Date Published: May 19, 2016
Publisher: Public Library of Science
Author(s): Jun Lee, Dong-Min Kim, Na Ra Yun, Young Dae Kim, Chan Guk Park, Man Woo Kim, John Green.
Scrub typhus is an infectious disease caused by Orientia tsutsugamushi-induced systemic vasculitis, but the involvement of the gastrointestinal tract and the endoscopic findings associated with scrub typhus are not well understood. We performed a prospective study and recommend performing esophagogastroduodenoscopy (EGD) for all possible scrub typhus patients, regardless of gastrointestinal symptoms. Gastrointestinal symptoms, endoscopic findings and clinical severity based on organ involvement and ICU admission were analyzed. Gastrointestinal symptoms occurred in up to 76.4% of scrub typhus patients. The major endoscopic findings were ulcers (43/127, 33.9%). Interestingly, 7.1% (9/127) of the patients presented with esophageal candidiasis. There was no correlation between the presence or absence of gastrointestinal symptoms and the endoscopic grade (P = 0.995). However, there was a positive correlation between the clinical severity and the endoscopic findings (P = 0.001). Sixty-three percent of the patients presented with erosion or ulcers on prospectively performed endoscopic evaluations, irrespective of gastrointestinal symptoms. Gastrointestinal symptoms did not reflect the need for endoscopy. Scrub typhus patients could have significant endoscopic abnormalities even in the absence of gastrointestinal symptoms.
Scrub typhus is endemic in Korea, Japan, Southeast Asia, the western Pacific Islands, Australia, China, south-central Russia, India, and Sri Lanka [1–3]. More than 1 million cases occur annually worldwide . The number of scrub typhus patients has increased in South Korea, and 69,210 scrub typhus cases were reported in South Korea from 2001–2013 .
From September 2006 to December 2008, 283 patients visited Chosun University Hospital with a chief complaint of fever or rash. Scrub typhus was diagnosed when a four-fold or greater increase in IgM or IgG antibody titers, measured by indirect immunofluorescent assay, was observed in the acute and convalescent stages or when PCR was positive, as described previously with slight modification . Of these patients, 90 did not meet the diagnostic criteria for scrub typhus (19 cases of other viral infections, such as hemorrhagic fever with renal syndrome [HFRS], hepatitis or influenza; 14 cases of bacterial infections; seven cases of spirochetal disease, such as leptospirosis; four cases of protozoal infections, such as malaria; four cases of rheumatoid diseases, such as systemic lupus erythematosus or adult-onset Still’s disease; nine cases of other illnesses; and 33 cases of possible scrub typhus without confirmed diagnoses). The diagnosis of scrub typhus was confirmed in 193 patients. Patients with possible scrub typhus were asked to enroll in the study, and 150 patients underwent an endoscopy (43 patients refused endoscopic examinations) using a video endoscope (GIF-Q260, Olympus Co, Tokyo, Japan) within three days after admission. We excluded 23 of these patients because they had a medical history of taking non-steroidal anti-inflammatory drugs (NSAIDs); thus, 127 patients were included, and their medical and endoscopic records were analyzed. (Fig 1) To minimize the inter-observer variation, two endoscopists (authors) reviewed the endoscopic records. The study was approved by the institutional review board of Chosun University Hospital. All participants provided their written informed consent to participate in our study.
The present study shows that gastrointestinal symptoms developed frequently in scrub typhus, and the major endoscopic findings were erosion and ulcers. Although the precise mechanism of gastrointestinal involvement associated with scrub typhus is not yet known, it can be speculated that direct involvement of systemic vasculitis leads to gastrointestinal symptoms and signs. It has been speculated that when there is gastrointestinal involvement in systemic vasculitis, a biopsy of the superficial mucosal erosion in Henoch-Schonlein purpura (HSP) patients could confirm vasculitis of the small vessels associated with the deposition of immunoglobulin A . However, the gastrointestinal symptoms and endoscopic findings are significantly different between HSP and scrub typhus. Gastrointestinal symptoms occur in up to 85% of HSP patients, and they manifest as severe problems, such as intussusception, obstruction, and perforation [12–15]. In the reports by Aung-Thu et al, the gastrointestinal symptoms of scrub typhus patients were vomiting (65%), nausea (60%), diarrhea (45%), melena or hematemesis (25%) . These gastrointestinal symptoms are consistent with those found in the present study, but the frequency of the symptoms was different. In our study, the frequency of gastrointestinal symptoms in scrub typhus patients was as follows: dyspepsia (49.6%), nausea (44.1%), abdominal pain (2.6%), vomiting (14.2%), and melena or hematemesis (7.1%). The reason for the difference is that the Aung et al study enrolled small number of septic patients with scrub typhus (n = 20). Gastrointestinal symptoms occurred in up to 76.4% of scrub typhus patients but usually did not manifest as severe problems, as in HSP. The characteristic endoscopic findings of HSP are erythema, petechiae, and hemorrhagic erosion [16,17]. The duodenum and the small intestine are the most frequently involved sites [11,18]. In our study, the major endoscopic findings observed in scrub typhus were erythema, erosion, and ulcers (79.5%). The preferred sites were the antrum and the duodenal bulb. For this reason, the distinction between the systemic vasculitis of scrub typhus and other types of vasculitis must be considered. A previous Korean study reported erosion and ulcers manifesting in any preferred site in scrub typhus patients . Our data showed that there were predominant sites, including the antrum and duodenal bulb. This discrepancy could have occurred because our data were prospective and our study had a larger sample size than the previous study.
In summary, gastrointestinal symptoms occurred in up to 76.4% of scrub typhus patients. The major endoscopic findings in scrub typhus were erosion and ulcers. Our study suggests that the presence or absence of gastrointestinal symptoms does not reflect the need for endoscopy; however, further, more completely planned systematic studies are needed. Our study is the first report to present an association between esophageal candidiasis and scrub typhus.