Immunocompromised Hosts Flashcards
Physical Defense Barriers
- Skin and mucosa ⇒ 1° defense against endogenous and exogenous infection
- Causes for disruption:
- Trauma
- Tumor invasion
- Effects of chemo- or radiotherapy
- Use of invasive procedures (IV catheters)
Neutropenia
Overview
- Quantitative Phagocyte Defect
- Absolute neutrophil count < 1,000 mm3 ⇒ ↑ risk of infection
- Absolute neutropenia < 500 cells/mm3 ⇒ sign. neutropenia
- Risk of infection is higher if count is falling
- ↑ Duration of neutropenia ⇒ ↑ risk
Neutropenia
Etiologies
- Congenital cyclic neutropenia
- Malignancy and Rx w/ cytotoxic effect
- Hematologic malignancies
- Primary bone marrow failure, e.g. aplastic anemia
Neutropenic Fever
Etiologies
-
Bacterial infections
- Gram ⊖s
- Enterics (E.coli, Klebsiella, Enterobacter) and Pseudomonas aeruginosa
- Presumed sources are lines, GI tract, GU tract, respiratory tract, or exogenous sites
- Gram ⊕s
- S. aureus, Coagulase ⊖ staph, Enterococci, Bacillus species, Corynebacterium
- Common source is indwelling vascular catheters
- Gram ⊖s
-
Fungal Infections
- Candida species
- Usually occurs after at least 3-5 days of neutropenia
- ↑ in pts on abx
- Albicans is most common
- Types of infection include candidemia, catheter infection, disseminated candidiasis often w/ hepatosplenic involvement, mucosal candidiasis (oral, esophageal, lower GI), or skin infection
- Aspergillus
- Primary sites upper airways (oral or nasal cavity, sinuses) or lungs
- Other fungi
- Mucor, Fusarium, Trichosporon beigelli
- Candida species
Phagocyte Qualitative Defects
Major functions of neutrophils for microbicidal activity include:
- Chemotaxis
- Cell activation
- Phagocytosis
- Intracellular and extracellular killing
- Defects in any of these may ↑ risk for infection
Chronic Granulomatous Disease
- PMNs do not make peroxide
- Defective oxidative metabolism ⇒ impaired oxidative burst
- ↑ infections occur 1° due to catalase ⊕ organisms
- Catalase ⊖ organisms produce peroxidase which is sufficient for polys to use for killing
- In catalase producing organisms, catalase degrades the peroxide produced by the bacteria
- Infections usually begin in 1st year of life
- Common pathogens: S. aureus, Enteric gram-⊖ rods, Pseudomonas, Nocardia, Aspergillus
- Common sites of infections: lung common (pneumonia and abscesses), skin and soft tissue infections, visceral abscesses, osteomyelitis
Myeloperoxidase Deficiency
- Most common granulocyte disorder
- Myeloperoxidase ⇒ lysosomal enzyme that catalyzes H2O2 → hypochlorous acid
- Despite defect, infectious complications rare; most individuals are healthy
Chediak Higashi
- AR, rare disease
- Characterized by impaired degranulation and defective chemotaxis of neutrophils
- Pts may have recurrent infections, oculocutaneous albinism, central and peripheral neuropathy, and ↑ bleeding time
- Some have neutropenia
- Typically see infections of skin, mucous membranes, and respiratory tract
- Common organisms: S. aureus, Gram ⊖ bacilli
Lazy Leukocyte Syndrome
Gingivitis, recurrent otitis media, stomatitis
Hyperimmunoglobulin E Syndrome (Job’s syndrome)
Multiple cutaneous abscesses due to staphylococci
Malignancy or Myelodysplasia
- Neutrophils are functionally defective d/t impaired phagocytosis, chemotaxis, and/or bactericidal activity
- Infectious complications ↑ but still rare
- However, borderline ↓in neutrophil number can lead to significant infectious complications
Phagocyte Qualitative Defects
Non-Malignant Hematologic Disease
- Aplastic anemia
- In addition to neutropenia, neutrophils also have impaired bactericidal activity
- Paroxysmal Nocturnal Hemoglobinuria (PNH)
- Impaired chemotaxis
- Sickle cell anemia
- Impaired bactericidal activity
Phagocyte Qualitative Defects
Iatrogenic Causes
- Pharmacologic agents
- Glucocorticoids
- ↑ risk of infection
- Several effects on neutrophils:
- impaired chemotaxis
- impaired phagocytosis
- impaired microbicidal activity
- Steroids also contribute to infection by multiple other mechanisms:
- impair wound healing
- ↑ skin fragility
- ↓ lymphocyte function
- ↓ cytokine production
- ↓ humoral immune responses
- In addition, signs and symptoms of infection may be dangerously masked in pts on steroids
Disorders of Cell-mediated Immunity
Overview
Causes infections predominantly due to intracellular pathogens
Organisms include bacteria, fungi, viruses and protozoa Mycobacteria, Legionella, Nocardia, Salmonella, Cryptococcus, Histoplasma, Coccidiodes, VZV, HSV, CMV, EBV, Pneumocystis, Toxoplasma, Cryptosporidium, Strongyloides
Disorders of Cell-mediated Immunity
Etiologies
- Malignancy
- Hodgkin’s lymphoma, Leukemias
- HIV
- Pharmacologic agents:
- Corticosteroids
- Degree of immunosuppression depends on dose and duration of steroids
- Give prophylaxis w/ INH if previously untreated ⊕ PPD pt to start steroids
- Cytotoxic therapy ⇒ Methotrexate, Cyclophosphamide, 6-MP, Azathioprine
- Anti-rejection drugs ⇒ Cyclosporine, antilymphocyte Ab
- Radiotherapy, especially when combined w/ other immunosuppressive agents
Severe Combined Immunodeficiency Syndrome (SCID)
- 1° Disorder of Cell-Mediated Immunity
- Infants develop failure to thrive and recurrent infections in 1st few months of life
- Infections due to S. aureus, S. pneumoniae, H. influenzae, Pneumocystis, Candida and herpes group
- Children usually die by age 2
Wiscott-Aldrich Syndrome
Ataxia-Telangectasia
- 1° Disorder of Cell-Mediated Immunity
- Absent serum and secretory IgA
- Pts have recurrent sinopulmonary infections w/ encapsulated bacteria
- W/ progressive loss of T cell function they develop additional associated infections
Digeorge Syndrome
- 1° Disorder of Cell-Mediated Immunity
- Absence of thymus and parathyroid glands
- Susceptible to overwhelming infections w/ HSV, VZV, albicans, pneumocystis
Disorders of Humoral Immunity
Overview
- Major components:
- Immunoglobulins
- Complement
- Infection risk:
- Infection w/ encapsulated bacteria
- Infections w/ other streptococci, S. aureus, gram ⊖ rods
- To a lesser extent see infections w/ enteroviruses and Giardia
Multiple Myeloma
- Malignant plasma cells induce a protein that selectively suppresses B cell function
- Recurrent infections are predominantly due to encapsulated bacteria
- Infections due to enteric GNR and S. aureus are also seen
- Infections usually occur in the upper respiratory tract, urinary tract or skin.
