K.Gohari Moghadam MD. Azar 1394

1- Increased survival of patients by intense immunosuppression. 2-The lung is the most frequently affected organ. 3- Emergence of resistant microorganisms

4- Unusual and subtle clinical manifestations ( absence of fever, sputum ) More complicated clinical course. 5- The changes in immunosuppression regimens, prophylactic regimens and increased graft survival altogether alter the typical clinical presentation.

6- Unusual and subtle radiography ( Normal CXR in neutropenics) 7-Radiologic abnormalities in the background of systemic disease ( SLE, scleroderma )

8- Progressive and fatal nature of infection in the context of decreased immunity. 9-Need for prompt diagnosis, decision ( often invasive ) and treatment. 10- Concomitant pulmonary diseases, which are not infectious ( edema, atelectasis, emboli, drug toxicity, radiation )

11-Presence of simultaneous and sequential infections ( CMV,Pneumocystis,Aspergillus and G- bacteria ).

12-Limitation of diagnostic assays and procedures 13- Significant adverse reactions to antimicrobial regimens.

14-Invasive Fungal infections are increased in spite of prophylaxis and treatment during recent years.

Risk Factors ( Net state of immunosuppression ) Overally, neutropenia is the most important risk factor. Anti TNF ( TB, Fungi) Corticosteroid ( Nocardia, Pneumocystis,TB) Conditioning and engraftment ( CMV, pneumocystis,Aspergillus, Nocardia, TB,Bacterial ) HSCT (Aspergillus ) SOT ( Candida ) T cell depleting Abs ( CMV, EBV, HIV )

Dominant Clinical presentation Net state of immuno suppression Epidemiologic Exposure

Donor-derived ( CMV, TB, Toxoplasma ) Recipient –derived ( TB, CMV, strongyloides ) Nosocomial : gram negative, S.aureus, HSV, HBV, HCV, HIV. Community acquired ( Aspergillus, Nocardia )

Role of CT scan In patients with febrile neutropenia, Fever and normal CXR with respiratory symptoms Greater confidence in DDx Improve sampling by precise localization

Pyogenic bacteria DM : S.aureus, S.pneumoniae, Klebsiella in the form of increased frequency and severity ESRD : Mortality rates from pulmonary infections are higher by a factor of # 20.

A case of SLE following splenectomy

TB Lower Lobe TB Mediastinal LAP Extrapulmonary involvement Less cavitation Higher probability of smear negative samples

A case of Systemic Sclerosis and LLL cavity ( TB)

Miliary TB

Nocardia Nocardia has two characteristics: 1- The ability of invasion to any organ ( as TB ) 2-The tendency to relapse or progression despite appropriate treatment ( as Aspergillus )

Lungs are affected in 2/3 of cases. Risk factors are: BMT,steroid use,CD4< 100,DM, Malignancies,Chronic lung disease,alcoholism. Lung involvement is usually primary rather than metastatic from skin.

Has acute, subacute or chronic presentation. Different radiographic patterns. About 45 days to 1 year delay from clinical onset to diagnosis. Recovery of Nocardia from lung samples is diagnostic.

Nocardia in a case of behcet

Nocardia in a WG

Aspergillus Prolonged and severe neutropenia is the most important risk factor. HSCT ( severity of GVHD ),SOT ( specially in lung transplantation ) Chronic glucocorticoid use Advanced AIDS Chronic Granulomatous disease Uncommon in HIV

Hemoptysis,dyspnea, Pleuritic chest pain in DD of PTE. Fever,which is unresponsive to broad spectrum antibiotics and even amphotericin is suggestive of Aspergillus infection.

Important Radiologic patterns of Aspergillus 1-Halo sign is suggestive. (pseudomonas and in Zygomycosis, neoplasms, Kaposi, WG), 2-Cavitation, crescent sign 3-Wedge shaped peripheral consolidation.

The best method of diagnosis is smear and culture from lung tissue. Positive smear and specially culture from BAL specimen in a relevant clinical and radiographic pattern

Galactomannan is validated for serum samples.( about 90% sp.,Se, NPV). BAL GM has more yield. GM in circulation is transient, so it is advised to measure twice a week.

Bronchial biopsy. Leukemia and…. © A.J.France 2010

Zygomycosis ( Mucormycosis ) Risk factors include : DM,Glucocorticoid use,Leukemia,HSCT,SOT,deferroxamine use,Iron overload,AIDS,IV users,Malnutrition. In comparison to Aspergillus : Numbers of nodules >10 in CT scan, Presence of sinusitis, Pleural effusion and Previous prophylaxis with voriconazole are in a favor of diagnosis of mucormycosis. The most common cause of reverse halo sign is mucor infection.

Pneumocystis ( HIV ) Indolent course Diffuse interstitial-alveolar pattern in CXR Patchy or nodular GGO in HRCT HRCT has 100% sensitivity Associated with CD4< 200 as an AIDS defining illness Induced sputum is more diagnostic in HIVs when compared with non HIVs,who have often low burden of organism.

Giemsa Gomori PCR ( For Non HIV ) (low burden of microorganism ) Culture : not BAL : 50%-90%

Pneumocystis pneumonia. Lung biopsy, silver stain. © A.J.France 2010

Pneumocystis ( Non HIV ) Steroid use Hx specially in tapering or increasing period Transplantation, Sirolimus Hematologic malignancies Progressive course with abrupt respiratory failure Diffuse reticular pattern in CXR and GGO in HRCT Sirolimus cause a noninfectious idiosyncratic pneumonitis mimicing PCP pneumonia.

Radiographic patterns Early interstitial GGO Perhilar or central opacities Suspicion of PCP should increase when pneumothorax is obsereved in a HIV patient. Adenopathy and pleural effusion are uncommon. A negative HRCT may allow exclusion of PCP.

CMV CMV infection vs. CMV disease CMV infection is defined by : Either finding of virus by culture,molecular technique or serology CMV disease is defined by : symptoms and signs such as fever, leukopenia, liver, lung,pancreas,colon,meningoencephalitis, chorioretinitis ( AIDS )

CMV DNA by PCR > 500 copies per microgram DNA in peripheral blood is defined as disease. Cytopathic effect in BAL cytology, PP65 quantity (with limitation of WBC<1000) and TBLB.

CMV pneumonia in a RTx

CMV Pneumonia 1 30/9/91

CMV pneumonia 2/10/91