Mycophenolate mofetil–induced oral ulcers in a pediatric kidney transplant recipient

A 4-year-old boy with bilateral kidney dysplasia received a kidney transplant from his father. The post-operative period was uneventful, and his immunosuppressive regimen consisted of basiliximab, tacrolimus, mycophenolate mofetil (MMF), and steroids. He was discharged on day 25 with a serum creatinine of 21 µmol/L. Four months later he presented with two oral aphthous ulcers accompanied by odynophagia. At that time his tacrolimus trough level was 6.5 µg/L and mycophenolate mofetil was being administered at a dose of 430 mg/m2 twice daily, together with prednisone 5 mg daily. Initial treatment with a local oral topical anesthetic solution did not bring relief. A swab sample from the spreading lesions was taken and antibiotic (cefuroxime) and antimycotic (fluconazol) therapy was initiated. Neither bacterial culture nor viral serology (PCR EBV, CMV, HSV1,2, BKV) was positive, and empiric anti-infective therapy was ineffective. One month after onset, three deep oral ulcers, accompanied by ulcerative stomatitis, developed (Figure 1). Suspecting an iatrogenic problem, MMF was discontinued and was replaced with azathioprine. At the same time, oral hygiene was enhanced. Complete resolution of the mucosal lesions was seen within 2 weeks. Two deep oral aphthous ulcers in the lower dentition bilaterally. Good oral health and guidance on dental care represent an important part of pre-transplant assessment, as oral disease may compromise health during the post-transplant period. Oral ulcers are a relatively common complication in pediatric kidney transplant recipients. The most common causes are infectious, while drug toxicity occurs less frequently and malignant lesions are rare.1 Mycophenolate mofetil is mostly used in patients with autoimmune diseases, and together with tacrolimus and prednisone, is a cornerstone of maintenance immunosuppressive therapy in pediatric kidney transplant recipients. Although oral ulcerations associated with MMF have been sporadically reported in adults (2), this is the first documented case in a child with kidney transplantation. Two underlying mechanisms have been proposed: direct MMF-induced cytotoxicity, and secondary viral infections facilitated by immunosuppression. Therapeutic strategies include switching to alternative treatments or, less frequently, reducing the dose of MMF.2 We assume that oral ulcers were caused by MMF in our patient, as other etiologies could not be identified and rapid healing of the lesions was observed after MMF discontinuation. This case highlights the association between MMF and oral ulcers in children.3 Conceptualization, MB, JZ; Data curation, MB, NH; Investigation, MB, NH, MJ; Writing - original draft, MB, JZ, NH; Writing - review and editing, JZ, MJ This work was supported by the Ministry of Health, Czech Republic) for the conceptual development of research organization 00064203 (University Hospital Motol, Prague, Czech Republic). All data generated during this case are included in the published manuscript. This study involves human participants. Board approval was not required for this study in accordance with national guidelines and has exempted this study. Consent was obtained from the patient’s parents.