A 31‐Year‐Old Man With A Fungal Infection, Elevated Alkaline Phosphatase Level, and Polyarthritis

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 , …”

“…The second most common patient population reported in the literature with voriconazole-related periostitis is in patients with apparent immunocompetent status ( n = 19, 21.32%)[ 23 , 38 , 51 , 52 ]. Sixteen out of 19 patients with periostitis were observed in patients with Exserohilum rostratum or Aspergillus fumigatus meningitis from contaminated methylprednisolone epidural steroid injection[ 23 ].…”

“…Sixteen out of 19 patients with periostitis were observed in patients with Exserohilum rostratum or Aspergillus fumigatus meningitis from contaminated methylprednisolone epidural steroid injection[ 23 ]. Eighteen patients reported daily voriconazole dose and duration of voriconazole therapy[ 23 , 51 , 52 ] while 17 patients included voriconazole trough levels in their reporting[ 23 , 51 ]. Among 19 immunocompetent patients, the median daily dose of voriconazole was 750 mg (range 500-1300 mg) with the interquartile range of 700-875 mg[ 23 , 38 , 51 , 52 ], which was notably higher than doses observed in SOT recipients presenting with periostitis (Table 2 ).…”