Immunocompromised Host Flashcards
Define an immunocompeomised host
A patient who’s immune system is unable to respond appropriately and effectively to infectious microorganisms due to a defect in one or more components of the immune system.
What are the two types of immunodeficiencies
- Primary immunodeficiency : this is congenital ( due to an intrinsic gene defect - which could lead to a missing protein ( eg cytokines ) , missing cell ( B /T cells )
- Secondary immunodeficiency: acquired immunodeficiency as a result of an underlying disease or treatment. For example chemotherapy. And cancer. For example , shingles.
Why is primary immunodeficiency a problem currently ?
Because they are poorly recognised and diagnosed. This is due to the vast array of different defects ( over 350 different mutations).
It is believed that in most cases (60%) , patients will be diagnosed at 18years of age +.
This delay in diagnosis can leave patients with permanent tissue and organ damage (37% often do).
What mneumonic is used to suspect an immunodeficiency patient ?
SPUR
S - severe : can the presenting complaint be life threatening ?
P - Persistent : Does patient not respond appropriately to conventional treatment ?
U - unusual : is the site of infection and type of microbe unusual ? Eg deep tissue infections ( this doesn’t usually happen in someone who is immunocompetent )
R - recurrent : does the patient have more frequent infections than an average immunocompetent person ? For example organ / vagina Candida
What are the 10 warning signs for children who may have a primary immunodeficiency disorder ?
- 4 or more new ear infections within one year
- 2 serious sinus infections within 1 year
- 2 pneumonia’s within one year
- Recurrent , deep skin or organ abscesses
- Failure of an infant to gain weight or grow normally ( failure to thrive)
- Need for IV antibiotics to clear infections
- Persistent thrush in mouth or fungal infections on skin
- A family history of PID
What are the 10 warning signs of primary immunodeficiency in an adult ?
Same as children , but with additional recurrent viral infections such as heroes , colds , warts.
Chronic diarrhoea with weight loss
But instead of 4 or more new ear infections , it is 2 or more.
What is the limitation of the Jeffrey model foundational medical advisory model ? ( 10 warning signs for adults and kids)
- There is a lack of population based evidence to support it ( most acquired through family history , diagnosis of sepsis is treated with IV antibiotics).
- Some patients may have non-infectious manifestations such as autoimmunity , malignancy or inflammatory responses.
- There are different variations of PID with different rates of malignancies.
What laboratory investigations will you carry out if immunodeficiency is suspected ?
- Carry out FBC
- Test humoral immunity ( IgG , IgA, IGM )
- Test for cell mediated immunity ( lymphocyte count )
- Test for phagocytic cells ( neutrophil count , neutrophil function test - oxidative burst eg , adhesion molecule expesssion.
- Test for complement - test for individual components.
- Definitive tests - eg molecular testing and gene mutations.
What is the majority of PID caused by ?
65% of cases are caused by antibody defects
What are 5 examples of antibody deficiencies?
- Defect in B cell development - Bruton’s disease
- Defect in Antibody production : common variable immunodeficiency
- Defect in Antibody production : selective IgA deficiency
- Defect in Antibody production : IgG subclass deficiency
- Defect in Antibody production : hyper IgM syndrome
What is bruton’s disease ?
X-linked recessive condition ( so more boys will be affected than girls )
This is where patients lack B cells so they cannot produce antibodies
What is common variable immunodeficiency? (CVID)
- this is the most common type of PID that requires treatment.
This is where the patient has B cells but they cannot produce any antibodies.
What is IgA deficiency?
This is the most common primary immunodeficiency
90% of patients are asymptomatic and prevalence is between 1 in 100 ton1 in 1000.
These patients only have a slight risk of autoimmune conditions.
The microbes affected will be bacteria because antibodies are required to fight off bacterial infections. The sites mainly affected will be mucosal membranes. If you give a blood transfusion , can make the patient worse because patients with have IgA deficiency tend to have anti-IgA so the blood transfusions contain IgA which the patient will react to. Treatment involves : immunoglobin replacement therapy.
What is Hyper IgM syndrome ?
