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Korean J Crit Care Med > Volume 29(3); 2014 > Article
Kim, Jang, Kim, Shin, Kim, Lee, Kim, Park, and Lee: Patients with Acute Respiratory Distress Syndrome Caused by Scrub Typhus: Clinical Experiences of Eight Patients

Abstract

Background

The aim of this study is to describe the clinical course and outcome of patients who were diagnosed with acute respiratory distress syndrome (ARDS) caused by scrub typhus and who received ventilator care in the intensive care units (ICU) of two university hospitals.

Methods

We performed a retrospective analysis of all adult ventilated patients who were diagnosed with ARDS caused by scrub typhus.

Results

Eleven (1.7%) of 632 scrub typhus patients were diagnosed with ARDS (median age 72; seven were male). Eight patients had underlying diseases, the most common of which was hypertension (four patients). Eight patients (72.7%) were admitted in November. The most common chief complaints of the patients were fever and rash (63.6%). All patients had skin eschar and rash; seven were treated for shock. On the day of diagnosis with ARDS, the median Acute Physiology and Chronic Health Evaluation score was 20 (range 11–28) and Sequential Organ Failure Assessment score was 7 (range 4–14). All patients had PaO2/FiO2 < 200 mmHg, high serum aspartate aminotransferase level (> 40 IU/L), and hypoalbuminemia (< 3.3 g/dl). Nine patients were treated with doxycycline on the day of admission. Their median lengths of stay in the ICU and hospital were 10 (range 4–65) and 14 (4–136) days, respectively. The mortality rate during treatment in the hospital was 36.4%.

Conclusions

In our study, the risk of ARDS among patients diagnosed with scrub typhus was at least 1.7%, with a hospital mortality rate of 36.4%.

Introduction

Scrub typhus is a mite-borne infectious disease caused by Orientia tsutsugamushi[1] distributed throughout the Asia–Pacific area.[2] Scrub typhus, an acute febrile disease, is characterized by a typical primary necrotic lesion (eschar), generalized lymphadenopathy, rash, and non-specific symptoms such as fever, headache, myalgia and cough. Rarely, severe complications, including prominent encephalitis, interstitial pneumonia, acute respiratory distress syndrome (ARDS), acute renal and hepatic failure, and acute hearing loss, have been reported.[38] Serious pulmonary involvement such as ARDS has rarely been seen, likely because of the introduction of specific antibiotic therapy. Although one observational study reported the clinical characteristics of eight patients with ARDS,[9] scrub typhus complicated by ARDS has seldom been discussed; few case reports have been published.[1013] Moreover, no reports include data on the clinical characteristics of these patients in South Korea.
The aim of this study was to investigate the clinical course and outcome of patients diagnosed with ARDS caused by scrub typhus and received ventilator care in the intensive care units (ICU) of two university hospitals in Busan, South Korea. Also, we examined potential differences from previous reports.[9]

Materials and Methods

1) Study subjects

We performed a retrospective search of all adult patients (age ≥ 17 years) admitted to the ICU who met the criteria for both code A753 (scrub typhus) and J80 (ARDS) according to the International Statistical Classification of Diseases and Related Health Problems, 10th revision (ICD-10). A total of 11 ventilated patients diagnosed with ARDS caused by scrub typhus were enrolled in this study. Of these patients, nine were from Pusan National University Hospital between 1 January 1995 and 31 December 2012 and two were from Haeundae Baik Hospital between 1 January 2010 and 31 December 2012. ARDS patients were managed according to the therapeutic guideline for lung-protective ventilation.[14] Medical records and laboratory and radiographic findings of all patients were collected. Investigators from each center completed a case report form, and data were collected from September to October 2013. Three investigators (SYK, KS and KL) confirmed that the study objectives and procedures were honestly disclosed, and both had full access to all of the data. The protocol for this study was approved by the Institutional Review Boards of the two participating institutions.

