Immunodeficiencies Flashcards
How can you recognise patients who are immunocompromised?
S - severe ie life threatening
P - persistent
U - unusual - opportunist pathogens
R - recurrent
Define immunocompromised
State in which immune system is unable to respond appropriately and effectively to infectious microorganisms
Features of a primary immunodeficiency?
Caused by an intrinsic (immune defect)
Congenital or acquired
Relatively rare
Features of secondary immunodeficiencies?
Relatively common
Secondary to another condition
Acquired
What can a secondary immunodeficiency be caused by?
Infection (HIV) Malnutrition Liver disease Splenectomy Drug-induced neutropenia Lymphoproliferative diseases
What is neutropenia?
Abnormally low neutrophils in the blood, leading to increased susceptibility to infection
What can cause neutropenia?
Drugs Autoimmune neutropenia Bone marrow infiltration with malignancy B12/folate/iron deficiency Chemo-cytotoxic/immunosuppressant Chemical agents Radiotherapy
Management of suspected neutropenic sepsis?
Treat as acute medical emergency
Empiric antibiotics immediately
Assess risk of septic complications
What are asplenic patients more susceptible to? Give examples
Encapsulated bacteria
H influenzae
Streptococcus pneumoniae
N meningitidis
What are asplenic patients more at risk of?
Overwhelming post-splenectomy infection
-sepsis and meningitis
What do asplenic patients have to have?
Lifelong penicillin prophylaxis
Immunisation against encapsulated bacteria
Medical alert bracelet
What does the spleen do?
Immune function against blood-borne pathogens
Antibody production
- acute response: IgM
- long-term protection: IgG
Splenic macrophages
- remove opsonised microbes
- remove immune complexes
What can cause loss of catabolism of immune components and the fore secondary immunodeficiency?
Protein losing conditions eg nephropathy, enter ovary
Burns
What can primary immunodeficiencies be classified into?
B cell (50%)
Phagocytes (18%)
T cell (30%)
Complement (2%)
When are primary deficiencies normally seen?
First few months of life
What are the B cell deficiency types?
Common variable immunodeficiency (CVID)
IgA deficiency
Bruton’s disease (X-linked agammaglobulinaemia)
What is common variable immunodeficiency?
Inability of B cels to mature into plasma cells.
Low IgG
How does IgA deficiency happen?
B cells are unable to switch to IgA
What is Bruton’s disease?
Impaired B cell development
Present in first 6 months
What are people with Bruton’s disease at increased risk of?
Streptococcus pneumoniae
Mycoplasma amphoriforme
Non-capsulated Haemophilus influenzae
What is hyper IgM syndrome?
CD40 ligand on activated T cells prevents them from switching from IgG to IgM
Therefore keep making IgM
Presentation and management of patients with primary antibody (B cell?) deficiencies?
Recurrent upper and lower respiratory bacteria infections causing bronchiectasis
GI complications including infections
Anthropathies (joints - including Mycoplasma spp and Ureaplasma spp)
Increased incidence of autoimmune disease
Increased incidence of lymphoma and gastric carcinoma
Management of primary antibody deficiencies?
Prompt/prophylactic antibiotics
Immunoglobulin replacement therapy (gold standard)
Management of respiratory function - physiotherapist
Avoid unnecessary exposure to radiation eg CT scan
Goal of immunoglobulin replacement therapy?
Serum IgG > 8g/L
Life long
What is immunoglobulin replacement therapy given for?
CIVD
XLA (Bruton’s)
Hyper-IgM syndrome
What are some clinically important phagocyte deficiencies?
Cyclic neutropenia - cause unknown
Leukocyte Adhesion deficiency
Chronic granulomatous disease
CH syndrome
What is leukocyte adhesion deficiency?
Lack of CD18 protein on phagocytes - defects adhesion to endothelium
What is chronic granulomatous disease?
Lack of respiratory burst
What is CH syndrome?
Failure of phagolysosome formation
Presentation of phagocyte deficiencies?
Prolonged and recurrent infection
- ulcers
- osteomyelitis
- deep abscesses
- commonly staphylococcal (catalase positive)
- invasive aspergillosis
- inflammatory problems
Management of phagocyte deficiencies?
Prophylactic antibiotics and antifungals
Immunisation
Surgical management
Stem cell transplantation
Clinically important T cell deficiencies?
DiGeorge syndrome
Severe combined immunodeficiency
What is DiGeorge syndrome caused by?
Defect in thymus embryogenesis and incomplete development
Signs and symptoms of DiGeorge syndrome?
Cardiac abnormalities Abnormal face (low ears, wide eyes) Thymic hypoplasia Cleft palate Hypocalcaemia
22 - chromosome abnormality
Management of DiGeorge syndrome?
Neonatal cardiac surgery
Correct hypocalcaemia
Low T cell number
Bone marrow transplant
Presentation of SCID?
Failure to thrive Long term antibiotic therapy Deep skin and organ abscesses Low lymphocyte count High susceptibility to fungal and viral infections
Management of SCID?
Antibiotics and prevention
IV Ig
Long term
- bone marrow/stem cell transplant
- gene therapy
Where can Aspergillus be found?
Soil
AC systems
What can Aspergillus do in immunocompromised patients?
Breathed into upper respiratory tract
Causes invasive aspergillosis
Starts in lungs and may involve other organs through haematogenous spread
Why is Aspergillus difficult to fight?
Combination of low neutrophils (caused by immunodeficiency) and toxic metabolites produced by the fungi
Symptoms of Aspergillus?
Cough Fever Shortness of breath Pleuritic chest pain Haemoptysis Nasal congestion Pain
What is Aspergillus treated with?
Amphotericin
Echinocandin derivatives
