Case In Point: Massive, fatal hemoptysis in a patientwith AIDS and B-cell lymphoma

July 1, 2006

A 49-year-old man presented to theemergency department (ED) andcomplained of fever and cough thatproduced bloody sputum for 1 day.He had AIDS and recently receiveda diagnosis of large B-cell lymphoma.His most recent CD4+ cellcount was 24/µL. He had optedagainst receiving highly active antiretroviraltherapy and prophylaxisfor opportunistic infection.

The authors describe an immunocompromised patient who had massive hemopty- sis caused by pseudomonal pneumonia in the community setting.

The case

A 49-year-old man presented to the emergency department (ED) and complained of fever and cough that produced bloody sputum for 1 day. He had AIDS and recently received a diagnosis of large B-cell lymphoma. His most recent CD4+ cell count was 24/µL. He had opted against receiving highly active antiretroviral therapy and prophylaxis for opportunistic infection.

He had received chemotherapy with cyclophosphamide, adriamycin, vincristine, and prednisone 1 week before presentation. At the time of presentation, he was neutropenic (white blood cell count, 90/µL) and thrombocytopenic (platelet count, 13,000/µL).

Shortly after arrival to the ED, the patient started to expectorate large amounts of bright red blood. Hypoxic respiratory failure and hypotension subsequently developed, requiring endotracheal intubation; mechanical ventilation; and aggressive resuscitation with crystalloids, blood products, and platelets.

His chest radiograph showed a new confluent opacity in the left mid-lung zone and the retrocar-diac area (Figure 1). Broad-spectrum antibiotic coverage with meropenem and vancomycin was immediately started.

Emergent bronchoscopy revealed pulsatile bleeding from the left lower lobe without a visible endobronchial source. Endobronchial tamponade of the massive bleeding from the left lower lobe was ineffective. However, contralateral single-lung ventilation resulted in acceptable oxygenation.

The patient underwent urgent bronchial arteriography with the goal to selectively embolize a possible feeding vessel(s) to the left lower lobe. The angiogram demonstrated a dilated descending branch of the left bronchial artery, which was successfully embolized. However, on return from this intervention, the patient had recurrent massive bleeding from the left lower lobe and worsening coagulopathy despite replacement with fresh frozen plasma and cryoprecipitate.

Repeated attempts to bronchoscopically control the bleeding and to clear the contralateral airway remained unsuccessful. The family, honoring the patient's directives, did not want to consider surgical resection and approached the medical staff to discontinue further resuscitative efforts. The patient expired 5 hours after presentation.

An autopsy revealed severe diffuse pulmonary hemorrhage in the left lower lobe. Microscopic examination showed widespread destruction of the entire lobe with invasion and obliteration of the large and small arteries by Gram-negative rods without associated inflammation (Figure 2). His blood cultures grew Pseudomonas aeruginosa.

Discussion

Bacterial infection remains a common pulmonary complication in HIV-infected patients despite the decline in incidence of respiratory infections with Pneumocystis jiroveci.1,2 In an autopsy series, P aeruginosa was identified in 16% of HIV-infected patients with bacterial pneumonia and was the most common bacterial pathogen.1 Pseudomonal pneumonia with associated bacteremia occurs most commonly in patients with hematologic malignancies, those with neutropenia induced by chemotherapy, and in patients with HIV infection.3 Patients with HIV infection and a low CD4 count have even been reported to have community-acquired bacteremic pseudomonal pneumonia.4

Two pathologic types of bacteremic pseudomonal pneumonia have been described.5 The first type consists of poorly defined, hemorrhagic, nodular, indurated areas found frequently in the subpleural area and occasionally surrounded by a small, central area of firm, gray, necrotic parenchyma. Microscopically, these lesions are located in the vicinity of small and medium-sized pulmonary arteries, and they lack inflammatory cell infiltration.