2) Data collection

The following data were gathered from the medical records of each patient: age, gender, duration of mechanical ventilation, length of stay in the ICU and in the hospital, hospital mortality, month of admission and chief complaint at admission. Acute Physiology and Chronic Health Evaluation (APACHE) and Sequential Organ Failure Assessment (SOFA) scores were calculated on the day of ARDS diagnosis.[15,16] The Charlson Comorbidity Index was calculated from medical records.[17] The following laboratory data collected on the day of ARDS diagnosis were obtained from medical records: white blood cell count, lowest PaO2/FiO2 ratio, C-reactive protein, blood urea nitrogen (BUN), creatinine, aspartate aminotransferase (AST), alanine aminotransferase (ALT), total bilirubin, and albumin level. In addition, we recorded the occurrence of septic shock at ARDS diagnosis, tracheostomy during hospitalization, and time from admission to the beginning of treatment with doxycycline.

3) Definition

A diagnosis of scrub typhus was based on an indirect microimmunofluorescence antibody (IFA) test for O. tsutsugamushi. Diagnostic IFA results were positive if total antibody titer showed a fourfold increase in paired positive serum samples or the antibody titer was ≥ 1:160.[18,19] The diagnosis of ARDS was based on the consensus criteria of the American-European Consensus Conferences, which was defined as acute onset, PaO2/FiO2 ≤ 200 mmHg regardless of positive end-expiratory pressure, bilateral infiltrates seen on frontal chest radiograph, and pulmonary artery wedge ≤ 18 mmHg when measured or no clinical evidence of left atrial hypertension.[20] Sepsis, severe sepsis, and septic shock were defined using criteria from the American College of Chest Physicians/Society of Critical Care Medicine.[21] Acute kidney injury was defined as oliguria and marked increase in BUN and creatinine, and ventilator-associated pneumonia was defined as a modified Clinical Pulmonary Infection Score of 6 or greater.[22] Survivors were defined as patients who survived to discharge from hospital.

4) Statistical analysis

Continuous variables are expressed as medians and ranges and compared using the Mann-Whitney U-test. Categorical variables were compared using chi-square and Fisher’s exact tests. All statistical analyses were performed using the Statistical Package for the Social Sciences (version 18.0, SPSS, Chicago, IL, USA). A two-tailed p < 0.05 was considered to indicate statistical significance.

Results

During enrolled period, a total of 632 patients were diagnosed with scrub typhus. Of these patients, eleven were diagnosed with ARDS. Patients’ characteristics and their clinical courses are summarized in Table 1. The median patient age was 72 (range 29–85) years, and seven (63.6%) patients were male. Eight patients (72.7%) had underlying diseases and most common underlying disease was hypertension (four patients). The median Charlson Comorbidity Score was 1 (range 0–3). Eight patients (72.7%) were admitted in November. The most common chief complaint of the patients was fever and dyspnea (63.6%). All patients had skin rash and eschar; seven were also treated for shock. The median APACHE and SOFA score on the day of diagnosis with ARDS were 20 (range 11–28) and 7 (4–14), respectively. All patients had PaO2/FiO2 < 200 mmHg, high serum AST levels (> 40 IU/L), and hypoalbuminemia (< 3.3 g/dl). Seven patients had diagnostic IFA results, which all patients had the antibody titer was ≥ 1:160. Nine patients were treated with doxycycline on the day of admission (range of interval from hospital admission to commencement of antibiotic, 0–5). The two most common complications in the study population were hospital-acquired pneumonia and acute kidney injury (each occurring in 2 of 11 or 18.2% of patients). The median duration of ventilator care was 6 days (range 1–61), and median length of stay in the ICU and hospital were 10 (range 4–65) and 14 (4–136) days, respectively. One patient was received tracheostomy. The hospital mortality rate was 36.4% (4 of 11). However, there were no significant differences regarding the above clinical characteristics and laboratory data between survivors and non-survivors (data not shown).

