Association between MIS-C and Functional Gastrointestinal Disorders in Children: A Cross-Sectional Study

Abstract

Objective Multisystem inflammatory syndrome in children (MIS-C) is a serious complication of coronavirus disease 2019 which causes a hyperinflammatory syndrome that can affect all organ systems. Functional gastrointestinal disorders (FGIDs) are a heterogeneous disease spectrum with unclear etiology. Today, it is known that low-grade inflammation can cause FGIDs. Our aim in this study was to investigate whether there is a higher frequency of FGID in children diagnosed with MIS-C.

Methods In this study, 48 pediatric patients diagnosed with MIS-C were evaluated for functional gastrointestinal diseases according to the Rome IV criteria at least 6 months after diagnosis. The control group consisted of 61 pediatric patients without any chronic disease.

Results In our study, the overall prevalence of FGIDs was 54.1% (n = 26) in the patient group and 22.9% (n = 14) in the control group. The difference between the groups was statistically significant (p < 0.001). The frequencies of undiagnosed abdominal pain, irritable bowel syndrome, constipation, and dyspepsia were 41.6% (n = 20), 12.5% (n = 6), 8.3% (n = 4), and 6.2% (n = 3) in the patient group, respectively. In the control group, the corresponding rates were 9.8% (n = 6), 3.2% (n = 2), 4.9% (n = 3), and 4.9% (n = 3), respectively. A significant difference was observed between the patient and control groups in terms of functional abdominal pain (p < 0.001).

Conclusion The overall frequency of FGIDs and the prevalence of functional abdominal pain were higher in MIS-C patients than in control subjects. The data from this study support the hypothesis that FGIDs are more common in patients diagnosed with MIS-C than in healthy controls.

Keywords

children - functional gastrointestinal disorders - MIS-C - pediatric - Rome IV

Ethics Approval

This study was performed in line with the principles of the Declaration of Helsinki. Approval was granted by the Adıyaman University Faculty of Medicine Non-Interventional Clinical Research Ethics Committee.

Consent to Participate

Informed consent was obtained from legal guardians to participate.

Consent for Publication

Informed consent was obtained from legal guardians for publication.

