Voriconazole-induced periostitis

Last revised by Dr Henry Knipe on 14 Jun 2022

Voriconazole-included periostitis is a type of drug-induced periostitis and is a rare cause of diffuse bone pain in those on high dose or prolonged voriconazole therapy. 

Voriconazole-induced periostitis primarily occurs in the immunocompromised and transplant patient populations, however, it has also been described in immunocompetent hosts 1.

Clinical presentation includes:

  • diffuse bone pain 1​
  • dental fluorosis: whitish specks and discolouration 2
  • fracture
  • high serum ALP level and plasma fluoride concentration 3,4

Voriconazole is a broad-spectrum triazole antifungal medication. Triazole antifungal agents contain varying amounts of fluorine. Voriconazole contains three fluorine atoms, and a 400-mg dose of voriconazole contains a substantial 65 mg of fluoride 5. In comparison, the fluoride content of the municipal tap water is 1 mg per liter 6; thus, daily fluoride consumption from municipal tap water has been estimated at 2-4 mg per day 6.

Absorbed excess fluoride is incorporated into the crystal structure of bony matrix called hydroxyapatite, forming fluorapatite 7. Unlike normal calcium hydroxyapatite, high fluorapatite deposit causes disorganized osteoblastic reaction, resulting in periosteal thickening or ossification, exostosis, and osteosclerosis, a condition known as skeletal fluorosis 2

Common locations include the clavicles, ribs, proximal long bones, scapula, hands and acetabula ref.

Voriconazole-induced periostitis has been described as having a variable appearance of periosteal reaction including a fluffy, feathery, nodular or irregular morphology on imaging with an asymmetric distribution 8

The mainstay of imaging modality includes plain x-ray, CT and nuclear medicine bone scan. Advanced imaging modalities such as MRI and PET can be utilized if the diagnosis remains elusive, however, are not recommended as first-line 9.

  • technetium-99m bone scan demonstrates high radiotracer uptake due to increased osteoblastic activity 1

Discontinuation of voriconazole usually results in rapid resolution of symptoms. No known mortality has been associated with voriconazole-induced periostitis ref.

General imaging differential considerations include ref:

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Cases and figures

  • Case 1: voriconozole-induced periostitis
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