Shazia M. Jamil
The immunocompromised patient has an increased susceptibility to infection as a result of qualitative or quantitative defects in inflammatory and immunologic host defenses. These defects are caused by a wide range of processes and diseases that include, but are not limited to, primary congenital syndromes, cancer, rheumatologic diseases, retroviral infection, malnutrition, alcoholism, cirrhosis, diabetes mellitus, and immunosuppressive therapy. Pulmonary complications in immunocompromised patients are becoming more common, owing to increases in solid organ transplantation, hematopoietic stem cell transplantation, the use of more potent chemotherapeutic regimens in cancer, and immunosuppressive therapy in rheumatologic disorders. Lung involvement in this group may be either infectious or noninfectious; however, infectious causes are reported in the majority (50%–75%) of cases. They carry a high risk of morbidity and mortality, which warrants a careful diagnostic and therapeutic approach. Immunocompromised hosts are susceptible to pulmonary infections because of decreased granulocyte number and function, compromised immune function (i.e., lymphocyte activity), mechanical barriers to colonization/infection, and exposure to pathogens.
Infections in immunocompromised patients can be bacterial, viral, fungal, parasitic, or mycobacterial. Bacterial pneumonia is the most common cause of focal pulmonary infiltrates in patients with the AIDS or leukemia (before, during, and after chemotherapy). Pneumococcus and Haemophilus are as common in the general population as they are in immunocompromised hosts, while encapsulated Gram-positive cocci (e.g., Staphylococcus aureus) and the Enterobacteriaceae species (e.g., Escherichia coli, Klebsiella, and Pseudomonas species) are more prevalent among those with granulocytopenia (<500/mm3) and hospitalized patients. Nosocomially acquired Legionella infection has also been reported in immunocompromised patients. Rhodococcus equi, a Gram-positive coccobacilli, has been increasingly reported to cause pneumonia and lung abscesses in AIDS patients and in solid organ transplant recipients, especially those with heart transplant. Due to its variable acid-fast staining and pleomorphic appearance, it has been misdiagnosed as “diphtheroids” and mistaken as a contaminant.
Fungal infections common in immunocompromised patients include both the filamentous fungi (e.g., Aspergillus species and the mucormycosis) and the dimorphic fungi (e.g., Candida species, Cryptococcus neoformans, Blastomycoses dermatitidis, Coccidioides immitis, and Histoplasma capsulatum). Other fungi, including Ochroconis, Trichosporon, Fusarium, Zygomycetes, and Scedosporium apiospermum and Scedosporium prolificans are involving the lung with increasing frequency. Scedosporium carries a high mortality rate, particularly in transplant recipients and is resistant to amphotericin B and most other antifungals.
Aspergillus is the most common cause of fungal pneumonia; patients with hematopoietic stem cell transplantation are particularly prone to invasive aspergillosis. A. fumigatus and A. flavus are the two most common. Recently, A. ustus and A. terrus are being recognized among severely immunocompromised transplant recipients and frequently involve the lung. Early differentiation of the later two from the more common aspergillus infections is important since these species are resistant to amphotericin B.
Local overgrowth of normal flora such as Candida albicans in the mouth (thrush) and esophagus is frequent in patients with deficient granulocyte number or function and those receiving broad-spectrum antibiotics. Candida pneumonia however is rare, with the exception of lung transplant recipients. Prophylactic fluconazole is increasingly being used in immunocompromised patients, a practice that leads to a decreased incidence of C. albicans infection, but a rise in more antifungal-resistant C. krausei and C. glabrata.
The fungus Ochroconis gallopavum is a dematiaceous hyphomycete that produces characteristic darkly pigmented, septate hyphae and is an emerging opportunistic and possibly fatal fungal infection that occurs almost exclusively in immunocompromised patients. Brain, lung, and spleen involvement is reported and surgical excision in combination with amphotericin B has been utilized.
