Eur J Pediatr. 2024 Dec;183(12):5411-5418. doi: 10.1007/s00431-024-05772-4.Epub 2024 Oct 15.

Matteo Bramuzzo ¹, Mara Cananzi ², Patrizia Alvisi ³, Sabrina Cardile ⁴, Claudio Romano ⁵, Marina Aloi ⁶, Serena Arrigo ⁷, Enrico Felici ⁸, Luisa Lonoce ⁹, Elena Sofia Pieri ¹⁰, Luca Scarallo ^11 12, Caterina Strisciuglio ¹³, Andrea Di Siena ¹⁴, Sara Lega ¹⁵

Author information

¹Institute for Maternal and Child Health (IRCCS) "Burlo Garofolo", Via Dell' Istria 65, 34137, Trieste, Italy. matteo.bramuzzo@burlo.trieste.it.

²Unit of Gastroenterology, Digestive Endoscopy, Hepatology and Care of the Child With Liver Transplantation, Dpt. of Women's and Children's Health, University Hospital of Padova, Padua, Italy.

³Pediatric Gastroenterology Unit, Maggiore "CA Pizzardi" Hospital, Bologna, Italy.

⁴Gastroenterology, Digestive Endoscopy and Nutrition Unit, Bambino Gesù Children Hospital IRCCS, Rome, Italy.

⁵Pediatric Gastroenterology and Cystic Fibrosis Unit, Department of Human Pathology in Adulthood and Childhood "G. Barresi", University of Messina, Messina, Italy.

⁶Pediatric Gastroenterology and Hepatology Unit, Sapienza University of Rome, Umberto I Hospital, Rome, Italy.

⁷Pediatric Gastroenterology and Endoscopy, IRCCS Istituto Giannina Gaslini, Genoa, Italy.

⁸Pediatric and Pediatric Emergency Unit, Children Hospital, AOU SS Antonio E Biagio E C. Arrigo, Alessandria, Italy.

⁹Clinical Pediatrics, Department of Molecular Medicine and Development, Azienda Ospedaliera Universitaria Senese, University of Siena, Siena, Italy.

¹⁰Pediatric Clinic, Perugia University, Perugia, Italy.

¹¹Gastroenterology and Nutrition Unit, Meyer Children's Hospital IRCCS, Florence, Italy.

¹²Department of NEUROFARBA, University of Florence, Florence, Italy.

¹³Department of Woman, Child and General and Specialized Surgery, University of Campania "Luigi Vanvitelli", Naples, Italy.

¹⁴Division of Pediatrics, Department of Medicine (DAME), University of Udine, Udine, Italy.

¹⁵Institute for Maternal and Child Health (IRCCS) "Burlo Garofolo", Via Dell' Istria 65, 34137, Trieste, Italy.

Abstract

Hemophagocytic Lymphohistiocytosis (HLH)/Macrophage Activation Syndrome (MAS) in children with inflammatory bowel disease (IBD) has been reported only anecdotally. This study aimed at describing the clinical features and outcomes of children diagnosed with both IBD and HLH/MAS. Data on IBD and HLH/MAS characteristics, biochemical, microbiological and genetic assessments, treatments, and outcomes were collected from the Italian Pediatric IBD Registry and presented using descriptive statistics. Out of 4643 patients with IBD, 18 (0.4%) were diagnosed with HLH/MAS, including 12 with ulcerative colitis and 6 with Crohn disease. Among the 18 patients, 7 (39%) had early-onset IBD, but the median age at HLH/MAS diagnosis was 14.0 years (IQR 11.9-16.0). Half of the patients had active IBD at HLH/MAS diagnosis, 11 (61%) patients were on thiopurines, and 6 (33%) were on anti-TNF biologics. An infectious trigger was identified in 15 (83%) patients. One (5%) patients was diagnosed with XIAP deficiency. All patients discontinued thiopurines and 5 (83.3%) discontinued anti-TNF biologics; 16 (80%) patients received steroids for HLH/MAS. Three (17%) patients had a relapse of HLH/MAS. No patient developed lymphoma or died during a median follow-up of 2.7 years (IQR 0.8-4.4). Conclusions: HLH/MAS mainly affects children with early-onset IBD but primarily develops during adolescence, following an infection while on immunosuppressant treatment. Although the prognosis is generally favorable, it is crucial to investigate an underlying immune deficiency.