IL-10 is a key anti-inflammatory cytokine, which is produced predominantly by leukocytes, including T cells, B cells, monocytes, macrophages, and dendritic cells, as well as by some epithelial cells. 1, 2 Polymorphisms in IL-10 and its receptors IL-10RA and IL-10RB have been observed in individuals with several immune-mediated diseases, such as very early onset inflammatory bowel disease (VEOIBD), 3 autoimmune thyroid diseases, 4 and diabetes. IL-10 polymorphisms are also associated with some infectious diseases, including otitis media, rhinovirus infection, and pulmonary tuberculosis. 5, 6 However, whether these variants are associated with severe infections because of influenza has not been reported. We reported the first case of a child with influenza virus-related systemic inflammatory response syndrome. CASE REPORT The patient, who was born at the 38th week of gestation, developed chronic diarrhea soon after his birth. His father had chronic nephritis. However, none of his family members had a history of inflammatory bowel diseases. His parents were not consanguineous, although they were from the same geographical region in Japan. He first developed fever at 10 days of life and recurrent fever thereafter, particularly after immunizations. A perianal skin tag developed at 21 days of life, and growth failure gradually became apparent. Ketotifen was used for skin eczema. However, no improvement was observed. At 5 months, he was referred to our hospital. On consultation, he presented with eczema, and anal fistula with rectal stenosis was observed during rectal examination (Fig 1). Bloody diarrhea was also observed. His IL-10RA Mutation as a Risk Factor of Severe Influenza-Associated Encephalopathy: A Case Report Takashi Ishige, MD, PhD, a,b Yoshiko Igarashi, MD, a Reiko Hatori, MD, PhD, a Maiko Tatsuki, MD, a Yoji Sasahara, MD, PhD, c Takumi Takizawa, MD, PhD, a Hirokazu Arakawa, MD, PhD a Influenza-associated encephalitis and encephalopathy (IAE) is a severe complication of influenza infection with high morbidity and mortality. We present the case of a patient with IL-10RA mutation who developed encephalopathy after influenza infection. A 10-day-old boy developed recurrent fever and anal fistula. Growth failure gradually became apparent. He had been treated with antibiotics and elemental nutrition. However, the patient did not respond to the treatments. At 11 months, he suddenly developed shock with encephalopathy and multiple organ failures. He was then diagnosed with IAE. A cytokine study revealed elevated levels of IL-1 receptor antagonist, IL-2, IL-6, IL-8, IP-10, eotaxin, G-CSF, MCP-1, and IL-10. These cytokines are normally downregulated by IL-10. Genetic testing revealed a IL-10RA mutation at the 3′ end of exon 4 (c.537G→A). These findings might reflect an increased risk of severe IAE in patients with IL-10RA mutation. abstract To cite: Ishige T, Igarashi Y, Hatori R, et al. IL-10RA Mutation as a Risk Factor of Severe Influenza- Associated Encephalopathy: A Case Report. Pediatrics. 2018;141(6):e20173548 a Department of Pediatrics, Graduate School of Medicine, Gunma University, Maebashi, Japan; b Cell Biology Program, Inflammatory Bowel Disease Centre, The Hospital for Sick Children, Toronto, Canada; and c Department of Pediatrics, Graduate School of Medicine, Tohoku University, Miyagi, Japan Dr Ishige participated in the diagnosis of the patient, was involved in the administration of medical care, and drafted the initial manuscript; Dr Igarashi participated in the diagnosis of the patient and was involved in the administration of medical care; Drs Hatori and Tatsuki collected data and conducted the cytokine analysis; Dr Sasahara conducted the patient’s IL-10RA sequencing and performed the functional study on IL-10RA; Drs Takizawa and Arakawa designed the cytokine study and coordinated and supervised data collection; and all authors reviewed and revised manuscript and approved the final manuscript as submitted. DOI: https://doi.org/10.1542/peds.2017-3548 Accepted for publication Feb 14, 2018 Address correspondence to Takashi Ishige, MD, PhD, Department of Pediatrics, Graduate School of Medicine, Gunma University, 3-39-22 Showamachi, Maebashi, Gunma 371-8511, Japan. E-mail: ishiget@ gunma-u.ac.jp PEDIATRICS (ISSN Numbers: Print, 0031-4005; Online, 1098-4275). Copyright © 2018 by the American Academy of Pediatrics FINANCIAL DISCLOSURE: The authors have indicated they have no financial relationships relevant to this article to disclose. FUNDING: No external funding. POTENTIAL CONFLICT OF INTEREST: The authors have indicated they have no potential conflicts of interest to disclose. PEDIATRICS Volume 141, number 6, June 2018:e20173548 CASE REPORT by guest on May 23, 2020 www.aappublications.org/news Downloaded from