clinical- PID Flashcards
What are the main features of a primary immune deficency?
SPUR
Serious infection- unresponsive to antibiotics
Persistent infections- early structural damage/chronic infections
Unusual infections- unusual organism/site
Recurrent infections- two/one major infections which are recurrent in one year
What other signs and symptoms are present in primary immune deficiency?
weight loss
failure to thrive
severe skin rash
mouth ulceration
chronic diarrhoea
cancer
family history of PID
lymphoproliferative disorders
what are the causes of PID?
- inherited
- Treatment via drugs
- Infection:
i. Bacteria
ii. mycobacteria (both Tb and atypical)
iii. fungi (candida, aspergillus)
what is the difference between Primary and secondary immune deficiency?
- secondary more common
- secondary more subtle
- secondary involves more than one component of immune system
what are the upper respiratory complications of PIDs?
- sinusitis
- Otitis media
- Laryngeal angioedema
what are the lower respiratory complications of PIDs?
- malignancies
- ILD
- Pneumonia
- bronchitis
- bronchiectasis
What is Primary antibody deficiency (PAD)?
consists of four main diseases:
- selective IgA deficiency
- Common variable immunodeficiency (CVID)
- Specific antibody deficiency (SAD)
- X linked agammaglobulinemia (XLA)
What are the main signs and symptoms of PAD?
Otitis media
sinusitits
What are the signs and symptoms of laryngeal angioedema?
localised swelling this is generally asymmetric due to increased vascular permeability
what can angioedema cause?
Obstruction and asphyrxiation
angioedema is an allergic reaction true or false?
false
what is the congenital form of angioedema
ii. what is its cause?
hereditary angioedema
c1 esterare inhibitor defects
what is neutropenia?
abnormally low concentration of neutrophils in the blood
major signs of PIDs in children
what is Kostmann syndrome?
rare autosomal recessive disorder causing the specific failure of neutrophil maturation- leads to severe chronic neutropaenia
what is Kostmann syndrome most common form?
SCN1- autosomal DOMINANT
what are the clinical features of Kostmann syndrome?
severe chronic neutropenia
accumulation of precursor cells in the bone marrow
recurrent bacterial/fungal infection (no pus)
within 2 weeks of birth
weight loss
oral ulcers
How do you diagnose Kostmann syndrome
genetic testing: positive for autosomal recessive
How do you treat Kostmann syndrome ( SCN)
G-CSF (granulocyte colony-stimulating factor) increases neutrophil count
What is Leukocyte adhesion deficiency?
very rare autosomal recessive PID
caused by genetic defect in CD18 intergrin gene
What does Leukocyte adhesion defiency cause?
impaired migration causes
blocked migration from blood to site of infection
reduced uptake and degradation of opsonised bacteria
How do you manage LAD?
Hematopoietic stem cell transplant
prophylactic antibiotics
What is chronic granulomatous disease?
Defiency of the intracellular killing mechanism of phagocytes
causes inability to clear organisms and an excess inflammation
What are the clinical features of CGD?
Recurring deep bacterial infections (staph, aspergillus, pseudomonas cepacia)
recurrent fungal infections
failure to thrive
lymphadenopathy and hepatosplenomegaly
granuloma formation
What are the main ways to manage a PID?
- Immunoglobulin replacement therapy
- aggressive management of infection:oral/IV antibiotics and anti fungals
- surgical draining of abscesses
- definitive therapy ( haematopoietc stem cell transplantation and gene therapy)
what are the main PIDs associated with respiratory complications in children?
- transient hypogammaglobulinaemia of infancy- should be fine after supportive therapy
- X-linke agammaglobulinemia
- severe combined immunodeficiencies (SCID)
what are the classical features of SCID?
- unwell by 3 months of age
- persistent diarrhoea
- failure to thrive
- multiple recurring infections (all types) - can have vaccine associated diseases
- unusual skin disease ( graft versus host disease e.g. when infants bone marrow is colonised by maternal lymphocytes)
- family history of early infant death
What are the main causes of SCID?
- pathways ( deficiency of cytokine receptors or deficiency of signalling molecules)
- presence of different lymphocyte subsets (T,B,NK) depend on exact mutation
What is X-linked SCID?
most common form of SCID
mutation of a component of the IL-2 receptor- causes failure of T cell and NK development. Leads to production of immature B cells
what are the clinical features of X-linked SCID?
- very low or absent T cell count
- Normal or increased B cell count
- poorly developed lymphoid tissue and thymus
How do you manage SCID?
- prophylactic treatment
avoid infections
give prophylactic antibiotics
prophylactic antifungals
no live attenuated vaccines
antibody replacement
- definitive treatment
stem cell transplant from HLA identical sibling if possible
- Gene therapy
if lymphoid cells dysfunctional stem cells can be treated ex vivo to express missing component
What occurs in x-linked hypogammaglobulinaemia?
Mutation leading to deficiency in Bruton tyrosine kinase gene which is essential for B cell development
this causes
- No circulating B cells
- no plasma cells
- no circulating antibody after first 6 months
