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COLLEAGUES IN RESPIRATORY MEDICINE

Approach to Imaging Pulmonary Disease in the ImmuneCompromised Host

Theodore J. Lee, MD, and Brett M. Elicker, MD

Abstract: The increasing number and variety of patients withcompromised immune systems poses a diagnostic challenge for thechest physician. Manifestations of pulmonary disease on imagingstudies are diverse, with substantial overlap possible between enti-ties. This article reviews radiologic findings in common diseasestates encountered when treating immune compromised patients andprovides a framework for approaching common imaging manifes-tations, such as air-space consolidation, ground-glass opacities, andnodules.

Key Words: immune compromise, chest radiology, HIV/AIDS

(Clin Pulm Med 2008;15: 81–96)

Patients who have compromised immunity present a chal-lenge to the chest physician. Causes of immune compro-

mise are varied and include intrinsic disorders of the immunesystem, acquired diseases such as infection with humanimmunodeficiency virus (HIV), and medical therapies such aspost-transplantation immunosuppression. The spectrum ofpulmonary diseases in these patients is broad and varies withthe type and degree of immune compromise. Although themost frequent clinical concern in this population is for infec-tion, disorders associated with immune compromise rangefrom noninfectious inflammatory diseases to malignancies.Radiologic studies play an important role in diagnosis andmust be reviewed with consideration for the immune defi-ciency of the host. In this article, we review mechanisms ofimmune compromise, common infectious and noninfectiousdiseases in immune compromised patients, and key radio-logic patterns as a foundation for an organized approach toradiologic findings in this diverse and challenging patientpopulation.

Mechanisms of Immunity andImmunodeficiency

An immunocompromised host is conventionally de-fined as a patient with decreased function of the immune

system, resulting primarily in a decreased resistance to infec-tion. There are 3 main groups of immunocompromised pa-tients: those with congenital defects in immunity, those withacquired defects in the immune system, and those withdefects secondary to medical therapies, which suppress anotherwise normal immune response. Understanding themechanisms of normal and disordered immunity is an impor-tant step toward understanding the diseases that occur inpatients with immune compromise.

Host defenses can be divided into 3 basic categories.First are physical barriers such as skin and mucous mem-branes. Second is cellular immunity, including phagocytes,neutrophils, natural killer cells, T lymphocytes, and macro-phages. Third is humoral immunity consisting of the comple-ment cascade, lysozymes, interferons, interleukins, and im-munoglobulins. Each of these defenses can be altered bygenetic defect, disease, or immunosuppressive therapy.1

Specific deficiencies in immunity are associated withspecific pulmonary diseases. Neutropenia, a cellular immunedeficiency commonly associated with post-transplant immu-nosuppression, bone marrow transplantation, and chemother-apy, occurs when levels of circulating neutrophils fall and ismost pronounced when the absolute neutrophil count fallsbelow 500/�L. Typical infections in the setting of neutrope-nia include those caused by gram-positive bacteria such asStaphylococcus aureus and Streptococcus pneumoniae, andgram-negative bacteria such as Escherichia coli, Klebsiellaspecies, and Pseudomonas species. Fungal infections withAspergillus and Candida species are also common. Heredi-tary causes of neutrophil defects include Chediak-Higashidisease (an autosomal recessive defect in lysozyme function),and chronic granulomatous disease.

The most common acquired defect in cellular immunityis infection with HIV, which leads to impairment of cell-mediated immunity from both natural killer and cytotoxic Tcells and a decreased humoral response. The incidence ofpulmonary infection increases as the number of CD4 Tlymphocytes fall. T-cell deficiency results in infections withorganisms such as Mycobacteria, Pneumocystis jiroveci,Cryptococcus neoformans, S. pneumoniae, and viruses suchas cytomegalovirus (CMV) and human herpes virus 8 (asso-ciated with Kaposi sarcoma). Congenital defects in cellularimmunity include severe combined immunodeficiency dis-ease, DiGeorge syndrome, and Wiskott-Aldrich syndrome.

Humoral immune deficiencies result from impairedantibody production caused by defects either in B cellsthemselves or the interaction between B and T cells. Humoral

From the Department of Radiology, University of California San Francisco,San Francisco, California.

Address correspondence to: Theodore J. Lee, MD, San Francisco GeneralHospital, 1001 Potrero Avenue, Room 1X57, San Francisco, CA 94110.E-mail: [email protected].

Copyright © 2008 by Lippincott Williams & WilkinsISSN: 1068-0640/08/1502-0081DOI: 10.1097/CPM.0b013e3181677022

Clinical Pulmonary Medicine • Volume 15, Number 2, March 2008 81

immunity defects include congenital defects such as X-linkedagammaglobulinemia, and acquired defects caused by B-cellmalignancies such as chronic lymphocytic leukemia, multiplemyeloma, and non-Hodgkin lymphoma. These patients haverecurrent sinus, pulmonary and systemic infections, typicallyfrom encapsulated bacteria such as S. pneumoniae and Hae-mophilus influenzae.1,2

Immunosuppression with corticosteroids, chemother-apeutic agents, and other immunosuppressive agents makeup another large category of immunocompromised pa-tients. Corticosteroids have multiple effects including in-hibiting cytokine production, secretion of inflammatoryfactors, and reducing T-cell activation and proliferation,leading to defects mainly in cellular immunity. Otherdrugs such as cyclosporine, azathioprine, mycophenolate,tacrolimus, antitumor necrosis factor antibodies, and anti-lymphocyte antibodies block various specific pathwaysrequired for lymphocyte activation.2,3

Inborn diseases that compromise barriers to infectionsuch as immotile cilia syndrome and cystic fibrosis also makeup an important group of patients with immune deficiencies.In the adult population, however, it is more common toencounter acquired immunodeficiencies.

HIV/AIDS in the Era of Highly ActiveAntiretroviral TherapyChanging Pattern of Disease With Highly ActiveAntiretroviral Therapy

Patients with HIV and acquired immunodeficiency syn-drome (AIDS) may be considered as 2 subpopulations. Pa-tients who are taking highly active antiretroviral therapy(HAART) with prophylactic antibiotics have seen a dramaticdecrease in mortality and pulmonary morbidity, whereasthose who do not have access to or do not take thesemedications continue to have a high incidence of opportunis-tic infections and other conventional manifestations of HIV.One large series of 1538 patients demonstrated that HAARTdecreased the incidence of PCP by 35%, Kaposi sarcoma by34%, and cryptosporidiosis by 60%.4 Mocroft and col-leagues5 reported a reduction of 39% in the incidence of KSbetween 1994 and 2003 in the EuroSIDA cohort. As morepatients are treated with HAART, a different set of clinicalentities has emerged because of the short- and long-termsuppression of HIV, such as immune reconstitution inflam-matory syndrome, lymphoma, and pulmonary hypertension.Pulmonary diseases, however, remain the main cause ofmorbidity and mortality in patients with HIV, with or withouttreatment.4,6,7

Relationship to CD4The epidemic of HIV/AIDS has largely defined the role

for imaging in the immunocompromised patient. The types ofinfection seen in the HIV/AIDS population vary as the degreeof immune compromise increases. Knowledge of the CD4lymphocyte count is therefore an important part of the historyin these patients. As the CD4 count falls below normal levels,patients experience a higher risk of bacterial pneumonia.

