Back
 JBM  Vol.4 No.11 , November 2016
Voriconazole-Induced Periostitis & Enthesopathy in Solid Organ Transplant Patients: Case Reports
Abstract: Background: Voriconazole is frequently used to treat fungal infections in solid organ transplant patients. Recently, there have been reports suggesting that prolonged voriconazole therapy may lead to periostitis. Aim: Here we present two cases of voriconazole-induced periostitis in solid organ transplant patients. Case Presentation: Voriconazole was given to two transplant patients-one with a liver transplant and the second with a heart transplant, to treat their fungal infections. Both developed voriconazole-induced toxicity. While undergoing voriconazole therapy, they had incapacitating bone pain. The liver transplant patient had to be taken off voriconazole, and the heart transplant patient succumbed to non-voriconazole related causes. Conclusions: Voriconazole therapy in two solid organ transplant patients resulted in periostitis. We provide potential etiologies underlying voriconazole-induced periostitis, including fluoride toxicity, abnormalities in the pulmonary vascular bed leading to the production of downstream inflammatory mediators, and abnormal pharmacokinetics of hepatic drug metabolism. In addition to monitoring blood voriconazole trough levels, we suggest careful assessment for musculoskeletal pain in patients undergoing voriconazole treatment for two months or more, particularly if their daily dosages of voriconazole exceed 500 mg per day. Appropriate workup should include measurement of alkaline phosphatase and fluoride levels, voriconazole trough and bone scan. Overall, early recognition of voriconazole-induced musculoskeletal toxicity is important for better morbidity outcomes.
Cite this paper: Sircar, M. , Kotton, C. , Wojciechowski, D. , Safa, K. , Gilligan, H. , Heher, E. , Williams, W. , Thadhani, R. and Tolkoff-Rubin, N. (2016) Voriconazole-Induced Periostitis & Enthesopathy in Solid Organ Transplant Patients: Case Reports. Journal of Biosciences and Medicines, 4, 8-17. doi: 10.4236/jbm.2016.411002.
References

[1]   Wang, T.F., Wang, T. and Altman, R. (2009) Periostitis Secondary to Prolonged Voriconazole Therapy in Lung Transplant Recipients. American Journal of Transplantation, 9, 2845-2850.
http://dx.doi.org/10.1111/j.1600-6143.2009.02837.x

[2]   Becce, F., Malghem, J. and Lecouvet, F.E. (2012) Clinical Images: Voriconazole-Induced Periostitis Deformans. Arthritis & Rheumatism, 64, 3490.
http://dx.doi.org/10.1002/art.34618

[3]   Martinez-Lavin, M., Matucci-Cerinic, M. and Jajic, I. (1993) Hypertrophic Osteoarthopathy: Consensus on Its Definition, Classification, Assessment and Diagnostic Criteria. The Journal of Rheumatology, 20, 1387-1397.

[4]   Wermers, R.A., Cooper, K. and Razonable, R.R. (2011) Fluoride Excess and Periostitis in Transplant Patients Receiving Long-Term Voriconazole Therapy. Clinical Infectious Diseases, 52, 604-611.
http://dx.doi.org/10.1093/cid/ciq188

[5]   Lustenberger, D.P., Granata, J.D. and Scharschmidt, T.J. (2011) Periostitis Secondary to Prolonged Voriconazole Therapy in a Lung Transplant Recipient. Orthopedics, 34, e793-e796.

[6]   Chen, L. and Mulligan, M.E. (2011) Medication-Induced Periostitis in Lung Transplant Patients: Periostitis Deformans Visited. Skeletal Radiology, 40, 143-148.
http://dx.doi.org/10.1007/s00256-010-0997-y

[7]   Tejda, R., El-Sherief, A., Olbrych, T. and Gordon, S. (2013) Multifocal Periostitis as a Complication of Chronic Use of Voriconazole in a Lung Transplant Recipient. Transplant Infectious Disease, 15, 424-429.
http://dx.doi.org/10.1111/tid.12088

[8]   Bucknor, M.D., Gross, A.J. and Link, T.M. (2013) Voriconazole-Induced Periostitis in Two Post-Transplant Patients. Musculoskeletal Radiology, 7, 10-17.
http://dx.doi.org/10.3941/jrcr.v7i8.1458

[9]   Ayub, A., Kenney, C.V. and McKiernan, F.E. (2011) Multifocal Nodular Periostitis Associated with Prolonged Voriconazole Therapy in a Lung Transplant Recipient. Journal of Clinical Rheumatology, 17, 73-75.
http://dx.doi.org/10.1097/RHU.0b013e31820aff12

[10]   Wise, S.M. and Wilson, M.A. (2011) A Case of Periostitis Secondary to Voriconazole Therapy in a Heart Transplant Recipient. Clinical Nuclear Medicine, 36, 242-244.
http://dx.doi.org/10.1097/RLU.0b013e31820902d8

[11]   Moon, W.J., Scheller, E.L. and Suneja, A. (2014) Plasma Fluoride Level as a Predictor of Voriconazole-Induced Periostitis in Patients with Skeletal Pain. Clinical Infectious Diseases, 59, 1237-1245.
http://dx.doi.org/10.1093/cid/ciu513

