To the Editor, Mpox, caused by the monkeypox virus (MPXV), is an emerging infectious disease with important implications for immunocompromised populations, including solid organ transplant recipients (SOTRs) 1-3. Although mpox is generally self-limited in immunocompetent individuals, immunocompromised patients are at increased risk for severe and disseminated disease 4, 5. Data describing mpox in SOTRs remain limited 6-10. We describe three kidney transplant recipients hospitalized with mpox at Jackson Memorial Hospital/Miami Transplant Institute (Miami, Florida, USA) between May 2022 and December 2024 (Table 1). Median time from transplant to infection was 53.5 months (range 7–164.5 months). All patients developed the characteristic rash with umbilicated papules evolving into vesicles, pustules, and crusts; two had disseminated disease with > 200 lesions. No pneumonitis, encephalitis, keratitis, myocarditis, or deaths occurred. A 54-year-old man with Type 1 diabetes and end-stage renal disease (ESRD) due to diabetic nephropathy underwent a simultaneous kidney-pancreas transplantation 15 years earlier. Maintenance immunosuppression included tacrolimus 1 mg twice daily, mycophenolic acid (MPA) 720 mg twice daily, and prednisone 10 mg daily. He had stable graft function and denied prior rejection episodes. He was an MSM individual in a monogamous relationship, denied recent sexual activity, and had not received orthopoxvirus vaccination. He reported attending a large Halloween street event shortly before symptom onset. He presented with diffuse rash, abdominal pain, and nausea. Examination showed > 200 pustular and umbilicated lesions involving the face, trunk, extremities, and buttocks. Skin lesion MPXV PCR was positive, with MPXV clade typing unavailable. Oral tecovirimat 600 mg PO twice daily was initiated, and MPA was held. CT imaging demonstrated rectosigmoid inflammation and perirectal lymphadenopathy consistent with infectious proctitis. STI screening was negative. Hospitalization was complicated by secondary bacterial skin infection requiring intravenous vancomycin. He completed 14 days of oral tecovirimat and was discharged after 2 weeks. At 60-day follow-up, lesions had resolved completely, and graft function remained stable. A 48-year-old man with a history of HIV infection (CD4 870 cells/mm3, undetectable viral load), hypertension, and ESRD due to HIV-associated nephropathy underwent deceased-donor kidney transplantation (DDKT) 7 months earlier. His antiretroviral regimen included raltegravir 400 mg twice daily and etravirine 200 mg twice daily, which he had been taking for over a decade. Maintenance immunosuppression included tacrolimus extended-release 12 mg once daily, MPA 540 mg twice daily, and prednisone 20 mg daily. He had no prior rejection episodes, and his graft function was stable. He was an MSM individual who denied recent sexual activity. He had not received orthopoxvirus vaccination and worked as an international flight attendant. He presented with lesions involving the trunk, face, and scalp and completed a 14-day course of oral tecovirimat after a positive MPXV PCR. Symptoms initially improved but recurred shortly after treatment completion, with painful lesions on the hands and feet (Figure 1), prompting hospitalization. Examination revealed > 200 lesions involving the face, scalp, oral cavity, trunk, extremities, buttocks, and penis. Repeat MPXV PCR remained positive, and clade typing was unavailable. Upon admission, oral tecovirimat 600 mg twice daily was restarted, MPA was held, and prednisone was reduced to 10 mg daily. Under an emergency investigational protocol, he received oral brincidofovir 200 mg weekly for four doses. Due to concerns about impaired absorption in the setting of mucocutaneous disease, therapy was later switched to intravenous tecovirimat 200 mg twice daily per CDC expert guidance. He also received two doses of vaccinia immunoglobulin (9000 units/kg) administered 72 h apart. Dermatology recommended topical imiquimod 5% daily. His clinical course was complicated by Staphylococcus epidermidis line-related bacteremia, secondary bacterial skin infection, and CMV DNAemia. He was hospitalized for 36 days and discharged after most lesions had crusted, completing more than 5 weeks of antiviral treatment at that time. He was readmitted 2 weeks later with persistent cutaneous lesions and fever. He had left hand and bilateral feet purulent cellulitis with wound cultures growing Klebsiella pneumoniae and Pseudomonas aeruginosa, for which he