With CD4 counts below 500/�L, patients become increas-ingly susceptible to bacterial pneumonias and postprimarytuberculosis (TB). With CD4 counts below 200/�L, thethreshold for AIDS, P. jiroveci becomes the most commoncause of pneumonia in absence of prophylaxis, althoughbacterial pneumonia is still frequent. Primary tuberculosis isincreasingly seen. With CD4 counts below 100/�L, toxoplas-mosis, nocardiosis, cryptococcosis, and atypical appearancesof tuberculosis are seen. Viral infections with CMV andherpes simplex viruses become more common.8–10 ThoracicKaposi sarcoma generally is seen with CD4 counts below100/�L.11 Non-Hodgkin lymphoma may occur at any CD4level, but increases with falling CD4 counts, particularlybelow 100/�L, where relative risk to patients with normalCD4 levels has been reported to reach 11.2.12

Immune Reconstitution Inflammatory SyndromeIt is increasingly recognized that treatment of AIDS

with HAART can result in mild-to-severe worsening ofunderlying pulmonary disease, classically in the setting oflatent mycobacterial infection.13–16 This is associated withimmunologic recovery and is termed immune reconstitutioninflammatory syndrome (IRIS), sometimes referred to asimmune restoration or immune reconstitution disease. Themechanisms underlying the syndrome are not fully under-stood, and there is no universally agreed-upon definition, butsome consensus as to unifying features is emerging. Thesyndrome typically occurs in patients infected with AIDS anda low initial CD4 count, most commonly below 50/�L.Symptoms occur following initiation of HAART, generally inthe first 2 weeks to 6 months, although there have beenreports of cases occurring within days of antiretroviral ad-ministration, and beyond 1 year of treatment. Patients usuallyhave a significant virologic response to treatment, with de-crease in viral load and increase in CD4 count. Drug-resistantinfection, adverse drug reactions, or newly acquired infec-tions are not considered part of the syndrome, and attemptsshould be made to exclude them.

At least 20 infectious agents have been linked to IRIS,including Mycobacteria, C. neoformans, P. jirovecii, hepati-tis viruses, herpes viruses, and CMV. IRIS has been linked tosarcoidosis, Kaposi sarcoma, and anal carcinoma. Specificfeatures of IRIS depend on the latent disease. Fever is acommon clinical manifestation seen in most cases. The mostcommon pulmonary causes are Mycobacterium tuberculosisand Mycobacterium avium complex, accounting for up to40% of cases. Radiographic findings in the setting of tuber-culosis include lymphadenopathy, pulmonary nodules, andpleural effusion, although consolidation and hepatospleno-megaly have been described. In M. avium complex, IRISmost commonly presents as fever and lymphadenitis. Ex-trathoracic nodes may be involved, and unusual cases of softtissue abscesses and osteomyelitis have been reported.14,16–19

In general, treatment for IRIS consists of initiation oftreatment of the underlying pathogen, corticosteroid or otheranti-inflammatory administration to suppress inflammation,and in severe cases, cessation of HAART.13,15–17,20–22

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© 2008 Lippincott Williams & Wilkins82

Specific Infections in HIV/AIDSPneumocystis Pneumonia

P. jirovecii (formerly P. carinii) pneumonia remainsthe most common opportunistic infection in patients withHIV/AIDS,23 although there are reports in some populationson HAART of bacterial infections becoming more preva-lent.24 This organism, now considered a fungus rather than aprotozoan, is an AIDS-defining illness in HIV infection.Pneumocystis uniquely targets the lung, where it exists pri-marily as an alveolar pathogen, although disseminated infec-tion in severe immunocompromise is known. Symptoms ofinfection typically include low-grade fever, progressive dys-pnea, and nonproductive cough. Among AIDS patients withPneumocystis pneumonia, mortality rate is 10% to 20%, thusearly identification is critical.25 Typical features on chestradiography consist of bilateral perihilar ground-glass air-space opacities that become increasingly widespread (Fig. 1).Indistinct centrilobular nodules are sometimes present. Geo-graphic patchy opacities may occur, and a “crazy paving”appearance (ground-glass opacity associated with interlobularseptal thickening, often with sharp, nonanatomic demarca-tions between normal and abnormal lung) has been de-scribed.24,26 Pattern of distribution can be altered by aerosol-ized pentamidine prophylaxis, in which upper lobe predominantdisease is seen, because of the distribution of the inhaledmedication. With progression of infection, pneumatoceles arefrequently seen, favoring the upper lobes. Pneumothorax inthe setting of AIDS is most commonly caused by Pneumocystispneumonia.27 Cysts are useful in distinguishing PCP from othercauses of ground-glass opacities.26 Consolidation is atypical,occurring in about 10% to 12%.24,28 High-resolution CT hasgreater sensitivity for detecting infection, which often ismanifested by diffuse ground-glass opacities not visible onplain radiographs. Pleural effusions and lymphadenopathyare unusual findings.29,30 Although CXR may often be normalin 10% to 20% of patients with PCP, abnormality is almostinvariably present on HRCT, and a normal HRCT effectivelyexcludes Pneumocystis pneumonia.31,32

TuberculosisInfection with HIV is the most important risk factor for

development of tuberculosis, and tuberculosis is the leadingopportunistic infection and cause of death in HIV-infectedpatients worldwide.33,34 The association of tuberculosis withHIV/AIDS, in part, accounts for the resurgence of tubercu-losis in the late 20th century. Diagnosing tuberculosis infec-tion is complicated by the high incidence of negative skintests because of failing cell-mediated immunity and the in-creased likelihood of normal chest radiographs.35 HIV infec-tion may be associated with development of drug resis-tance,36 although the association between multidrug resistantTB and HIV seems to largely represent an effect of the suscep-tibility to transmission of drug resistant TB in HIV patients.37