Publikationsverlauf

Eingereicht: 30. März 2023

Angenommen: 17. August 2023

Artikel online veröffentlicht:
22. September 2023

• References

• 1 Castagnoli R, Votto M, Licari A. et al. Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infection in children and adolescents: a systematic review. JAMA Pediatr 2020; 174 (09) 882-889
• 2 Royal College of Paediatrics and Child Health. Guidance: paediatric multisystem inflammatory syndrome temporally associated with COVID-19. Accessed April 3, 2022 at: https://www.rcpch.ac.uk/work-we-do/bpsu/study-multisystem-inflammatory-syndrome-kawasaki-disease-toxic-shock-syndrome
• 3 Centers for Disease Control and Prevention. Multisystem Inflammatory Syndrome in Children (MIS-C) Associated with Coronavirus Disease 2019 (COVID-19). Accessed April 3, 2022 at: https://www.cdc.gov/mis/mis-c.html
• 4 World Health Organization. Multisystem inflammatory syndrome in children and adolescents with COVID-19. Accessed April 3, 2022 at: https://www.who.int/news-room/commentaries/detail/multisystem-inflammatory-syndrome-in-children-and-adolescents-with-covid-19
• 5 Esposito S, Principi N. Multisystem inflammatory syndrome in children related to SARS-CoV-2. Paediatr Drugs 2021; 23 (02) 119-129
• 6 Dufort EM, Koumans EH, Chow EJ. et al; New York State and Centers for Disease Control and Prevention Multisystem Inflammatory Syndrome in Children Investigation Team. Multisystem inflammatory syndrome in children in New York state. N Engl J Med 2020; 383 (04) 347-358
• 7 Feldstein LR, Rose EB, Horwitz SM. et al; Overcoming COVID-19 Investigators, CDC COVID-19 Response Team. Multisystem inflammatory syndrome in U.S. children and adolescents. N Engl J Med 2020; 383 (04) 334-346
• 8 Yilmaz Ciftdogan D, Ekemen Keles Y, Cetin BS. et al. COVID-19 associated multisystemic inflammatory syndrome in 614 children with and without overlap with Kawasaki disease-Turk MIS-C study group. Eur J Pediatr 2022; 181 (05) 2031-2043
• 9 Sahn B, Eze OP, Edelman MC. et al. Features of intestinal disease associated with COVID-related multisystem inflammatory syndrome in children. J Pediatr Gastroenterol Nutr 2021; 72 (03) 384-387
• 10 Talley NJ. Functional gastrointestinal disorders as a public health problem. Neurogastroenterol Motil 2008; 20 (Suppl. 01) 121-129
• 11 Boronat AC, Ferreira-Maia AP, Matijasevich A, Wang YP. Epidemiology of functional gastrointestinal disorders in children and adolescents: a systematic review. World J Gastroenterol 2017; 23 (21) 3915-3927
• 12 Koloski NA, Talley NJ, Boyce PM. Epidemiology and health care seeking in the functional GI disorders: a population-based study. Am J Gastroenterol 2002; 97 (09) 2290-2299
• 13 Keely S, Walker MM, Marks E, Talley NJ. Immune dysregulation in the functional gastrointestinal disorders. Eur J Clin Invest 2015; 45 (12) 1350-1359
• 14 Kassinen A, Krogius-Kurikka L, Mäkivuokko H. et al. The fecal microbiota of irritable bowel syndrome patients differs significantly from that of healthy subjects. Gastroenterology 2007; 133 (01) 24-33
• 15 Annaházi A, Ferrier L, Bézirard V. et al. Luminal cysteine-proteases degrade colonic tight junction structure and are responsible for abdominal pain in constipation-predominant IBS. Am J Gastroenterol 2013; 108 (08) 1322-1331
• 16 Matricon J, Meleine M, Gelot A. et al. Review article: associations between immune activation, intestinal permeability and the irritable bowel syndrome. Aliment Pharmacol Ther 2012; 36 (11–12): 1009-1031
• 17 Vanheel H, Vicario M, Vanuytsel T. et al. Impaired duodenal mucosal integrity and low-grade inflammation in functional dyspepsia. Gut 2014; 63 (02) 262-271
• 18 Martínez C, Lobo B, Pigrau M. et al. Diarrhoea-predominant irritable bowel syndrome: an organic disorder with structural abnormalities in the jejunal epithelial barrier. Gut 2013; 62 (08) 1160-1168
• 19 Deshmukh V, Motwani R, Kumar A, Kumari C, Raza K. Histopathological observations in COVID-19: a systematic review. J Clin Pathol 2021; 74 (02) 76-83
