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Clinical Pharmacy and Pharmacology

Severe Polyarthralgia After Kidney Transplant

Educational Objective
Based on this clinical scenario and the accompanying image, understand how to arrive at a correct diagnosis.

1 Credit CME

JAMA

Published Online: December 16, 2021

JAMA Clinical Challenge

Article Information and Disclosures

Nur Azizah Allameen, MBBS, MMed¹;

Jiacai Cho, MBBS, MMed^1,2

Author Affiliations

¹Division of Rheumatology, University Medicine Cluster, National University Health System, Singapore
²Department of Medicine, Yong Loo Lin School of Medicine, National University of Singapore, Singapore

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A 51-year-old woman presented with a 1-month history of intense and worsening polyarthralgia and swelling of bilateral fingers and toes. There was no history of alopecia, oral ulcers, rashes, or Raynaud phenomenon. She did not report preceding fever, diarrhea, or dysuria. There was no history of weight loss or anorexia. Medical history included tertiary hyperparathyroidism related to end-stage kidney disease from chronic glomerulonephritis. The patient had successfully received an ABO-incompatible kidney transplant 1 year ago, but this was complicated by invasive fungal (Volvariella volvacea) infection of the central nervous system. Medications included tacrolimus (0.5 mg twice daily), prednisolone (10 mg daily), cinacalcet (12.5 mg daily), and voriconazole (500 mg daily). On examination, her fingers and toes were symmetrically and diffusely swollen and tender. There was no rash, enthesitis, psoriatic nail changes, clubbing, or lower limb edema. The rest of the physical examination was unremarkable.

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Voriconazole-induced periostitis

D. Stop voriconazole

The key to the correct diagnosis in this case is the radiographic appearance of periostitis (defined as inflammation of the connective tissue surrounding bone) in the setting of chronic voriconazole use and a high alkaline phosphatase level. Hypertrophic osteoarthropathy is an unlikely cause of the periostitis, given the absence of clubbing or clinical suggestion of malignancy. Therefore, a positron emission computed tomography scan (choice A) to assess for occult malignancy would not be appropriate. A bone biopsy (choice B) may aggravate the periostitis and would likely reveal nonspecific osteoblastic proliferation and reactive new bone formation—changes that would not discriminate between the causes of periostitis.¹ While hyperparathyroidism may cause subperiosteal resorption and pseudoperiostitis, pain and florid new bone formation visible on the hand radiograph cannot be attributed to hyperparathyroidism. Therefore, parathyroidectomy (choice C) is not appropriate.

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Article Information

Corresponding Author: Jiacai Cho, MBBS, MMed, Division of Rheumatology, Department of Medicine, National University Hospital, Singapore, 1E Kent Ridge Rd, Level 10, NUHS Tower Block, Singapore 119228 (jiacai_cho@nuhs.edu.sg).

Published Online: December 16, 2021. doi:10.1001/jama.2021.18866

Conflict of Interest Disclosures: None reported.

Additional Contributions: We thank Vincent Tiong Tze Yang, MBChB, MMed (Department of Diagnostic Radiology, National University Health System, Singapore), for helping us acquire the images for this article; he received no compensation for his contributions. We thank the patient for providing permission to share her information.

References

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Gerber B , Guggenberger R , Fasler D , et al. Reversible skeletal disease and high fluoride serum levels in hematologic patients receiving voriconazole. Blood. 2012;120(12):2390-2394. doi:10.1182/blood-2012-01-403030 PubMed Google Scholar Crossref

Moon WJ , Scheller EL , Suneja A , et al. Plasma fluoride level as a predictor of voriconazole-induced periostitis in patients with skeletal pain. Clin Infect Dis. 2014;59(9):1237-1245. doi:10.1093/cid/ciu513 PubMed Google Scholar Crossref

Adwan MH . Voriconazole-induced periostitis: a new rheumatic disorder. Clin Rheumatol. 2017;36(3):609-615. doi:10.1007/s10067-016-3341-7 PubMed Google Scholar Crossref

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Tailor TD , Richardson ML . Case 215: voriconazole-induced periostitis. Radiology. 2015;274(3):930-935. doi:10.1148/radiol.14122800 PubMed Google Scholar Crossref

Martínez-Lavín M . Hypertrophic osteoarthropathy. Best Pract Res Clin Rheumatol. 2020;34(3):101507. doi:10.1016/j.berh.2020.101507 PubMed Google Scholar

Institute of Medicine (US) Standing Committee on the Scientific Evaluation of Dietary Reference Intakes. Dietary Reference Intakes for Calcium, Phosphorus, Magnesium, Vitamin D, and Fluoride. National Academies Press; 1997.

Sircar M , Kotton C , Wojciechowski D , et al. Voriconazole-induced periostitis & enthesopathy in solid organ transplant patients: case reports. J Biosci Med (Irvine). 2016;4(11):8-17.PubMed Google Scholar

AMA CME Accreditation Information

Credit Designation Statement: The American Medical Association designates this Journal-based CME activity activity for a maximum of 1.00  AMA PRA Category 1 Credit(s)™. Physicians should claim only the credit commensurate with the extent of their participation in the activity.

Successful completion of this CME activity, which includes participation in the evaluation component, enables the participant to earn up to:

1.00 Medical Knowledge MOC points in the American Board of Internal Medicine's (ABIM) Maintenance of Certification (MOC) program;;
1.00 Self-Assessment points in the American Board of Otolaryngology – Head and Neck Surgery’s (ABOHNS) Continuing Certification program;
1.00 MOC points in the American Board of Pediatrics’ (ABP) Maintenance of Certification (MOC) program;
1.00 Lifelong Learning points in the American Board of Pathology’s (ABPath) Continuing Certification program; and
1.00 CME points in the American Board of Surgery’s (ABS) Continuing Certification program

It is the CME activity provider's responsibility to submit participant completion information to ACCME for the purpose of granting MOC credit.