Patterns of radiographic abnormalities differ in thesetting of HIV/AIDS, depending on the degree of immunecompromise. In the absence of significant depression of CD4levels, tuberculosis presents as it does in the non-HIV pop-ulation. Patchy consolidation predominating in the upper

lobes and superior segment of the lower lobes is most common,with cavitation in about half of patients. Tree-in-bud type cen-trilobular nodules with branching opacities from bronchiolarinflammation is also frequent, likely caused by endobronchialspread of infection. As CD4 counts decrease, particularly below200/�L, CT findings are those of primary TB, regardless of priorexposure to TB. Lymphadenopathy becomes the dominant fea-ture of presentation, often with central low density consistentwith necrosis. Central necrosis is suggestive of tuberculosis, butcan be seen in other infections and malignancies such as squa-mous cell carcinoma.38–41 The presence of visibly enlargedlymph nodes on CXR in HIV-positive patients with CD4counts of less than 200/�L suggests tuberculosis.39 Dissem-inated disease, in the form of miliary tuberculosis, is alsomore common.42 Miliary disease is generally not associated

FIGURE 1. A, Frontal chest radiograph of a 51-year-old manwith AIDS (CD4 count 81/�L) demonstrates diffuse ground-glass opacities caused by P. jirovecii pneumonia. B, Axialthoracic CT image confirms diffuse ground-glass opacities.Note that these opacities do not obscure pulmonary vessels.

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© 2008 Lippincott Williams & Wilkins 83

with lymphadenopathy and random nodules may also be seenwith concomitant confluent nodules and consolidation (Fig.2).38,40 Once treatment for tuberculosis is started, there maybe transient worsening in the radiographic appearance causedby immune reconstitution inflammatory syndrome. In theabsence of evidence, clinical or radiographic for response,infection with multidrug resistant tuberculosis should beconsidered.

Nontuberculous MycobacteriaNontuberculous mycobacteria are common environ-

mental organisms of varying pathogenicity, distinct from M.tuberculosis and Mycobacterium leprae (the causative agentof leprosy). Atypical mycobacterial infections are AIDS-defining illnesses. M. avium complex is the most commonatypical mycobacterium in the setting of immune compro-mise, and disease presents differently than in the immuno-competent host. Clinical features include fever, night sweats,and weight loss. The syndrome of middle lobe and lingularbronchiectasis and tree-in-bud nodules or upper lobe cavita-tion should not be expected. These patients usually presentwith hilar and mediastinal lymphadenopathy as the dominantfinding. Hilar masses can mimic bronchogenic carcinoma,and may be asymptomatic (Fig. 3). Also seen are diffusepulmonary opacities including small centrilobular nodulesand areas of air-space consolidation.39,43 Pleural effusion andcavitation are uncommon.38 Mycobacterium kansasii infec-tion is uncommon, particularly since the advent of HAART,and is associated with CD4 counts below 50/�L. M. kansasiifrequently presents with heterogeneous air-space opacities ornodules, and may cause cavitation. Lymphadenopathy is lessprominent. Miliary disease is very unusual.44–48

Nonmycobacterial Bacterial PneumoniaBacterial pneumonias increase in frequency as CD4

counts fall. Bacterial pneumonia is at least 6 times more

FIGURE 2. Axial thoracic CT image of a 70-year-old manwith history of liver transplantation for cirrhosis demon-strates miliary nodules from disseminated M. tuberculosisconfirmed by sputum induction.

FIGURE 3. A, Frontal chest radiograph of a 37-year-old manwith AIDS (CD4 count 60/�L), who recently was started onHAART demonstrates a right hilar mass (arrow). B, Axial tho-racic CT image reveals an irregularly marginated right hilarmass (arrow) corresponding to the radiograph. C, Lymphnode enlargement and central low density suggesting necro-sis (white arrow) was noted on the same CT scan. Broncho-scopic biopsy with cultures yielded M. avium, and no evi-dence of neoplasm. The mass resolved on subsequentradiographs following antibiotic treatment.



frequent in the patient with AIDS than in the general popu-lation (Fig. 4). Most bacterial pneumonia is community-acquired, with S. pneumoniae being the most common organ-ism isolated. Clinical presentation of pneumococcalpneumonia is similar in the setting of HIV. H. influenzae, S.aureus, E. coli, and Pseudomonas species account for mostother cases. Although consolidation is the most frequentimaging finding, as in the non-AIDS population, atypicalpatterns including nodules and ground-glass opacities occurfrequently, and there is an increased incidence of cavitation,effusion, and empyema. The presence of an ipsilateral effu-sion should increase suspicion for bacterial infection. Nocar-dia should also be considered in the setting of cavitatingnodules and consolidation, and also often presents with pleu-ral effusion.39,46,49,50

Some unusual bacterial infections are seen almost ex-clusively in the setting of AIDS. Rhodococcus equi is agram-positive rod associated with soil and animal manure.Although the first reported human infection was of the skin ina renal transplant patient, it is now recognized as a rare causeof pneumonia in patients with AIDS. Patients present withcough and fever, and imaging most commonly reveals seg-mental consolidation and cavitation, that may resemble tu-berculosis. Small centrilobular nodules with “tree-in-bud”configuration or mediastinal adenopathy are also frequentlypresent. Pleural effusion is unusual.51–56 Bartonella henselae,the cause of cat-scratch disease (bacillary angiomatosis), canon rare occasions also cause pulmonary infection in thepatient with AIDS. Pulmonary nodules and were first re-ported, subsequently endobronchial nodules and lymphade-nopathy have been described.57–59

Non-PCP Fungal PneumoniasCryptococcus is the most common fungal infection in

patients with AIDS, particularly with CD4 counts of less than100/�L. Although the peripheral nodule typical of infectionin the nonimmunocompromised host can occur, atypical pat-

terns are common findings on thoracic CT in the immunecompromised population, including segmental or lobar con-solidation, patchy airspace opacities, masses, multiple nod-ules with a tendency to cavitate, and miliary disseminateddisease (Fig. 5). Lymphadenopathy is seen in about one-thirdof patients, but tends to be mild. Candida pneumonia isassociated with random nodules, with nodules seen in up to95% of patients. Although Pneumocystis pneumonia is a riskfactor for mycetoma, Aspergillus infections tend to be rare inthe setting of HIV infection and will be discussed in thesetting of organ transplantation.39,60–63

Viral PneumoniasViral pneumonias typically occur in the setting of

severe suppression and reduction in CD4 cells below 50/�L.These are discussed below in the section on organ transplan-tation.

