Multisystem Inflammatory Syndrome in Children Mimicking Surgical Pathologies

Abstract

The current coronavirus 2019 (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has resulted in unprecedented devastation worldwide with a total of 6,152,160 cases diagnosed globally and 371,700 deaths as of May 31, 2020.1 New York City (NYC) quickly became a major focus of the pandemic with 200,547 diagnosed cases to date, 5513 of which are pediatric patients 17 years of age or younger.2 The true prevalence of pediatric COVID-19 cases is likely several fold higher than currently published numbers reflect as pediatric patients are less likely to exhibit symptoms of the disease and therefore less likely to undergo testing.3,4 Although early literature suggested that SARS-CoV-2 primarily affected adult patients, the development of a multiorgan inflammatory syndrome linked to COVID-19 in pediatric patients suggests that age is not protective against complications related to COVID-19 infection. The Center for Disease Control (CDC) established multisystem inflammatory syndrome in children (MIS-C) on May 14, 2020.5 Diagnostic criteria include individuals <21 years of age who have subjective or objective fever for at least 24 hours, laboratory evidence of inflammation, multiorgan involvement requiring hospitalization with recent SARS-CoV-2 infection, positive serology, or a known COVID-19 exposure in the previous 4 weeks.5 This syndrome was first reported in the United Kingdom (UK) in mid-April at which time 8 previously healthy patients presented with hyperinflammatory shock and features similar to Kawasaki disease, with all patients testing positive for SARS-CoV-2 antibodies.6 Subsequently, multiple reports throughout Europe surfaced of patients presenting with similar symptoms, most notably a report from Bergamo, Italy, of a 30-fold increase in incidence of Kawasaki-like disease in pediatric patients since the start of the COVID-19 outbreak.7,8 Currently, the number of children diagnosed with MIS-C is on the rise with up to 150 cases diagnosed in NYC alone. Patients most commonly present with a combination of fever, diffuse erythema multiforme like rash, conjunctivitis, gastrointestinal (GI) symptoms, and shock with or without myocardial depression. As the number of newly diagnosed COVID-19 cases is decreasing in NYC, we are now treating an increasing number of children with MIS-C. Interestingly, 95.5% of these patients have presented to our institution with GI symptoms including abdominal pain, anorexia, vomiting, and diarrhea. The abdominal pain is most often reported in the right lower quadrant (RLQ), mimicking appendicitis and resulting in abdominal imaging and surgical consultation. Additionally, lower quadrant pain in a female can also mimic ovarian torsion, a diagnosis requiring emergent surgical attention. We discuss our experience with MIS-C patients at MSCHONY from a surgical perspective and present 2 cases that closely mimicked surgical pathology to heighten awareness of this novel disease process and its similarities to common surgical pathology. CASE PRESENTATIONS Case 1 A 7-year-old female was referred to the emergency department (ED) for appendicitis by her primary care physician with a rash and a 5-day history of RLQ pain, emesis, diarrhea, and anorexia. She was also noted to be febrile, significantly tachycardic, and mildly hypotensive with RLQ pain and rebound tenderness. She underwent an abdominal ultrasound significant for mural thickening of the cecum and ileum with borderline enlargement of the appendix. Mild hyperemia of the tip of the appendix was noted as well as evidence of inflammation of the surrounding mesenteric fat. At this time, antibiotics were started in the ED for presumed appendicitis and the surgical team was consulted. Follow-up magnetic resonance imaging (MRI) was performed and significant for a normal-appearing appendix; however, extensive inflammatory changes were noted within the terminal ileum with surrounding mesenteric inflammatory changes. Inflammatory changes were also noted in the rectosigmoid colon as well as a moderate amount of ascites layering in the pelvis and lower quadrants. The MRI results in conjunction with elevated inflammatory markers and the additional clinical findings of rash, hypotension and tachycardia out of proportion to the appendiceal inflammation seen on imaging resulted in our decision to attribute the significant bowel inflammation to MIS-C rather than a surgical diagnosis such as acute appendicitis. At this time, Solumedrol 2 mg/kg/day was started with improvement in abdominal pain within 12 hours and resolution of GI symptoms with toleration of oral intake within 36 hours. Additionally, her rash and ectopy resolved and inflammatory markers improved within 48 hours. Early recognition of similar cases is crucial to prevent surgical intervention and avoid the use of unnecessary antibiotics in pediatric patients. Significant tachycardia and/or hypotension, rash and elevated c-reactive protein, erythrocyte sedimentation rate, ferritin, and procalcitonin should be used to differentiate a typical surgical abdomen from MIS-C. Case 2 A 7-year-old female with a history of right ovarian teratoma excision in 2019 presented with significant intermittent abdominal pain, non-bloody, non-bilious (NBNB) emesis, and diarrhea for 2 days. She was noted to be