Newly formed cystic lesions for the development of pneumomediastinum in Pneumocystis jirovecii pneumonia
© Cho et al; licensee BioMed Central Ltd. 2009
Received: 29 January 2009
Accepted: 18 October 2009
Published: 18 October 2009
Pneumocystis jirovecii, formerly named Pneumocystis carinii, is one of the most common opportunistic infections in human immunodeficiency virus (HIV)-infected patients.
We encountered two cases of spontaneous pneumomediastinum with subcutaneous emphysema in HIV-infected patients being treated for Pneumocystis jirovecii pneumonia with trimethoprim/sulfamethoxazole.
Clinicians should be aware that cystic lesions and bronchiectasis can develop in spite of trimethoprim/sulfamethoxazole treatment for P. jirovecii pneumonia. The newly formed bronchiectasis and cyst formation that were noted in follow up high resolution computed tomography (HRCT) but were not visible on HRCT at admission could be risk factors for the development of pneumothorax or pneumomediastinum with subcutaneous emphysema in HIV-patients.
Pneumocystis jirovecii, formerly named Pneumocystis carinii, is one of the most common opportunistic infections in human immunodeficiency virus (HIV)-infected patients [1, 2]. Spontaneous pneumothorax has been recognized as a frequent complication in patients with P. jirovecii pneumonia (PCP) since it was first described in 1984 , and pneumomediastinum is an uncommon complication associated with pneumothorax in the aforementioned population. We report two cases of spontaneous pneumomediastinum with subcutaneous emphysema in HIV-infected patients being treated for P. jirovecii pneumonia with trimethoprim/sulfamethoxazole.
A 33-year-old man presented with fever, dyspnea, and odynophagia. Five months prior to admission, the patient had been treated for dental caries at a local hospital, and at that time examination revealed seropositivity for human immunodeficiency virus. On admission, temperature was 39.0'C, pulse 92 beats per minute, respiratory rate 20 breaths per minute and blood pressure 130/80 mmHg. Physical examination revealed oral thrush, consistent with findings of extensive esophageal candidiasis in endoscopic gastroduodenscopy performed five days before admission. Laboratory data on admission revealed a WBC count of 1,760/uL, Hb 10.9 g/dL, and platelet count of 297,000/uL. Arterial blood gas analysis while breathing room air revealed PaO2 of 48.0 mmHg, PaCO2 of 32.7 mmHg, and saturation of 88.5%, and the calculated (A-a)DO2 was 53.7. CD4 count and HIV viral load were 4/uL and 130,000 IU/mL, respectively. Diffuse bilateral infiltrates of both lung fields were noted, and no cystic lesions were observed on the chest X-ray and high resolution computed tomography (HRCT) taken on admission. Bronchoscopic alveolar lavage for diagnosis of P. jirovecii was carried out, and microscopic examination of the bronchoalveolar lavage fluid obtained showed P. jirovecii; no other microorganisms were detected by culture. Treatment with trimethoprim/sulfamethoxazole, fluconazole and corticosteroids at standard dosages was started. The patient had never been on HAART therapy prior to admission. HAART therapy was added to the treatment on the 8th hospital day. During the treatment with trimethoprim/sulfamethoxazole, pancytopenia worsened. Bone marrow biopsy revealed inflamed marrow and partial necrosis. Granulocyte colony stimulating factor was used without avail. On the 22nd hospital day, the chest X-ray obtained as the patient's hypoxemia worsened revealed pneumomediastinum. HRCT showed newly formed cystic lesions in both lung fields. Pneumomediastinum was treated conservatively with high oxygen supply. CD4 cell count and HIV levels were not followed during treatment. However, as the general condition of the patient deteriorated, the patient was started on intravenous pentamidine on the 23rd hospital day. On the 25th hospital day, his oxygen requirement increased. Without intubation, as the patient and guardian refused the patient being put on a ventilator due to multiple economical and sociological reasons, the patient died on the 26th hospital day.