The second type is strikingly different and is characterized by 2- to 15-mm firm, yellow-brown or tan, necrotic umbilicated nodules that are surrounded by a narrow halo of dark red, hemorrhagic parenchyma. Microscopically, some of these lesions resemble typical abscesses composed of leukocytes and liquefied necrosis of pulmonary parenchyma. Other lesions impose as coagulation necrosis with abundant bacteria and bacterial invasion of necrotic small muscular arteries and veins.

Bacteremic pseudomonal pneumonia manifests suddenly with high fever, confusion, tachypnea, and dyspnea. Cough is present, but sputum production is usually scant and the sputum is thin.6 Pseudomonal pneumonia can mimic pulmonary embolism because of its potential to invade blood vessels and cause vasculitis.7

Early in the clinical course, the chest radiograph may show vascular congestion. The radiographic findings demonstrate the rapid progression to pulmonary edema and, after 48 hours, to necrotizing bronchopneumonia with pleural effusion and cavity formation.8 The formation of lung abscesses by P aeruginosa is common in HIV-infected patients, even those with low CD4 counts.9 In contrast, abscess and cavity formation are uncommon with other pulmonary pathogens, such as Mycobacterium tuberculosis, in patients with AIDS.10

Despite the pathologic features of vascular invasion by P aeruginosa, the incidence of massive hemoptysis in bacteremic pseudomonal pneumonia has not been reported. Nelson and Forman11 studied 50 HIV-infected patients with hemoptysis. Infection was the leading cause of hemoptysis in 80%. One patient in their report had pseudomonal pneumonia and died as a result of hemoptysis. Panos and associates12 reviewed 24 patients with hematologic malignancies and hemoptysis; 3 (13%) of the patients had a bacterial cause of hemoptysis, with a 66% fatality rate.

Before the development of more active antipseudomonal ß-lactam agents, the mortality associated with bacteremic pseudomonal pneumonia approached 100%.5 Despite improvements in antipseudomonal coverage, the mortality for HIV-infected patients remains high at 33% to 50%.13,14 Inappropriate antibiotic selection is associated with a high risk of mortality in HIV-infected patients with pseudomonal bacteremia.14 Those who survive the pneumonia have a high rate of relapse and an increased mortality.2 Highly active antiretroviral therapy has helped patients achieve remission from relapsing respiratory involvement.15

The high mortality rate of pseudomonal pneumonia may be the result of the ability of certain strains to cause necrosis of the lung epithelium and to disseminate rapidly into the patient's circulation.16 Different strains of P aeruginosa have been found to express virulence factors and cytotoxins (such as ExoU, a type III secretory cytotoxin) and many exoproducts (such as elastase, LasA protease, alkaline protease, and exotoxin A). The relationship between the expression and regulation of these factors in vitro and in vivo and their importance for the clinical phenotype is under active investigation.

Prophylaxis of pseudomonal infection in immunocompromised patients is debated. Although prophylaxis with trimethoprim/sulfamethoxazole is effective in reducing the risk of infection with P jiroveci as well as with Haemophilus, Salmonella, Toxoplasma, and Staphylococcusaureus, it is not effective against disease caused by Pseudomonas.17

A recent randomized controlled trial in patients receiving chemotherapy for solid tumors and lymphoma showed a reduction in fever, probable infection, and hospitalization with the prophylactic use of levofloxacin.18 However, the routine use of fluoroquinolone prophylaxis remains controversial because of the increasing emergence of fluoroquinolone-resistant Gram-negative bacilli and the documented lack of impact on mortality.19

In summary, bacteremic pseudomonal pneumonia in immunocompromised patients can occur in the community setting. The exact incidence of massive hemoptysis, as seen in our patient, is not known. Bacteremic pseudomonal pneumonia is rapidly progressive and life-threatening. Unfortunately, symptoms are nonspecific, and early radiographic findings may not correlate well with the severity of illness. Given the lack of effective prophylaxis, a high index of suspicion and the early administration of appropriate antibiotics are essential for successful treatment.

References:

REFERENCES


1. Afessa B, Green W, Chiao J, Frederick W. Pulmonary complications of HIV infection: autopsy findings.

Chest.

