126 Correspondence widely in the Asia-Pacific region and is common in some parts of Taiwan. It is an acute febrile illness characterized by a typical primary lesion (eschar), generalized lymphadenopathy, rash, and non- specific symptoms such as fever, chills, cough, abdominal pain and myalgia. Clinically, the mani- festations and complications of scrub typhus are protean. Serious complications are not uncommon and may be fatal if diagnosis is delayed. Complica- tions include myocarditis, meningitis, acute renal failure and interstitial pneumonia.1,3–5 Acute respir- atory distress syndrome (ARDS) is a rarely reported but serious complication of scrub typhus. It is important to know that ARDS may develop in scrub typhus and the possible risk factors, because it is treatable if considered and diagnosed early. Downloaded from http://qjmed.oxfordjournals.org by on March 11, 2010 From June 1993 to July 1997, among 33 hos- pitalized patients with scrub typhus, five fulfilled the criteria of ARDS. Scrub typhus was confirmed by either a four-fold or greater rise of IgGqIgAqIgM titre, for Karp, Kato and Gilliam strains of O. tsutsugamushi, to at least 1 : 320 in indirect immunofluorescent antibody (IFA) in paired sera; or a single IgGqIgAqIgM titre 01 : 320 and IgM 01 : 160 in acute and convalescent sera; these IFA assays were performed in the laboratory of the National Institute of Preventive Medicine, Depart- ment of Health, Executive Yuan, Taiwan. The criteria for ARDS were defined as an acute onset of severe hypoxaemia with a ratio of arterial pO2 to inspired oxygen fraction (PaO2/FiO2) of )200 mmHg and bilateral diffuse infiltrates on a frontal chest radiograph when left atrial or pulmon- ary capillary hypertension (PCWP )18 mmHg) had been excluded. Thrombocytopenia was defined as platelet count -130 000/mm3 at presentation. Early pneumonitis was defined as evidence of infiltrates on chest radiograph at least 2 days before the development of ARDS. Patients were divided into two groups, scrub typhus with ARDS (n = 5) and scrub typhus without ARDS (n = 28). The demographic, clinical and laboratory characteristics of the two groups were compared. Statistical analyses included the x2 test, Fisher’s exact test and Student’s t test as appropriate. Mantel-Haenszel x2 test was used to adjust the confounding influ- ence of age. A p value of -0.05 was considered statistically significant. Patients with ARDS were older than patients without ARDS (39"22 vs. 23"9 years, p = 0.009). Acute respiratory distress syndrome Thrombocytopenia (100% vs. 50%, p = 0.049) and early pneumonitis (100% vs. 25%, p = 0.003) in scrub typhus were more frequently noted in patients with ARDS Sir, than patients without ARDS. Otherwise, there were Scrub typhus, caused by Orientia tsutsugamushi, is no significant differences between the two groups transmitted to humans by the bite of the larval stage in the frequency of fever, headache, cough, abdom- of thromboculid mites or chiggers. It is distributed inal pain, eschar, skin rash, lymphadenopathy, Correspondence 127 and the values of blood white cell counts, alanine from 1 to 9 days (median, 1 day). Non-specific symp- aminotransferase, aspartate aminotransferase (AST), toms such as fever, cough, shortness of breath, right and creatinine. When the patients were stratified upper quadrant abdominal pain, and general into (20/)20 and (30/)30 years age groups, malaise were common. Forty-four percent (4/9) of early pneumonitis was a significant risk factor for patients had an eschar; 33% (3/9) had a maculo- ARDS ( p = 0.009), but thrombocytopenia was papular skin rash; 56% (5/9) had hepatospleno- insignificant ( p = 0.09). megaly. Only one patient had lymphadenopathy. In our 4-year experience, 36% (12/33) of scrub Seventy-eight percent (7/9) of patients had a normal typhus patients developed pneumonitis. Notably, WBC count. Two patients had a mildly elevated 42% (5/12) of the patients with pneumonitis WBC count. All of the patients (8/8) with available progressed to ARDS. Previous reports also showed data had thrombocytopenia, which ranged from 55% (39/71) of scrub typhus patients as having 32 800/mm3 