The Immunocompromised Host

Question 1

• why is immunodeficiency a difficult problem to diagnose?
• define immunocompromised host.
• describe primary and secondary immunodeficiency.
• when should we suspect an immunodeficiency? Use SPUR.

Answer 1

-different clinical phenotypes, large spectrum of primary immunodeficiencies, need for better diagnostic criteria.
-state in which the immune system is unable to respond appropriately and effectively to infectious microorganisms. Due to defect in one or more components in the immune system.
-primary= congenital, due to intrinsic gene defect eg missing protein or cell or non functional parts
Secondary=acquired, due to underlying disease of treatment ie decreased production of immune cells or increased loss of immune cells eg neutropenia in chemo.
-S=severe, P=persistent, U=unusual, R=recurrent., age at presentation v important, site(s) of infection, family history, type of microorganism.

Question 2

• the 10 warning signs for PIDs can be used to recognise and diagnose PIDs. Give an example and some limitations.
• what are the different ages of symptoms onset and what do they suggest?
• name the 3 different types primary immunodeficiency and describe them.

Answer 2

• 4 or more new ear infections in past year, persistent thrush etc. It’s for general use, lack of population based evidence.
• less than 6 months=t cell or phagocyte defect(bc maternal IgG antibodies persist for first 6 months so must be a T cell problem if before this), 6 months to 5 yrs = B cell-antibody or phagocyte defect, after 5 yrs & later in life= B cell/antibody/complement or secondary immunodeficiency.
  1) caused by antibody defects (65% of cases)-can be a defect in B cell development (X linked, Burton’s disease) or in antibody production (common variable immunodeficiency, selective IgA deficiency, hyper IgM syndrome etc)
  2) caused by T cell defects (15% of cases)-can be just T cell defect (Di George syndrome, MHC II deficiency) or Combined T and B cell defects (SCID-severe combined immunodeficiency).
  3) Phagocytic defects (10% of case)-defects in respiratory burst (chronic granulomatous disease).

Question 3

Example case. A 12 month old boy with four episodes of severe gram-positive bacteria pneumonia in the last six months. He has had recurrent diarrhoea and his tonsils are barely detectable. Below the norm for height and weight. Low IgG, undetectable IgA, IgE and IgM and no B cells. Patient has three healthy sisters aged 3, 5 and 7. the family lost a boy at 10 months old to bacterial pneumonia 8 years ago. What could this be and why?
-A young patient who developed since the age of four weeks multiple staphylococcal abscesses in the chest, skin, face and buttock requiring surgical incision and a course of systemic antibiotics for 10 days.By the age of two he was admitted to the hospital 5 times for staphylococcal infections and pulmonary aspergillosis. Height and weight below average. Three older brothers died of infections at an early age but sisters are healthy. In lab results neutrophils fail to produce oxygen radicals (respiratory burst). What is happening here?

Answer 3

• he’s failed to thrive as he’s smaller than usual, he’s 12 months and symptoms started at 6 months meaning first 6 months he was fine due to protection from mothers IgG supply. His antibodies are undetectable and 4 episodes of the same infection in such a small slave of time means he could,d t develop immunity. He has an antibody deficiency due to lack of B cells to produce them, it’s also X linked therefore must be Burtons disease.
• he is having numerous infections from the same type of bacteria but isn’t developing any type of immunity. He has had a failure to thrive as his height and weight or below average. Seems to be excellent since only the brothers have been affected. There was a problem with respiratory burst indicating that he has a phagocyte deficiency therefore it’s chronic granulomatous disease (CGD)

Question 4

• how are PIDs managed?
• give examples of secondary immune deficiencies. What sorts of patients will be at increased risk?
• what lab tests would you do for IDS?

Answer 4

• supportive=infection prevention, treat infections promptly and aggressively, specific=regular immunoglobulin therapy (lifelong treatment, IgG serum) or stem cell therapy. Consider co morbidities=autoimmunity and malignancies, organ damages
• decreased production=malnutrition, infection eg HIV, liver diseases, splenectomy, therapeutic treatment eg chemo. OR increased loss of immune cells= protein losing conditions eg nephropathy , burns.
• patients w vascular catheters, chemo induced neutropenia, chemo induced damage to mucosal barriers. Treat neutropenia as emergency and assess risk of sepsis.
• suspect Ab/B cell deficiency= IgA, IgG, IgM measure Ab response to test vaccine
• suspect T cell deficiency=lymphocyte count (fbc), in vitro tests of T cell function
• suspect phagocyte deficiency=neutrophil count (fbc), neutrophil functions tests.