1998;113:1225-1229.
2. Baron AD, Hollander H.

Pseudomonas aeruginosa

bronchopulmonary infection in late human immunodeficiency virus disease.

Am Rev Respir Dis.

1993;148:992-996.
3. Pollack M.

Pseudomonas aeruginosa

. In: Mandell GL, Bennett JE, Dolin R, eds.

Mandell, Douglas, and Bennett's Principles & Practice of Infectious Diseases.

5 ed. New York: Churchill Livingstone; 2000:2310-2335.
4. Schuster MG, Norris AH. Community-acquired

Pseudomonas aeruginosa

pneumonia in patients with HIV infection.

AIDS.

1994;8:1437-1441.
5. Fetzer AE, Werner AS, Hagstrom JW. Pathologic features of pseudomonal pneumonia.

Am Rev Respir Dis.

1967;96:1121-1130.
6. Goetz MB, Finegold SM. Pyogenic bacterial pneumonia, lung abscess, and empyema. In: Murray JF, Nadel JA, eds.

Textbook of Respiratory Medicine.

3rd ed. Philadelphia: WB Saunders Co; 2000:1011-1013.
7. Soave R, Murray HW, Litrenta MM. Bacterial invasion of pulmonary vessels.

Pseudomonas

bacteremia mimicking pulmonary thromboembolism with infarction.

Am J Med.

1978;65:864-867.
8. Iannini PB, Claffey T, Quintiliani R. Bacteremic

Pseudomonas

pneumonia.

JAMA.

1974;230: 558-561.
9. Furman AC, Jacobs J, Sepkowitz KA. Lung abscess in patients with AIDS.

Clin Infect Dis.

1996;22:81-85.
10. Fournier AM, Dickinson GM, Erdfrocht IR, et al. Tuberculosis and nontuberculous mycobacteriosis in patients with AIDS.

Chest.

1988;93:772-775.
11. Nelson JE, Forman M. Hemoptysis in HIV- infected patients.

Chest.

1996;110:737-743.
12. Panos RJ, Barr LF, Walsh TJ, Silverman HJ. Factors associated with fatal hemoptysis in cancer patients.

Chest.

1988;94:1008-1013.
13. Mendelson MH, Gurtman A, Szabo S, et al.

Pseudomonas aeruginosa

bacteremia in patients with AIDS.

Clin Infect Dis.

1994;18:886-895.
14. Vidal F, Mensa J, Martinez JA, et al.

Pseudomonas aeruginosa

bacteremia in patients infected with human immunodeficiency virus type 1.

Eur J Clin Microbiol Infect Dis.

1999;18:473-477.
15. Domingo P, Ferre A, Baraldes MA, et al. Remission of relapsing

Pseudomonas aeruginosa

bronchopulmonary infection following antiretroviral therapy.

Arch Intern Med.

1998;158:929-930.
16. Sawa T, Ohara M, Kurahashi K, et al. In vitro cellular toxicity predicts

Pseudomonas aeruginosa

virulence in lung infections.

Infect Immun.

1998; 66:3242-3249.
17. Dworkin MS, Williamson J, Jones JL, Kaplan JE; Adult and Adolescent Spectrum of HIV Disease Project. Prophylaxis with trimethoprim- sulfamethoxazole for human immunodeficiency virus-infected patients: impact on risk for infectious diseases.

Clin Infect Dis.

2001;33:393-398.
18. Cullen M, Steven N, Billingham L, et al; Simple Investigation in Neutropenic Individuals of the Frequency of Infection after Chemotherapy +/2 Antibiotic in a Number of Tumours (SIGNIFICANT) Trial Group. Antibacterial prophylaxis after chemotherapy for solid tumors and lymphomas.

N Engl J Med.

2005;353:988-998.
19. Yoshida M, Ohno R. Antimicrobial prophylaxis in febrile neutropenia.

Clin Infect Dis.

2004;39 (suppl 1):S65-S67.