[12]   Gladue, H.S. and Fox, D.A. (2013) Voriconazole-Induced Periostitis Causing Arthralgias Mimicking a Flare of Granulomatosis with Polyangiitis. Journal of Clinical Rheumatology, 19, 444-445.
http://dx.doi.org/10.1097/RHU.0000000000000045

[13]   Hirota, K., Yasoda, A., Fuji, T. and Inagaki, N. (2014) Voriconazole-Induced Periostitis in a Patient with Overlap Syndromes. BMJ Case Reports.
http://dx.doi.org/10.1136/bcr-2013-203485

[14]   Tarlock, K., Johnson, D. and Cornell, C. (2015) Elevated Fluoride Levels and Periostitis in Pediatric Hematopoeitic Stem Cell Transplant Recipients Receiving Long-Term Voriconazole. Pediatric Blood & Cancer, 62, 918-920.
http://dx.doi.org/10.1002/pbc.25283

[15]   Rad, B., Saleem, M. and Grant, S. (2015) Fluorosis and Periostitis Deformans as Complications of Prolonged Voriconazole Treatment. Annals of Clinical Biochemistry, 52, 611-614.
http://dx.doi.org/10.1177/0004563214568873

[16]   Raghavan, M. and Hayes, A. (2014) Voriconazole-Associated Soft Tissue Ossification: An Undescribed Cause of Glenohumeral Joint Capsulitis. Skeletal Radiology, 43, 1301-1305.
http://dx.doi.org/10.1007/s00256-014-1865-y

[17]   Glushko, T. and Colmegna, I. (2015) Voriconazole-Induced Periostitis. CMAJ, 187, 1075.
http://dx.doi.org/10.1503/cmaj.141025

[18]   Tailor, T.D. and Richardson, M.L. (2015) Voriconazole-Induced Periostitis. Radiology, 274, 930-935.
http://dx.doi.org/10.1148/radiol.14122800

[19]   Baird, J.H., Birnbaum, B.K., Porter, D.L. and Frey, N.V. (2015) Voriconazole-Induced Periostitis after Allogeneic Stem Cell Transplantation. Diagnostic Imaging in Hematology, 90, 574-575.

[20]   Rossier, C., Dunet, V. and Tissot, F. (2012) Voriconazole-Induced Periostitis. European Journal of Nuclear Medicine and Molecular Imaging, 39, 375-376.
http://dx.doi.org/10.1007/s00259-011-1922-x

[21]   Skiles, J.L., Imel, E.A. and Christenson, J.C. (2011) Fluorosis Because of Prolonged Voriconazole Therapy in a Teenager with Acute Myelogenous Leukemia. Journal of Clinical Oncology, 29, e779-e782.

[22]   Gerber, B., Guggenberger, R. and Fasler, D. (2012) Reversible Skeletal Disease and High Fluoride Serum Levels in Hematologic Patients Receiving Voriconazole. Blood, 120, 2390-2394.
http://dx.doi.org/10.1182/blood-2012-01-403030

[23]   Product Information. VFEND (voriconazole). Pfizer U.S. Pharmaceuticals, New York.

[24]   Venkataramanan, R., Zang, S., Gayowski, T. and Singh, N. (2002) Voriconazole Inhibition of the Metabolism of Tacrolimus in a Liver Transplant Recipient and in Human Liver Microsomes. Antimicrobial Agents and Chemotherapy, 46, 3091-3093.
http://dx.doi.org/10.1128/AAC.46.9.3091-3093.2002

[25]   Cakaloglu, Y., Tredger, J.M., Devlin, J. and Williams, R. (1994) Importance of Cytochrome P-450IIIA Activity in Determining Dosage and Blood Levels of FK 506 and Cyclosporine in Liver Transplant Recipients. Hepatology, 20, 309-316.
http://dx.doi.org/10.1002/hep.1840200207

[26]   Cebeiro, I., Dai, K. and Devlin, S.M. (2015) Safety of Voriconazole and Sirolimus Coadministration after Allogenic Hematopoietic SCT. Bone Marrow Transplantation, 50, 438-443.
http://dx.doi.org/10.1038/bmt.2014.286

[27]   Shalhoub, S., Luong, M.L. and Howard, S.J. (2015) Rate of cyp15A Mutation in Aspergillus fumigatus among Lung Transplant Recipients with Targeted Prophylaxis. Journal of Antimicrobial Chemotherapy, 70, 1064-1067.

[28]   Hsu, A.J., Dabb, A. and Arav-Boger, R. (2015) Autoinduction of Voriconazole Metabolism in a Child with Invasive Pulmonary Aspergillosis. Pharmacotherapy, 35, e20-e26.
http://dx.doi.org/10.1002/phar.1566

[29]   Naito, T., Takahiro, Y., Yasuaki, M. and Junichi, K. (2015) Impact of Inflammation and Concomitant Glucocorticoid Administration on Plasma Concentration of Triazole Antifungals in Immunocompromised Patients. Clinica Chimica Acta, 441, 127-132.
http://dx.doi.org/10.1016/j.cca.2014.12.024

[30]   Evans, W.E. and Relling, M.V. (1999) Pharmacogenomics: Translating Functional Genomics into Rational Therapeutics. Science, 286, 487-491.
http://dx.doi.org/10.1126/science.286.5439.487

 
 
Top