Parasitic InfectionsAIDS constitutes one of the major risk factors for

parasitic pulmonary infection in industrialized countries, al-though parasitic infections remain a rare cause of pulmonarydisease.64 Pulmonary infections with Toxoplasma gondii andCryptosporidium have been reported in patients with severeimmune suppression in the setting of AIDS and organ trans-plantation, although the role of organisms isolated from lungsin the setting of infection is not well defined. Ground-glassopacities and interstitial opacities are reported, with progres-sion to acute respiratory distress syndrome described.65–67

Strongyloides stercoralis, an intestinal nematode usually as-sociated with mild pulmonary symptoms such as cough, cancause fulminant respiratory illness in the setting of immunecompromise (Fig. 6). Hyperinfection syndrome occurs withmassive infection and widespread dissemination of Strongly-loides larvae, and causes ARDS with diffuse pulmonaryopacities. Diagnosis is made by serologic testing or isolationof the organism from the GI tract or pulmonary aspirates.68,69

FIGURE 4. Axial thoracic CT image of a 33-year-old manwith AIDS (CD4 count 100/�L) demonstrates bilateralconsolidation and effusions caused by methicillin-sensitiveS. aureus pneumonia. Note air bronchograms (arrowheads)and pleural effusions (arrows).

FIGURE 5. Axial thoracic CT image of a 26-year-old manwith AIDS (CD4 count 1/�L) shows subtle miliary nodules(arrowheads). C. neoformans was isolated following bron-choalveolar lavage.



Noninfections Pulmonary Complications ofHIV/AIDSKaposi Sarcoma

AIDS-related Kaposi sarcoma is the most common of 4main variants of Kaposi sarcoma. Kaposi sarcoma is the mostcommon tumor in AIDS patients, and is an AIDS-definingillness, although incidence has fallen with the advent ofHAART.5,11 Kaposi sarcoma is a systemic illness with fre-quent pulmonary involvement. Patients typically present withcough, fever, and dyspnea. Thoracic disease is found in about45% of patients with mucocutaneous disease, whereas onlyabout 15% of cases occur in the absence of mucocutaneousfindings.11 Imaging features on high-resolution CT includeperibronchovascular interstitial thickening and irregular“flame shaped” or ill-defined nodules also in a peribroncho-vascular distribution (Fig. 7). Lymphadenopathy and pleuraleffusion may be present.30 Median survival has been reportedas 1.6 years from time of diagnosis.70

LymphomaPatients with HIV have an increased incidence of lym-

phoma, which along with Kaposi sarcoma and cervical can-cer, is an AIDS-defining malignancy.71 The lung is frequentlyinvolved in AIDS-related lymphoma. This most commonly isof an aggressive B-cell non-Hodgkin type. Although lym-phoma risk is elevated in patients with non-HIV relatedimmunosuppression, rates are generally higher in the settingof HIV.6,12 In an early study of CT findings in 38 patientswith thoracic lymphoma, nodules (50% of patients), lobarinfiltrates (27%), and lung masses (19%) were the mostcommon parenchymal findings, with a large number of pa-tients having pleural effusions (68%) and thoracic lymphad-enopathy (54%).72 Multiple nodules and masses 1 to 5 cm in

diameter are typical (Fig. 8). Peribronchovascular thickeningmay be seen because of tumor infiltration of the interstitium.30

This pattern can mimic Kaposi sarcoma. Rates of non-Hodgkin lymphoma have fallen since the introduction ofHAART, but not as dramatically as with some other HIV-associated diseases.12,73,74

Non-AIDS-Defining MalignanciesSeveral malignancies are linked to HIV/AIDS in addi-

tion to the AIDS-defining malignancies described above. In areview of cancer registries identifying 375,933 patients withAIDS, Engels et al73 noted lung cancer to be the mostcommon non AIDS-defining malignancy. Other reported dis-eases associated with immune suppression include cancers ofskin, liver, breast, and prostate. It is postulated that defects incell-mediated immunity caused by HIV result in decreasedtumor surveillance by the immune system, and increased

FIGURE 6. Axial thoracic CT image of a 58-year-old womanwith respiratory distress and history of Pneumocystis pneu-monia demonstrates diffuse ground-glass opacities andconsolidation. Findings are nonspecific and may be seen inassociation with a number of etiologies including infection,aspiration, and acute respiratory distress syndrome. Strongy-loides was identified on bronchoalveolar lavage.

FIGURE 7. A, Frontal chest radiograph of a 45-year-old manwith AIDS (CD4 count 1/�L) demonstrates bilateral irregularnodules and masses (arrows). B, Axial thoracic CT image inthe same patient demonstrates “flame-shaped” nodules(arrow) and peribronchovascular thickening (arrowhead) ofKaposi sarcoma.



susceptibility to oncogenic viruses. It is not clear whether therisk is directly associated with suppression of CD4 lympho-cyte counts. Like Kaposi sarcoma and non-Hodgkin lym-phoma, rates of lung cancer have decreased since the intro-duction of HAART; however, the rate of Hodgkin lymphomahas increased in the past decade.71,73

Interstitial Lung DiseaseInterstitial pneumonitis can occur in the setting of HIV.

Lymphocytic interstitial pneumonitis has a demonstrated as-sociation with HIV infection, and is particularly common inchildren. There is a reported predominance in patients ofAfrican descent. Radiographic findings are not specific, anddiagnosis relies on biopsy.75,76 Typical high-resolution CTfindings include ill-defined centrilobular nodules and ground-glass opacities, with thickened and sometimes nodular peri-bronchovascular interstitium (Fig. 9).8,30,77 The early litera-ture in AIDS referred to a nonspecific interstitial pneumonitisthat occurred in the setting of AIDS with clinical featuresresembling Pneumocystis pneumonia but without detectableinfection, with diffuse alveolar damage and variable intersti-tial inflammation on transbronchial or open lung biopsy.78–80

These reports in the 1980s predated NSIP as first described byKatzenstein and Fiorelli in 1994 and differ from the his-topathologic description currently recognized in the Ameri-can Thoracic Society/European Respiratory Society consen-sus classification of idiopathic interstitial pneumonias.81,82 Itis therefore likely that the early description of a nonspecificinterstitial pneumonitis in AIDS reflected a common inflam-matory reaction to an unrecognized infection or inflammatoryprocess distinct from the idiopathic pneumonia presentlydesignated NSIP.

