The Immunocompromised Host

Question 1

Immunocompromised host

Answer 1

Many patients will come into hospitals saying - I’ve had symptoms for as long as I can remember

E.g. In childhood, repeated episodes of ear infections, colds and mouth sores

In adulthood, was overall OK but experienced severe infections : ear infection (worst one), brain abscess (surgery), meningitis (hospitalized)

Diagnosed in 2014 at age 33 with CVID* Jonathan, 35 yo
Today, symptoms free because of intravenous Immunoglobulin (IVIG) therapy

Question 2

Why is immunodeficiency an un,et clinical problem

Answer 2

Large spectrum of PIDs (primary immuno-deficiencies)
Different clinical phenotypes (>300 diseases)
Update knowledge in medical school/training
Need for better diagnostic criteria

Failure to recognize and diagnose PIDs*
8-12.4 years from onset symptoms
>60% of patients will be 18 years old and older when diagnosis is made
37% of them will have permanent tissue/organ damage

Question 3

Definition of immunocompromised hose

Answer 3

Wha

Question 4

Recognition and diagnosis of Primary immuno-deficiency in kids and adults

Answer 4

For kids -

1) 4 or more new ear infection in a year
2) 2 or more serious sinus infections in a year
3) 2 or more months on antibiotics with little affect
4) 2 or more pneumonias in a year
5) Failure of infant to grow or gain weight
6) Recurrent deep skin/organ abscesses
7) Persistent thrush in mouth
8) Need for IV antibiotics to clear infections
9) Family history of PID
10) 2 or more deep seated infections including septicaemia

For adults -

1) 2 or more ear infections in 1 year
2) 2 or more new sinus infections in 1 year
3) 1 pneumonia per year for more than a year
4) chronic diarrhoea with weight loss
5) recurrent viral infections (colds, herpes, warts)
6) Recurrent need for IV antibiotics to clear infections
7) Recurrent deep abscesses of skin or internal organs
8) persistent thrush on skin or elsewhere
9) infection with normally harmless TBlike bacteria
10) family history of PID

Limitations of the “

Question 5

Immunodeficiency cause by antibody defects account for ~65% of all PIDs

Answer 5

Can be a defect in the B cell development - e.g. X-linked agammaglobulinaemia (Brutons’s disease)

Or can be a defect in the antibody production from B cells - 
E.g. Selective IgA deficiency 
	IgG subclass deficiency 
	Hyper IgM syndrome 

Or Can be combined B and T cell defects -
E.g. Severe combined immunodeficiency (SCID)
Wiskott-Aldrich syndrome

Or can be T cell defects - 
E.g. CD3 deficiency
	MHC class 2 deficiencies - no helper CD4+ cells 
	Thymus deficiency - T cells dont mature

Question 6

Immunodeficiency caused by phagocytic defects: ~10% of all PIDs

Answer 6

Defects in respiratory burst - Chronic granulomatous disease (CGD)

Defect in fusion of lysosome/phagosomes - Chediak-Higashi syndrome

Defect in neutrophil production and chemotaxis -Cyclic neutropenia and LAD protein deficiencies

Question 7

Presentation of primary immunodeficiency diseases - age of symptom onset could indicate what part of the immune system is affected

Answer 7

Onset < age 6 months highly suggests a T-cellular 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.

Question 8

Presentation of primary immunodeficiency disease - types of common microbes you would get

Answer 8

E.g. For bacteria - may get neisseria meningitis, Staph aureus, strep

For virus - enterovirus

For fungi - Candida albicans (thrush) or aspergillus

For Protozoa - Taxoplasma gondii

Recurrent severe infections of these would indicate immune problems

Question 9

Management of PIDs

Answer 9

Supportive treatment -
Infection prevention (prophylactic antimicrobials)
Treat infections promptly and aggressively (passive immunization)
Nutritional support (Vitamins A/D)
Use UV-irradiated CMVnegblood 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

Question 10

Immunoglobulin replacement therapy

Answer 10

Goal
To get a Serum IgG (specific to disease antibody) > 8g/l
Its a Life long treatment

Different formulations
IvIg
ScIg (young patients)

Conditions
Can treat CVID, XLA (B

Question 11

Secondary immune deficiencies

Answer 11

Decreased production of immune components - due to
Malnutrition
Infection (HIV)
Liver diseases
Haematologicalmalignancies
Therapeutic treatment (corticosteroids, cytotoxic drugs)
Splenectomy

Increased loss of immune components
Protein-losing conditions (Nephropathy, Enteropathy)
Burns

Patients with haematological malignancies - Increased susceptibility to infections - e.g.
Chemotherapy-induced neutropenia (lack of neutrophils)

Chemotherapy-induced damage to mucosal barriers

Vascular catheters - due to constant bacteria access to blood

Treat suspected febrile neutropenia as an acute medical emergency and offer empiric antibiotic therapy immediately. - assess patients risk of septic complications