bioRxiv2019
ObjectiveTo demonstrate different entities of appendicitis and causal association between microbiota and different types of appendicitis through studying cluster/outbreak, and providing guidance to find new cluster/outbreak of appendicitis and the epidemiological evidences of infectious etiology of appendicitis.\n\nData SourcesPubMed, Embase, CNKI, WanFang, VIP, CBM from their establishment to Jan, 2019, and the references lists from retrieved reports.\n\nStudy EligibilityReports on cluster/outbreak of appendicitis and reports of case series occurring in cluster/outbreak worldwide according to CDCs definition of cluster/outbreak.\n\nData Extraction and SynthesisTwo researchers independently assessed report quality and extracted data according to Moose. We used random effect model for meta-analysis by Meta-Analyst {beta}3.13 software. Study-level assessment was conducted according to investigation methods introduced by Reingold and outcome-level assessment by GRADE system. We selected outcome measures before data collection began.\n\nResultsWe included 10 clusters/outbreaks of appendicitis from China and USA with total 626 patients. We demonstrated two entities, type 1 appendicitis (455 patients) and type 2 appendicitis (151patients). 20 patients left were unclassified type. For type 1 appendicitis, Natural history showed progression from a non-perforated appendicitis to perforated appendicitis as described traditionally. More than 88% of patients had elevated body temperature, WBC and neutrophil percentage. For type 2 appendicitis, natural history showed that only a few patients developed into phlegmonous appendicitis (6.9%,) or acute gangrenous appendicitis (1.4%) and no perforation or periappendicular abscess. More than 78% of patients had normal body temperature, WBC and NP. The patients time of type 1 appendicitis is shorter than that of type 2 appendicitis. Type 2 appendicitis had different histological features from type 1 appendicitis and was associated with fusobacteria. 9 of 10 cluster/outbreak occurred in group living unity such as school and camps, and many of them showed features of infectious diseases. The bodies of evidence were high quality in Meta analysis.\n\nConclusionCluster/outbreak of appendicitis is more often than expected worldwide and occurred in group living unity. Sporadic perforated appendicitis and non-perforated appendicitis may be not two different entities, but different stages of a same entity, which is inconsistent with modern classification of appendicitis. Type 2 appendicitis is a new entities. Studying cluster/outbreak is a new method in finding of new entity and causal association between microbiota and different types of appendicitis. Epidemiological evidence supported infectious etiology of appendicitis.