Case Report: Voriconazole-Induced Periostitis

Periostitis manifests as multifocal periosteal thickening with dense, irregular, nodular, and usually bilateral new bone formation. Enthesopathic changes in affected long bones are common, sometimes with smooth or asymmetric periosteal reactions.^2,4

X-ray imaging reveals multifocal periostitis with periosteal thickening and reaction, showing new bone formation that can be nodular or fluffy. Osteoblastic lesions, periosteal and ligament calcifications, osteosclerosis and entheseal ossification are commonly reported. More rare X-ray findings include bony exostoses at multiple sites, interosseous membrane calcification, metadiaphyseal widening and sacroiliac joint involvement. Isotope bone scans demonstrate increased tracer uptake in affected bones, typically showing fluffy or lamellar periosteal reactions. MRI may reveal periosteal edema.^2,10

Discontinuation, and occasionally dose reduction, of voriconazole is essential for improving pain symptoms, representing the only curative treatment for VIP.

Gerber et al. reported clinical improvement in all cases of VIP upon ceasing voriconazole.¹¹

Pain should improve with medication discontinuation, with some patients experiencing relief within days and most seeing resolution within two to four months. ALP and radiologic abnormalities typically normalize within three to four months.^4,5,10 However, elevated blood fluoride levels may persist for an extended period, reflecting fluoride sequestration in, and slow release from, the skeleton.¹

Supportive care includes pain management and addressing other conditions that may impact bone health such as hyperparathyroidism or malnutrition if present. Some less studied strategies, such as urinary alkalinization for pH-dependent fluoride excretion, have been suggested but have yet to be widely studied or used.

Conclusion

The patient described in this case exhibited classic findings of VIP, including diffuse bone pain, multifocal periosteal reactions on X-rays, enthesopathy, calcific tendinitis, elevated ALP levels and high fluoride levels. Notably, the patient’s symptoms and elevated ALP levels quickly resolved following the discontinuation of voriconazole. This case underscores the importance of rapid recognition and diagnosis of VIP by rheumatologists, which can prevent unnecessary and costly invasive procedures and significantly enhance the patient’s quality of life.

References

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