Pulmonary HypertensionPulmonary hypertension is seen with increased inci-

dence in patients with HIV, without correlation with severity

of HIV infection. No predisposing factor other than HIVinfection is found in a majority of cases. Patients present withsymptoms and signs including chest pain and progressivedyspnea. Chest radiographs and CT may demonstrate dilatedpulmonary arteries and right chamber cardiac enlargement.Prognosis is poor, with mean survival in the Swiss HIVCohort Study Group of 2.7 years. Recent studies suggestsurvival is improved with HAART.83–86

Emphysema in HIVEmphysema has been shown to occur with increased

incidence in HIV-positive patients. In a study of 114 HIV-positive patients in whom other pulmonary complications ofAIDS were excluded, Diaz et al87 found that when comparedwith age, sex, and smoking history matched HIV-negativevolunteers, incidence of emphysema was higher (15% vs.2%) and of increased severity. Bronchoalveolar lavage in asubset of these patients demonstrated a higher concentrationof lymphocytes in the setting of HIV infection. In non-HIVinfected smokers, there have been reports of a high correla-tion between such lymphocytes and emphysema, and thusviral activation of lymphocytes in the lungs of patients withHIV is thought to contribute to lung destruction.

Organ Transplantation and ImmuneSuppressive Therapy

Organ transplantation relies on an increasing pharma-cologic ability to suppress host immune response as a meansof preventing tissue rejection. However, the same immunesuppression that permits organ engraftment exposes the re-cipient to potential complications including post-transplantinfection, lymphoproliferative disorders, and an increasedrisk of certain cancers. Cancer therapy may also result inimmune suppression.

Lung TransplantationLung transplantation for pulmonary or systemic dis-

eases has been performed in over 13,000 patients in the past

FIGURE 8. Axial thoracic CT image of a 44-year-old manwith AIDS (CD4 count 144/�L) who presented with low-grade fever and multiple pulmonary and hepatic masses.Percutaneous fine-needle aspiration biopsy of a lung lesionconfirmed Burkitt lymphoma.

FIGURE 9. Axial thoracic CT image of a 42-year-old manwith AIDS (CD4 count 481/�L) and biopsy-confirmedlymphocytic interstitial pneumonitis. Ill-defined centrilobularnodules and subtle ground-glass opacities are present, withnodular thickening of the fissures (arrowheads).



10 years and continues to gradually increase in frequency,with 1815 transplants reported in 2004 among 158 centersparticipating in the registry of the International Society forHeart and Lung Transplantation.88 Infection is the mostcommon cause of morbidity and mortality following lungtransplantation, with infectious complications accounting forat least half of deaths. Most infections involve the respiratorytract, and infection is also a risk factor for development ofbronchiolitis obliterans, which is the primary manifestation ofchronic rejection. Bacterial infection is most common, withoverall incidence during the first year after transplant of about70%. Pseudomonas species, Enterobacteraceae, S. aureus,and H. influenzae predominate.89 The complex interplay ofevents in transplantation ranging from initial postoperativerecovery to long-term suppression of rejection result in atemporal pattern of pulmonary diseases.90,91

In the first week after transplantation, the most commoncauses of radiographic opacities are reperfusion pulmonaryedema, volume overload, infection, or acute rejection. Radio-graphic findings are nonspecific and include diffuse or peri-hilar opacities with occasional patchy airspace consolidation.Although pleural effusion is common, persistent or worsen-ing effusions suggest acute rejection or infection. Acuterejection manifests histologically as perivascular and intersti-tial mononuclear infiltrates, and radiographically as new orworsening airspace opacities. Acute rejection often occurs inthe first 5 to 10 days after transplantation, and is treated withhigh-dose steroid administration. Early acute rejection cannotbe distinguished radiographically from reperfusion edemaand volume overload. Absence of ground-glass opacities onhigh-resolution CT is useful for excluding moderate or severerejection.35,62,63

In the first month after transplantation, bacteria are themost common cause of pneumonia, and risk of bacterialinfection is highest in the first 3 months. Infection may occurvia transmission with the donor organ, or from a nosocomialsource. Typical patterns of opacification on CT include con-solidation, ground-glass opacification, and nodules. After 1month, opportunistic infection with CMV, the second mostcommon cause of infection, or fungus becomes more com-mon. Nodules are typically seen in CMV and fungal infec-tion, but as with bacterial pneumonia, ground-glass opacifi-cation and consolidation are common in both entities.35,90

Beyond 1 year, infections remain an important cause ofmorbidity and mortality; however, bronchiolitis obliterans(obliterative bronchiolitis) is the most common cause ofdeath. Bronchiolitis obliterans is a manifestation of chronicrejection, and typically develops 6 to 12 months after trans-plantation. Patients present with progressive dyspnea and drycough. Radiographic assessment is very useful in suggestingthe diagnosis, as transbronchial biopsy has limited sensitivity.Air trapping demonstrated on expiratory high-resolution CTis the most sensitive radiographic feature, and may be ac-companied by bronchiectasis. Severity of involvement clini-cally is measured by declines in FEV1 on pulmonary functiontesting.88,90,92,93 Although less common, malignancies in-cluding PTLD (post-transplantation lymphoproliferative dis-order) also should be considered when more than 1 year from

transplantation. Malignancy contributes to as much as 10% ofdeaths in the period exceeding 1 year after transplanta-tion.88,91

CT is useful to evaluate patients following transplanta-tion, both for detecting immediate complications includingbronchial or vascular complications, and for evaluating thewide range of other infectious, inflammatory, and neoplasticprocesses that can occur.94 In post-transplant patients, there issubstantial overlap in the appearance of bacterial, viral, andfungal pneumonias, limiting specificity. Bacterial pneumo-nias tend to have consolidation in almost all cases, with ahigh incidence of associated ground-glass opacities and fre-quent nodules.95 Nodules or masses following transplantationsuggest infection, including bacterial, fungal, or mycobacte-rial, but bronchogenic carcinoma and PTLD also must beconsidered in the later post-transplant period. Pulmonarynodules occur in approximately 10% to 12% of lung trans-plant patients, typically in the transplanted lung. Multiplenodules may be caused by Aspergillosis, Nocardiosis, CMVpneumonia, bronchiolitis obliterans, and metastases. Whenfound in the native lung, nodules should raise the prospect ofbronchogenic cancer, particularly in the setting of pulmonaryfibrosis.96 Solitary nodules also favor cancer and PTLD.Cavitation suggests Aspergillus, other fungal infection, orNocardia (Fig. 10).97

AspergillusAspergillus infection is most commonly caused by

Aspergillus fumigatus, Aspergillus flavus, and Aspergillusniger.98 Aspergillus manifestations are typically seen in thesetting of neutropenia, and vary with degree of granulocytedysfunction, ranging from aspergillomas and allergic bron-chopulmonary aspergillosis to airway invasive aspergillusand angioinvasive aspergillus. Colonization occurs in up to85% of lung transplant recipients, with invasive diseaseoccurring in up to 26%, with averages in a recent review ofpooled patients from the literature of 26% with colonizationand 5% with invasive aspergillosis.89,99

FIGURE 10. Axial thoracic CT image of a 59-year-old manwho underwent left lung transplant demonstrates multiplenodules, including this right lung nodule with central cavita-tion (arrow). Note the relative lucency of the native lungcaused by emphysema. Nocardia was isolated.



