Immunocompromised Host Flashcards
What is the most common. Form of antibody deficiency
Cvid
Define immunocompromised
– “State in which the immune system is
unable to respond appropriately and effectively to infectious microorganisms”
– Due to defect in one or more components of
the immune system….
What is primary immunodeficiency
Primary immunodeficiency: congenital
• Due to intrinsic gene defect (~275 genes)
• Missing protein
• Missing cell - eg no T cells bc certain t proteins lacking, = immune uysstem dead
• Non-functional components
What is secondary immunodeficiency
Secondary immunodeficiency: acquired
• Due to an underlying disease/treatment
• ↓ Production/function of immune components
• ↑ Loss or catabolism of immune components
Malnutrition is the most common cause
When to suspect an immunodeficiency?
The infection is
– S severe (death if not treating, life threatening)
– P persistent (patient does not respond to conventional antimicrobial therapy, or you have to use longer duration to achieve affect)
– U unusual (unusual site, the of microbe - certain ones should not give infection in certain places, opportunistic microbes)
– R recurrent (keeps coming back)
What are some warning signs of PID in children
-
What are some of the warning signs o pid in adults
0
What are the limitations of the 10 warning signs?
General use: Lack of population-based evidence*
- Family history (25% of cases)
- Failure to thrive
- Diagnosis of Sepsis treated with IV antibiotics
PID patients with different defects/presentations
- T cells/ B cells/ Phagocytes/ complements
- Infections with a subtle presentation
PID patients with non-infectious manifestations
- Autoimmunity
- Malignancy (4-25% - importance of early diagnosis)
- Inflammatory responses
What does the age of onset suggest
• Onset < age 6 months highly suggests a T-cell or
phagocyte defect.
• Onset > 6 months and <5 years old often suggests a B-cell/antibody or phagocyte defect .
• Onset >5 years old and later in life usually suggests a B-cell/antibody/complement or secondary immunodeficiency.
What does the type of microbe suggest
Complement deficiency
• Pyogenic infections (C3)
• Meningitis /Sepsis/Arthritis (C5-C9)
• Angioedema (C1 inhibitor)
Phagocyte defect
• Skin/mucous infections
• Deep seated infections
• Invasive fungal infection (aspergillosis)
Antibody deficiency • Sinorespiratory infections (upper resp tract) • Arthropathies • GI infections • Malignancies • Autoimmunity
T cell defect - susceptible to almost anything • Death if not treated • Failure to thrive • Deep skin and tissue abscesses • Opportunistic infections
Describe the presentation of cod
See slide
Describe teh management of primary immunodeficiency diseases
Supportive treatment
• Infection prevention (prophylactic antimicrobials)
• Treat infections promptly and aggressively (passive immunization)
• Nutritional support (Vitamins A/D)
• Use UV-irradiated CMVneg blood products only
• Avoid live attenuated vaccines in patients with severe PIDs (SCID)
Specific treatment
• Regular Immunoglobulin therapy (IVIG or SCIG)
• SCID: Hematopoietic Stem Cell therapy (HSCT, 90% success)
Comorbidities
• Autoimmunity and malignancies
• Organ damages (lung function assessment)
• Avoid non essential exposure to radiation
What is immunoglobulin replacement therapy
Goal
• Serum IgG > 8g/l
• Life long treatment
Different formulations
• IvIg
• ScIg (young patients)
Conditions
• CVID
• XLA (Bruton’s disease)
• Hyper-IgM syndrome
What are secondary immune deficiencies
• Decreased production of immune components
– Malnutrition
– Infection (HIV, see group work)
– Liver diseases
– Lymphoproliferative diseases
– Splenectomy
» Causes: infarction (eg sickle cell anaemia), trauma, autoimmune haemolytic disease, infiltration (tumour), coeliac disease, congenital
What s the function of the spleen
Immune function - immune reaction against ll microbes in the body
– Bloodborne pathogens
» Encapsulated bacteria!
– Antibody production
» Acute response : IgM production
» Long term protection: IgG production
– Splenic macrophages
» Removal of opsonized microbes
» Removal of immune complexes
Describe the presentation and management of asplenic/splenectomised patient
Presentation
• ↑ susceptibility to encapsulated bacteria Haemophilus influenzae,
Streptococcus pneumoniae and Neisseria Meningitidis
• OPSI (overwhelming post-splenectomy infection) ⇒ sepsis and meningitis (1-2% risk of death over 15 years)
Management
• Penicillin prophylaxis (life-long)
• Immunisation against encapsulated bacteria
• Medic Alert bracelet
Why might patients with haematological malignancy become immunocompromised and how should they be tratead
Increased susceptibility to infections
• Chemotherapy-induced neutropenia
• Chemotherapy-induced damage to
mucosal barriers
• Vascular catheters
- Treat suspected neutropenic sepsis as an acute medical emergency and offer empiric antibiotic therapy immediately.
- Assess patient’s risk of septic complications
What happens to immune components in secondary immune deficiencies
• ↑ loss or catabolism of immune components – Protein-losing conditions • Nephropathy • Enteropathy – Burns
What should be looked at to recognise IDs
The pattern and type of infections always
reflect the nature of immunological defect
– Age - at presentation
– Sex – Site(s) and frequency of infection(s)
– Type of organism(s)
• Viruses and fungi ⇒ T cell deficiency
• Bacteria and fungi ⇒ B cell/granulocytes deficiency – Sensitivity and type of treatment (surgery)
– Family history
What are lab tests for IDs
Look for secondary immunodeficiency General
• Full blood count and differential Tests of humoral (antibody) immunity
• IgG, IgA, IgM (+/- IgE)
• IgG1-4 subclasses
• IgG levels to specific previous vaccines
- tetanus toxoid/HiB/pneumococcus, MMR
- measure antibody in response to test immunisation
Tests for Cell mediated immunity
• Lymphocyte count (FBC)
• Lymphocyte subset analysis (CD4+, CD8+ T, NK & B cells) extended marker panel(s)
• in vitro
tests of T cell function Tests for phagocytic cells
• Neutrophil count (FBC)
• Neutrophil function tests (eg oxidative burst for CGD)
• Adhesion molecule expression (for LAD)
Tests for Complement
• Individual components
• Tests of complement function (CH50 /AP50)
Definitive tests – molecular testing and gene mutations
