In this report, we present two cases of voriconazole-induced periostitis presenting with myalgias as well as a review of the relevant medical literature.

Case #1

A 71-year-old male with a history of alpha-1-antitrypsin deficiency and bilateral lung transplant presented with a complaint of diffuse myalgias six weeks after starting voriconazole for septic arthritis due to Scedosporium infection. Imaging showed myoedema and periostitis. An EMG/NCS was not suggestive of myopathy. Alkaline phosphatase was elevated at 183 IU/L (40-129 IU/L) with normal CK and aldolase. A dose reduction of voriconazole improved but did not resolve his symptoms.  

Case #2

A 66-year-old male with a history of chronic lymphocytic leukemia and allogeneic stem cell transplant on voriconazole prophylaxis for over 6 months presented with joint and muscle pain. Imaging showed multifocal periosteal thickening and labs revealed elevated fluoride and alkaline phosphatase levels at 15.6 umol/L (0-4 umol/L) and 424 IU/L (40-129 IU/L), respectively. Discontinuation of voriconazole resulted in gradual improvement over several months.

Voriconazole-induced periostitis is thought to be the result of the high levels of fluoride in this medication which can be up to 15-times normal daily intake. We theorize the inflammation in the periosteum leads to secondary inflammation at the site of muscle attachment. Discontinuation of the medication usually results in significant improvement clinically and radiographically. 

As the use of voriconazole becomes more routine, it is important to identify potential adverse effects for the timely discontinuation of the medication to prevent possible long-term complications and improve patient outcomes.