Aspergillomas occur in preexisting cavities within lungtissue, most commonly in patients with a history of tuberculosis,sarcoidosis, or PCP, and is usually present in patients withoutimmune compromise although a series in patients with HIV hasbeen reported.63 Allergic bronchopulmonary aspergillosis is ahypersensitivity disease also occurring in immunocompetentpatients, classically presenting with upper lobe bronchiectasiswith mucus impaction, often of high density.98,100

Semiinvasive aspergillosis, also known as chronic ne-crotizing aspergillosis, occurs in patients with disorders thatmildly compromise host immunity, typically diabetes, alco-holism, or chronic obstructive pulmonary disease. Semiinva-sive aspergillosis causes local invasion of lung tissue and isan indolent process that progresses over months. Typicalimaging findings include segmental consolidation in the up-per lobes or the superior segments of the lower lobes, some-times with cavitation, with adjacent pleural thickening.98,100

Airway invasive aspergillosis and angioinvasive as-pergillus occur in frankly immunocompromised patients withneutropenia or AIDS. Airway invasive disease causes tra-cheal and bronchial thickening, but often radiologic studiesare normal. Centrilobular nodules or tree-in-bud appearancemay be present from bronchiolitis.61 Angioinvasive aspergil-losis is an aggressive infection that occurs in patients withsevere immune compromise. Major risk factors include pro-longed neutropenia or intrinsic neutrophil dysfunction, high-dose corticosteroid therapy, transplantation (especially oflung or bone marrow), AIDS, hematologic malignancy, orchemotherapy. Patients typically present with fever, cough,pleuritic chest pain, and hemoptysis.98 Characteristically,x-rays are nonspecifically abnormal with patchy consolida-tion and nodules. On CT, nodules with a rim of surroundingground-glass opacity, the “halo sign,” suggest the diagnosis,and represent hemorrhagic infarcts caused by vascular inva-sion (Fig. 11A). The halo sign can be seen on occasion withother fungal diseases such as Mucor and Candidal infection,as well as CMV and HSV, Wegener’s granulomatosis, andKaposi sarcoma. Amphotericin B and itraconazole are em-ployed for treatment, but response is variable and mortality issignificant. Confirmation of diagnosis should be pursued, asmortality is high and mucormycosis is often managed surgically.Lung resection has also been proposed in some cases of invasivepulmonary aspergillosis in patients with neutropenia.39,61,101–103

Two variants of the “air crescent” sign exist. An as-pergilloma may be associated with a rim or air crescentbetween the mass and the wall of the cavity. Such aspergil-lomas are typically mobile. In patients with more severeimmune deficiency and angioinvasive aspergillosis, there is asecond air crescent seen when lung necrosis occurs becauseof vascular invasion (Fig. 11B). As lung cavitates and ne-crotic lung consolidates, a rim of air can be seen forming anair crescent. The air crescent in angioinvasive disease tends tooccur several weeks after infection and is associated withimproved survival.39,98,100

Post-transplantation Lymphoproliferative DisorderPTLD is an important consideration in transplant recip-

ients. Most common in patients with lung transplants, it

occurs in all transplant populations, including both solidorgan and bone marrow, with an overall incidence of 1% to10%. Mortality is estimated at 40% to 70%. PTLD accountsfor approximately 3% of deaths in lung transplant recipientsin the first year after transplant. Most cases occur within 2years of transplantation, with median time to onset of 6months in solid organ recipients. Presently, the development

FIGURE 11. A, Axial thoracic CT image of a neutropenic 32-year-old patient (absolute neutrophil count 50/�L) with feverand history of bone marrow transplant. Note the halo (be-tween arrowheads) of ground-glass opacity surrounding theleft upper lobe nodule, consistent with angioinvasive aspergillusinfection confirmed by bronchoscopic lavage. B, Repeat CTscan 8 days into antifungal therapy demonstrates air-crescentsign (arrow) and resolution of the ground-glass halo.



suggests that PTLD results from infection of B-cells byEpstein-Barr virus with subsequent proliferation in the settingof compromised T-cell immunity. High levels of immunesuppression, in particular with antilymphocyte therapy, in-creases the risk of disease. Thoracic PTLD typically presentsas solitary or multiple well-circumscribed solid masses ornodules, up to 5 cm in size (Fig. 12). These tend to occur inthe mid and lower lungs, with peribronchovascular distribu-tion. Growth is slow, and a subtle halo of ground-glassopacity may be seen. Lymphadenopathy is variably present.Less common are consolidation, ground-glass opacity, endo-bronchial lesions, or pleural effusion. Patients with focaldisease do better than those with widespread disease, anddisease outside the chest is frequent.35,90,91,104,105

Bone Marrow TransplantationBone marrow transplantation is used to treat hemato-

logic malignancies and some tumors. Transplantation of au-tologous harvested marrow or donor marrow typically occursafter ablation of native host marrow. As in solid organtransplantation, the chronologic course of immune systemablation and reengraftment is useful in predicting the likelycauses of infection in such patients, and follows a similarcourse. The first month following transplant, during whichtime patients are usually neutropenic, is characterized bysusceptibility to organisms such as gram-negative bacterialinfection, Candida infection, and Aspergillus infection. Pul-monary edema and drug toxicity may present as diffuseground-glass opacities, diffuse alveolar damage, and hyper-sensitivity pnemonitis.106 Engraftment is signaled by an in-crease in absolute neutrophil counts above 500/�L. Thefollowing period, to 100 days after transplant, is the earlypostengraftment phase. CMV is a frequent pathogen. CMVpneumonia occurs in up to 15% of bone marrow transplantpatients 1 to 3 months following transplant, and will bediscussed further to follow.107 Toxoplasmosis is a rare para-sitic infection occurring in up to 1% of patients undergoing

allogenic transplant, with presentation averaging 59 daysafter transplant in one large study.108 Rare cases of fatalARDS in early postengraftment toxoplasma pneumonitishave been reported.65 Beyond 100 days, a reconstitutedimmune system is expected, although the host is still suscep-tible to possible complications such as graft-versus-host dis-ease. Bacterial infection remains a risk, particularly to com-munity-acquired organisms, whereas risk of opportunisticinfection is reduced.109,110