• 20 Britton GJ, Chen-Liaw A, Cossarini F. et al. Limited intestinal inflammation despite diarrhea, fecal viral RNA and SARS-CoV-2-specific IgA in patients with acute COVID-19. Sci Rep 2021; 11 (01) 13308
• 21 Whittaker E, Bamford A, Kenny J. et al; PIMS-TS Study Group and EUCLIDS and PERFORM Consortia. Clinical characteristics of 58 children with a pediatric inflammatory multisystem syndrome temporally associated with SARS-CoV-2. JAMA 2020; 324 (03) 259-269
• 22 Gruber CN, Patel RS, Trachtman R. et al. Mapping systemic inflammation and antibody responses in multisystem inflammatory syndrome in children (MIS-C). Cell 2020; 183 (04) 982-995.e14
• 23 Consiglio CR, Cotugno N, Sardh F. et al; CACTUS Study Team. The immunology of multisystem inflammatory syndrome in children with COVID-19. Cell 2020; 183 (04) 968-981.e7
• 24 Kindt S, Van Oudenhove L, Broekaert D. et al. Immune dysfunction in patients with functional gastrointestinal disorders. Neurogastroenterol Motil 2009; 21 (04) 389-398
• 25 Rajindrajith S, Zeevenhooven J, Devanarayana NM, Perera BJC, Benninga MA. Functional abdominal pain disorders in children. Expert Rev Gastroenterol Hepatol 2018; 12 (04) 369-390
• 26 Hyams JS, Di Lorenzo C, Saps M, Shulman RJ, Staiano A, van Tilburg M. Functional disorders: children and adolescents. Gastroenterology 2016; 16: 181-185
• 27 Akiho H, Ihara E, Nakamura K. Low-grade inflammation plays a pivotal role in gastrointestinal dysfunction in irritable bowel syndrome. World J Gastrointest Pathophysiol 2010; 1 (03) 97-105
• 28 Lewis ML, Palsson OS, Whitehead WE, van Tilburg MAL. Prevalence of functional gastrointestinal disorders in children and adolescents. J Pediatr 2016; 177: 39-43.e3
• 29 Korterink JJ, Diederen K, Benninga MA, Tabbers MM. Epidemiology of pediatric functional abdominal pain disorders: a meta-analysis. PLoS One 2015; 10 (05) e0126982
• 30 Youssef NN, Murphy TG, Langseder AL, Rosh JR. Quality of life for children with functional abdominal pain: a comparison study of patients' and parents' perceptions. Pediatrics 2006; 117 (01) 54-59
• 31 Chang L. Review article: epidemiology and quality of life in functional gastrointestinal disorders. Aliment Pharmacol Ther 2004; 20 (Suppl. 07) 31-39
• 32 Yasuhara J, Watanabe K, Takagi H, Sumitomo N, Kuno T. COVID-19 and multisystem inflammatory syndrome in children: a systematic review and meta-analysis. Pediatr Pulmonol 2021; 56 (05) 837-848
• 33 Bautista-Rodriguez C, Sanchez-de-Toledo J, Clark BC. et al. Multisystem inflammatory syndrome in children: an international survey. Pediatrics 2021; 147 (02) e2020024554
• 34 Walker MM, Talley NJ, Prabhakar M. et al. Duodenal mastocytosis, eosinophilia and intraepithelial lymphocytosis as possible disease markers in the irritable bowel syndrome and functional dyspepsia. Aliment Pharmacol Ther 2009; 29 (07) 765-773
• 35 Barbara G, Grover M, Bercik P. et al. Rome Foundation Working Team report on post-infection irritable bowel syndrome. Gastroenterology 2019; 156 (01) 46-58.e7
• 36 Schmulson M, Ghoshal UC, Barbara G. Managing the inevitable surge of post-COVID-19 functional gastrointestinal disorders. Am J Gastroenterol 2021; 116 (01) 4-7
• 37 Börekci E, Celikbilek M, Soytürk M, Akar S, Börekci H, Günaydin I. Functional gastrointestinal disorders in patients with familial Mediterranean fever. Int J Rheum Dis 2017; 20 (12) 2101-2105
• 38 Miller J, Cantor A, Zachariah P, Ahn D, Martinez M, Margolis KG. Gastrointestinal symptoms as a major presentation component of a novel multisystem inflammatory syndrome in children that is related to coronavirus disease 2019: a single center experience of 44 cases. Gastroenterology 2020; 159 (04) 1571-1574.e2
• 39 Cabrero-Hernández M, García-Salido A, Leoz-Gordillo I. et al. Severe SARS-CoV-2 infection in children with suspected acute abdomen: a case series from a tertiary hospital in Spain. Pediatr Infect Dis J 2020; 39 (08) e195-e198
• 40 Diorio C, Henrickson SE, Vella LA. et al. Multisystem inflammatory syndrome in children and COVID-19 are distinct presentations of SARS-CoV-2. J Clin Invest 2020; 130 (11) 5967-5975