Korean J Transplant.  2021 Dec;35(4):262-267. 10.4285/kjt.21.0017.

Concurrent cytomegalovirus enteritis and atypical hemolytic uremic syndrome with gastrointestinal tract involvement: a case report

• Kim MH
• Cho MH
• Ahn YH
• Bae JM
• Moon JS
• Kang HG

• KMID: 2523677
• DOI: http://doi.org/10.4285/kjt.21.0017

Abstract

Atypical hemolytic uremic syndrome (aHUS) is a rare disease caused by complement dysregulation that may involve the extra-renal system. Without appropriate prophylactic treatment, aHUS commonly recur after kidney transplantation (KT). In contrast, cytomegalovirus (CMV) infection is common in KT recipients and may affect various organ systems. Herein, we report a case of recurrent aHUS complicated by CMV enteritis. This 17-year-old KT recipient with aHUS having a CFH mutation was admitted to the hospital for gastric pain and vomiting. With worsening hemogram, recurrence of aHUS involving the gastrointestinal (GI) system was suspected. Upon treatment with anti-C5 antibody, the patient’s blood counts soon improved, but her GI symptoms did not. Esophagogastroduodenoscopy revealed multiple ulcers in the duodenum with pathologic findings consistent with aHUS and CMV enteritis; however, she did not have CMV antigenemia despite these findings. Treatment with ganciclovir resolved GI symptoms within 7 days. This case shows that recurrence of aHUS is often induced by intercurrent infection, and common infections after allograft transplantation, such as CMV, should always be suspected and confirmed for a proper treatment, particularly because CMV enteritis may not accompany CMV antigenemia.

Keyword

Atypical hemolytic uremic syndrome; Cytomegalovirus; Kidney transplantation; Case report

Figure

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  Fig. 1 Chart showing the clinical course and trends in hemoglobin (Hb), platelet, serum creatinine, and lactate dehydrogenase (LDH) levels after admission. FFP, fresh frozen plasma; GI, gastrointestinal; IV, intravenous.

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  Fig. 2 Patient’s medical history and laboratory values including before admission. RRT, renal replacement therapy; KT, kidney transplantation; FFP, fresh frozen plasma; Hb, hemoglobin; Cr, creatinine.

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  Fig. 3 Endoscopic findings of the patient. (A) Hemorrhagic gastritis and edema in the stomach. (B) Multiple longitudinal ulcers in the 3rd portion of the duodenum.

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  Fig. 4 Histologic findings of the patient. (A-C) Duodenal biopsy (H&E, ×20). Chronic active duodenitis with ulcer and hyalinized capillaries with microthrombi. (D) Immunohistochemical cytomegalovirus (CMV) staining (arrow, CMV-positive cell).

Reference

1. Nester CM, Barbour T, de Cordoba SR, Dragon-Durey MA, Fremeaux-Bacchi V, Goodship TH, et al. 2015; Atypical aHUS: state of the art. Mol Immunol. 67:31–42. DOI: 10.1016/j.molimm.2015.03.246. PMID: 25843230.

2. Hofer J, Rosales A, Fischer C, Giner T. 2014; Extra-renal manifestations of complement-mediated thrombotic microangiopathies. Front Pediatr. 2:97. DOI: 10.3389/fped.2014.00097. PMID: 25250305. PMCID: PMC4157546.

3. Ito S, Hidaka Y, Inoue N, Kaname S, Kato H, Matsumoto M, et al. 2019; Safety and effectiveness of eculizumab for pediatric patients with atypical hemolytic-uremic syndrome in Japan: interim analysis of post-marketing surveillance. Clin Exp Nephrol. 23:112–21. DOI: 10.1007/s10157-018-1610-2. PMID: 30039480. PMCID: PMC6344608.

4. Ramanan P, Razonable RR. 2013; Cytomegalovirus infections in solid organ transplantation: a review. Infect Chemother. 45:260–71. DOI: 10.3947/ic.2013.45.3.260. PMID: 24396627. PMCID: PMC3848521.

5. Olie KH, Goodship TH, Verlaak R, Florquin S, Groothoff JW, Strain L, et al. 2005; Posttransplantation cytomegalovirus-induced recurrence of atypical hemolytic uremic syndrome associated with a factor H mutation: successful treatment with intensive plasma exchanges and ganciclovir. Am J Kidney Dis. 45:e12–5. DOI: 10.1053/j.ajkd.2004.09.012. PMID: 15696434.

6. Bhutani D, Dyson G, Manasa R, Deol A, Ratanatharathorn V, Ayash L, et al. 2015; Incidence, risk factors, and outcome of cytomegalovirus viremia and gastroenteritis in patients with gastrointestinal graft-versus-host disease. Biol Blood Marrow Transplant. 21:159–64. DOI: 10.1016/j.bbmt.2014.10.004. PMID: 25445637. PMCID: PMC4283200.

7. Ljungman P, Griffiths P, Paya C. 2002; Definitions of cytomegalovirus infection and disease in transplant recipients. Clin Infect Dis. 34:1094–7. DOI: 10.1086/339329. PMID: 11914998.

8. George JN, Nester CM. 2014; Syndromes of thrombotic microangiopathy. N Engl J Med. 371:1847–8. DOI: 10.1056/NEJMc1410951. PMID: 25119611.

9. Noris M, Remuzzi G. 2009; Atypical hemolytic-uremic syndrome. N Engl J Med. 361:1676–87. DOI: 10.1056/NEJMra0902814. PMID: 19846853.

10. Lopes da Silva R. 2011; Viral-associated thrombotic microangiopathies. Hematol Oncol Stem Cell Ther. 4:51–9. DOI: 10.5144/1658-3876.2011.51. PMID: 21727765.

11. Ariceta G, Besbas N, Johnson S, Karpman D, Landau D, Licht C, et al. 2009; Guideline for the investigation and initial therapy of diarrhea-negative hemolytic uremic syndrome. Pediatr Nephrol. 24:687–96. DOI: 10.1007/s00467-008-0964-1. PMID: 18800230.

12. Loirat C, Fakhouri F, Ariceta G, Besbas N, Bitzan M, Bjerre A, et al. 2016; An international consensus approach to the management of atypical hemolytic uremic syndrome in children. Pediatr Nephrol. 31:15–39. DOI: 10.1007/s00467-015-3076-8. PMID: 25859752.

13. Formeck C, Swiatecka-Urban A. 2019; Extra-renal manifestations of atypical hemolytic uremic syndrome. Pediatr Nephrol. 34:1337–48. DOI: 10.1007/s00467-018-4039-7. PMID: 30109445. PMCID: PMC8627279.

14. De Keyzer K, Van Laecke S, Peeters P, Vanholder R. 2011; Human cytomegalovirus and kidney transplantation: a clinician's update. Am J Kidney Dis. 58:118–26. DOI: 10.1053/j.ajkd.2011.04.010. PMID: 21684438.

15. Asberg A, Humar A, Rollag H, Jardine AG, Mouas H, Pescovitz MD, et al. 2007; Oral valganciclovir is noninferior to intravenous ganciclovir for the treatment of cytomegalovirus disease in solid organ transplant recipients. Am J Transplant. 7:2106–13. DOI: 10.1111/j.1600-6143.2007.01910.x. PMID: 17640310.