Immunocompromised host Flashcards
Why is immunodeficiency a problem that is unmet?
1) Large spectrum of primary immune deficiencies:
- Different phenotypes
- Lack of new knowledge
- Need better criteria for diagnosing
2) Failure to recognise and diagnose primary immune deficiencies
When are PIDs usually diagnosed? (2)
Why is this a problem?
- 8-12.4 years from onset
- > 60% patients 18+ years old when a diagnosis is made
- By this point, more than 37% of them will have permanent organ/tissue damage
Definition immunocompromised host
State in which immune system is unable to respond appropriately and effectively to infectious micro-organisms
Due to defect in one or more components of immune system (either the innate or adaptive immune system).
Types of immunocompromised host
Primary immunodeficiency: congenital
Due to intrinsic gene defect
Leads to:
- Missing protein
- Missing cell
- or non-functional components
Secondary: acquired
Due to underlying disease/treatment (eg HIV/chemo)
- Decrease in production/function of immune components or
- Increase in loss/catabolism of immune components
When should you suspect immunodeficiencies?
When infections are SPUR
Severe - can be life-threatening and requiring IV antibiotics or hospital admission - death if left untreated
Persistent - still remains after conventional treatment
Unusual (site/type of microbe is unusal, Site: eg deep infections or infections in the brain and Type: eg opportunistic infections like candida )
The 10 warning signs (PID) For children VS Adults
Four or more new infections within 1 year Serious sinus infections Antibiotics with little effect Pneumonias Failure to gain weight/grow Thrush/fungal infection NEED IV antibiotics to clear infection DEEP SEATED infections (eg brain) Family history
Limitations 10 warning signs
General use (lack of population based evidence)
PID patients differ in presentations/defect type
Non-infectious manifestations occur (eg autoimmunity, malignancy, inflammatory responses)
3 signs to use for instead of 10
- Family history
- Failure to thrive (grow) in infancy
- Diagnosis of sepsis with the need for IV antibiotic treatment
Malignancies with primary immunodeficiency disorder
Lymphoma (MOST and common with common variable immunodeficiency)
Leukaemia
Hodgkin disease
Adenocarcinoma
What are most immunodeficiencies caused by?
Antibody defect (65%)
Types of antibody defects
X linked agammaglobulinaemia (Bruton’s disease)
(B cell development defect)
Common Variable Immunodeficiency (CVID) Selective IgA deficiency IgG subclass deficiency Hyper-IgM syndrome
Most common antibody defects
CVID - most common symptomatic
Selective IgA - most common asymptomatic
Problem with selective IgA deficiency
Host can create antibodies against IgA
Can have transfusion reactions and reactions to IRT
Immunodeficiency caused by T cell defects percent
15%
Combined B and T cell defects
T cell defects
Combined B and T cell defects
Need T cells to activate B cells
Severe combined immunodeficiency (SCID) - most common
Wiskott-Aldrich syndrome
Ataxia telangectasia
T cell defects
Di George syndrome (THYMUS) - most common, cardiac problems presentation CD3 deficiency MHC class 2 deficiency TAP 1 or 2 deficiency (MHC class 1)
Immunodeficiencies caused by phagocytic defects types
Respiratory burst problems
Defect in fusion of lysosome and phagosome
Defect in neutrophil production and chemotaxis
Respiratory burst problem
Chronic granulomatous disease (CGD)
Defect in fusion of lysosome and phagosome
Chediak-Higashi syndrome
Defect in neutrophil production/chemotaxis
Cyclic Neutropenia
LAD protein deficiency (protein on phagocytes that allow it to enter tissues)
Age of onset and what deficiency
<6 months old - T cell/phagocyte deficiency (still have mothers antibodies)
6 months - 5 years - B cell/antibody/phagocyte defect
> 5 years - B cell/antibody/complement (MOST COMMON CVID) or secondary immunodeficiency
Types of microbes and sites/signs with complement deficiency
Bacteria (eg Neisseria, streptococci, encapsulated bacteria)
Pus producing (pyogenic), meningitis, sepsis, arthiritis, angioedema
Phagocytic defects microbes and site/signs
Bacteria (Staph aureus)
Fungi (candida albicans)
Skin/mucous infections
Deep-seated (eg brain) infection
Invasive fungal
Antibody defect microbes and site
Bacteria (Streptococci, staph, haemophilus)
Virus (enterovirus)
Protozoa (Giardia Lamblia)
Sino respiratory infection Arthropathies (joint) GI infection Malignancy Autoimmunity
T cell defects types of microbe
ALL SUBTYPES MICROBE Bacteria (similar to antibody with intracellular bacteria too eg salmonella typhi) Virus (all) Fungi (candida) Protozoa (pneumocystis, toxoplasma)
T cell defects infection types
Death if not treated
Failure to thrive
Deep skin and tissue abscesses
Opportunistic infections
Most likely diagnosis T cell defect
Severe combined immunodeficiency
Most likely diagnosis B cell defect (more males affected)
X linked Brutons disease
Most likely diagnosis if unable to produce respiratory burst
Chronic granulomatous
Most likely diagnosis antibody defect
Common Variable Immunodeficiency
Manage PID
Support (infection prevention prophylaxis)
Treat infections fast
Treat autoimmunity/malignancies
Assess organ damage
Treatment PID
Immunoglobulin replacement therapy (IRT)
Stell cell therapy
IRT facts and goals
Get serum IgG > 8g/L
Life long
Types:
IVIg (intravenous every 3 weeks)
ScIg (young patients, subcutaneous every week at home)
Conditions to give IRT
CVID
XLA (Bruton’s disease)
Hyper-IgM syndrome
Hyper IgM syndrome
Only IgM no IgG
Deficient CD40 ligand (cant change IgM to IgG)
Secondary immune deficiency cause
Decreased production of immune components:
Malnutrition (elderly) Infection (HIV) Liver disease Haematological deficiencies Therapeutic treatments (CORTICOSTEROIDS) Spenectomy
Secondary immune deficiency cause
Increased loss of immune components
Protein losing conditions (Nephropathy)
Burns
(test for albumin in urine)
Why are patients with haematological malignancies more at risk OF INFECTION?
Chemo induced neutropenia
Chemo induced damage to mucosal barriers
Vascular catheters (staphylococcus)
Lab tests antibody/b cell deficiency
IgG, IgA, IgM (+/-IgE)
IgG 1-4 subclasses
IgG levels from previous vaccines
Measure antibody response to test immunisation
Tests for suspected T cell deficiency
Lymphocyte count (FBC) Lymphocyte sub set analysis (CD4+, CD8+, Natural killer cells) In vitro test T cells function
Test for phagocyte deficiency
Neutrophil count (FBC) Neutrophil function test (oxidative burst working?) Adhesion molecule (is LAD expressed?)
Test for complement deficiency
Test individual components
Tests of complement function (CD50/AP50)
What can you test to definitively determine cause?
Molecular testing for gene mutations
