Multisystem inflammatory syndrome in children (MIS-C) is an immune activation syndrome associated with prior SARS-CoV-2 infection. Clinical manifestations of MIS-C develop 2-6 weeks after SARS-CoV-2 infection with possible involvement of the heart, lungs, kidneys, skin, central nervous system, and digestive tract. Five children with MIS-C (6.6 ± 1.3 years, M:F = 3:2) were admitted to our hospital from January 2021 to March 2022. They all presented with gastrointestinal manifestations, with SARS-CoV-2 molecular swab negativity and positive serology. One child was reported to have a known previous asymptomatic SARS-CoV-2 infection (more than 4 weeks prior to admission). Another one was reported to have received COVID-19 vaccine (second dose four weeks prior to admission). Three/5 were obese children (BMI greater than 95th percentile). All patients experienced fever, abdominal pain, and lack of appetite. Four/5 had vomiting, 3/5 presented diarrhea, 2/5 had constipation, and two male patients had scrotal edema. Three/5 presented with severe gastrointestinal involvement, mimicking appendicopathy; one of them underwent exploratory laparoscopy without histological features of appendicitis. None of them had increased levels of transaminases but one child showed pancreatitis. The median peak value of: IL-6 was 186.5 pg/mL (range: 15.1-692.5; normal values: 0.5-6.4); CRP was 191.4 mg/L (range: 131-386.7; normal values: 0-2); procalcitonin was 19.8 ng/mL (range: 4.27-100; normal value: < 0.5). We treated all patients with intravenous immunoglobulins and steroids. One patient needed oxygen therapy and parenteral nutrition. Nobody died. According to published data, patients with MIS-C have a high rate of abdominal symptoms. Fever and gastrointestinal symptoms were reported in all cases, some of them mimicking acute appendicitis. In the literature, appendectomy was performed in the majority of patients admitted as suspected appendicitis. Moreover, histopathology demonstrated only serosal inflammation, without the typical involvement of acute appendicitis. Following the diagnosis of MIS-C, specific therapy was started, leading to clinical improvement. In conclusion, during the COVID-19 pandemic, MIS-C should always be taken into account in children with persistent fever and severe gastrointestinal symptoms to avoid unnecessary surgical exploration.

Patients with appendicitis-like abdominal pain but negative laboratory and radiological findings can have rare alternative aetiologies such as obstructive appendicopathy. A normal appendix may be seen in surgery, and removal with consent is curative.

In 1921; Masson and Maresch first coined the term "neurogenic appendicitis (NA)" to describe "neuroma-like" lesions in the appendix. To date, our knowledge about NA is limited; therefore, we conducted a comprehensive analysis of the literature (1921 to 2020) to examine the clinicopathological features of NA. We also addressed the pathophysiology of acute abdominal pain and fibrosis in this entity. We performed a meta-analysis study by searching the PubMed database, using several keywords, such as: "appendix," "neurogenic," "obliterative," "neuroma," "fibrous obliteration," "appendicopathy," and "appendicitis." Our study revealed that patients with NA usually present clinically with features of acute appendicitis, bud2t they have grossly unremarkable appendices. Histologically, the central appendiceal neuroma was the most common histological variant of NA, followed by the submucosal and intramucosal variants. To conclude, NA represents a form of neuroinflammation. The possibility of NA should be considered in patients with clinical features of acute appendicitis who intraoperatively show a grossly unremarkable appendix. Neuroinflammation and neuropeptides play roles in the development of pain and fibrosis in NA.