Fusarium species are important causes of opportunistic fungal infections, risk factors of which include prolonged neutropenia and T-cell immunodeficiency, especially in hematopoietic stem cell transplantation with severe graft-versus-host disease and lung transplant recipients. F. solani is the most virulent species. The principal portal of entry is the airways. The clinical presentation mimics aspergillosis. However, clues to the diagnosis include the pattern of new pulmonary infiltrates (interstitial, nodular or cavitary), sinusitis especially with periorbital cellulitis, cutaneous lesions, and positive 1-3-β-D glucan test but negative aspergillus galactomannin test. Recommended empirical treatment includes voriconazole and amphotericin B as first line, and posaconazole for refractory disease. Since Fusarium species have intrinsic resistance to caspofungin and micafungin, susceptibility testing should be performed. Immunotherapy with growth factors (G-CSF) for neutropenic patients and gamma interferon and/or GM-CSF for patients with adequate neutrophil counts is also recommended since nearly ubiquitous mortality is observed in patients with persistent neutropenia and disseminated disease.
Commonly recognized respiratory viruses in immunocompromised patients include influenza A and B, parainfluenza 1 to 4, respiratory syncytial virus (RSV), and adenovirus. In the last decade, novel coronaviruses, enteroviruses, rhinovirus, and human metapneumovirus (hMPV) have also been recognized as pathogens. Newly emerged viruses such as bocavirus, parvovirus 4 and 5, KI and WU polyomaviruses, and mimivirus have been reported to involve lung, however currently there is very limited literature in immunocompromised patients. Herpes simplex, varicella, and cytomegalovirus infections may occur, either as newly acquired infections or as reactivations of dormant processes. Cytomegalovirus is the most common viral respiratory pathogen in non-HIV immunocompromised patients.
After transplantation, the risk of cytomegalovirus is closely related to the donor and recipient’s prior cytomegalovirus serostatus. RSV is possibly the most important cause of morbidity and mortality of all respiratory viruses affecting the transplant recipient. Several cases of coronavirus-associated severe acute respiratory syndrome (SARS) were diagnosed among solid organ transplant and hematopoietic stem cell transplantation recipients during the 2003 epidemic. The prevalence of respiratory viruses in a given season depends on exposure, virulence, the types of circulating viruses, and the detection methods used.
The outcome of respiratory viral infections in hematopoietic stem cell transplantation recipients depends on several factors including whether the transplant was myeloablative versus non-myeloablative, the presence of lymphopenia, and the intensity of immunosuppression. Lung transplant recipients have a greater frequency of respiratory viral infections than other transplant recipients. This may be due to direct communication of the allograft with the environment and the poor immune response in the allograft. Respiratory viral infections occurring after lung transplantation has been associated with greater incidence of acute rejection and bronchiolitis obliterans syndrome. One possible mechanism could be a cytokine-mediated inflammatory cascade that recruits T cells to the allograft, further resulting in intraluminal proliferation of fibroblasts. Treatment consists of specific antiviral therapy for symptomatic infections regardless of the duration of symptoms and if possible a decrease in immunosuppression. Some centers also use high-dose steroids (5–10 mg/kg/day for 3 consecutive days) in addition to specific antiviral therapy to prevent acute rejection and progression to bronchiolitis obliterans syndrome.
Pneumocystis jiroveci (previously P. carinii) is an opportunistic infection that can cause fulminant and fatal pneumonia in AIDS patients and other immunocompromised patients. Although its incidence is decreased in at-risk patients who use trimethoprim–sulfamethoxazole for prophylaxis, cases still arise in those with adjustments in immunosuppressives (e.g., tapering of corticosteroids), those noncompliant with prophylaxis, and patients with lymphoid malignancies treated with fludarabine.
Mycobacterium tuberculosis (MTB) infections are particularly common in AIDS patients and recipients of solid organ transplant (especially renal transplant recipients), compared with other immunocompromised hosts. The infection is either newly acquired (in endemic areas) or a reactivation of a latent infection. Tuberculosis may involve the lung very early during HIV infection, whereas extrapulmonary or atypical manifestations are associated with more profound immunodeficiency. Immunocompromised patients may present with mycobacteremia and multidrug resistance. In AIDS patients with relatively high CD4+ T-cell counts, a typical pattern of pulmonary reactivation occurs with fever, cough, weight loss, night sweats, and a radiograph revealing cavitary apical upper lobe disease. Disseminated tuberculosis infection is more common in patients with low CD4+
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