Discussion

This study investigated the clinical characteristics of patients with ARDS caused by scrub typhus in South Korea. According to the literature, the pulmonary manifestations of scrub typhus are varying grades of bronchitis and interstitial pneumonitis progressing to ARDS.[23] ARDS might arise as a result of the immunological response of the lung to previous O. tsutsugamushi infection without direct invasion of the organism.[9,10] Also, interstitial pneumonia might be associated with disease severity as reported in a previous study.[24]
In the present study, we found that all patients had low comorbidity scores, and most patients were hospitalized in November. These findings suggest that development of ARDS caused by scrub typhus does not correlate with underlying diseases and that November might be a period during which development of ARDS is prevalent.
Also, the five major clinical symptoms are well known to include fever, headache, eschar, rash, and lymphadenopathy; 83% of the cases presented with one to three clinical symptoms and 10% with four to five symptoms.[25] However, in this study, the chief complaint was dyspnea and fever, which was consistent with a previous report;[9] initial respiratory symptoms at the time of diagnosis with scrub typhus might be an indication for careful evaluation for progression to ARDS.
Several published case reports and study described clinical manifestations in patients with ARDS caused by scrub typhus which are summarized in Table 2.[913] Compared with these previous reports, all our patients presented with hypoalbuminemia, which was consistent with previous reports.[9,1113] In the reported data in Taiwan, hypoalbuminemia was an independent predictor for development of ARDS. Though we hypothesized this feature would also indicate prognosis in our patients, the small sample size prevented a clear conclusion.
Treatment with doxycycline usually lowers fever within 24 hours, and severe complications such as sepsis and ARDS are typically the result of delayed diagnosis and treatment. In our study, all patients were treated with doxycycline, and 10 patients (91%) received antibiotics within 2 days after hospitalization. This interval was somewhat shorter than in a previous report[9] (median: 0 vs. 8 days). However, the mortality rate we observed was higher than in that study.[9] This difference may be due to the fact that all patients included in our analysis had low PaO2/FiO2, and 63.6% were experiencing shock at ARDS diagnosis. Our results suggest that the mortality rate in patients with ARDS caused by scrub typhus is higher than that for scrub typhus overall, even with prompt treatment using appropriate antibiotics.
There were several limitations to our research because of its retrospective design and the small number of patients. First, we hypothesized that all patients would have serious neurologic complications caused by scrub typhus at admission; because a previous study showed that the presence of pneumonitis was associated with the occurrence of scrub typhus meningitis and meningoencephalitis.[26] However, we could not identify additional complications as shown in Table 1 because the study was retrospective. Second, there would be different serotype of Orientia tsutsugamushi depending on the region, which might be associated with different disease severity and clinical outcome. Therefore, our study reflected the regional characteristics, especially focused on Busan area.
In conclusion, our study found the risk of ARDS among patients diagnosed with scrub typhus was at least 1.7%, and their hospital mortality rate was 36.4%. Further, large-scale studies are needed to identify prognostic indicators for development of ARDS and to establish whether the clinical outcomes of scrub typhus differ according to the respiratory reaction.

NOTES

No potential conflict of interest relevant to this article was reported.

Table 1.
Characteristics and clinical courses of eleven scrub typhus patients with acute respiratory distress syndrome
N Age/Sex Month of admission Chief complaint APACHE II score SOFA score CCI MV LOS ICU LOS Hospital LOS Shock PaO2/FiO2 (mmHg) Complication during hospital course Hospital outcome
1 77/M November RUQ pain, fever 23 11 2 17 20 26 Yes 66.6 Pneumonia Survived
2 72/M December Dyspnea, fever 15 6 1 6 7 13 Yes 70.5 None Survived
3 72/M October Fever 23 6 3 1 10 19 No 155.2 None Survived
4 83/F November Fever 17 7 0 5 9 18 No 106.6 None Survived
5 66/M November Dyspnea, fever 22 5 0 6 6 13 No 101.8 None Survived
6 64/M November Dyspnea, fever 25 11 1 61 65 136 Yes 107.5 Pneumonia, TEN Survived
7 85/M November Hematochezia 18 10 1 1 14 14 No 73.5 Ischemic colitis Died
8 67/F November Dyspnea, fever 15 9 1 12 12 12 Yes 114.1 None Died
9 73/M November Dyspnea 28 14 1 4 4 4 Yes 41.8 Acute kidney injury, encephalitis Died
10 66/F November Dyspnea 20 4 3 18 19 20 Yes 88.0 Acute kidney injury Died
11 29/F October Dyspnea 11 5 0 5 5 13 Yes 53.0 None Survived

APACHE: acute physiology and chronic health evaluation; SOFA: sequential organ failure assessment; CCI: charlson comorbidity index; MV: mechanical ventilation; ICU: intensive care unit; LOS: length of stay; RUQ: right upper quadrant; TEN: toxic epidermal necrolysis.