The overall incidence of P. jirovecii pneumonia has decreased with the use of highly active antiretroviral therapy . However, approximately 85% of patients with advanced HIV infections continue to experience P. jirovecii pneumonia in the course of their disease when management is inadequate . The most common radiographic finding in P. jirovecii pneumonia is the presence of diffuse, bilateral perihilar interstitial infiltrates (ground-glass opacity) in both lungs . Atypical radiographic manifestations of PCP include cystic spaces and bullae, adenopathy, pleural effusions and pneumothorax [7–10]. The exact mechanism behind the development of the pulmonary cysts and P. jirovecii is not yet known. However, various mechanisms have been proposed including direct lung destruction by P. jirovecii, over-distension of the lungs caused by obstructive bronchiolitis acting as a ball-valve (inflammatory exudates in the small bronchioles), interstitial emphysema and abnormal remodeling of pulmonary architecture due to interstitial fibrosis, and release of elastase and other proteolytic enzymes [5, 10–12]. A review of the literature indicates that the development of spontaneous pneumomediastinum with subcutaneous emphysema in HIV patients is rare. The pathophysiology of pneumomediastinum depends on a pressure gradient between the alveoli and the lung interstitium; this leads to alveolar rupture, and consequently air in the interstitial space flows towards the mediastinum along a pressure gradient between the lung periphery and the mediastinum . Other mechanisms leading to this outcome have been attributed to gas-producing microorganisms present in the pneumomediastinum, and rupture of the mucosal barrier of the esophagus or tracheobronchial tree . However, how the presence of P. jirovecii contributes to the development of pneumomediastinum is unknown.
Spontaneous pneumothorax occurs in as many as 35% of patients with active cystic P. jirovecii pneumonia . Even though it is not known exactly how the disease progresses to pneumothorax or pneumomediastinum, it is important to identify associated factors and be able to predict their occurrence. A history of cigarette smoking, pentamidine aerosol treatment, and detection of pneumatoceles by chest radiography, are reported risk factors associated with spontaneous pneumothorax [15, 16].
In relation to the aforementioned risk factors, a 22 pack-year history of smoking was noted in one of our two patients. Pneumatoceles or cysts were not seen on the chest X-rays or HRCT scans taken on admission in either patient. However, cystic lesions and bronchiectasis developed de novo in spite of the standard trimethoprim/sulfamethoxazole treatment, and they are presumed to have developed into pneumomediastinum with subcutaneous emphysema . Staphylococcus aureus that was cultured in the second case may have attributed to the development of pneumomediastinum . However, the use of trimethoprim/sulfamethoxazole was adequate for treating Staphylococcus aureus without the need for an additional antibiotic . Treatment of spontaneous pneumomediastinum is generally limited to observation without the need for invasive measures . However, in the above patients, P. jirovecii pneumonia may have been an underlying cause to the development of pneumomediastinum. Therefore, the standard trimethorpim/sulfamethoxazole was analyzed as a treatment failure warranting a change of antibiotics to pentamidine.
There is no guideline regarding the treatment of the acute phase of P. jirovecii pneumonia in HIV-infected patients with HAART. However, administration of HAART therapy early in the acute phase of P. jirovecii pneumonia was done in both patients as improved survival rates in HIV-infected patients with severe P. jirovecii pneumonia was associated with HAART therapy [21, 22]. Although the developement of pneumothorax was not anticipated in our patients when HAART therapy was initiated, Morris et al reported decreased rates of pneumothorax development in P. jirovecii infected HIV-patients receiving HAART therapy. The possible contribution of antiretroviral therapy to the clinical worsening of the patients was considered. Wislez et al reported of acute respiratory failure following HAART in P. jirovecii pneumonia due to immune reconstitution inflammatory syndrome . HRCT of both patients in this study did not reveal any findings relevant to the development of acute respiratory failure.
The occurrence of newly formed cystic lesions or bronchiectasis despite treatment may be risk factors for the development of pneumothorax or pneumomediastinum with subcutaneous emphysema in HIV-patients. Therefore close follow up with HRCT in HIV-patients with P. jirovecii pneumonia might assist in predicting the development of pneumothorax or pneumomediastinum. Our findings suggest that clinicians should be aware of the clinical importance of newly formed cystic lesions and bronchiectasis for the development of pneumomediastinum and pneumothorax in P. jirovecii pneumonia.
In conclusion, clinicians should be aware that cystic lesions and bronchiectasis can develop in spite of trimethoprim/sulfamethoxazole treatment for P. jirovecii pneumonia. Newly formed bronchiectasis and cyst formation may be risk factors for the development of pneumomediastinum with subcutaneous emphysema.
Written consent was obtained from the patient or their relative for publication of study.
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