The Immunocompromise Patient

The immunocompromise patient 1. AIDS. 2. Other form of immunocompromise: a. Neutropenia. b. Reduced cell-mediated immunity. c. Reduced humoral immunity. d. Incompetence of cellular element. e. Nonspecific reduction in host resistance. 1. AIDS - Pyogenic pneumonia - Mycobacterial infection o Tuberculosis o Nontuberculous (atypical) mycobacterial infection. - Fungal infection o PCP o Candida albicans o Cryptococcus neoformans o Coccidiodes immitis o Histoplasmosis o Aspergilus - Protozoal infection o Toxoplasma o Cryptosporidium - Human Herpesvirus infections - AIDS associated airway disease. - Thoracic neoplasm and non infectious complication o AIDS-related lymphoma, kaposi sarcoma, lymphocytic interstitial pneumonia, persistent generalized lymphadenopathy and bronchogenic carcinoma 2. Other form of immunocompromise -

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Neutropenia; defense againts microorganism. Neutropenia may be feature of disease itself or due to drug or radiation. Neutropenia= PMN count <1,000 cell/mm3 Reduced cell-meidated immunity; T-lymphocyte are important line of defence against intracellular parasites and non pathologic organism. Reduced humoral immunity; Impaired B-lymphocyte>> reduce circulating antibody i.e.; thymic aplasia, asplenia or splenectomy. Lead to marked susceptibility to infection with encapsulated organism such as Streptococcus spp. Incompetence of cellular element; enzymatic defect of neutrophils>> chronic granulomatous disease or silicosis lung may not adequate response to pulmonary tuberculosis. Nonspecific reduction in host resistance; advanced age, alcoholism, DM, , malneutrition or cancer.

Radiologic evaluation and diffential diagnosis of pulmonary opacities in immunocompromise host. Impared cell

Nature of immunocompromise

Cause of immunocompromise

Common infection organism

Granulocyte

Altered inflammatory response

- Acute and chronic myelocytic leukemia Steroid - Chemotherapeutic agents Irradiation - Chronic granulomatous disease

T lymphocyte

Reduced cellmediated immunity

- Lymphoma - AIDS - Steroid - Chemotherapeutic agent - Irradiation - Renal insufficiency - Solid organ transplant

B lymphocyte

Reduce antibody formation

- Lymphoma - Acute and chronic lymphocytic leukemia - Multiple myeloma - Hypogammaglobulinemia - Steroid - Chemotheraputic agent

Macrophage

Impair granulomatous response

- Silica

Bacteria Escherichia coli Staphylococcus aureus Serratia marcescens Pseudomonas aeruginosa Klebsiella pneumonia Enterobacter spp Proteus spp Legionella pneumophila Nocardia asteroids Fungi Aspergillus spp Mucor spp Bacteria Legionella micdadei Salmonella spp N. asteroids Tb Viruses Cytomegalovirus Varicella-zoster virus Herpes simplex Respiratory syncytial virus Fungi Aspergillus spp Cryptococcus neoforman Histoplasma capsulatum Coccidiodes immitis Pneumocytis jeroveci Parasite Toxoplasma gondii Helminth Strongiloides stercolaris Bacteria E. coli P. aeruginosa K. pneumonia Streptococcus pneuoniae Haemphilus influenza Viruses Cytomegaluvirus Respiratory syncytial virus Fungi P.jiroveci Bacteria M. tuberculosis Fungi Blastomyces dermatitidis

H. capsulatum

Bone marrow transplantation Pulmonary complication are seen in 40-60% of BMT recipients and many complications have significant motality Intravenous hematopoietic element into a patient whose bone marrow has been ablate by high dose CMT and total body irradiation. A 2-3 weeks period of profound bone marrow dysfunction before graft engufment is common. Neutropenic render the patient susceptible to bacterial and fungal infection. Process of severe neutropenia usually last only approximately 4 weeks. Lymphocyte is the most sensitive cellular element in the body. After the first month, there is a continuous recovery of immune function that usually complete at 1 year. Autologous (patient own marrow) recipient have much lower incidence of CMV, fungal infection and idiopathic pneumonia syndrome. Further more they are not subject to graft-versus-host or obliterative bronchiolitis.  Complication within first month Most common infection are caused by bacterial, Aspergillus or Candida spp. Bacterial sepsis occurs in up to 50% particularly in the first 2 weeks. Gram-negative organism is common due to venous catheter. Radiographically evidence of bacterial pneumonia is uncommon in this period, presumably due to prophylactic antibiotic. But when it occurs radiographic manifestations are nonspecific; focal or multifocal consolidation, rapid progression to more diffused opacification. Aspergillus or Candida spp. Infection are most common fungal in this period. Airway-invasive or angioinvasive form encountered during this period. Viral infections are uncommon. Common noninfectious complications include pulmonary edema, hemorrhage and drug toxicity. “Engraftment syndrome” is characterized by fever, skin rash and capillary leak. It occurs in one third to half of effected patient. Diffused alveolar hemorrhage occurs in up to 21% of transplant patient and has high motality rate, between 50-80%. It not associated with coagulation disorder. May represents a complication of leukostasis caused by neutrophil suddent influx into the lungs. Chest radiograph show diffused consolidation, but one third show diffused reticular opacity. CT can show scatter or diffused ground glass opacity. These finding can not be distinguishable from other complication especially pulmonary edema. However the two conditions can usually be distinguished by clinical. Drug toxicity should always be considers in the form of diffused alveolar damage.  Early phase complications (30-100 day after transplantation) Depressed cellular and humoral immunity Two most important pulmonary complications are CMV pneumonia and the idiopathic pneumonia. CMV pneumonia is the most important infection in BM transplant patient. More than 70% of all recipients develop clinical or subclinical infection of CMV. The clinical manifestations are extremely varies include retinitis, encephalitis, esophagitis, enterocolitis, hepatitis and nephritis. Pneumonia is the most

serious manifestations with incidence of 10-40% in allogenic transplantation; 85% mortality rate has been report.

Other viural pneumonia is higher incidence such as herpes simplex virus, adenovirus. Pneumonia occurs for 40% of transplantation related death. Approximately half of patients are noninfectious. This condition is called”Idiopathic pneumonia syndrome” (IPS). Mortality is high (>70%). IPS is manifested as diffuse alveolar damage. Chest radiograph show scatter or diffused opacities which may progress to consolidation. CT show ground-glass opacities in the early stage, later stage may show more linear opacities with evidence of architectural distortion Clark criteria for diagnosis include (1) sign and symptoms of pneumonia; (2) chest radiograph show multilobar opacity; (3) abnormal pulmonary physiology increase A-a gradient and restrictive pulmonary function test abnormality (4) rigorous exclusion of infection pathology by bronchoalveolar larvage. Acute graft versus host (GVHD) is also occurs in this period (20-100days). GVHD; result from transplantation of immunocompetent donor lymphocytes that attack recipient host. The GVHD effect predominately extrapulmonary; exforiative dermatitis, diarrhea and liver dysfunction. However GVHD may potentiate the effect of more common pulmonary complication such as infection.  Late phase complication(>100 days) The major late phase complication is chronic GVHD occurs in one third or one half of patient surviving in first 100 days. Clinical manifestation are similar to those autoimmune disease; scleroderma, primary biliary cirrhosis and sicca syndrome. 50% of late complication had NSIP or diffuse alveolar damage. Which obliterated bronchiolitis and obliterate pneumonia may occur. Varicellar zoster infection also occur in this time frame. Most case manifestations are cutaneous.