Infection Session 10 Flashcards
How long is the delay between onset of symptoms and diagnosis of immunodeficiency which causes high morbidity and mortality?
7-9 years
What proportion of pts are diagnosed with immunodeficiency at 18 years or older?
> 50%
What percentage of immunodeficiency pts will have permanent tissue/organ damage as a result of being ID?
37%
What is the definition of an immunocompromised host?
State in which the immune system is unable to respond appropriately and effectively to infectious micro organisms
What is a qualitative immunocompromised host?
One defect of component of immune system e.g. HIV causing decreased CD4+ cells
What is a quantitative immunocompromised host?
More than one component of immune system defective
What does SPUR stand for in recognition and diagnosis of ID?
Severe (life threatening)
Persistent - despite Tx
Unusual - site of infection and causative organism
Recurrent
What is primary ID?
Inherited intrinsic defect of the immune system
What is secondary ID?
Underlying disease or condition affects immune components
Is primary or secondary ID more common?
Secondary
How are primary ID classified?
According to which immune component is defective
Which immune component defect causes the majority of primary ID?
B cell
Why do primary ID manifest in the first moths of life?
Intrinsic defects
What is the most common primary ID needing Tx?
Common variable ID where B cells don’t form plasma cells
Under what circumstance is IgA deficiency symptomatic?
If B cells don’t form IgA and there is an IgG subclass deficiency due to an unknown defect
What causes Bruton’s disease?
Impaired B cell development due to lack of enzyme
What is Hyper-IgM syndrome?
Defective CD40 ligand on activated T cells means IgM -X-> IgG so the IgM cannot enter tissues
What inherited intrinsic defects can cause primary ID?
Single gene defect
Polygenic
HLA polymorphisms
How does an underlying disease/chronic condition affect immune components?
Decreased production
Increased loss
Increase in catabolism
How do pts with primary antibody deficiencies present?
Recurrent bacterial URTI and LRTI
GI complications (inc. Giardia infection)
Arthropathies
Increased incidence of autoimmune disease
Increased incidence of lymphoma and gastric carcinoma
How are primary ID pts managed?
Prompt/prophylactic Abx
IRT (best Tx)
Manage resp infections and avoid unnecessary radiation
Give some examples of phagocyte deficiencies.
Cyclic neutropenia
Leukocyte adhesion deficiency
Chronic granulomatous disease
Chediak-Higashi syndrome
What happens to neutrophil number in cyclic neutropenia?
Decreases every 3/4 weeks
How do pts with phagocyte deficiencies present?
Ulcers of skin and mucous membranes Osteomyelitis Deep abscesses Invasive pulmonary aspergillosis Granulomas
What is a halo sign, seen on HRCT?
Alveolar haemorrhage, seen in invasive pulmonary Asperigllosis
How are pts with phagocyte deficiencies managed?
Prophylactic Abx, antifungals and immunisations
Surgery
Interferon-g and steroids for CGD
Stem cell transplant
What is Di George syndrome?
Lack of thymus
What defects can cause severe combine immunodeficiency?
Stem cells defects or death of developing thrombocytes
What disease is caused by defective genes for TCR rearrangement and T cell maturation?
Severe combined immunodeficiency and Omenn’s syndrome
How do pts with severe combined immunodeficiency present?
Failure to thrive
Deep skin and organ abscesses
Decreased lymphocyte count
Increased susceptibility to bacterial, fungal and viral infections
How are pts with severe combine immunodeficiency managed in the short and long term?
Short term: no live vaccines, irradiated blood products, aggressive Tx of infections and infection prevention inc. IRT
Long term: BM or stem cell transplant, gene therapy
What is the outcome of an opportunistic infection is left untreated in a pt with severe combine immunodeficiency disease?
Death
What complement deficiency is associated with recurrent bacterial infection?
C3
What can cause decreased production of immune components in secondary ID?
Malnutrition Infection Liver disease Lymphoproliferatife disease Splenectomy
What action does the spleen take against bloodborne pathogens?
Opsonises encapsulated bacteria
What antibody production function is the spleen involved in?
Acute response: IgM production
Long term protection: IgG production
Why might a pt need a splenectomy?
Sickle cell anaemia --> infarction Coeliac disease --> infarction Infiltration by tumour Autoimmune haemolytic disease Trauma
How will an asplenic pt present?
With encapsulated infections
Overwhelming post-splenectomy infection –> sepsis and meningitis
How are asplenic pts managed?
Life-long penicillin prophylaxis
Immunisation against encapsulated bacteria
Medic alert bracelet
Why are pts w/haematological malignancy more susceptible to infections?
Chemo-induced neutropenia
Chemo-induced damage to mucosal barriers
Insertion of vascular catheters used for Tx
What should neutropenic sepsis be treated as and how?
Acute medical emergency
Immediate empiric Abx and assess septic complication risk
How does liver disease cause secondary ID?
Decreased synthesis of complement and cytokines
What can a cause increased loss or catabolism of immune components in secondary ID?
Protein losing conditions such as nephropathy, enteropathy or burns
What are immunodeficiencies importantly associated with?
Increase in frequency and severity of infections
Autoimmune diseases
Malignancy
What will the pattern and type of infections seen in ID always reflect?
Immunological defect
What lab investigation approaches can be used in secondary ID?
FBC Test humoral immunity Test cell-mediated immunity Test for phagocytic cells Test for complement components and function Molecular testing Gene mutations
What definitive tests can be used in investigation of secondary ID?
Molecular testing
Gene mutations
Why should tonsils and adenoids be large in infection?
They consist mainly of B cells
What type of ID do recurrent viral and fungal infections indicate?
T cell deficiency
What type of ID do recurrent bacterial and fungal infections indicate?
B cell/ granulocyte deficiency
What might a pt with primary ID not present until aged 6 months?
Has some protection from maternal IgE antibodies
