter to the editor (2 articles)[ 41 , 44 ], and clinicopathologic conference (1 article)[ 52 ]. One case report was published in both Danish and English, and it was included in our analysis because there was ample amount of information in English[ 51 ].…”

“…The vast majority of voriconazole-associated periostitis cases have been reported in SOT recipients ( n = 40, 45%)[ 5 , 7 , 8 , 11 - 13 , 16 , 18 , 21 , 24 , 26 , 29 , 30 , 32 - 36 , 39 , 43 , 44 , 47 , 48 , 50 ], immunocompetent hosts ( n = 19, 21.34%)[ 23 , 38 , 51 , 52 ], hematologic malignancy and HSCT patients ( n = 18, 20.3%)[ 6 , 10 , 11 , 14 , 15 , 18 , 25 , 28 , 31 , 35 , 37 , 40 , 41 , 46 , 49 , 53 ]. It is followed by autoimmune diseases ( n = 4, 4.44%), including 2 patients with granulomatosis with polyangiitis[ 19 , 42 ], and 2 patients with mixed connective tissue disease[ 22 , 27 ].…”

“…The daily voriconazole dose was reported in 59 cases, consisting of 24 SOT patients[ 5 , 7 , 8 , 11 , 13 , 21 , 26 , 30 , 33 - 35 , 39 , 43 , 44 , 47 , 48 ], 8 hematologic malignancy and HSCT recipients[ 10 , 11 , 28 , 31 , 35 , 49 , 53 ], 18 immunocompetent hosts[ 23 , 51 , 52 ], and 9 others[ 19 , 22 , 23 , 42 , 45 ]. The duration of voriconazole therapy was described in 77 cases (30 SOT patients[ 5 , 7 , 8 , 11 - 13 , 16 , 18 , 21 , 26 , 30 , 32 , 35 , 39 , 43 , 44 , 47 , 48 , 50 ], 16 HSCT recipients[ 6 , 10 , 11 , 14 , 15 , 28 , 31 , 35 , 37 , 40 , 41 , 49 , 53 ], 18 immunocompetent hosts[ 23 , 38 , 51 , 52 ], and 13 others[ 19 , 20 , 22 , 23 , 27 , 42 , …”

“…Among 40 patients with SOT, lung transplants accounted for 26 patients (65%)[ 5 , 7 - 9 , 11 , 21 , 24 , 29 , 30 , 35 , 36 , 43 , 44 , 48 , 50 ], followed by 6 liver transplants (15%)[ 13 , 26 , 32 , 34 , 35 , 39 ], 6 orthotopic heart transplants (15%)[ 11 , 12 , 16 , 18 , 33 , 39 ], and 2 kidney transplants (5%)[ 11 , 47 ]. It is not unexpected that majority of these cases occurred in lung transplant recipients as invasive pulmonary fungal infection is most commonly seen post-lung transplantation[ 2 ].…”

“…It is not unexpected that majority of these cases occurred in lung transplant recipients as invasive pulmonary fungal infection is most commonly seen post-lung transplantation[ 2 ]. One third of lung transplant patients ( n = 6, 23%) developed periostitis on the treatment dose regimen of voriconazole[ 21 , 24 , 30 , 35 , 36 , 43 ]. Indication of voriconazole therapy was not mentioned in 8 patients (31%) of lung transplant recipients with periostitis[ 8 , 9 , 11 , 29 , 44 ].…”