CMV and Other Viral PneumoniasCMV pneumonia is a herpes virus that occurs as an

opportunistic pathogen in patients with impaired cellularimmunity. CMV infection occurs most commonly in thesetting of lung transplantation, bone marrow, and other organtransplantation, with rates typically between 53% and 75%but reported as high as 90%.89,111,112 Clinical presentationincludes fever, cough, and hypoxemia. Infection in the settingof immune compromise is likely caused by reactivation oflatent infection.113 Incidence has been reduced by antiviralprophylaxis.89,114 Radiographic findings are typically bilat-eral, and include ground-glass opacities in 66% to 69%,ground-glass opacities or poorly marginated centrilobularnodules in 59% to 69%, and lobular or patchy areas ofconsolidation in 31% to 59%, with combinations of thesepatterns frequent (Fig. 13). No specific finding alone ischaracteristic, but the combination of findings in the correctclinical context is suggestive.115–118

Other viral pneumonias encountered in the immuno-compromised host include respiratory syncytial, varicella-zoster, herpes, adenovirus, influenza, parainfluenza, and mea-sles viruses. As in CMV infection, the lungs histologicallyshow diffuse alveolar damage with hemorrhage, edema, lym-phocyte infiltration, and hyaline membrane formation. Thereis significant overlap of radiographic appearance among viralinfections. Typical manifestations include poorly definedsmall centrilobular or random nodules and patchy areas ofperibronchial ground-glass opacities with patchy consolida-

FIGURE 12. Axial thoracic CT image of a 58-year-old womanwho underwent right lung transplant for emphysema dem-onstrates an isolated nodule along the major fissure (arrow).Percutaneous biopsy confirmed post-transplantation lympho-proliferative disorder.

FIGURE 13. Axial thoracic CT image of a 16-year-old patientwho underwent renal transplant 1 year before, now present-ing with pancytopenia, fever, and dry cough. Diffuseground-glass opacities are present. CMV was confirmed atbronchoscopy.



tion. Varicella virus often heals with 1 to 2 mm randomlydistributed calcified nodules (Fig. 14).118–120 Mortality ofrespiratory viral infection in one recent series of 343 adultpatients with stem cell transplantation for hematologic ma-lignancy was reported at 15%.121

Cancer ChemotherapyNeutropenia is one of the major side effects of cancer

chemotherapy, and is associated with an increased incidence ofbacterial and fungal infection. Bacterial infections are generallycaused by pyogenic or enteric bacteria such as Staphylococcusspecies, Streptococcus species, and Enterococcus, or gram-negative organisms such as E. coli, Pseudomonas, and Kleb-siella. Invasive pulmonary aspergillosis occurs in about 5% ofpatients with chemotherapy for hematologic malignancies. Non-infectious pulmonary disease including toxicity of cytotoxicchemotherapy agents with resulting pneumonitis or alveolardamage must also be considered.122,123

Intrinsic Disorders of Immunity in AdultsMucociliary Dysfunction

Disorders of the mucociliary defenses of the airwayspredispose the host to infections caused by decreased clear-ance of inhaled infectious agents. Mucus serves to traprespiratory pathogens, which are then cleared by a combina-tion of coughing and ciliated respiratory epithelium, whichlines the nasal cavity, sinuses, trachea, bronchi, and bronchi-oles to the terminal bronchioles.124 The classic disorders ofmucociliary dysfunction are cystic fibrosis and Kartagener’s.These diseases are characterized by bronchiectasis caused bychronic airways inflammation, which is best assessed using

thin section CT. Acquired disorders are occasionally seen,from inhalational injury.

Cystic FibrosisCystic fibrosis is caused by mutation of a transmem-

brane protein causing dysfunction of chloride transport, aswell as dysregulation of other ion channels. Increased viscos-ity of the mucus layer coating the airways results in ciliarydysfunction and retention of secretions, causing airway in-flammation and increasing susceptibility to infection, al-though other mechanisms for the chronic airway damagehave been proposed.125,126 Survival is increasing, and adultswith cystic fibrosis are an increasingly large segment of thepatient population. Median survival for patients with cysticfibrosis reached 36.8 years in 2005.127 Prevalence of patho-gens causing respiratory infection in cystic fibrosis varieswith patient age, with Pseudomonas aeruginosa being mostcommon in patients from teens to adulthood, followed bystaphylococcal infection. Other common pathogens includeH. influenzae, Stenotrophomonas maltophilia, and Burkhold-eria cepacia complex.128 The Cystic Fibrosis Foundationpresently recommends chest radiographs every 2 years asstandard of care, with increased frequency as dictated bypulmonary exacerbations. CT, particularly HRCT, is superiorin both detecting disease and monitoring severity of compli-cations such as bronchiectasis and consolidation. Findings onCT correlate with pulmonary function tests, and CT candetect findings such as central bronchiectasis that may notmanifest as PFT abnormalities (Fig. 15).126,129 Findings onCT may also be predictive of outcome in cystic fibrosistherapy.130 Typical findings in cystic fibrosis in one study of47 patients who underwent HRCT include, in order of fre-quency, bronchiectasis (98%), atelectasis/consolidation(81%), bronchial wall thickening (77%), tree-in-bud nodules(74%), and mucus plugging (72%).131

Primary Ciliary Dyskinesia (Kartagener)Primary ciliary dyskinesia is a rare disorder of ciliary

function caused by dynein protein derangement. Abnormalfunction of dynein in cilia and flagella causes dysmotility inthese structures including in the respiratory tract and inspermatozoa. A randomization of body symmetry occurs, sothat in half of patients with primary ciliary dyskinesia, thereis situs inversus totalis, an entity described in 1962 byKartagener and Stucki.132 Clinical findings include recurrentupper and lower respiratory tract infections, bronchiectasis,and infertility.133 Radiographic findings resemble cystic fi-brosis, with bronchial wall thickening, consolidation, andbronchiectasis, although generally are less severe.134 Al-though primary ciliary dyskinesia is associated with chronicinfection much like cystic fibrosis, pulmonary function de-clines can be stabilized with aggressive antibiotic treatmentand physiotherapy.135,136

Inborn Disorders of ImmunityChronic Granulomatous Disease

Chronic granulomatous disease (CGD) is a geneticimmunodeficiency occurring in approximately 1 of 250,000

FIGURE 14. Frontal chest radiograph of a 37-year-old manwith longstanding history of AIDS (CD4 count 46/�L) dem-onstrates dense, calcified nodules caused by previous infec-tion with Varicella pneumonia.



