35 Pneumonia in the Immunocompromised Host Flashcards
1
Q
Commonly encountered immunocompromising conditions:
Congenital immunodeficiencies
- Immuncompromize can be broadly defined as…
- Frequency
- Patients usually have…
- Bruton’s X-linked agammaglobulinemia
A
- Immuncompromize can be broadly defined as…
- A state in which the response of the host to a foreign antigen is subnormal
- Frequency
- Now much less common than acquired causes
- More frequently observed in patients in pediatric ICUs than in adult ICUs
- Patients usually have…
- Repeated infections, especially those affecting the respiratory tract and sinuses
- “Pure” defects in the response of the host to foreign antigens that are usually specific and well-defined
- Bruton’s X-linked agammaglobulinemia
- Associated with a defect in the normal maturation process of immunoglobulin-producing B cells
- As a result, mature circulating B cells, plasma cells, and serum immunoglobulin are absent
- Therefore, the patient is susceptible to (encapsulated) organisms that are normally dealt with by immunoglobulin, such as Streptococcus pneumoniae and Haemophilus influenzae
2
Q
Commonly encountered immunocompromising conditions:
Congenital causes of immunodeficiencies
- T lymphocyte deficiencies
- Di George’s syndrome (thymic aplasia with reduced CD4 and CD3 cells)
- Di George’s syndrome (thymic aplasia with reduced CD4 and CD3 cells)
- Bruton’s X-linked agammaglobulinemia (absence of B cells, plasma cells, and antibody)
- Selective IgG subclass deficiencies
- Selective IgA deficiency
- Mixed T and B lymphocyte deficiencies
- Common variable immuno-deficiency (leads to various B cell activation or differentiation defects and gradual deterioration of T cell number and function)
- Severe combined immuno-deficiency (severe reduction in IgG and absence of T cells)
- Wiskott-Aldrich syndrome (decreased T cell number and function; low IgM; occasionally low IgG)
- Phagocyte defects
- Chronic granulomatous disease (defect in NADPH oxidase, phagocytic cells)
- Chediak-Higashi syndrome (impaired microbicidal activity of phagocytes)
A
-
T lymphocyte deficiencies
- __Di George’s syndrome (thymic aplasia with reduced CD4 and CD3 cells)
- Viruses (especially HSV and measles), PJP, fungi or Gram negative bacteria
- __Di George’s syndrome (thymic aplasia with reduced CD4 and CD3 cells)
-
B lymphocyte deficiencies
- __Bruton’s X-linked agammaglobulinemia (absence of B cells, plasma cells, and antibody)
- H. influenzae, S. pneumoniae
- Selective IgG subclass deficiencies
- S. pneumonia, H.influenzae, N. meningitidis
- Selective IgA deficiency
- S. pneumoniae, H. influenzae, Giardia
- __Bruton’s X-linked agammaglobulinemia (absence of B cells, plasma cells, and antibody)
-
Mixed T and B lymphocyte deficiencies
- Common variable immuno-deficiency (leads to various B cell activation or differentiation defects and gradual deterioration of T cell number and function)
- S. pneumoniae, H. influenzae, CMV, VZV, PJP
- Severe combined immuno-deficiency (severe reduction in IgG and absence of T cells)
- PJP, viruses, Legionella
- Wiskott-Aldrich syndrome (decreased T cell number and function; low IgM; occasionally low IgG)
- S. pneumoniae, H. influenzae, HSV, PJP
- Common variable immuno-deficiency (leads to various B cell activation or differentiation defects and gradual deterioration of T cell number and function)
-
Phagocyte defects
- Chronic granulomatous disease (defect in NADPH oxidase, phagocytic cells)
- S. aureus, P. aeruginosa, Aspergillus
- Chediak-Higashi syndrome (impaired microbicidal activity of phagocytes)
- S. aureus, H. influenzae, Aspergillus
- Chronic granulomatous disease (defect in NADPH oxidase, phagocytic cells)
3
Q
Commonly encountered immunocompromising conditions:
Acquired immunodeficiencies
- Frequency
- Four categories of immunocompromized patients
A
- Frequency
- The vast majority of immunocompromized adult patients
- Four categories of immunocompromized patients
- (1) patients receiving chemotherapy for hematologic malignancies and solid tumors
- (2) patients receiving immunosuppressive therapy in the context of solid-organ transplantation
- (3) patients receiving corticosteroids, methotrexate, monoclonal antibodies to tumor necrosis factor alpha and other disease modifying agents for rheumatoid arthritis, Crohn’s disease and autoimmune disorders
- (4) patients with human immunodeficiency virus (HIV) infection
4
Q
Commonly encountered immunocompromising conditions:
Hematologic malignancies and solid tumors
- Prolonged neutropenia from chemotherapy
- Organisms associated with severe neutropenia
- The severity and duration of neutropenia influence…
- Aggressive chemotherapy and radiotherapy for Hodgkin’s lymphoma, coupled with splenectomy, significantly impairs humoral defense against…
- Alemtuzimab and rituximab
- Hematopoietic stem cell transplantation carries with it a risk of…
A
- Prolonged neutropenia from chemotherapy
- Carries a significant risk of bacterial and fungal infection
- Organisms associated with severe neutropenia
- Gram negative organisms such as Pseudomonas aeruginosa
- Fungal organisms such as Aspergillus spp.
- The severity and duration of neutropenia influence…
- The risk of infection
- Aggressive chemotherapy and radiotherapy for Hodgkin’s lymphoma, coupled with splenectomy, significantly impairs humoral defense against…
- Encapsulated organisms such as Streptococcus pneumoniae, Haemophilus influenzae and Neisseria meningitidis
- Alemtuzimab and rituximab
- Used in treatment of lymphoma’s
- Can cause a profound T-cell mediated immunocompromized state
- Hematopoietic stem cell transplantation carries with it a risk of…
- Graft versus host disease
5
Q
Commonly encountered immunocompromising conditions:
Hematologic malignancies and solid tumors
- Prophylaxis against, and treatment of, graft versus host disease may involve…
- Patients receiving therapy for graft versus host disease may be prone to…
A
- Prophylaxis against, and treatment of, graft versus host disease may involve…
- Cyclosporine or tacrolimus
- Inhibit calcineurin, an enzyme important in the lymphocyte activation cascade
- Corticosteroids
- Also have effects on lymphocyte function, as well as depressing functions of activated macrophages
- Cyclosporine or tacrolimus
- Patients receiving therapy for graft versus host disease may be prone to…
- Fungal infections (PJP, histoplasmosis, cryptococcosis, coccidiomycosis, blastomycosis, Aspergillus)
- Viral infections (CMV)
- Mycobacterial infections (tuberculosis and atypical mycobacteria)
6
Q
Commonly encountered immunocompromising conditions:
Solid organ transplantation
- Solid-organ transplant recipients
- In the early post-transplant period, transplant recipients are susceptible to…
- Solid-organ transplant recipients, by virtue of their iatrogenic immunosuppression (mostly T-cell mediated) are also susceptible to…
A
- Solid-organ transplant recipients
- Uniquely susceptible to infection
- Undergo significant surgery that breach the defenses provided by the skin
- Remain in ICUs for prolonged periods of time, requiring intravenous access and mechanical ventilation, breaching cutaneous and pulmonary barriers to infection
- Receive immunosuppressive therapy to prevent graft rejection
- In the early post-transplant period, transplant recipients are susceptible to…
- Nosocomially-acquired bacterial infections, such as pneumonia and central line-associated bloodstream infection associated with general ICU care
- Wound infections and intra-abdominal infections associated with their surgical procedure
- Opportunistic infections from the organ graft (ex. cytomegalovirus, histoplasmosis, or West Nile virus)
- Solid-organ transplant recipients, by virtue of their **iatrogenic immunosuppression **(mostly T-cell mediated) are also susceptible to…
- Reactivation of latent infection (such as cytomegalovirus infection, tuberculosis or histoplasmosis)
- Infections acquired through the hospital environment (such as aspergillosis, legionellosis or tuberculosis)
7
Q
Commonly encountered immunocompromising conditions:
Rheumatoid arthritis and autoimmune disorders
- Simple therapy
- Drugs with the potential to cause significant immunocompromize
- “Anti-cytokine” agents
- Ex
- Also treat…
- Associated risks
A
- Simple therapy
- Simple analgesics or non-steroidal anti-inflammatory drugs
- Drugs with the potential to cause significant immunocompromize
- Corticosteroids or disease-modifying anti-rheumatic drugs such as azathioprine, cyclosporine, gold salts, hydroxychloroquine, leflunomide, methotrexate or sulfasalazine
- “Anti-cytokine” agents
- Ex. etanercept or infliximab
- Also treat Behcet’s disease, Crohn’s disease, graft-versus-host disease, hairy cell leukemia, psoriasis, pyoderma gangrenosum, sarcoidosis and ulcerative colitis
- Associated risks
- Pulmonary tuberculosis
- The risk is sufficiently high that it is recommended that tuberculin skin testing or interferon gamma release assay be performed for the presence of latent tuberculosis prior to the initiation of these agents
- Invasive aspergillosis, coccidioidomycosis, cryptococcosis, histoplasmosis and Pneumocystis (PJP) infection
- As is the case with transplant-associated immunocompromize, such infections may be reactivation of latent infection or new acquisitions of organisms acquired through the environment
- Pulmonary tuberculosis
8
Q
Commonly encountered immunocompromising conditions:
Human immunodeficiency virus infection
- Frequency of HIV infection
- Frequency of acquired immunodeficiency syndrome (AIDS)
- Untreated HIV infection
- The risk of opportunistic infections causing pneumonia
