Disorders Associated with Severe Immune Suppression

Pneumocystis carinii Pneumonia
PCP is the most common lung disease in persons with advanced HIV infection. The presentation tends to be indolent, characterized by slowly progressive shortness of breath and nonproductive cough, usually accompanied by fever. In the PCHIS cohort, it was noted that virtually all episodes of PCP were marked by cough or shortness of breath, or both. If at least one of these symptoms was not present, PCP was not found. This study also examined the utility of screening for P. carinii by performing chest radiographs, pulmonary function tests, and examination of induced sputum on asymptomatic subjects. No cases of PCP were found. Based on these data, an evaluation for P. carinii should not be undertaken unless an HIV-infected person complains of cough and/or shortness of breath.

The radiographic findings of PCP are extremely varied. Most frequently there is diffuse “interstitial” infiltration, but there may be any manner of focal infiltrations, nodules or cavitary lesions, pneumatoceles, or miliary infiltration. Focal upper lobe involvement that mimics tuberculosis is more common in persons who have been given aerosol pentamidine as prophylaxis against PCP. Pneumatoceles and spontaneous pneumothorax may occur with first episodes of PCP but are more common with subsequent episodes.

Commonly, the response to antipneumocystis therapy is slow, and radiographic abnormalities and gas exchange may worsen during the first 4 to 6 days of treatment. Co-administration of corticosteroids may minimize this initial worsening. Generally, particularly if the diagnosis has been established by bronchoscopy, most clinicians who repeat bronchoscopy early in the course of therapy find that it does not yield any additional diagnoses. However, worsening later in the course may be associated with a second, superimposed disease.

Nontuberculous Mycobacterial Disease
Soon after AIDS was initially described, it was recognized that a group of closely related mycobacteria collectively named Mycobacterium avium complex was a common cause of disseminated infection in patients with the syndrome. Although M. avium complex organisms are commonly isolated from respiratory tract specimens in persons with advanced HIV infection, actual lung disease is unusual. Occasionally, however, the organism may cause focal lung disease.

Endobronchial lesions may be seen on bronchoscopy, and on biopsy these lesions may contain granulomas, a histologic feature that is unusual in other organs involved in disseminated M. avium disease. Colonization of the lungs may precede and be a marker for subsequent disseminated M. avium infection. Disseminated M. avium complex disease occurs late in the course of HIV disease, usually when the CD4 + lymphocyte count is < 50 cells per microliter. Fever, weight loss, diarrhea, and abdominal pain are common symptoms. Pulmonary involvement is usually indicated by cough. Because it is difficult to distinguish between colonization and infection, the radiographic features of M. avium pulmonary disease are not well-defined. As noted above, focal infiltration may occur. Rarely, there may be diffuse lung involvement with an interstitial pattern on chest films. However, in the presence of a diffusely abnormal chest film, M. avium complex should not be accepted as the cause until other diseases have been excluded.

Among the nontuberculous mycobacteria, M. kansasii is a distant second to M. avium complex as a cause of disease in HIV-infected persons; although its frequency seems to be increasing. As with M. avium complex, M. kansasii infections tend to be disseminated in persons with HIV infection. However, when M. kansasii is isolated from a respiratory tract specimen, it is more likely to be a cause of lung disease than is M. avium complex. As with most lung infections, M. kansasii usually presents with fever, cough, and, subsequently, shortness of breath. M. kansasii is probably more likely to cause diffuse infiltration on chest film than M. avium complex.

Fungal Infections
Both histoplasmosis and coccidioidomycosis are common HIV-associated infections in the areas in which the causative organisms are endemic and are seen sporadically outside of the endemic regions. The presenting clinical features of both histoplasmosis and coccidioidomycosis are nonspecific and variable. Histoplasmosis is commonly a protracted, febrile, wasting illness. Both infections are usually disseminated, with respiratory symptoms and abnormal chest films reported in varying proportions. Both histoplasmosis and coccidioidomycosis can present with an acute sepsis syndrome including acute respiratory failure.

