L16: The immunocompromised Host Flashcards
Why is immunodeficiency an unmet clinical problem?
Large spectrum of PIDs
–> different clinical phenotypes >300 disease
–> update knowledge in medical school/training
–> need for better diagnositic criteria
Failure to recognise and diagnose PIDs
–> 8-12.4 years from onset of symptoms to diagnose
–> >60% of patients will be 18 years old (adults) and older when the diagnosis is made
–> 37% will have permanent tissue/organ damage
Define immunocompromised?
State in which the immune system is unable to respond appropriately and effectively to infectious microorganisms
Defect in one or more components of the immune system
Why is a host immunocompromised?
Primary immunodeficiency: congenital - Intrinsic gene defect- 275 genes --> missing protein --> missing cell --> non-functional components Secondary immunodeficiency: acquired - Due to underlying disease/ treatment --> ↓ production/ function of immune components --> ↑ loss or catabolism of immune components
What components in the immune system can lead to immunodeficiency?
Defect on one or more components of the immune system
Defects in T cells, B cells (antibodies), phagoctyes (macrophages, neutrophils), antigens
When should a patient be considered as potentially immunodeficient?
‘SPURs’
Severe infection–> hospitalisation, IV antibiotics and risk of death
Persistent–> takes a long while to respond to antibiotics
Unusual–> unusual site, type of infection–> opportunistic microogranisms
Recurrent–> Infection keeps coming back
What are opportinuistic microorganisms?
Microorganism that don’t usually cause infection, lay dormant for long periods of time until the immune system is suppressed and then they attack
What are the 10 signs used to recognise and diagnose primary immunodeficiencies in children?
Four or more new ear infections within one year
Two or more serious sinus infections within 1 year
Two or more months of antibiotics with little effect
Two or more pneumonias within 1 year
Failure of an infant to gain weight or grow normally
Recurrent, deep skin or organ abscesses
Persistent thrush in mouth or fungal infection on skin
Need for intravenous antibiotics to clear infections
Two or more deep-seated infections including septicemia
A family history of PID
How does the 10 warning signs to recognise and diagnose PID differ in adults?
Two or more ear infections within 1 year
Two or more new sinus infections within 1 year in the absence of allergy
One pneumonia per year for more then 1 year
Chronic diarrhoea with weight loss
Recurrent viral infections (colds, herpes, wart and condyloma)
Recurrent need for IV antibiotics to clear infections
Recurrent, deep abscesses of the skin or internal organs
Persistent thrush or fungal infection on skin or elsewhere
Infections with normally harmless tuberculosis-like bacteria
A family history of PID
What are the limitations of the 10 warning signs?
General use–> only done in certain populations, lacks population-based evidence
- Family history (only 25%)
- Failure to thrive (T cell defect)
- Diagnosis of spesis treated with IV antibiotics
PID patients with different defect/presentations not represented
- T cells/ B cells/ Phagocyte defects have different presentations
- Infections with subtle presentations
PID patients with non infectious presentation no represented
- Autoimmunity
- Malignancy
- Inflammation response
What causes antibody defects leading to immunodeficiency’s?
65% PIDs
Defect in B cell production/deveopment
Defect in antibody production
What condition leads to defect in B cell development?
X-linked agammaglobulinaemia- Brutons disease
Stop B cells being produced–> No antibodies produced
What conditions leads to defect in antibody production?
Common variable immunodeficiency (CVID) Selective IgA deficiency (IgG subclass deficiency (IgG2)) (Hyper-IgM syndrome--> CD4 ligand mutated cant convert to IgG or IgA etc...)
What is the most common antibody deficiency requiring treatment?
Common variable immunodeficiency
What is the most prevalent antibody deficiency?
Selective IgA deficiency
Asymptomatic–> no symptoms so cannot be treated
What causes T cell defects leading to immunodeficiency’s?
15% PID
Combined B and T cell defects
T cell defects