B Cell CLL
- Unbalanced immunoglobulin chain synthesis results in hypogammaglobulinemia
- Infection risk is associated w/ duration and stage of disease and IgG levels
- Recurrent infections are predominantly due to encapsulated bacteria
- Infections due to enteric GNR and S. aureus are also seen
- Infections usually occur in the upper and lower respiratory tract, urinary tract or skin
Disorders of Humoral Immunity
Non-malignant Etiologies
- Non-malignant Etiologies
- Etiologies include ↑ immunoglobulin loss or ↑ immunoglobulin catabolism
- Examples
- Nephrotic syndrome, burns, protein-losing enteropathy
- ↓ Ab levels result in ↑ infection risk
B-Cell Immunodeficiency States
1° Disorders of Humoral Immunity
- Sex-linked hypogammaglobulinemia
- Recurrent pyogenic infections and septicemia due to S. pneumonia, H. influenzae, S. aureus, N. meningitidis, P. aeruginosa
- Hyperimmunoglobulin M
- Recurrent respiratory, soft tissue and GI infections
- Selective IgM Deficiency
- Recurrent pyogenic infections
- Selective IgA Deficiency
- Some pts have ↑ upper respiratory tract infections or chronic diarrhea due to Giardia
- Common Variable Immunodeficiency
- Respiratory infections w/ S. pneumonia, H. influenza and S. aureus, diarrhea due to Giardia lamblia
Complement Deficiencies
1° Disorders of Humoral Immunity
-
Early components (C1, C2, C4) deficiencies
- Infection is rare
-
C3 or C5 deficiencies
- Pts develop severe infections w/ encapsulated bacteria, S. aureus and enteric GNR
-
Deficiencies of later components (C5b, C6, C7, C8, C9)
- Pts present w/ recurrent Neisseria infections (both N. menigitidis and N. gonorrhoeae)
- Infectious episodes typically begin in the teen years
Splenectomy or Splenic Dysfunction
- Major infectious complication can be fulminant infection due to encapsulated organisms
- Classic organisms include S. pneumoniae, H. influenzae, Neisseria species and Capnocytophaga
- Sickle cell asplenia ⇒ ↑ risk for Salmonella infection
Prevention of Infection
- Prevent acquisition or suppress flora
- Hand Washing
- Isolation
- Prophylactic antibiotics, antivirals, antifungals, and antiparasitics as indicated
- Useful in high risk neutropenic and transplant pts
- Improve or Modify Host Defenses
- Immunization
- Active
- Pneumococcus, VZV
- Passive
- VZIG
- Accelerate granulocyte recovery
- G-CSF, GM-CSF
- Cell component replacement
- Leukocyte transfusions
Clinical Pearls
Time
Clinical Pearls
Neutropenia:
1st few days ⇒ bacterial
4-5 days ⇒ fungal
Transplant:
1st month ⇒ bacterial, HSV
> 1 month ⇒ HSV, VZV, CMV, Aspergillus, Nocardia, Pneumocystis pneumonia (PCP)
> 3 months ⇒ Cryptococcus
Pace
Clinical Pearls
Fast ⇒ bacterial
Indolent ⇒ Nocardia, Cryptococcus, Mycobacterial
Symptoms
Clinical Pearls
Pleuritic chest pain, think fungus, especially aspergillus
Chest XR or CT
Nodules ⇒ Aspergillus, Nocardia
Interstitial ⇒ CMV, Pneumocystis pneumonia (PCP)
Focal ⇒ bacterial, mycobacterial, fungal
Sinus involvement
Think fungus, especially Mucor or Aspergillus
Common Management Approach
Fever and Neutropenia
History
P.E.
Cultures
Chest x-ray
Begin broad spectrum abx active vs gram ⊖ enteric pathogens + S. aureus (esp. if central venous catheter in place)
If fever persists for > 3 days on broad antibiotics, add antifungal Rx
G-CSF may shorten duration of neutropenia and resultant infectious complications