in the United States. The cause of CGD is a defect innicotinamide adenine dinucleotide phosphate-oxidase inphagocytic cells, preventing intracellular oxidative killingof catalase-positive bacteria and fungi. Although the ma-jority of patients are diagnosed in childhood, some patientsare not diagnosed until adulthood. CGD most commonlypresents as recurring infections of the skin and lungs.Incidence of pneumonia is 80% in this population. As-pergillus is the most common causative agent of pulmo-nary infection, followed by staphylococcal species, andinfection with Aspergillus is the most common cause ofdeath.137,138

Miscellaneous Disorders of Immunity in AdultsAlcoholism

Alcohol abuse is associated with suppression of hostimmunity and an increased risk of aspiration. An increasedincidence of varied infections has been described includingcommunity-acquired pneumonias, anaerobic abscess, tuber-culosis, and Legionella pneumophilia. Patients who abusealcohol have an increased incidence of pneumococcal pneu-monia, and mortality from pneumonia is increased relative tononalcoholic control.139,140

DiabetesDiabetes mellitus suppresses host immunity through a

number of mechanisms including a reduction in granulocytefunction. An increase in pulmonary infections is seen, includ-ing influenza, mucormycosis, staphylococcal pneumonia, tu-berculosis, and gram-negative organisms. Diabetes mellitus isan independent predictor of mortality from pneumonia.141,142

Pattern-Based Approach to ImagingGround-Glass Opacity

Ground-glass opacities are areas of increased lungopacity that do not obscure lung interstitium and pulmonaryvascularity. If ground-glass opacity is present in isolation inthe immune compromised patient, differential diagnosis isrelatively compact, and centers on opportunistic infection.Ground-glass opacity in the setting of AIDS and hypoxemiaand dry cough is strongly suggestive of Pneumocystis pneu-monia.24,26 Other considerations include CMV pneumoniaand HSV pneumonia. CMV pneumonia does not form cystsas in PCP, but the 2 entities may not be otherwise distin-guishable on imaging. CMV pneumonia may occur as smallground-glass nodules. In one series, the presence of centri-lobular nodules, rare in PCP, helped to differentiate viralpneumonia from PCP.26 HSV pneumonia is a rare cause ofisolated ground-glass opacities, more commonly causing con-solidation and effusion. A clinical history of mucous mem-brane ulcers is helpful, as these tend to precede pulmonarysymptoms.143 Respiratory syncytial virus pneumonia is typ-ically associated with ground-glass opacities. Mycoplasmapneumonia also presents as ground-glass opacities, althoughmore commonly in immunocompetent patients, and oftenwith a more focal lobular ground-glass pattern with frequentill-defined centrilobular nodules. Noninfectious causes ofground-glass opacity are occasionally seen, and includeedema, hypersensitivity or drug-induced pneumonitis, radia-tion pneumonitis, pulmonary hemorrhage, and idiopathic in-terstitial pneumonitis such as respiratory bronchiolitis-inter-stitial lung disease.24,143

ConsolidationMost causes of consolidation in the setting of immune

compromise are from bacterial pneumonia, such as Staphy-lococci and gram-negative pneumonias. Streptococcal pneu-monia is reduced in prevalence in the setting of immunecompromise likely because of the relative increase in otheropportunistic infections.39 The most common causes of con-solidation in AIDS are bacteria, tuberculosis, atypical myco-

FIGURE 15. A, Frontal chest radiograph of a 34-year-oldman demonstrating severe bronchiectasis in the setting ofcystic fibrosis. Note thick-walled dilated bronchi seen incross-section (arrow) and lengthwise (arrowheads). B, Axialthoracic CT image also demonstrates thickened dilated bron-chi, some with mucus plugging filling the airway (arrow).



bacteria, and Cryptococcus. Legionella, Nocardia, andRhodococcus also present with segmental or lobar consolida-tion, with the latter seen almost exclusively in the setting ofAIDS.24,144 Tumors such as lymphoma and Kaposi sarcomaas well as primary pulmonary neoplasms are an importantcause of consolidation. Infections more commonly associatedwith ground-glass opacities or nodules can, with progressionof disease, result in consolidation, although substantial con-solidation is rare in viral infection.26

NodulesPulmonary nodules are a frequent finding on thoracic

CT in patients with immune compromise.28 Size and distri-bution of nodules is helpful in narrowing the differential, asis the presence of cavitation. Miliary nodules, typically pre-senting as numerous nodules 1 to 3 mm in diameter withrandom distribution, are seen in the setting of tuberculosisand fungal infection. The miliary form of tuberculosis is notassociated with lymphadenopathy.24 Small centrilobular nod-ules with tree-in-bud distribution suggest airways invasiveaspergillus, tuberculosis, and endobronchial spread of bacte-rial pneumonia.

Larger nonmiliary nodules may be caused by a largenumber of diseases. In the immunocompromised patient,common causes are fungal infection, viruses, and septicemboli. In one study, a diameter of �10mm was the onlyindependent predictor of a viral etiology for multiple lungnodules, exclusive of tree-in-bud nodules, although no mili-ary tuberculous or fungal infections were noted in the sam-ple.145 Aspergillus, Candida, and Cryptococcus are commonfungal agents. Mucormycosis is indistinguishable from As-pergillus radiographically. Cavitary nodules are seen in no-cardiosis, septic emboli, and in angioinvasive aspergillosis.24

Primary and metastatic neoplasms such as lymphomaand Kaposi sarcoma may present as nodules. Lymphoma maypresent without hilar or mediastinal lymphadenopathy in thesetting of immune compromise. Irregular or “flame-shaped”nodules are commonly seen in Kaposi sarcoma, as are peri-bronchovascular nodules. PTLD should be considered in thesetting of transplantation.11,24,72,105

ReticulationIntralobular and interlobular septal thickening is seen

most commonly in the setting of interstitial edema, but it isassociated with infections and lymphangitic spread of malig-nancy. Reticulation can be seen in about 20% to 30% ofpatients with bacterial, atypical bacterial, fungal, and viralpneumonias, and does not allow differentiation between theseetiologies.26

SummaryThe type and severity of immunocompromise can serve

as an important guide in approaching radiologic findings inpatients with both infectious and noninfectious pulmonarydiseases. Refine considerations based on clinical factors suchas the use of antiretroviral or prophylactic medications, ortime from transplantation. Then, consider patterns of diseaseat imaging. Although arriving at a specific diagnosis fromimaging may be difficult, imaging may provide a useful guide

to diagnosis and complements clinical, bronchoscopic, andlaboratory investigation.

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