to 125 000/mm3. All had elevation interstitial pneumonitis of varying severity.2 Scrub of AST. typhus is suggested as a more common cause of In the pre-antibiotic era, the mortality in scrub pneumonitis in an endemic area than previously typhus with extensive pneumonitis and cyanosis realized. Therefore, the pulmonary manifestations unrelieved by oxygen, was 100%.1 Mortality was Downloaded from http://qjmed.oxfordjournals.org by on March 11, 2010 of scrub typhus ranged from bronchitis, interstitial 22% (2/9) in this review. The major cause of pneumonitis to ARDS. mortality was delay in diagnosis. This could be An additional four patients with ARDS in scrub reflected by a long period of symptoms before typhus were identified from English-language art- antibiotics started (range: 4 to 19 days, median: icles since 1966.3–5 One patient died of multiple 9 days). From our experiences, despite the occur- organ failure after delay in diagnosis.4 One patient rence of serious complications, good response to presented with meningo-encephalitis and pneu- antibiotic therapy was obtained and the average monitis. Although serious complications usually duration of defervescence was 2 days. All but occurred during the second and third week in one received endotracheal intubation with vent- the pre-antibiotic era,1,2 44% (4/9) of patients ilator support. Seventy-seven percent (7/9) of developed ARDS within 4–7 days of onset in this patients recovered without serious sequela after review (Table 1). appropriate antimicrobial therapy and intensive Their ages ranged from 21 to 65 years (mean care. 43 years) (Table 1). There were five males and four In conclusion, older age, thrombocytopenia, and females. Two had diabetes, with good metabolic presence of early pneumonitis were identified as control. Others had good health before the illness. risk factors for ARDS in patients with scrub typhus. Duration of symptoms before effective antibiotics Scrub typhus should be in the list of differential ranged from 4 to 19 days (median, 9 days). Days of diagnoses in ARDS patients in endemic areas. Early hospitalization before effective antibiotics ranged appropriate antimicrobial therapy and intensive care Table 1 Clinical characteristics of patients with acute respiratory distress syndrome complicating scrub typhus Patient Reference Age/sex Skin rash/eschar Associated complications Days of symptoms Outcome before antibiotic 1 PR 61/F À/q Multi-organ failure 9 Died 2 PR 21/M q/À Myocarditis with 7 Survived AV dissociation, DIC 3 PR 25/M q/À No 7 Survived 4 PR 23/M À/À No 10 Survived 5 PR 65/F À/q No 7 Survived 6 4 61/F À/q Multi-organ failure 4 Died 7 4 62/F À/q No 11 Survived 8 3 21/M q/À Meningoencephalitis, 11 Survived septic shock 9 5 48/M À/À Tubulointerstitial nephritis 19 Survived with acute renal failure, UGI bleeding, DIC PR, present report; AV, atrioventricular; DIC, disseminated intravascular coagulation; UGI, upper gastrointestinal. 128 Correspondence are crucial for the recovery of ARDS complicating scrub typhus. R.-W. Tsay F.-Y. Chang Division of Infectious Diseases and Tropical Medicine Department of Internal Medicine Tri-Service General Hospital National Defense Medical Center Taipei Taiwan References 1. Sayen JJ, Pond HS, Forrester JS, Wood FC. Scrub typhus in Assam and Burma. Medicine 1946; 25:155–214. Downloaded from http://qjmed.oxfordjournals.org by on March 11, 2010 2. Allen AC, Spitz S. A comparative study of the pathology of scrub typhus (tsutsugamushi disease) and other rickettsial disease. Am J Pathol 1945; 21:602–81. 3. Fang CT, Fergn WF, Hwang JJ, Yu CJ, Chen YC, Wang MH, Chang SC, Hsieh WC. Life-threatening scrub typhus with meningoencephalitis and acute respiratory distress syndrome. J Formos Med Assoc 1997; 96:213–16. 4. Lee WS, Wang FD, Wang LS, Wong WW, Young D, Fung CP, Liu Y. Scrub typhus complicating acute respiratory distress syndrome: A report of two cases. Chin Med J (Taipei) 1995; 56:205–10. 5. Chi WC, Huang JJ, Sung JM, Lan RR, Ko WC, Chen FF. Scrub typhus associated with multi-organ failure: a case report. Scand J Infect Dis 1997; 29:634–5.
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