E-Poster Presentation 30th Australian and New Zealand Bone and Mineral Society Annual Scientific Meeting 2020

Case

A 68-year-old male presented in May 2020 with a 6-week history of severe, diffuse bone pain, which was refractory to analgesics. He appeared frail and mobilised, with difficulty, with a four-wheeled walker. This was a marked deterioration from his baseline function just three months prior (fully independent with mobility and activities of daily living).

His background was significant for high-risk acute myeloid leukaemia, diagnosed 9 months prior, with induction and consolidation chemotherapy being complicated by severe Aspergillus fumigatus pneumonia, despite posaconazole prophylaxis. Voriconazole 200mg BD was commenced in October 2019, and he underwent allogeneic stem cell transplant in January 2020.

Technetium-labelled bone scintigraphy showed diffuse periarticular radiotracer uptake (Fig.1), and initial biochemistry is shown in Table 1.  Skeletal survey revealed areas of increased uptake on bone scintigraphy corresponding to sites of multifocal periosteal reaction and soft tissue calcification/ossification, affecting both the axial and appendicular skeleton (Fig. 2).

The differential diagnosis included chemoradiation versus voriconazole-induced periostitis. Notably, the voriconazole dose was increased to 400mg BD in February 2020 due to subtherapeutic voriconazole levels, with pain onset six weeks later. A serum fluoride level demonstrated a toxic result of 26 μmol/L (1-4 μmol/L). Voriconazole was ceased, and pain improved within two weeks, confirming a diagnosis of voriconazole-induced periostitis (skeletal fluorosis).

By eight weeks, his pain had resolved, and he was mobilising independently. Serum fluoride levels reduced to <10 μmol/L and bone turnover markers had decreased (Table 1). Repeat bone scintigraphy showed interval decrease in osteoblastic activity.

Discussion

Awareness of this debilitating condition, which manifests as severe bone pain, elevated serum alkaline phosphatase and periostitis on imaging, is of paramount importance in patients on long-term voriconazole. Serum fluoride levels are helpful in confirming the diagnosis. Pathophysiology and predisposing risk factors for voriconazole-induced skeletal fluorosis will be further discussed.

Figure 1. Technetium-labelled bone scintigraphy (performed two weeks prior to initial metabolic bone clinic review), showing intense uptake in the posterior 6^th-8^th ribs bilaterally, diffuse periarticular uptake in bilateral knees, elbows and wrist joints, and focal uptake in bilateral femoral diaphyses, proximal tibiae and bilateral proximal forearms.

Table 1. Baseline biochemistry and post voriconazole cessation

Figure 2. Skeletal survey (x-ray and computed tomography) highlighting multifocal solid periosteal reaction, as well as focal soft tissue calcification/ossification most prominent adjacent to the lateral epicondyles bilaterally (right > left), and lesser trochanters bilaterally.