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A 47-Year-Old Woman from Thailand with Worsening Dyspnea 

A 47-Year-Old Woman from Thailand with Worsening Dyspnea
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A 47-Year-Old Woman from Thailand with Worsening Dyspnea
Author(s):

Daniel Caplivski

and W. Michael Scheld

DOI:
10.1093/med/9780199735006.003.0034
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Case Presentation

A 47-year-old woman from Thailand, with a history 14 years prior to admission of orthotopic liver transplant for autoimmune hepatitis, presented with fevers, abdominal pain, diarrhea, and dry cough for 5 days. She had recently been admitted with jaundice, increasing liver transaminases, hyperbilirubinemia (14 mg/dl), and her liver biopsy showed chronic evolving graft rejection. She was born in Thailand but had lived in the United States for 20 years, and denied any recent travel, illicit drug use, animal contact, or contact with patients with tuberculosis. Her tuberculin skin test was negative less than one year ago.

On physical examination she was afebrile, with scleral icterus but in no acute distress. Laboratory values were significant for neutropenia (2.1 × 103 WBC/μ‎l) and elevated total bilirubin (16 mg/dl). Initially, her pulmonary examination and chest radiography were both unremarkable; however, over the next several days, her fevers progressed and she developed increasing cough and dyspnea. By hospital day 5, she was hypoxic with 85% oxygen saturation on ambient air, and increasingly tachypneic. Repeat chest radiography showed diffuse bilateral infiltrates (Figure 7d.1) and chest CT showed diffuse bilateral ground-glass opacities with honeycombing (Figure 7d.2). Direct fluorescent antibody (DFA) testing on a sputum sample was positive for Pneumocystis jirovecii. (Figure 7d.3).

Figure 7d.1 Chest radiography, posterior-anterior view showing diffuse bilateral infiltrates.

Figure 7d.1
Chest radiography, posterior-anterior view showing diffuse bilateral infiltrates.

Figure 7d.2 Chest CT, axial view showing diffuse bilateral ground-glass opacities with honeycombing.

Figure 7d.2
Chest CT, axial view showing diffuse bilateral ground-glass opacities with honeycombing.

Figure 7d.3 Sputum sample positive with direct fluorescent antibody testing for Pneumocystitis jirovecii.

Figure 7d.3
Sputum sample positive with direct fluorescent antibody testing for Pneumocystitis jirovecii.

Case 7d Discussion: Pneumocystis jiroveci

Pneumocystis jirovecii, formerly called Pneumocystis carinii, is an agent of pneumonia that is the most frequent opportunistic infection in patients with AIDS. In other immunocompromised patient populations, it has been less well-described, particularly in the post-transplant population. There are several differences in the epidemiology, clinical presentation, diagnostic methods, and mortality between HIV-positive and HIV-negative patients.

The number of patients with Pneumocystis pneumonia (PCP) in non-HIV-infected patients has steadily risen in the last decade. The majority of these infections have occurred in patients with hematologic malignancies or solid organ (such as kidney and liver) transplant recipients. In addition, 90% of these patients were reported to have been receiving steroids prior to the diagnosis of PCP.24 In AIDS patients, PCP has classically presented as a subacute illness over several weeks in a patient with a CD4 count 〈 200 cells/mm3 with fever, dry cough, and dyspnea. Some patients, in fact, may be treated in an ambulatory setting.

In contrast, non-HIV-infected patients with PCP present more acutely over several days, with a more severe illness. Median CD4 counts in these patients vary greatly in the literature. In addition, the burden of organism is much greater in HIV-infected patients compared to non-HIV-infected patients, making diagnosis by GMS, Gram-Weigert, and DFA staining much more sensitive in the former, particularly on bronchoalveolar lavage (BAL) specimens. Our patient represents a rare case in which PCP was diagnosed on a single sputum sample via DFA. Other methods of diagnosis include polymerase chain reaction (PCR) of sputum or BAL specimens, though its positive predictive value (PPV) is much lower in non-HIV-infected patients compared to HIV-infected patients.5

Antimicrobial treatment for PCP, however, remains the same in both immunocompromised populations. Table 7d.1 lists first-line and alternative therapy based on the clinical severity of disease. A clear benefit of steroids for the treatment of PCP in AIDS patients who are hypoxic has been shown in the literature. The standard dose of prednisone is 40 mg twice daily over 5 days, then tapered over the ensuing 16 days of the illness. The benefit in non-HIV-infected patients has been less apparent. Few studies have been able to demonstrate a clear benefit to giving steroids in this population, with two major studies showing conflicting data.6,7

Table 7d.1 Management of Pneumocystis Pneumonia

Not Acutely Ill (Ambulatory setting)

FIRST LINE

TMP/SMX

1 DS tablet every 8 hours × 21 days

Dapsone + TMP

100 mg orally every 24 hours + 5 mg/kg every 8 hours every 8 hours × 21 days

SECOND LINE

Clindamycin + Primaquine

300–450 mg orally every 6 hours + 15 mg base every 24 hours × 21 days

Atovaquone

1500 mg orally every 24 hours × 21 days

Acutely Ill

FIRST LINE

TMP/SMX

15 mg/kg/day IV divided every 6–8 hours × 21 days

SECOND LINE

Clindamycin + Primaquine

600 mg IV every 8 hours + 30 mg base orally every 24 hours × 21 days

Pentamidine

4 mg/kg/day IV × 21 days

Despite similar treatment regimens for PCP in both HIV-positive and HIV-negative patients, reported mortality rates between the two groups have differed widely, with the latter showing reports double that of the former. In addition, complication rates, including rates of respiratory failure and those requiring intensive care, have been higher in HIV-negative immunocompromised patients.13

References

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3. Roblot F, Godet C, Le Moal G, et al. Analysis of underlying diseases and prognosis factors associated with Pneumocystis carinii pneumonia in immunocompromised HIV-negative patients. Eur J Clin Microbiol Infect Dis. 2002;21:523–531.Find this resource:

4. Weig M, Klinker H, Bögner BH, Meier A, Gross U. Usefulness of PCR for diagnosis of Pneumocystis carinii pneumonia in different patient groups. J Clin Microbiol. 1997;35(6):1445–1449.Find this resource:

5. Delclaux C, Zahar J-R, Amraoui G, et al. Corticosteroids as adjunctive therapy for severe Pneumocystis carinii pneumonia in non-human immunodeficiency virus-infected patients: retrospective study of 31 patients. Clin Infect Dis. 1999;29:670–672.Find this resource:

6. Pareja JG, Garland R, Koziel H. Use of adjunctive corticosteroids in severe adult non-HIV Pneumocystis carinii pneumonia. Chest. 1998;113:1215–1224.Find this resource:

7. Mansharamani NG, Garland R, Delaney D, Koziel H. Management and outcome patterns for adult Pneumocystis carinii pneumonia, 1985 to 1995: comparison of HIV-associated cases to other immunocompromised states. Chest. 2000;118(3):704–711Find this resource: