Infection S10 (Will not be completed) Flashcards
Why are immunodeficiencies important to recognise in clinical practice?
Associated with:
Increased frequency and severity of infections
Autoimmune disease and malignancy
Failure to recognise leads to increased morbidity and mortality
37% of immunodeficient patients will have permanent tissue/organ damage
Define ‘Immunocompromised host’
State in which the immune system quantitatively or qualitatively defective and hence is unable to respond appropriately and effectively to infectious micro-organisms
What key components of the immune system are commonoly affected by immune deficiency?
Innate:
Innate barriers
Phagocytes
Complement
Adaptive:
B Cells
Antibodies
T Cells
What features of infections may suggest an underlying immune deficiency?
SPURS:
Severe
Persistent
Unusual (microbe or site)
Reccurent
What organisms or infection sites might be suggestive of immune deficiency?
Organisms:
Natural commensals
Sites:
Deep skin/organ infections (often ulceration present)
Contrast Primary and Secondary Immunodeficiency (ID)
Primary:
Intrinsic defect
E.g. Single gene disorders, polygenic disorders or defective HLA polymorphisms
Secondary:
Underlying disease affection immune components
Either lack of production of immune factors or increased loss or catabolism
How do we classify Primary IDs?
Classified by which immune component is affected:
B Cell (50%)
T Cell (30%)
Phagocytes (18%)
Complement (2%)
What is the prevalence of Primary IDs?
How are patients distributed across age and gender?
1:400 to 1:400,000 depending on disease
80% of Patients <20yrs at onset:
Often onset is in first few months of life
70% Male:
Often X-Linked defects
What are the 10 major warning signs for Primary IDs?
4+ new ear infection/yr
2+ new serious sinus infections/yr
2+ months of antibiotic treatment with little effect
2+ pneumonias/yr
Failure to thrive
Reccurent deep skin/organ abscesses
Persistent buccal thrush or fungal skin infections
Need for IV antibiotics to clear infections
2+ deep seated infections (incl. septicaemia)
Family history of PID
Give 2 B Cell deficiencies
For each give the defect, when they present and important serological findings
Common variable immunodeficiency (CVID):
Inability of B cells to mature to plasma cells
Can present at any stage of life
IgG < 5g/l
IgA/M variable
Bruton’s Disease (X-Linked agammaglobulinaemia):
Impaired B cell development
Generally presents in first year of life
IgA < 2g/l
IgA undetectable
Low B cells
How might a patient with Primary ID present?
Any of the below:
With reccurent upper and lower resp infections (bacterial infections can lead to bronchiectasis)
With GI complications including infections (Giardia)
With an Arthropathy (Mycoplasma/Ureaplasma spp.)
With an Autoimmune disease (increased incidence)
With lymphoma or gastric carcinoma (+50% risk with CVID)
How might a patient with Primary ID be managed?
Primary:
Prompt/prophylactic antibiotics
Ig replacement therapy
Accessory:
Management of resp function
Avoidance of radiation exposure (reduce cancer risk)
Describe a typical presentation of a patient with CVID
Any age
Reccurent bacterial infections (Esp. URTI/LRTI)
May be associated with autoimmune disease
Some have granulomatous disease
Generally no family history of CVID
Low IgG
Variable IgA/IgM (Normally low, pan-hypogammaglobulinaemia)
What is the goal of effective Ig replacement therapy (IRT)?
What conditions is it useful for?
How long is a treatment course of IRT?
Serum IgG <8g/l
Conditions:
CVID
XLA (Bruton’s)
Hyper-IgM syndrome
Treatment length:
Lifelong
Give 3 examples of important primary phagocyte deficiencies, give the defect seen in each
Leukocyte adhesion deficiency:
Lack of CD18 protein on phagocytes that prevent adhesion to epithelium
Chronic granulomatous disease (GCD):
Difficulty forming ROS impairing oxidative burst and intracellular killing of ingested pathogens
Chediak-Higashi Syndrome:
Failure of phagolysosome formation leading to a lack of effective phagocytosis
How might a patient with primary phagocyte deficiency present?
Prolonged reccurent infections, for example:
Catalase +ve staphyloccocal infection:
- Skin and mucous membrane ulcers*
- Osteomyelitis*
- Deep abscesses*
Invasive aspergillosis
Inflammatory problems (granuloma formation)
How might a patient with primary phagocyte deficiency be managed?
Prophylactic antibiotics/anti-fungals/immunisation
Surgical mangement
Interferon-G (CGD specific)
Steroids (CGD specific)
Stem cell transplantation (Potential cure)
Describe the presentation of a patient with CGD
Pulmonary aspergillosis
Skin infections where scarring occurs at infection site
List 2 important primary T cell deficiencies and briefly state their cause
Di George syndrome:
Lack of thymus (defect in embryogenesis)
Severe combined immunodeficiency (SCID):
Stem cell defect
Or
Death of developing thymocytes (haemopoietic progenitor cells that develop into T cells)
Describe the common features of Di George Syndrome
What is the prevalence?
CATCH-22:
Cardiac abnormalities
Abnormal facial features
Thymic hypoplasia
Cleft palate
Hypocalcaemia
22 is the chromosome abnormality
Prevalence:
1:4000 live births
How might someone with DiGeorge syndrome be managed?
Neonatal cardiac surgery
Supplements to correct hypocalcaemia
Depending on immune defect:
If <0.4x10^9/l T cells then pneumocystis pneumonia prophylaxis (antibiotics)
Severe forms requires bone marrow transplant
No Live vaccines (BCG, MMR, Oral Polio)
How might a patient with SCID present?
Failure to thrive (seen in young children)
Long term antibiotic therapy patient
Deep skin/organ abscesses
Low lymphocyte count (<4.0 - 10.0/ul)
High susceptibility to all infections, particularly fungal and viral infection:
- Pneumocystis pneumonia*
- Varicella zoster virus*
- CMVs*
- Epstein Barr virus*
Describe the management of a patient with SCID
Short term:
No Live vaccines
Only irradiated CMV- blood products
Aggressive infection treatment
Prophylactic antibiotics/antifungals
IV Ig Therapy
Long term:
Bone marrow transplant/Stem cell transplant
Gene therapy
What are the possible categories of dysfunction seen in patients with complement component deficiencies?
For each, give the complement component(s) that might be deficient
Immune complex disease:
C1
C2
C4
Reccurent bacterial infections:
C3
Reccurent nesserial infections
C5-9
D, B, P
