Voriconazole-Induced Periostitis After Allogeneic Stem Cell Transplantation

Abstract

A 34-year-old man with history of Hodgkin lymphoma presented 7 months after allogeneic stem cell transplantation with an unexplained severe musculoskeletal pain syndrome. A 99mTc-MDP bone SPECTCT showed multiple foci with moderate to intense bone uptake across the axial and appendicular skeleton consistent with periostitis. The patient had been on voriconazole daily for 4 months to treat an Aspergillus pneumonia, and in the absence of other causes, a drug-induced periostitis was suspected. Voriconazole was changed to posaconazole with complete resolution of the musculoskeletal symptoms within 3 weeks.

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 , …”

“…In this category, there were a total of 18 patients (20.3%, out of 89 total patients) identified, comprising 3 patients with hematologic malignancy and 15 HSCT recipients[ 6 , 10 , 11 , 14 , 15 , 18 , 25 , 28 , 31 , 35 , 37 , 40 , 41 , 46 , 49 , 53 ]. One of the stem cell transplant patients was a 3-mo-old infant[ 37 ].…”

“…One of the stem cell transplant patients was a 3-mo-old infant[ 37 ]. Notably, less than half of the cases (8 patients) reported the daily dose of voriconazole[ 10 , 11 , 28 , 31 , 35 , 49 , 53 ] whereas more than two-third of cases (16 patients) described the duration of voriconazole therapy[ 6 , 10 , 11 , 14 , 15 , 28 , 31 , 35 , 37 , 40 , 41 , 49 , 53 ]. The median dose was 400 mg (range 200-1200 mg) with the interquartile range of 400-750 mg (Table 2 ).…”