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 presentationNet state

of immuno suppression

Epidemiologic Exposure

Epidemiologic ExposureDonor-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 scanIn patients with febrile neutropenia ,Fever and normal CXR with respiratory

symptomsGreater confidence in DDx Improve sampling by precise localization

Pyogenic bacteriaDM : 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

TBLower Lobe TBMediastinal LAPExtrapulmonary involvementLess cavitationHigher probability of smear

negative samples

A case of Systemic Sclerosis and LLL cavity

( TB)

Miliary TB

NocardiaNocardia 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

AspergillusProlonged 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 diseaseUncommon 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 Aspergillus1-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 courseDiffuse interstitial-alveolar pattern in CXRPatchy or nodular GGO in HRCTHRCT has 100% sensitivityAssociated with CD4< 200 as an AIDS

defining illnessInduced sputum is more diagnostic in HIVs

when compared with non HIVs,who have often low burden of organism .

Giemsa GomoriPCR ( For Non HIV ) (low burden of

microorganism )Culture : notBAL : 50%-90%

© A.J.France 2010

Pneumocystis ( Non HIV )Steroid use Hx specially in tapering or

increasing periodTransplantation , SirolimusHematologic malignanciesProgressive course with abrupt respiratory

failureDiffuse reticular pattern in CXR and GGO in

HRCTSirolimus cause a noninfectious

idiosyncratic pneumonitis mimicing PCP pneumonia .

Radiographic patternsEarly interstitialGGOPerhilar 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.

CMVCMV infection vs. CMV diseaseCMV 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