A case of miliary TB complicated by ARDS and pancytopenia

June 1, 2007

We present a case of a 35-year-old man with fever and pancytopenia, who had rapid progression to acute respiratory distress syndrome (ARDS), multiorgan failure, and disseminated intravascular coagulopathy secondary to disseminated tuberculosis (TB). Although both sputum and bronchoalveolar lavage (BAL) fluid smears were negative for acid-fast bacilli, the polymerase chain reaction (PCR) assay on the BAL fluid was positive for Mycobacterium tuberculosis. This case emphasizes the need to include TB in the differential for ARDS and the value of PCR testing of BAL fluid, especially in high-risk patients.

The case

A 35-year-old man presented to the emergency department (ED) with generalized malaise, fevers, chills, night sweats, dyspnea, chronic diarrhea, and a 60-lb weight loss during the past 6 months. He had emigrated from Mexico 6 months before presentation.

The patient denied any earlier hospitalizations. He did not recall being screened in the past with a tuberculin skin test and was not aware of previous immunizations.

In the ED, he appeared ill with mild respiratory distress. His initial vital signs were remarkable for a temperature of 39.4ºC (103ºF) taken orally, pulse rate of 97 beats per minute and regular, respiration rate of 18 breaths per minute, and blood pressure of 107/75 mm Hg. His oxygen saturation was 95% on 50% oxygen by face mask. Findings from his physical examination revealed mild scleral icterus, a soft grade 3/6 systolic murmur at the apex without any radiation, and no lymphadenopathy or hepatosplenomegaly. Chest examination showed diffuse bilateral respiratory crackles without any wheezing or rhonchi.

Laboratory studies revealed pancytopenia (total white blood cell count of 0.6 T/µL, hemoglobin level of 5.5 g/dL, and platelet count of 25,000 T/µL). The patient's aspartate aminotransferase and alanine aminotransferase levels were mildly elevated, and his serum albumin level was low (2.5 g/dL).A chest radiograph showed diffuse bilateral interstitial infiltrates (Figure 1). A CT scan revealed bilateral mediastinal lymphadenopathy, diffuse pulmonary nodular interstitial densities, and mild splenomegaly (Figures 2 and 3). The echocardiographic results were normal.

Owing to his clinical presentation and unknown HIV status, he was given broad-spectrum antibiotics and trimethoprim/sulfamethoxazole for possible Pneumocystis jiroveci pneumonia. Liposomal amphotericin B was added later for possible fungal infection. However, his condition worsened and on hospital day 3 he was intubated for respiratory distress.

The results from tests for HIV infection, hepatitis B and C, and syphilis were negative. The results from blood smear evaluation for malaria, serum antigen screening for Cryptococcus, and urine antigen screening for Histoplasma were all negative. The findings from urine and sputum smears for acid-fast bacilli (AFB) were also negative. Tuberculin skin testing revealed no induration.

Bronchoalveolar lavage (BAL) was performed, and empiric 4-drug antituberculosis therapy was initiated, despite negative findings from AFB smear on the BAL specimen. The patient's condition worsened to septic shock with disseminated intravascular coagulation and multisystem failure. A preliminary diagnosis of disseminated tuberculosis (TB) was made on the basis of a positive reverse transcriptase polymerase chain reaction (PCR) assay for Mycobacterium tuberculosis from the BAL specimen.

Bone marrow aspiration revealed a hypercellular marrow, 70% with increased plasma cells. Stool evaluation was positive for Ascaris lumbricoides eggs. The patient's condition rapidly deteriorated, and he died on hospital day 6. Autopsy was not performed. Cultures of blood, sputum, and bone marrow specimens grew M tuberculosis that was sensitive to all of the medications the patient had been receiving.

The patient's hypoxemic respiratory failure was attributed to the acute respiratory distress syndrome (ARDS), given his low ratio of PaO2 to fraction of inspired oxygen (165 at the time of intubation and 59 before he died) and normal echocardiographic findings in the setting of diffuse bilateral pulmonary infiltrates.

Discussion

ARDS is a common response to a number of infectious and noninfectious insults. ARDS resulting from TB, although rare, carries a high mortality rate of 70% to 100% compared with 40% to 60% in patients with ARDS alone or 16% to 38% in those with miliary TB alone.1,2 Survival depends on early recognition and treatment.3,4

Miliary TB is an uncommon but highly lethal cause of ARDS and pancytopenia.2 Studies have found that only about 7% of cases of miliary TB are complicated by ARDS.5 However, the mortality rate is much higher--70% to 100%--than it is in patients who have miliary TB without ARDS.1 The increased mortality rate may be attributed to the misleading radiologic presentation of miliary TB in the presence of ARDS, combined with low sen-sitivity (30% to 50%) of sputum smear for AFB.2,6The usual radiographic pattern of miliary TB is often hidden behind the pulmonary edema of ARDS. These factors combined may delay diagnosis and treatment.

In our patient, the diagnosis of TB was made by PCR assay of BAL fluid despite negative findings from smears for AFB. Although, to our knowledge, there are limited data about the utility of PCR testing of BAL fluid in patients with miliary TB, it appears to increase the sensitivity of the diagnosis of pulmonary TB in patients with negative findings from AFB smears of sputum and BAL fluid.6

Although the reason for the patient's presentation with such advanced disease is unclear, it may be related to underlying immunodeficiency as a result of malnutrition. His clinical presentation--specifically, hypoalbuminemia, chronic diarrhea, and Ascaris infestation--supports our impression that he was severely malnourished. This may have played a significant role in his clinical presentation, in the rapid progression of his condition to disseminated disease, and in his death. Malnutrition is known to affect cell-mediated immunity and is a risk factor for diseases such as pneumocystosis and TB.7,8 Persons with malnutrition are at an increased risk for both latent and primary infection to progress to active disease.9

Given the high mortality rate for patients with miliary TB complicated by ARDS, an emphasis should be placed on rapid diagnosis using invasive methods such as bronchoscopy and molecular techniques such as PCR to help improve patient outcomes.

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