febrile, tachycardic, and hypotensive with diffuse tenderness and guarding as well as a lactate of 1.8 mmol/L. Abdominal and pelvic ultrasounds were performed revealing a left ovarian cyst with the left ovary noted to be located to the right of the uterus with small volume ascites. This raised concern for intermittent ovarian torsion resulting in surgical evaluation. Due to her gradual onset of pain and borderline ultrasound results, a follow-up ultrasound was performed which showed uninterrupted blood flow to the ovary as well as more accurate positioning of the ovary, negating the concern for ovarian torsion. Additionally, increased volume of ascites was noted. These results, along with the patient's hypotension, tachycardia, and significant elevation in inflammatory markers, led us to attribute her GI symptoms to MIS-C. The patient was started on intravenous steroids with resolution of her abdominal symptoms and rash within 24 hours and hypotension within 48 hours. In this case, MIS-C mimics a common surgical emergency, again emphasizing the importance of considering MIS-C as a diagnosis before proceeding to surgery. CHARACTERISTICS OF MIS-C PATIENTS AT MSCHONY Currently at MSCHONY, we have treated 44 patients with MIS-C, with our first confirmed case on April 18, 2020. Patients have ranged in age from 15 months to 20 years’ old (mean 8.3 years), with 52.3% female and 47.7% male, as seen in Table 1. Ten patients (22.7%) had additional comorbidities, with asthma noted in 5 patients and obesity in 3. GI symptoms were reported at presentation in 95.5% of patients with the most common being abdominal pain, usually in the right lower quadrant (28/44, 63.6%), followed by NBNB emesis (26/44, 59.1%), nonbloody diarrhea (18/44, 40.9%), and anorexia (10/44, 22.7%). Of these patients, 20 underwent abdominal imaging, most commonly to rule out appendicitis. TABLE 1 - Characteristics of the 44 Patients Diagnosed With MIS-C at MSCHONY. Characteristics of 44 Patients With MIS-C at Morgan Stanley Children's Hospital of New York-Presbyterian Age, y, range (mean) 1.25–20 (8.3) Patient sex Female, n (%) 23 (52.3%) Male, n (%) 21 (47.7%) Comorbidities None, n (%) 34 (77.3%) Obesity, n (%) 3 (6.8%) Asthma, n (%) 5 (11.4%) Other, n (%) 4 (9.0%) Body mass index, range (mean) 13.2–41.8 (19.5) GI symptoms on admission Total, n (%) 42 (95.5%) Abdominal pain, n (%) 28 (63.6%) Emesis, n (%) 26 (59.1%) Diarrhea, n (%) 18 (40.9%) Anorexia, n (%) 10 (22.7%) Imaging Total, n (%) 20 (45.5%) Ultrasound, n (%) 14 (31.8%) x-Ray, n (%) 5 (11.4%) CT, n (%) 2 (4.5%) MRI, n (%) 2 (4.5%) SARS-CoV-2 PCR Positive, n (%) 15 (34.1%) Negative, n (%) 29 (65.9%) SARS-CoV-2 antibody Received test, n (%) 36 (81.8%) Positive, n (%)∗ 35 (97.2%) Negative, n (%)∗ 1 (2.8%) Both SARS-CoV-2 PCR andAntibody positive, n (%)∗ 10 (27.8%) ∗Percentage calculated out of 36 patients who were tested for SARS-CoV-2 antibodies. Thirty-six patients were tested for SARS-CoV-2 antibodies, 35 of which were positive. A total of 15 patients had positive SARS-CoV-2 polymerase chain reaction (PCR) results, 10 of which were also antibody positive. The majority of patients were tachycardic with varying degrees of hypotension on presentation, 35 of which were noted to have elevated lactate (0.4–5.0 mmol/L, average of 1.95 mmol/L). DISCUSSION Although pediatric patients do not commonly show symptoms while infected with SARS-CoV-2, an alarming rise in the number of post-COVID-19-related MIS-C cases have been reported. In current literature, cardiovascular effects of MIS-C are most often reported and feared; however, GI symptoms are more common and can lead to unnecessary operations if misdiagnosed.6,7,9 As initially reported from Wuhan, China, patients with COVID-19 who underwent surgical procedures were noted to have complicated postoperative courses with increased rates of acute respiratory distress syndrome, shock, arrhythmia, cardiac injury, and mortality.10 Although surgical outcomes in MIS-C patients are currently unknown, all attempts should be made to avoid surgical intervention in these patients due to the increased risk of perioperative morbidity and mortality. It is critical that pediatric surgeons be aware of the GI manifestation of MIS-C and be able to differentiate this novel syndrome from the surgical pathologies that it often mimics. It is necessary to be suspicious of COVID-19 even in cases that present like standard appendicitis, especially if your area has been significantly affected by the pandemic or the patient has a known exposure. A rash as well as tachycardia and/or hypotension and elevated inflammatory markers out of proportion to the amount of inflammation seen on imaging should be used to differentiate a typical surgical abdomen from MIS-C and prompt testing for active SARS-CoV-2 infection as well as antibodies. To date at our institution, none of the patients with MIS-C and abdominal pathologies have required an operation. Patients have been treated with a combination of steroids, intravenous immunoglobulin or immunomodulators, and aspirin with improvement in all clinical parameters and resolution of all GI pathology. As COVID-19 continues to spread, the cases of MIS-C will increase, requiring all pediatric physicians, most notably surgeons, to consider MIS-C high on their list of differential diagnoses, even when patients present as seemingly emergent surgical cases.