Chest radiographs are abnormal in the majority of patients, especially those who have respiratory symptoms. With histoplasmosis, the most common pattern is diffuse infiltration that is either reticulonodular or “alveolar.” Coccidioidomycosis is associated with either localized or scattered nodular lesions or diffuse infiltration. For histoplasmosis, the diagnosis is commonly established by stain and culture of bone marrow, buffy coat, or blood. With coccidioidomycosis involving the lungs, specimens from the respiratory tract usually serve to establish the diagnosis.

Cryptococcosis is not limited to an endemic area. The presenting complaints are nonspecific and include fever, weight loss, fatigue, and headache, often present for a long period prior to diagnosis. Most often pulmonary involvement is silent, although in one large retrospective review, 31% of patients had respiratory complaints at the time of presentation. The findings on chest radiographs have been varied. Focal and diffuse infiltration, localized or scattered nodules, some of which may be cavitary, pleural effusions, and hilar adenopathy all have been described.

Aspergillosis has been diagnosed in a small number of patients with HIV infection. There are two patterns of Aspergillus pulmonary disease, one characterized by tissue invasion and the second largely an airway disease, obstructive bronchial aspergillosis. Reported risks in the setting of HIV infection have been neutropenia, use of corticosteroids, marijuana smoking, and use of broad-spectrum antimicrobial agents. Fever and cough that is sometimes productive of bronchial casts are the usual presenting complaints. The radiographic findings include focal infiltration, cavitary lesions, and pleura-based densities. Atelectasis and airway filling patterns may be seen with obstructive bronchial aspergillosis.

CMV is commonly isolated from respiratory tract specimens in HIV-infected patients. However, it is unusual for lung disease to be attributable to this agent even when specific cytomegalic cells are seen on biopsy specimens. Thus, the diagnosis of CMV pneumonia can be made only when the virus is isolated in culture, specific histopathologic changes are seen on biopsy, and no other diagnosis is established. Because it is difficult to determine if CMV is the cause of lung disease in a given patient, the radiographic features of CMV pneumonia are not well-defined. In general, however, it is thought to cause diffuse infiltration that is not distinguishable from the pattern caused by many other organisms and by nonspecific interstitial pneumonitis.

Neoplastic Diseases
In the PCHIS cohort, KS involving the lungs occurred at a rate of 0.33 cases per 100 person-years of observation (14 [13%] pulmonary cases of 105 total cases), and pulmonary involvement with lymphoma occurred at a rate of 0.19 cases per 100 person-years. However, among persons with advanced HIV disease, pulmonary KS has been diagnosed in 8 to 14% of patients being evaluated for respiratory symptoms, in 21 to 49% of patients with respiratory symptoms and mucocutaneous lesions, and in 47 to 75% of patients with known KS undergoing autopsy. It is likely that the reported frequency of KS is less than actually occurs because the lung involvement may be clinically silent.

The diagnosis of pulmonary KS is nearly always established by the appearance of lesions on bronchoscopy. Typically, endobronchial KS is seen as flat, red or purple submucosal lesions that are similar in appearance to submucosal hemorrhages induced by bronchoscope trauma (see Color Plate 10 G). The lesions may be found in any location, from vocal cords to peripheral airways, and tend to favor airway bifurcations. Because of their submucosal location, the lesions are difficult to biopsy; however, the findings are sufficiently characteristic in appearance to enable a high degree of diagnostic certainty. In a few instances, pulmonary parenchymal KS has been diagnosed by transbronchial or open biopsy in persons with no endobronchial lesions seen.

The chest radiographs of patients who had pulmonary KS without coexisting infection showed lesions that were predominantly central and consisted mainly of bronchial wall thickening and nodules. Kerley B lines and pleural effusions were noted in 71 and 52%, respectively. Hilar or mediastinal adenopathy was present in 15%.

Non-Hodgkin’s lymphoma is the second most frequent malignancy involving the lungs in patients with HIV infection. The frequency of pulmonary involvement in reported series is 0 to 25%. The presentation, even in patients who have pulmonary involvement, is generally dominated by systemic symptoms. The most common chest radiographic findings are patchy parenchymal infiltrates, nodules, and solitary masses. Intrathoracic adenopathy has been reported in a minority of cases. The diagnosis can be established by transbronchial biopsy, needle aspiration biopsy, or thoracoscopic or open biopsy.

Provided by ArmMed Media
Revision date: July 5, 2011
Last revised: by David A. Scott, M.D.