Terminal illeitis and cytotoxic lesion of corpus callous as the presenting features of multisystem inflammatory syndrome in children: a case report

doi:10.21203/rs.3.rs-1438906/v1

Download PDF

Research Article

Terminal illeitis and cytotoxic lesion of corpus callous as the presenting features of multisystem inflammatory syndrome in children: a case report

https://doi.org/10.21203/rs.3.rs-1438906/v1

This work is licensed under a CC BY 4.0 License

Version 1

posted

You are reading this latest preprint version

Background

Multisystem inflammatory syndrome in children (MIS-C) is a postviral inflammatory vasculopathy characterized by persistent fever, multiorgan dysfunction, significant laboratory markers of inflammation, lack of an alternative diagnosis, and prior SARS-CoV-2 infection or exposure in children and adolescents. The most common early symptoms include a prolonged fever, as well as dermatologic, mucocutaneous, and GI symptoms such abdominal pain, vomiting, and diarrhea.

Case presentation

We present a pediatric patient with a multisystem inflammatory syndrome with the development of abdominal pain and seizure who was found to have a circumferential wall thickening of the terminal ileum and ileocecal junction in abdominal and pelvic CT, and brain MRI showed cytotoxic lesions of the corpus callosum (CLOCC) that have hypersignal intensity with a few diffusion restrictions in the splenium of the corpus calusom.

Conclusion

This case is being reported to raise awareness of MIS-C presenting characteristics. Given the rising number of MIS-C patients and a lack of understanding of early diagnostic clinical characteristics and therapy, further research into clinical presentations, treatment, and outcomes is urgently needed.

MIS-C

cytotoxic lesions of the corpus callosum

terminal ileitis

seizure

Multisystem inflammation syndrome in children (MIS-C), a severe and potentially lethal complication of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, has protean clinical manifestation (1). The pathophysiology of MIS-C is not well understood and may be related to an abnormal immune response to the virus (2). This syndrome is characterized by fever and clinical and laboratory evidence of multisystem inflammation leading to cardiovascular, pulmonary, nervous, hematological, and gastrointestinal dysfunction in patients with recent SARS-C0V-2 infection (3).

Gastrointestinal symptoms including abdominal pain, vomiting, and diarrhea are common in patients with COVID-19 infection and MIS-C and may mimic appendicitis due to involvement of the terminal ileum (4-6). Most patients with terminal ileitis related to SARAS-CoV2 infection have been reported in association with COVID-19 disease, but few studies have described terminal ileitis as the presenting manifestation of MIS-C.

In this article, we describe a child with MIS-C presenting with fever, clinical and radiologic evidence of terminal ileitis, and seizure who was referred to a tertiary hospital in Iran and improved with medical management.

The patient was an 11-year-old child weighing 38 kg admitted to Namazi Teaching Hospital affiliated to Shiraz University of Medical Sciences, southern Iran with complaints of fever and chills from three days before hospitalization in on June 15, 2021. He had also been suffering from watery diarrhea, several episodes of vomiting, abdominal pain, and two episodes of spastic abnormal movement in his upper and lower extremities, accompanied by a decreased level of consciousness, each lasting for about 10 minutes in this period. He was a known case of mitral valve regurgitation and had received propranolol. The patient had been exposed to a COVID 19 one month prior to the presentation, but he denied any symptoms.

On arrival, he seemed ill and was conscious with mild respiratory distress. The heart rate was 134 beats per minute, blood pressure 98/42, respiratory rate 40 beats per minute, oral temperature 38 degrees Celsius, and arterial oxygen saturation was 95% in room air. There was no meningeal sign. On abdominal examination, guarding and generalized tenderness with the greatest intensity in the right lower quadrant were detected. Other physical examinations, including evaluation of the nervous system, was normal. Based on the working diagnosis of systemic sepsis secondary to suspected appendicitis and COVID-19, the patient was isolated and ceftriaxone (100 mg/kg/day), metronidazole (30_40 mg/kg/day IV divided q8h) and phenytoin (loading dose, 20 mg/kg and then 5 mg/kg/day) were prescribed intravenously. The COVID-19 evaluation included polymerase chain reaction (PCR) on his nasopharyngeal sample for COVID-19, COVID-19 serology, and inflammatory markers for MIS-C (Table 1). On the 3^rd day of admission, he developed a maculopapular rash all over his body and redness in his oral mucosa and lips.

Table 1 shows the patient's laboratory data during hospitalization.

Seventh day of admission	Third day of admission	Second day of admission	first day of admission	Lab Data
	20800	4900	3500	WBC, count/mm³
	4/11	8/10	11/1	Hemoglobin, gm/dL
	1/73		3/70	MCV, fL
	152000	107000	105000	Platelet /mm³
	8/13	15	16/7	Prothrombin time, sec
	1	09/1	1/21	INR, index
	1/36	9/43	45/3	PTT, sec
		142	123	Blood sugar, mg/dL
	14	9	9	B.U.N, mg/dL
	7/0	7/0	7/0	Cr, mg/dL
		136	137	Na, mEq/L
		9/4	8/2	K, mEq/L
	27		140	AST, IU/L
	39		120	ALT, IU/L
	299		569	ALK.P, IU/L
	6/0		6/0	Bilirubin Total
	3/0		3/0	Bilirubin Direct
		62		Amylase
	3/7		8/5	Total protein, g/dL
	3		3.3	Albumin, g/dL
	549		674	LDH, IU/L
66			72	ESR, mm/h
	30		112	CPK, IU/L
	Negative		Negative	Wright
13	>150		>150	CRP, mg/L
		6/1514		Ferritin, ng/mL
			1/16	Troponin I rapid test
		7/15		D-dimer,(mg/L)
Negative				Blood culture
Negative				Urine culture
	Negative	Negative		Stool OB-OP
	Negative		negative	PCR COVID
		39/6		IgG COVID (Positive>1.1)
		57/0		IgM COVID (Positive>1.1)

INR, international normal ratio; MCV, mean corpuscular volume; PTT, partial prothrombin time;

The result of the COVID-19 PCR was negative, but the serology for SARS-CoV-2 was positive. Laboratory investigations revealed leukopenia, microcytic anemia, thrombocytopenia, hypoalbuminemia, and elevated levels of liver enzymes, C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), lactate dehydrogenase (LDH), and ferritin. Table 1 shows the patient's laboratory data during hospitalization. The patient underwent an ultrasound and then a computed tomography (CT) scan of the abdomen, which both showed thickening of the terminal ileum and ileoscal valve and also lymphadenopathy in the right iliac region (Figs 2 and 3). The EEG showed some paroxysmal generalized epileptic discharge and the brain MRI showed cytotoxic lesions of the corpus callosum that have a hypersignal intensity with a few diffusion restrictions in the splenium of the corpus calusom(SCC) in T2, FLAIR view (Fig 4). The CT scan of the lung showed ground glass opacity (GGO) in the lower parts of both lungs, especially on the right side (Fig 1). Echocardiography of the patient was only in favor of mitral valve regurgitation.

Therefore, considering the diagnosis of MIS-C, methyl prednisolone intravenously (2 mg/kg/d) and intravenous immunoglobulin (IVIG) infusion (2 g/kg/d) were started. During the 10-day hospitalization, fever, diarrhea, and abdominal pain gradually improved, and he was discharged in good general condition with prednisolone (1 mg/kg/d) and phenytoin (5 mg/kg/d) orally. During follow-up after discharge, the prednisolone was tapered and eventually discontinued after 2 weeks without any recurrence of symptoms. The patient's electroencephalogram was repeated, which was normal, and phenytoin was discontinued due to no recurrence of seizures.

We presented an 11-year-old boy with MIS-C, which was characterized by fever, multisystem involvement including the gastrointestinal tract (diarrhea, abdominal pain, terminal ileitis, and elevated liver enzymes), neurologic (seizure, lesions in SCC), respiratory (GGO in lung), and dermatologic (maculopapular rash), laboratory evidence of inflammation (lymphocytopenia, hypoalbuminemia, and elevated levels of CRP, ESR, ferritin, and LDH), no other obvious microbial cause of inflammation, and evidence of SARS-CoV-2 infection (positive serology for COVID-19). Both OCVID-19 and MIS-C have gastrointestinal manifestations, but terminal ileitis has been reported in a few children with COVID-19 and fewer patients with MIS-C.

Terminal ileitis refers to inflammation of the end of the ileum that may present acutely as lower right quadrant pain in the abdomen with or without diarrhea, chronic obstructive symptoms, and gastrointestinal bleeding that could mimic acute appendicitis (7). TI usually occurs in association with a wide range of etiologies, including inflammatory bowel diseases (Crohn's disease and, to a lesser frequency, ulcerative colitis), taking nonsteroidal anti-inflammatory drugs, ischemia, eosinophil enteritis, neoplasms (lymphoma), vasculitis, spondyloarthropathy, lymphoid hyperplasia, and infectious agents. Bacterial pathogens such as Mycobacterium tuberculosis, Yersinia, Salmonella, and Clostridium difficile have been reported as infectious agents leading to TI (8-11). Viral pathogens such as cytomegalovirus can also cause TI (12). Recently, in two case reports, TI was reported in two children (11-year old and 12 year old) with SARS-CoV-2 infection presenting with acute abdominal manifestations (13, 14).

Only a few cases of TI in children with MIS-C have been reported. In a short report from a single center in the UK, eight children with COVID-19 and symptoms of atypical appendicitis who had imaging confirming TI were reported. Three patients developed a systemic inflammatory response; two of them were initially planned for appendectomy, but the decisions for operative intervention were subsequently overturned due to hemodynamic instability or a positive SARS-CoV-2 PCR. Ultimately, all children improved without any surgical intervention (15). In a single -center study from the USA, 34 out of 35 (97%) children with MIS-C had gastrointestinal symptoms, and 19 of 35 had moderate to severe abdominal symptoms that warranted radiographic imaging. In four of seven patients for whom CT scans of the abdomen were done, terminal ileitis was detected, and in two of fourteen patients for whom abdominal ultrasonography was preformed, mild ileal thickening was reported. In one patient who presented with bowel obstructive symptoms and underwent ileocolic resection, there was a 6 cm mass in the ileocolic pedicle and a 3 cm span of granular, thickened terminal ileal mucosa. All other patients improved with medical therapy including, at least 1 dose of IVIG, Corticosteroids, aspirin, and infliximab were added based on clinical severity (3).

In another cohort study conducted on 32 children with MIS-C and left ventricular dysfunction or cardiogenic shock admitted to 15 hospitals in France and Switzerland, two patients underwent emergency laparotomy for suspected appendicitis, finally diagnosed as mesenteric adenolymphitis not TI. (16) In another short report from South Africa, two of 23 children with MIS-C had operation for suspected appendicitis. The etiology of acute abdomen was not explained to be mesenteric adenolymphitis or TI. (17).

The seizure was a neurologic manifestation in this patient, and there was hypersignal intensity with a few diffusion restrictions in the splenium of the corpus callosum (SCC) detected in brain MRI. There are a wide range of etiologies leading to lesions in SCC including callosal malformations, disorders of myelination (X-linked adrenoleukodystrophy and hereditary Krabbe's disease), tumors, hypoglycemia, ischemia due to hypoxia, epilepsy itself, diffuse axonal injury secondary to trauma , Marchiafava–Bignami disease secondary to chronic alcoholics and vitamin B12 deficiency, post shunt decompression in chronic hydrocephalus, certain antiepileptic drugs, encephalopathy due to hemolytic–uremic syndrome, infective agents (influenza, rotavirus, mumps, Escherichia coli, adenovirus, aspergillus, mycobacterium tuberculosis), AIDS dementia complex, mild encephalitis/encephalopathy with reversible isolated SCC lesion (MERS), posterior reversible encephalopathy syndrome, and multiple sclerosis(18-20) . The inflammation of brain tissue or vessels are the most probable etiology of lesions in SCC in this patient. We hypothesized that the cytotoxic lesion of the corpus callosum, in the index case, was secondary to the systemic inflammation from SARS-CoV-2 infection, resulting in multisystem inflammatory syndrome in children.

The occurrence of seizure secondary to the cytotoxic lesion of the corpus callosum and severe abdominal tenderness secondary to TI as the presenting manifestations in this patient urged us to report him to convey an important best practice message. Physicians should consider the possibility of cytotoxic lesion of the corpus callosum and TI in MIS-C patients that present with seizure and severe acute abdominal symptom and perform timely imaging studies and start proper medical treatment as soon as possible to avoid unnecessary surgical intervention.

MIS-C

Multisystem inflammatory syndrome in children

CLOCC

Cytotoxic lesions of the corpus callosum

SCC

Splenium of the corpus calusom

GGO

Ground glass opacity

IVIG

Intravenous immunoglobulin

Terminal ileitis

Ethical approval and consent to participate

The informed consent of the child's parents has been obtained for the publication of this report. Institutional approval from The Research Ethics Committee of Shiraz University of Medical Sciences has been obtained to publish. File number :( IR.sums.med.rec.1400.269).

Availability of data and materials

Not applicable

Competing interests

The authors declare that they have no competing interests

Funding

This article has not received any financial support

Acknowledgements

Not applicable

Authors’ contribution:

The disease was diagnosed by SSH. MD, AD, and AA were responsible for the care of the patient during hospitalization and follow-up. MD, GP, AD and MK contributed to the draft of the paper and literature research. SSH contributed to the writing and review of the paper. All authors read and approved the final manuscript.

1- Rowley AH. Understanding SARS-CoV-2-related multisystem inflammatory syndrome in children. Nature Reviews Immunology. 2020; 20(8):453-4.

2- Tsurikova N, Rodionocskaya S, Ligostaeva E, Avdeenko V, Kobzeva N, Tsiganok I. P053 Fulminant purpura in a patient with SARS-CoV-2. Rheumatology (Oxford). 2021 Apr 26; 60(Suppl 1):keab247.050. doi: 10.1093/rheumatology/keab247.050. PMCID: PMC8135528.

3- Sahn B, Eze OP, Edelman MC, Chougar CE, Thomas RM, Schleien CL, Weinstein T. Features of Intestinal Disease Associated With COVID-Related Multisystem Inflammatory Syndrome in Children. J Pediatr Gastroenterol Nutr. 2021 Mar 1;72(3):384-387. doi: 10.1097/MPG.0000000000002953. PMID: 32969960; PMCID: PMC7901530.

4-Belhadjer Z, Méot M, Bajolle F, et al. Acute heart failure in multisystem inflammatory syndrome in children (MIS-C) in the context of global SARS-CoV-2

Pandemic. Circulation 2020.

5-Tullie L, Ford K, Bisharat M, et al. Gastrointestinal features in children with COVID-19: an observation of varied presentation in eight children. Lancet Child

Adolesc Health 2020; 4:e19.

6- Mirahmadizadeh A, Borazjani R, Ebrahimi M, Hashemizadeh Haghighi L, Kamali K, et al. COVID-19 Presented with Gastrointestinal Manifestations in an 11-Days-Old Neonate: A Case Report and Review of the Literature, Arch Pediatr Infect Dis. 8(3): e104508. doi: 10.5812/pedinfect.104508.

7- Goulart RA, Barbalho SM, Gasparini RG, de Carvalho AC. Facing Terminal Ileitis: Going Beyond Crohn's Disease. Gastroenterology Res. 2016 Feb;9(1):1-9. doi: 10.14740/gr698w. Epub 2016 Mar 8. PMID: 27785317; PMCID: PMC5051106.

