[Skip to Content]
[Skip to Content Landing]

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

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.

Please finish quiz first before checking answer.

You answered correctly!

Read the answer below and download your certificate.

You answered incorrectly.

Read the discussion below and retake the quiz.

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.

Survey Complete!

Sign in to take quiz and track your certificates

Buy This Activity

JN Learning™ is the home for CME and MOC from the JAMA Network. Search by specialty or US state and earn AMA PRA Category 1 Credit(s)™ from articles, audio, Clinical Challenges and more. Learn more about CME/MOC

CME Disclosure Statement: Unless noted, all individuals in control of content reported no relevant financial relationships. If applicable, all relevant financial relationships have been mitigated.

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
1.
Soni  A , Weil  A , Wei  S , Jaffe  KA , Siegal  GP .  Florid reactive periostitis ossificans of the humerus: case report and differential diagnosis of periosteal lesions of long bones.   World J Orthop. 2015;6(7):559-563. doi:10.5312/wjo.v6.i7.559PubMedGoogle ScholarCrossref
2.
Johnson  LB , Kauffman  CA .  Voriconazole: a new triazole antifungal agent.   Clin Infect Dis. 2003;36(5):630-637. doi:10.1086/367933PubMedGoogle ScholarCrossref
3.
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-2012-01-403030PubMedGoogle ScholarCrossref
4.
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/ciu513PubMedGoogle ScholarCrossref
5.
Adwan  MH .  Voriconazole-induced periostitis: a new rheumatic disorder.   Clin Rheumatol. 2017;36(3):609-615. doi:10.1007/s10067-016-3341-7PubMedGoogle ScholarCrossref
6.
Tan  I , Lomasney  L , Stacy  GS , Lazarus  M , Mar  WA .  Spectrum of voriconazole-induced periostitis with review of the differential diagnosis.   AJR Am J Roentgenol. 2019;212(1):157-165. doi:10.2214/AJR.18.19991PubMedGoogle ScholarCrossref
7.
Tailor  TD , Richardson  ML .  Case 215: voriconazole-induced periostitis.   Radiology. 2015;274(3):930-935. doi:10.1148/radiol.14122800PubMedGoogle ScholarCrossref
8.
Martínez-Lavín  M .  Hypertrophic osteoarthropathy.   Best Pract Res Clin Rheumatol. 2020;34(3):101507. doi:10.1016/j.berh.2020.101507PubMedGoogle Scholar
9.
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.
10.
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.PubMedGoogle Scholar
Close
Want full access to the AMA Ed Hub?
After you sign up for AMA Membership, make sure you sign in or create a Physician account with the AMA in order to access all learning activities on the AMA Ed Hub
Buy this activity
Close
Want full access to the AMA Ed Hub?
After you sign up for AMA Membership, make sure you sign in or create a Physician account with the AMA in order to access all learning activities on the AMA Ed Hub
Buy this activity
Close
With a personal account, you can:
  • Access free activities and track your credits
  • Personalize content alerts
  • Customize your interests
  • Fully personalize your learning experience
Education Center Collection Sign In Modal Right
Close

Name Your Search

Save Search
With a personal account, you can:
  • Access free activities and track your credits
  • Personalize content alerts
  • Customize your interests
  • Fully personalize your learning experience
Close
Close

Lookup An Activity

or

My Saved Searches

You currently have no searches saved.

Close

My Saved Courses

You currently have no courses saved.

Close