We presented an 11-year-old boy with MIS-C, who presented with fever and multisystem involvement of the gastrointestinal tract (diarrhea, abdominal pain, terminal ileitis, and elevated liver enzymes), the nervous system (seizure, lesions in SCC), the respiratory system (GGO in the lungs), and the skin (maculopapular rash), with laboratory evidence of inflammation (lymphocytopenia, hypoalbuminemia, and elevated levels of CRP, ESR, Ferritin, and LDH), no other apparent microbial cause of inflammation, and evidence of SARS-CoV-2 infection (positive serology for COVID-19). Both COVID-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 is the inflammation of the end-portion of the ileum that may present acutely as abdominal pain, mainly in the right lower quadrant with or without diarrhea, chronic bowel obstruction symptoms, and gastrointestinal bleeding that could mimic acute appendicitis . 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, intestinal ischemia, eosinophilic 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 causing TI [8,9,10,11]. Viral pathogens such as Cytomegalovirus can also cause TI . In two case reports, TI was recently reported in two children (11and 12 years old) with SARS-CoV-2 infection who presented with acute abdomen [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 whose imaging studies confirmed TI were reported. Three patients developed Systemic Inflammatory Response Syndrome; two of them were initially planned for appendectomy, but the decisions for the surgical intervention were subsequently overturned due to hemodynamic instability or a positive SARS-CoV-2 PCR. Ultimately, all children improved without any surgical interventions . In a single-center study from the USA, 34 out of 35 (97%) children with MIS-C had gastrointestinal symptoms, and 19 out of 35 had moderate to severe abdominal symptoms that warranted radiographic imaging. In four out of seven patients for whom CT scan of the abdomen were done, terminal ileitis was detected. In two out of fourteen patients for whom abdominal ultrasonography was performed, mild ileal thickening was reported. In one patient with bowel obstruction symptoms who 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 Corticosteroids, Aspirin, Infliximab, and at least one dose of IVIG .
In a study by Yack-Corrales et al. 1010 pediatric patients with COVID-19 or MIS-C were evaluated for acute abdomen and appendicitis. Even though 34 patients were diagnosed with appendicitis, no case of terminal ileitis was found in that large cohort; therefore, such diagnoses are extremely rare .
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; however, they were finally diagnosed with mesenteric lymphadenitis . In another short report from South Africa, two of 23 children with MIS-C underwent operation for suspected appendicitis. The etiology of acute abdomen was not explained in the report .
Seizure was an indicative symptom of neurologic involvement in this patient. There was hypersignal intensity with a few diffusion restrictions in the splenium of the corpus callosum (SCC) detected in his brain MRI. There is 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 alcohol abuse and vitamin B12 deficiency, post-shunt decompression in chronic hydrocephalus, certain antiepileptic drugs, encephalopathy due to Hemolytic Uremic Syndrome, infectious agents (Influenza virus, Rotavirus, Mumps virus, Escherichia coli, Adenovirus, Aspergillus, Mycobacterium tuberculosis), AIDS dementia complex, Mild Encephalitis/Encephalopathy with Reversible isolated SCC lesion (MERS), Posterior Reversible Encephalopathy Syndrome (PRES), and Multiple Sclerosis (MS) [18,19,20]. The inflammation of brain tissue or vessels is the most probable etiology of lesions in SCC in this patient. We postulate 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.
Appleberry et al. reported a case with status epilepticus in the context of MIS-C with post-ictal cerebral edema. The patient received pulse steroids and IVIG which resulted in improvement of his condition; however, long-term neurologic deficits such as dysphagia and developmental regression persisted . Fortunately, the neurologic manifestations of our case were resolved after proper treatment with pulse steroids and IVIG.
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 essential best practice message. Physicians should consider the possibility of cytotoxic lesion of the corpus callosum and TI in MIS-C patients with seizure and severe acute abdomen symptoms, perform timely imaging studies, and start proper medical treatment as soon as possible to avoid unnecessary surgical interventions and complications.