Lecture 8.1 - The immunocompromised host.pdf

Definition of immunocompromised host: ◦"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 Types of immunodeficiencies: ◦Primary immunodeficiency ◦Seconda...

Definition of immunocompromised host: ◦"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 Types of immunodeficiencies: ◦Primary immunodeficiency ◦Secondary immunodeficiency Primary immunodeficiency: ◦Over 100 primary immune deficiency diseases ‣ Intrinsic or congenital defect ‣ Single gene defect (X chromosome linked) ‣ Passed on from generation to generation ‣ Random error during development (genetic mutations) ◦Problems with: ‣ B cells -> reduction in antibody production ‣ T cells -> reduction in Cytotoxic and helper T cells ‣ Both B and T cells ‣ Complement (opsonins, perforins etc) ‣ Phagocytes/phagocytosis -> control of infections is now not efficient Age of onset for primary immunodeficiency disease (PID): Secondary immunodeficiency: ◦Acquired - caused by a number of factors: ‣ Malnutrition - e.g. Zinc important in maturation of B and T lymphocytes) ‣ Stress ‣ Cancer (cancer itself or side effect of chemotherapy) ‣ Side effect (corticosteroids, chemotherapy, surgery, anaesthetics) ‣ Infection (HIV) How is a host immunocompromised?: ◦Primary immunodeficiency - congenital ‣ Due to intrinsic gene defect Missing protein  Missing cell Non-functional components ◦Secondary immunodeficiency - acquired ‣ Due to an underlying disease/treatment HIV Chemotherapy Immunodeficiency is caused by one or more components of the immune system: Immunodeficiency caused by antibody defects: ◦B cells may not work properly, may not carry out its function or may not be fully developed. ‣ Therefore, production of the wrong antibodies or no antibodies at all, so the B cell is defective ◦IgA is found in the mucous membranes of the body. IgA deficiency is associated with autoimmune diseases Immunodeficiency caused by T cell defects: Immunodeficiency caused by defects in phagocytosis:  Malignancies in primary immunodeficiency disorders: When to suspect immunodeficiency: ◦Infections suggesting underlying immune deficiency defined as "SPUR": ‣ S -> severe ‣ P -> persistent ‣ U -> unusual ‣ R -> recurrent The 10 warning signs of PIDs (primary immunodeficiency diseases): Limitations of the 10 warning signs: ◦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 ‣ Inflammatory responses Primary immunodeficiency disease - types of organisms causing infection:  Management of PIDs: ◦Supportive treatment ‣ Infection prevention (prophylactic antimicrobials) ‣ Treat infections promptly and aggressively ‣ Nutrition support ‣ Use UV-irradiated CMV negative blood products only -> CMV was common in liver transplants, but is now rare ‣ Avoid live attenuated vaccines in patients with severe PID (SCID) ◦Specific treatment ‣ Regular immunoglobulin therapy (IVIg or SCIg) ‣ SCID: Haematopoietic stem cell therapy (HSCT, 90% success) ◦Comorbidities: ‣ Autoimmune disease and malignancies ‣ Organ damage (lung function assessment) ‣ Avoid non-essential exposure to radiation Immunoglobulin replacement therapy: ◦Goal: ‣ Serum IgG > 8g/l ‣ Life long treatment ◦Different formulations: ‣ IvIg ‣ ScIg (young patients) ◦Conditions: ‣ CVID (common variable immunodeficiency is a primary immune deficiency disease characterised by low levels of protective antibodies and increased risk of infections ‣ XLA (Bruton's disease - X-linked agammaglobulinemia is an inherited immunodeficiency disorder characterised by the absence of mature B cells which in turn leads to severe antibody deficiency and recurrent infections ‣ Hyper-IgM syndrome (a group of rare primary immunodeficiency disorders characterised in some patients by abnormally high levels of immunoglobulin IgM. However, many affected individuals have normal levels of IgM Why is immunodeficiency an unmet clinical problem?: ◦Large spectrum of immunodeficiencies: ‣ Different types of diseases ‣ Needed for better awareness in medical school/training ‣ Need for better diagnostic criteria ◦Failure to recognise and diagnose ‣ 1-25 years from the onset of symptoms to diagnosis for primary immunodeficiency diseases ‣ > 60% of patients will be 18 years old or older when diagnosis is made ‣ >40 % of them will have permanent tissue/organ damage by the time they are diagnosed Secondary immunodeficiencies: ◦Decreased production of immune components: ‣ Malnutrition ‣ Infection (HIV)  ‣ Liver diseases ‣ Haematological malignancies ‣ Therapeutic treatment (corticosteroids, cytotoxic drugs) ‣ Splenectomy ◦Increased loss of immune components: ‣ Protein-losing conditions (nephropathy, enteropathy) ‣ Burns Immunodeficiency due to HIV infection: Patients with haematological malignancies: ◦Increased susceptibility to infections: ‣ Chemotherapy-induced neutropenia ‣ Chemotherapy-induced damage to mucosal barriers ‣ Vascular catheters (Hickman line) ◦Suspected febrile neutropenia: ‣ Must be treated as an acute medical emergency ‣ Patients must be given empiric antibiotic therapy immediately ‣ If untreated, patients are under risk of septic complications Recognition and diagnosis of immunodeficiency diseases: Laboratory investigation of immunodeficiency: