Acute respiratory distress syndrome in scrub typhus - PDF by rma97348


									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.

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                                                             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

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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

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   Assam and Burma. Medicine 1946; 25:155–214.

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   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.
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   typhus associated with multi-organ failure: a case report.
   Scand J Infect Dis 1997; 29:634–5.

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