received a course of cefepime. Skin biopsy showed a hyperkeratotic, acanthotic epidermis with reactive atypia, necrosis, ulceration, and mixed acute and chronic lymphohistiocytic inflammation; immunohistochemical stains for HSV and VZV, as well as GMS and Fite stains, were negative. Plasma microbial cell-free DNA testing and tissue PCR remained positive for MPXV. Dual antiviral therapy with oral tecovirimat 600 mg twice daily and brincidofovir 200 mg weekly was resumed after CDC consultation, and the patient was discharged. After the interruption of therapy because of loss to follow-up, lesions recrudesced, and he was readmitted with P. aeruginosa bacteremia secondary to superimposed foot cellulitis, treated with cefepime. Oral tecovirimat and brincidofovir were restarted, and daily topical cidofovir 3% was added for refractory cutaneous disease. After initiation of topical cidofovir, he reported significant clinical improvement and was discharged. Approximately 9 months after diagnosis, lesions had completely re-epithelialized, and antiviral therapy was finally discontinued. Graft function remained stable. A 34-year-old man with hypertension and ESRD due to tubulointerstitial nephritis underwent DDKT 4 years earlier. Maintenance immunosuppression included tacrolimus 3 mg twice daily, MPA 540 mg twice daily, and prednisone 5 mg daily. He had stable graft function and denied prior rejection episodes. He reported recent high-risk sexual activity with multiple female partners. He presented with one week of fever, right groin pain, and new skin lesions. Examination revealed bilateral inguinal lymphadenopathy and several umbilicated lesions involving the trunk, axilla, buttocks, inguinal region, leg, and foot. Lesion PCR confirmed MPXV clade II infection. Oral tecovirimat was initiated and MPA was reduced. Further testing identified early latent syphilis (RPR 1:128), and he received benzathine penicillin G. Screening for other STIs was negative. He improved rapidly and was discharged after 5 days to complete a 14-day course of oral tecovirimat. At 60-day follow-up, lesions had resolved completely and graft function remained stable. Our series highlights several important aspects of mpox infection in SOTRs. First, this population may develop disseminated and treatment-refractory disease requiring multimodal therapy. Second, management remains challenging because evidence supporting antiviral therapy and immunosuppression reduction is limited. Third, although one patient reported high-risk sexual exposure, two patients denied recent sexual contact, suggesting that transmission in SOTRs may also occur through close nonsexual exposure. All patients received tecovirimat, although its clinical benefit remains uncertain. Observational studies in immunocompetent individuals and people living with HIV have suggested that early initiation, particularly within the first week of symptom onset, may improve symptom resolution and reduce complications, but recent randomized trials failed to demonstrate clinical benefit 14, 15. Additional agents such as brincidofovir, vaccinia immunoglobulin, and topical therapies were used in refractory disease, although supporting evidence remains sparse. Reduction of immunosuppression, primarily involving MPA, was implemented in all cases without rejection during follow-up. Secondary bacterial infections occurred in patients with extensive skin disease, underscoring the importance of monitoring for coinfections. Notably, none of our patients had received orthopoxvirus vaccination, representing a missed preventive opportunity given current recommendations supporting vaccination of immunocompromised individuals during periods of increased mpox activity. In summary, mpox infection in SOTRs may result in prolonged disease with extensive cutaneous involvement and significant morbidity. Although no deaths occurred in our series, the clinical burden observed highlights the importance of preventive strategies, including vaccination, risk reduction-counseling, and early recognition, to reduce disease severity in immunosuppressed patients. All authors contributed to the study conception and design. Material preparation, data collection, and analysis were performed by Lubna Osman-Kardash and Julia Bini Viotti. The first draft of the manuscript was written by Lubna Osman-Kardash, and all authors commented on previous versions of the manuscript. All authors read and approved the final manuscript. The authors have nothing to report.
Osman‐Kardash et al. (Fri,) studied this question.