A
- HIV infection
- A relatively common infection
- Acquired immunodeficiency syndrome (AIDS)
- Less frequently encountered since the advent of highly active antiretroviral therapy
- Untreated HIV infection
- Can be associated with substantial decline in CD4 lymphocyte counts
- This creates a predisposition to Pneumocystis pneumonia, mycobacterial infection, fungal infection (such as cryptococcal meningitis) and viral infections (such as cytomegalovirus infections)
- The risk of opportunistic infections causing pneumonia
- Rises substantially when the CD4 lymphocyte count is less than 200
- Streptococcus pneumoniae and Mycobacterium tuberculosis can both cause pulmonary infections in HIV-infected individuals with CD4 lymphocyte counts of more than 200
9
Q
The general diagnostic approach to immunocompromised patients with pneumonia
- Immunocompromized patients are a heterogeneous group, for ex…
- Even within a particular category of immunocompromize (for example, kidney transplantation), patients may have…
- In solidorgan transplant recipients, the “net state of immunosuppression”…
- For example, a renal transplant recipient who is receiving tacrolimus monotherapy twice per week will be…
A
- Immunocompromized patients are a heterogeneous group, for ex…
- The infections commonly encountered by a patient with neutropenia as a consequence of chemotherapy may be quite different from those observed in a patient with rheumatoid arthritis who is receiving infliximab
- Even within a particular category of immunocompromize (for example, kidney transplantation), patients may have…
- A different degree of immunocompromize and therefore a different susceptibility to infection
- In solidorgan transplant recipients, the “net state of immunosuppression”…
- That is, the cumulative burden of immunosuppression with a special weighting towards recent T cell ablative therapy
- Influences the risk of infection
- For example, a renal transplant recipient who is receiving tacrolimus monotherapy twice per week will be…
- Less susceptible to opportunistic infection than a patient with recent acute cellular rejection treated with alemtuzimab, who has a CD4 lymphocyte count of 20
10
Q
The general diagnostic approach to immunocompromised patients with pneumonia
- In contrast with HIV infection, CD4 lymphocyte count and HIV “viral load”…
- Thus, it is important to determine…
- Those with CD4 counts greater than 200 are likely to be infected with…
- Those with CD4 counts of <200 may be infected with…
- A patient with a CD4 count of <50 may develop…
A
- In contrast with HIV infection, CD4 lymphocyte count and HIV “viral load”…
- Are predictive of risk of infection
- Thus, it is important to determine…
- The recent CD4 lymphocyte count in patients with HIV infection
- Those with CD4 counts greater than 200 are likely to be infected with…
- The usual pathogens such as Strep. pneumoniae and Mycobacterium tuberculosis
- Those with CD4 counts of <200 may be infected with…
- Aforementioned organisms and in addition with Pneumocystis
- A patient with a CD4 count of <50 may develop…
- CMV pneumonitis
11
Q
The general diagnostic approach to immunocompromised patients with pneumonia
- Specific environmental exposures may be potentially important for immunocompromized patients
- A travel history to the southwestern states of the United States may increase the likelihood that an immunocompromized patient has…
- What’s endemic in the Ohio River Valley
- Environmental risks within the ICU
- Linked to construction activity within the hospital
- Waterborne
- In units caring for transplant recipients or HIV-infected patients
- Thus, the “net state of immunosuppression” must be considered in the context of…
A
- Specific environmental exposures may be potentially important for immunocompromized patients
- A travel history to the southwestern states of the United States may increase the likelihood that an immunocompromized patient has…
- Coccidioidomycosis
- What’s endemic in the Ohio River Valley
- Histoplasmosis
- A travel history to the southwestern states of the United States may increase the likelihood that an immunocompromized patient has…
- Environmental risks within the ICU
- Linked to construction activity within the hospital
- Outbreaks of invasive pulmonary aspergillosis
- Waterborne
- Outbreaks of legionellosis and many fungal and bacterial infections
- In units caring for transplant recipients or HIV-infected patients
- Tuberculosis transmission
