Differential diagnosis and management for perforated appendicitis and non-perforated appendicitis are current hot topics. The aim of this study is to demonstrate a new entity of non-perforated appendicitis, “acute hemorrhagic appendicitis” through studying cluster of acute appendicitis among Tibetan students at a high school in central China. Over the 11-year period, there were 120 patients with more female patients (102 of 499, 20.4%) than male patients (18 of 474, 3.8%) among 973 Tibetan students. 117 patients’ clinical data were available. Clinical manifestations were identical to classic appendicitis. However, axilla temperature, white blood cell counts and neutrophil level were elevated mildly in 12 (10.3%), 19 (16.2%) and 12 (10.3%) patients respectively. Pathologically, the resected appendices exhibited focal or diffuse hemorrhages in mucosa and/or submucosa, and infiltration by eosinophil and by lymphocytes. No patients had perforated appendicitis. The median time from the onset to surgery was 3 days (IQR, 2–4). All patients were discharged with full recovery. In conclusion, “acute hemorrhagic appendicitis” represented a new entity of non-perforated appendicitis with unique cause and pathogenesis, which might be treated with antibiotics alone or self-limited. Studying the cluster is a reliable method to find new entity of appendicitis.

Objective Infectious etiology of acute appendicitis is a current hot topic. The most of study on appendicitis came from sporadic patients and focused on clinical treatment rather than control and prevention of appendicitis in the population. The present study aims to investigate the epidemiological features of cluster of acute appendicitis, risk factors, and evaluate effectiveness of control and prevention in population. Methods We conducted longitudinal study on a cluster of acute appendicitis among Tibetan students at a high school in eastern China, which was divided into three stages: 1. We retrospectively collected epidemiological data and clinical data to explore risk factor and possible transmission route in August of 2005; 2. We conducted targeted measures from August of 2005 and analyzed incidence trend from 2000 to 2010; 3. Since no new patients occurred in 2011, we conducted surveillance from the beginning of 2012 until July 2018. Results Among 973 Tibetan students, there were 120 patients with more female patients (102 of 499, 20.4%) than male patients (18 of 474, 3.8%) from January of 2000 to December of 2010. The 4-year cumulative incidence rates in female students enrolled in 2001, 2002, 2003, 2004, 2005, 2006 were 26.8% (11 of 41), 27.1% (13 of 48), 44.7% (21 of 47), 42.4% (14 of 33), 23.1% (9 of 39), and 19.3% (11 of 57), respectively before their graduation. There was a clustering feature. Mutual contact with patients before the onset of symptoms was an important risk factor (Adjusted OR 4.89, 95% CI: 1.67–14.35). Transmission route may be fecal-oral infection. Before conducting targeted measures, the incidence rate increased from 2000 and peaked in 2005. After conducting targeted measures, the incidence rate decreased year by year until 2010. Under surveillance from January of 2012 to July of 2018, only four sporadic patients occurred at this school. Conclusion This cluster of acute appendicitis had features of an infectious disease in epidemiology, which can be controlled and prevented by targeted measures. Our study may also be used for prevention of sporadic patients and be generalized in general population as cluster of appendicitis occurred in many provinces of China.

Objective To differentiate different entities of appendicitis through studying cluster/outbreak, ascertain common setting of cluster/outbreak, and provide the epidemiological evidences of infectious etiology of appendicitis. Background Differential diagnosis and management for perforated appendicitis and non-perforated appendicitis and the infectious etiology of appendicitis are current hot topics. Methods Field investigation for Tibetan students were carried out and reports published in English and Chinese medical journals were reviewed. Results The literature review included 473 patients in 7 cluster/outbreaks of appendicitis in 6 provinces and autonomous regions. All the clusters/outbreaks occurred in group living units. We found two classic entities of appendicitis with natural history from non-perforated appendicitis to perforated appendicitis and two entities of non-perforated appendicitis. In classic entities, one may represent majority of sporadic patients and the other may represent partial sporadic patients with obvious gastrointestinal manifestation. In entities of non-perforated appendicitis, one was identical to features of sporadic non-perforated appendicitis and the other one is identical to the following Tibetan students and associated with Fusobacterium. The field investigation for 120 Tibetan students with appendicitis showed that the resected appendices exhibited diffuse or focal hemorrhages and infiltration by eosinophils and by lymphocytes. Most patients had normal body temperature, white blood cell count and neutrophil count. This is a new entity of appendicitis. The clusters/outbreaks of appendicitis showed the features of infectious disease in epidemiology. The entity of perforated appendicitis was not found. Conclusion Studying cluster/outbreak is a good method to differentiate different entities of appendicitis and infectious etiology. ### Competing Interest Statement The authors have declared no competing interest. ### Funding Statement No funding ### Author Declarations All relevant ethical guidelines have been followed; any necessary IRB and/or ethics committee approvals have been obtained and details of the IRB/oversight body are included in the manuscript. Yes All necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines and uploaded the relevant EQUATOR Network research reporting checklist(s) and other pertinent material as supplementary files, if applicable. Yes I can prodide all data referred to in the manuscript.