8- Kim DH, Cheon JH. Intestinal Behcet's Disease: A True Inflammatory Bowel Disease or Merely an Intestinal Complication of Systemic Vasculitis? Yonsei Med J. 2016; 57(1):22–32. doi: 10.3349/ymj.2016.57.1.22. [PMC free article] [PubMed] [CrossRef] [Google Scholar]

9- Adamek HE, Schantzen W, Rinas U, Goyen M, Ajaj W, Esser C. Ultra-high-field magnetic resonance enterography in the diagnosis of ileitis (Neo-)terminalis: a prospective study. J Clin Gastroenterol. 2012; 46(4):311–316. doi: 10.1097/MCG.0b013e31822fec0c. [PubMed] [CrossRef] [Google Scholar]

10- Bojic D, Markovic S. Terminal ileitis is not always Crohn's disease. Ann Gastroenterol. 2011; 24(4):271–275. [PMC free article] [PubMed] [Google Scholar]

.11- Dilauro S, Crum-Cianflone NF. Ileitis: when it is not Crohn's disease. Curr Gastroenterol Rep. 2010; 12(4):249–258. doi: 10.1007/s11894-010-0112-5. [PMC free article] [PubMed] [CrossRef] [Google Scholar]

12-Wajsman R, Cappell MS, Biempica L, Cho KC. Terminal ileitis associated with cytomegalovirus and the acquired immune deficiency syndrome. Am J Gastroenterol. 1989 Jul; 84(7):790-3. PMID: 2545093.

13- Periyakaruppan M, Kumar S, Kandasamy S, Thiagarajan A, Sangaralingam T, Ganapathy N. COVID abdomen: SARS-CoV-2 infection presenting as 'acute abdomen' in a child. Crit Care Emerg Med. 2020. https://doi.org/10.21203/rs.3.rs-35865/v1.

14- Aslan, N., Yildizdas, D. & Sinanoglu, M.S. A Pediatric COVID19 Case with Suspected Acute Abdomen, Hyperferritinemic Sepsis and Developing MIS-C and Pancreatitis. Indian J Pediatr 88, 288 (2021). https://doi.org/10.1007/s12098-020-03544-0

15. Tullie L, Ford K, Bisharat M, Watson T, Thakkar H, Mullassery D, Giuliani S, Blackburn S, Cross K, De Coppi P, Curry J. Gastrointestinal features in children with COVID-19: an observation of varied presentation in eight children. Lancet Child Adolesc Health. 2020;4(7):e19. Epub 2020 May 20.

16. Belhadjer Z, Méot M, Bajolle F, Khraiche D, Legendre A, Abakka S, Auriau J, Grimaud M, Oualha M, Beghetti M, Wacker J, Ovaert C, Hascoet S, Selegny M, Malekzadeh-Milani S, Maltret A, Bosser G, Giroux N, Bonnemains L, Bordet J, Di Filippo S, Mauran P, Falcon-Eicher S, Thambo JB, Lefort B, Moceri P, Houyel L, Renolleau S, Bonnet D. Acute Heart Failure in Multisystem Inflammatory Syndrome in Children in the Context of Global SARS-CoV-2 Pandemic. Circulation. 2020; 142(5):429. Epub 2020 May 17.

17. Webb K, Abraham DR, Faleye A, McCulloch M, Rabie H, Scott C, Cape Town MISC-Team.

Multisystem inflammatory syndrome in children in South Africa. Lancet Child Adolesc Health. 2020;4(10):e38. Epub 2020 Aug 21.

18-Aamish Z Kazi, Priscilla C Joshi, Abhimanyu B Kelkar, Mangal S Mahajan, and Amit S Ghawate. MRI evaluation of pathologies affecting the corpus callosum: A pictorial essay. Indian J Radiol Imaging. 2013 Oct-Dec; 23(4): 321–332.

19-akanashi J, Barkovich AJ, Yamaguchi K, Kohno Y. Influenza-associated encephalitis/encephalopathy with a reversible lesion in the splenium of the corpus callosum: A case report and literature review. Am J Neuroradiol. 2004;25:798–802

20- Malhotra HS, Garg RK, Vidhate MR, Sharma PK. Boomerang sign: Clinical significance of transient lesion in splenium of corpus callosum. Ann Indian Acad Neurol. 2012;15:151–7.

Download PDF

Version 1

posted

You are reading this latest preprint version

Terminal illeitis and cytotoxic lesion of corpus callous as the presenting features of multisystem inflammatory syndrome in children: a case report

Status:

Version 1

Abstract

Figures

Background

Case Presentation

Discussion and conclusion

Abbreviations

Declarations

References

Status:

Version 1