- Linked to construction activity within the hospital
- Thus, the “net state of immunosuppression” must be considered in the context of…
- Recent environmental exposures
12
Q
The general diagnostic approach to immunocompromised patients with pneumonia
- Ockham’s razor
- Given all the patient’s symptoms, signs and non-invasive laboratory test results,…
- Immunocompetent
- Immunocompromized
- For example, a neutropenic patient may have…
- Immunocompetent
- Immunocompromized
A
- Ockham’s razor
- Caution must be exercised in use of the diagnostic principle which follows “Ockham’s razor” (“entities are not to be multiplied without necessity”)
- Given all the patient’s symptoms, signs and non-invasive laboratory test results,…
- In the immunocompetent patient, one unifying diagnosis usually explains all
- Immunocompromized patients may have more than one infection simultaneously
- For example, a neutropenic patient may have…
- Bacterial pneumonia and invasive pulmonary aspergillosis simultaneously in an immunocompetent patient
- An immunocompromized patient with HIV infection may have Pneumocystis pneumonia and pulmonary infiltrates due to complications from HHV-8 infection (Kaposi’s sarcoma)
13
Q
The general diagnostic approach to immunocompromised patients with pneumonia
- The potential for multiple diagnoses underscores the need for…
- For example, patients with unexplained severe community-acquired pneumonia may be best managed by…
- Bronchoalveolar lavage could be sent for…
- The bronchoalveolar lavage should be…
A
- The potential for multiple diagnoses underscores the need for…
- Early, invasive testing in immunocompromized patients with severe infection
- For example, patients with unexplained severe community-acquired pneumonia may be best managed by…
- Early bronchoalveolar lavage prior to antimicrobial therapy aimed at numerous pathogens
- Bronchoalveolar lavage could be sent for…
- Gram stain (Most bacteria)
- Ziehl Neelsen stain (Mycobacteria)
- Modified acid-fast stain (Nocardia)
- Calcofluor stain (fungi)
- Direct fluorescent antibody tests (Legionella)
- Methenamine silver stain (Pneumocystis)
- Cytologic analysis to enable rapid diagnosis of infection
- The bronchoalveolar lavage should be…
- Inoculated onto solid media and appropriate cell lines to enable culture of pathogens cultivable by such techniques
- Molecular diagnostic testing may be appropriate in some instances
14
Q
The diagnostic approach for severe infections in immunocompromised patients:
History-taking and review of prior records
- Likely degree of immunocompromize
- Prophylaxis against opportunistic infections
- Family history
- Potential environmental exposures
A
- Likely degree of immunocompromize
- Recent CD4 lymphocyte count and HIV “viral load”
- Time since transplantation
- Recent acute cellular rejection or graft versus host disease, and treatment thereof
- Current or recent receipt of immunosuppressive medications
- Current or recent receipt of antiretroviral medications
- Prophylaxis against opportunistic infections
- Receipt of antimicrobial prophylaxis against Pneumocystis, herpes simplex virus or cytomegalovirus
- Vaccination status (pneumococcus, influenza, N. meningitidis)
- Family history
- Personal or family history of tuberculosis or chickenpox
- Potential environmental exposures
- Travel history to southwestern United States
- Exposure to hospital construction activity (aspergillosis)
- Exposure to hospital water supply (legionellosis, aspergillosis)
- Exposure to patients with tuberculosis or chickenpox
- Donor and recipient serostatus for CMV or Toxoplasma gondii
15
Q
The diagnostic approach for severe infections in immunocompromised patients:
Physical examination
- Skin
- Mouth and other mucous membranes
- Respiratory system
- Cardiovascular system
- Abdominal examination
- Neurologic examination
A
- Skin
- Presence of cutaneous nodules consistent with cryptococcosis, nocardiosis etc
- Presence of cutaneous manifestations of graft versus host disease
- Kaposi’s sarcoma
- Line insertion site erythema or pus
- Peripheral embolic phenomena
- Scars consistent with prior surgery (splenectomy)
- Mouth and other mucous membranes
- Presence of candidiasis
- Respiratory system
- Presence of signs of focal versus multilobar pneumonia
- Cardiovascular system
- Murmurs, prosthetic heart sounds
- Abdominal examination
- Signs of peritonitis
- Hepatomegaly or splenomegaly
- Tenderness of renal allograft
- Neurologic examination
- Nuchal rigidity
- Cranial nerve signs