There is no type switching in B cells meaning IgG is not produced and IgM continues to be produced leading to unusually high levels in the serum.
Immunodeficiency caused by T cell defects represents what percentage of all PIDS? And what are a few examples
15% of all PIDS
Examples include :
1) Severe combined immunodeficiency ( SCID) - if you have a T cell defect , it is likely going to affect B cells too because they won’t be activated.
2) Di George Syndrome : this is where there is an absent of thymus so there is no T cell maturation. This occurs when there is a deletion on chromosome 22q11.2.
Immunodeficiency caused by phagocytise defects represent how much of PID ? And give a few examples
10% of all PID
- Defects in respiratory burst : this is called Chronic Granulomatous disease. This is where phagocytes can engulf and ingest pathogens but not actually kill them
- Defect in fusion of lysosome / phagosome : Chediak - Higashi syndrome
- Defect in neutrophil production and chemotaxis : Cyclic Neutropenia , LAD protein deficiencies
What are the two ways we can try and differentiate between the different types of primary immunodeficiencies ?
- By looking at the age on onset of first symptoms
- Looking at the presentation of infections ( type of microbe and site) as specific presentations are associated with specific defects of components of the immune system.
How can age be used to differentiate between different types of PID ?
- Onset before 6 months old : most likely to be a T cell or phagocyte defect. Not antibody defect because in the third trimester of pregnancy , mothers gives all antibodies to child so they are protected for the first 6 months.
- Onset between 6 months - 5 years : suggests a B cell / antibody , or phagocyte defect.
- Onset after 5 years : most likely to be a B cell / antibody / complement / or secondary immunodeficiency
How can the presentation of the infection be used to distinguish between different types of PID ?
Antibody deficiency : streptococci , staphylococcus , haemophilus influenza , mycoplasma pneumonia , enterovirus ,
T cell defect : similar to antibody defects + intracellular bacteria such as salmonella typhi , non-Tb mycobacterium. Also all viruses because you need cell-mediated immunity to fight off Viruses , Candida , aspergillus , pneumocystis
Phagocytotic defects : staphylococcus aures , non Tb Mycobacteia , Candida , Aspergillus
Complement deficiency: Nisseria , Streptococci , haemophilus influenza , other encapsulated bacteria
What are the three techniques we use to manage PID ?
- Supportive treatmenr
- Specific treatment
- Treatment of co-morbidities
What supportive treatment do we use to manage PID ?
- Infection prevention with the use of prophylactic antimicrobials
- Nutritional support ( Vit A/D)
- Passive immunisation
What specific treatment will be use to treat PID patients ?
- Regular immunoglobin therapy ( IVIG)
2. Hematopoietic stem cell therapy
How to treat co morbidities associated with PIS ?
Avoid non-essential exposure to radiation
Assess organ damage
Treat any autoimmunities and malignancies that may have arisen
What is immunoglobin replacement therapy ? And what conditions is used to treat ?
Goal : increase serum IgG above 8g/L
- Life long treatment , very effective
Conditions used to treat :
1) COmmon variable immunodeficiency
2) brutons disease
3) Hyper IgM syndrome
What are the two classifications of secondary immune deficiencies ?
- Decreased production of immune components
2. Increased loss of immune components
What are causes of decreased production of immune components in secondary immune deficiencies?
Malnutrition ( MAIN CAUSE )
infection ( HIV )
Liver diseases
Haemoralogical malignancies
Therapeutic treatment ( corticosteroids )
Splenectomy ( unable to recognise encapsulated bacteria )
What are causes of increased loss of immune components in secondary immune deficiencies ?
Protei. Losing conditions such as neohropathy , enteropathy
Burns
Why are patients with haemotalogical malignancies or undergone chemotherapy more susceptible to infections?
- This is due to chemotherapy induced neutropenia and damage to mucosal barriers.
Any suspected neutropenic sepsis should be treated as a medical emergency and patient should be given empiric oantibiotic immediately.
What are a couple of examples of common manifestation of secondary immunodeficiency?
Shingles
Candida albicans
Aspergillus