Table 2.
Summary of previous case reports and study of patients with acute respiratory distress syndrome caused by scrub typhus
Age/Sex Chief complaint MV LOS Hospital LOS PaO2/FiO2 (mmHg) WBC (/mm3) CRP (mg/dl) AST (IU/L) ALT (IU/L) Total bilirubin (mg/dl) Albumin (g/dl) Creatinine (mg/dl) Hospital outcome
Park et al.[10] (Korea, case report) 72/F Dyspnea 10 15 161.2 14,000 0.89 Unknow
n
Unknown Unknow
n
Unknow
n
Unknow
n
Died
Kurup et al.[11] (Singapore, case report) 35/M Fever 7 11 Unknown 12,300 18.2 113 140 0.22 2.4 1.54 Survived
Tseng et al.[12] (Taiwan, case report) 67/M Dyspnea Unknown Unknown 51.1 10,800 14.0 63 93 0.5 2.3 0.8 Survived
Ryu et al.[13] (Korea, case) 78/M Decreased mental status 87 Unknown Unknown 9,450 19.0 57 43 0.85 1.78 1.71 Survived
Wang et al.*[9] (Taiwan, 8 patients) Age: 55.3± 21.5
M/F: 3/5
Fever, cough (100%)
Dyspnea (87.5%)
14.8 ±10.4 Unknown Unknown 11,330± 4,660 148.3 ±81.8 133.7 ±78.0 3.5 ± 3.4 2.2 ± 0.4 1.0 ± 0.4 Mortality: 25%
This study* (Korea, 11 patients) Age: 68.6± 14.8
M/F:7/4
Fever, dyspnea (63.6%) 12.4 ±17.1 26.2 ±36.9 89.0 ± 32.3 12,022± 4,597 17.3 ±10.0 111.2 ±72.3 66.0 ± 39.7 1.4 ± 1.4 2.1 ± 0.4 1.1 ± 0.5 Mortality: 36%

* All data are presented as mean ± SD. MV: mechanical ventilation; LOS: length of stay; WBC: white blood cell; CRP: C-reactive protein; AST: aspartate aminotransferase; ALT: alanine aminotransferase.

