Voriconazole‐induced periostitis after allogeneic stem cell transplantation

Abstract

Image 1. Whole body bone scintigraphy utilizing Tc-99m MDA radiotracer. Panel A: prior to voriconazole discontinuation, demonstrates multiple areas of increased radiotracer uptake consistent with osteoblastic lesions throughout the axial and appendicular skeleton (arrows). Panel B: 2 months following voriconazole discontinuation, shows physiologic radiotracer distribution with no evidence of the previously noted lesions. Of note, the patient previously had a right nephrectomy for removal of a renal cell carcinoma, thus explaining the absence of its shadow on the posterior scintigraphs.

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

“…However, due to lack of controlled studies, it is not very well understood whether the levels or duration of voriconazole treatment predict the risk of developing periostitis. The duration of therapy for most published reports ranged between 6 weeks to 416 weeks before symptoms of periostitis ensued . The current patient received voriconazole for 6 months and had significantly more robust radiologic evidence of periostitis compared to other reported cases where the duration of voriconazole use was much longer.…”

“…It is a triazole derivative of fluconazole and disrupts fungal cell wall synthesis by inhibiting a cytochrome P450–dependent enzyme, 14‐alpha sterole demethylase . Voriconazole has been described as causing a painful periostitis of the long bones in various immunocompromised patients with associated elevation in alkaline phosphatase levels, with most cases involving lung, heart, liver, stem cell, and bone marrow transplant recipients . This phenomenon has been reported in patients receiving therapy with this antifungal as either prophylaxis or treatment.…”

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 ].…”

Voriconazole Enhances the Osteogenic Activity of Human Osteoblasts In Vitro through a Fluoride-Independent Mechanism

“…More recently, reports that document painful periostitis among patients receiving voriconazole for prolonged periods are accumulating (11)(12)(13)(14)(15). Periostitis is characterized by multiple areas of periosteal ossification of bones in the axial and appendicular skeleton, which typically abate following discontinuation of therapy, suggesting a direct causative role for voriconazole.…”