References

1). Tamura A, Ohashi N, Urakami H, Miyamura S. Classification of Rickettsia tsutsugamushi in a new genus, Orientia gen. nov., as Orientia tsutsugamushi comb. nov. Int J Syst Bacteriol 1995; 45: 589–91.
crossref pmid
2). Rapmund G. Rickettsial diseases of the Far East: new perspectives. J Infect Dis 1984; 149: 330–8.
crossref pmid
3). Tsay RW, Chang FY. Serious complications in scrub typhus. J Microbiol Immunol Infect 1998; 31: 240–4.
pmid
4). Aronoff DM, Watt G. Prevalence of relative bradycardia in Orientia tsutsugamushi infection. Am J Trop Med Hyg 2003; 68: 477–9.
crossref pmid
5). Silpapojakul K, Ukkachoke C, Krisanapan S. Rickettsial meningitis and encephalitis. Arch Intern Med 1991; 151: 1753–7.
crossref pmid
6). Premaratna R, Chandrasena TG, Dassayake AS, Loftis AD, Dasch GA, de Silva HJ. Acute hearing loss due to scrub typhus: a forgotten complication of a reemerging disease. Clin Infect Dis 2006; 42: e6–8.
crossref pmid
7). Chang JH, Ju MS, Chang JE, Park YS, Han WS, Kim IS, et al. Pericarditis due to Tsutsugamushi disease. Scand J Infect Dis 2000; 32: 101–2.
crossref pmid
8). Hu ML, Liu JW, Wu KL, Lu SN, Chiou SS, Kuo CH, et al. Short report: Abnormal liver function in scrub typhus. Am J Trop Med Hyg 2005; 73: 667–8.
crossref pmid
9). Wang CC, Liu SF, Liu JW, Chung YH, Su MC, Lin MC. Acute respiratory distress syndrome in scrub typhus. Am J Trop Med Hyg 2007; 76: 1148–52.
crossref pmid
10). Park JS, Jee YK, Lee KY, Kim KY, Myong NH, Seo PW. Acute respiratory distress syndrome associated with scrub typhus: diffuse alveolar damage without pulmonary vasculitis. J Korean Med Sci 2000; 15: 343–5.
crossref pmid pmc
11). Kurup A, Issac A, Loh JP, Lee TB, Chua R, Bist P, et al. Scrub typhus with sepsis and acute respiratory distress syndrome. J Clin Microbiol 2013; 51: 2787–90.
crossref pmid pmc
12). Tseng CC, Tung HH, Wu SF, Wang TJ. Acute respiratory distress syndrome following scrub typhus: a case report. J Am Acad Nurse Pract 2012; 24: 160–5.
crossref pmid
13). Ryu KH, Kim KH, Kim HD, Son JW, Na MJ, Choi E. A case of ARDS overlooked Tsutstugamushi disease that presented as simple cutaneous lesion. Tuberc Respir Dis 2006; 61: 389–93.
crossref
14). Ventilation with lower tidal volumes as compared with traditional tidal volumes for acute lung injury and the acute respiratory distress syndrome. The Acute Respiratory Distress Syndrome Network. N Engl J Med 2000; 342: 1301–8.
pmid
15). Knaus WA, Draper EA, Wagner DP, Zimmerman JE. APACHE II: a severity of disease classification system. Crit Care Med 1985; 13: 818–29.
crossref pmid
16). Vincent JL, Moreno R, Takala J, Willatts S, De Mendonca A, Bruining H, et al. The SOFA (Sepsis-related Organ Failure Assessment) score to describe organ dysfunction/failure. On behalf of the Working Group on Sepsis-Related Problems of the European Society of Intensive Care Medicine. Intensive Care Med 1996; 22: 707–10.
crossref pmid
17). Charlson ME, Pompei P, Ales KL, MacKenzie CR. A new method of classifying prognostic comorbidity in longitudinal studies: development and validation. J Chronic Dis 1987; 40: 373–83.
crossref pmid
18). Amano K, Suzuki N, Fujita M, Nakamura Y, Suto T. Serological reactivity of sera from scrub typhus patients against Weil-Felix test antigens. Microbiol Immunol 1993; 37: 927–33.
crossref pmid
19). Jiang J, Marienau KJ, May LA, Beecham HJ 3rd, Wilkinson R, Ching WM, et al. Laboratory diagnosis of two scrub typhus outbreaks at Camp Fuji, Japan in 2000 and 2001 by enzyme-linked immunosorbent assay, rapid flow assay, and Western blot assay using outer membrane 56-kD recombinant proteins. Am J Trop Med Hyg 2003; 69: 60–6.
crossref pmid
20). Bernard GR, Artigas A, Brigham KL, Carlet J, Falke K, Hudson L, et al. The American-European Consensus Conference on ARDS. Definitions, mechanisms, relevant outcomes, and clinical trial coordination. Am J Respir Crit Care Med 1994; 149(3 Pt 1):818–24.
crossref pmid
21). Bone RC, Sibbald WJ, Sprung CL. The ACCP-SCCM consensus conference on sepsis and organ failure. Chest 1992; 101: 1481–3.
crossref pmid
22). Luna CM, Blanzaco D, Niederman MS, Matarucco W, Baredes NC, Desmery P, et al. Resolution of ventilator-associated pneumonia: prospective evaluation of the clinical pulmonary infection score as an early clinical predictor of outcome. Crit Care Med 2003; 31: 676–82.
crossref pmid
23). Chayakul P, Panich V, Silpapojakul K. Scrub typhus pneumonitis: an entity which is frequently missed. Q J Med 1988; 68: 595–602.
pmid
24). Song SW, Kim KT, Ku YM, Park SH, Kim YS, Lee DG, et al. Clinical role of interstitial pneumonia in patients with scrub typhus: a possible marker of disease severity. J Korean Med Sci 2004; 19: 668–73.
crossref pmid pmc
25). Lee YS, Wang PH, Tseng SJ, Ko CF, Teng HJ. Epidemiology of scrub typhus in eastern Taiwan, 2000–2004. Jpn J Infect Dis 2006; 59: 235–8.
pmid
26). Kim DM, Chung JH, Yun NR, Kim SW, Lee JY, Han MA, et al. Scrub typhus meningitis or meningoencephalitis. Am J Trop Med Hyg 2013; 89: 1206–11.
crossref pmid pmc
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