Session 10 Immunocompromised Host Flashcards
Why should you care as a doctor?
- Immunodeficiency is associated with an increase in the frequency and severity of infections (more aggressive and life-threatening).
- Immunodeficiency is associated with autoimmune diseases and malignancy
- Failure to recognize and diagnose leads to increased morbidity and mortality.
- Average 7-9 years between the onset of symptoms and diagnosis. >50% of patients will be 18 years old and older when diagnosis is made. 37% of them will have permanent tissue/organ damage – delay in diagnosis associated with worse prognosis and high mortality.
- Studies have found that immunocompromised patients have increased mortality due to non-infectious complications e.g. GI disease, liver disease, lymphoma etc.
Describe how to recognise and fiagnose immunodeficiencies
[*] Recognition and Diagnosis of Immunodeficiencies: the pattern and type of infections always reflect the nature of an immunological defect
- Age – at presentation
- Sex (family history e.g. X-linked inheritance etc)
- 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
Describe laboratory investigations for immunodeficiencies
General:
- Full blood count and differential
- Exclusion of secondary immunodeficiency
Tests of humoral (antibody) immunity
- IgG, IgA, IgM (+/- IgE)
- IgG(1-4) subclasses
- IgG levels to specific previous vaccines e.g. tetanus toxoid / HiB / pneumococcus measles, mumps, rubella
- Measure antibody in response to “test” immunization
Tests for Cell mediated immunity
- Lymphocyte count (FBC)
- Lymphocyte subset analysys (CD4+, CD8+ T, NK and B cells) – extended marker panel (s)
- In vitro tests of T cell function
Tests for phagocytic cells
- Neutrophil count (FBC)
- Neutrophil function tests (e.g. 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
What is an immunocompromised host?
Immunocompromised host: “state in which the immune system is unable to respond appropriately and effectively to infectious microorganisms”
- Qualitative (dysfunctional immune component) or quantitative (lack of/absence of immune component) defect of one or more components of the immune system.
What does SPUR mean?
- S => Severe, sometimes life-threatening
- P => Persistent, despite appropriate treatment infection s still there
- U => Unusual – unusual organism, opportunistic infection, consider site of infection
- R => Recurrent (same infection or different infections)
What are the different types of primary immunodeficiencies?
Primary immunodeficiencies: classified according to which immune component is defective
- B cell (50%) – most common
- T cell (30% - worst kind, as it also ultimately leads to B cell deficiency as T helper cells drive B cells to produce antibodies)
- Phagocytes (18%)
- Complement (2%)
Incidence of 1:400 to 1:400000
Occur in the first months of life
80% of patients < 20 years
70% of patients are male (X-linked)
What are clinically important B cell deficiencies?
At what age do primary antibody deficiencies present at?
Certain primary antibody deficiencies can present at any age!
What are clinically important Phagocyte deficiencies?
- Disease: Cyclic neutropenia (abnormal low amount of neutrophils) (periodicity – every 3/4 weeks); Defect: unknown
- Disease: Leukocyte Adhesion Deficiency (Lack of CD18 protein on phagocyte); Defect: Adhesion to vascular endothelium
- Disease: Chronic Granulomatous Disease (CGD) (lack of respiratory burst due to lack of enzymes involved in producing free radicals); Defect: intracellular killing
- Disease: Chediak-Higashi Syndrome (failure of phagolysosome formation); Defect: Phagocytosis
- NB: Secondary phagocyte deficiency is much more common!!!!
What are clinically important T cell deficiencies?
- Disease: DiGeorge Syndrome (defect in thymus embryogenesis and incomplete development); Defect in: lack of thymus => lack of functional T cells
- Disease: Severe Combined Immunodeficiency (defect in gamma-chain used by many receptors (IL-2, IL-4, IL-7, IL-9) – involves T and B cell abnormalities); Defect: Stem cell defect
- Disease: Severe Combined Immunodeficiency (defect in adenosine deaminase (ADA), purine nucleoside phosphorylase (PNP)); Defect: death of developing thymocytes
- Disease: Severe Combined Immunodeficiency and Omenn’s Syndrome (defect in genes critical for TCR rearrangement, maturation); Defect: Defective T cell development
What are Complement Component deficencies?
C1 inhibitor deficiency => hereditary angioedema – risk of airway obstruction => suffocation. If this condition is not properly diagnosed, 30% mortality.
What could Secondary deficiencies be due to?
[*] Secondary Immune deficiencies: decreased production of immune components due to:
- Malnutrition (most common cause in the world)
- Infection e.g. HIV
- Liver diseases
- Lymphoproliferative diseases
- Drug-induced neutropenia – immunosuppressive / cytotoxic
- Splenectomy due to infarction e.g. sickle cell anaemia, trauma, autoimmune haemolytic disease, infiltration (tumour), coeliac disease, congenital
- “Physiological” – age
[*] Secondary Immune Deficiencies due to increased loss or catabolism of immune components
- Protein-losing conditions such as Nephropathy, Enteropathy
- Burns
What factors cause neutropenia and discuss the management of neutropenia
[*] Factors causing neutropenia (abnormal low levels of neutrophils)
- Drugs e.g. phenytoin, chloramphenicol, alcohol (abuse)
- Autoimmune neutropenia
- Infections e.g. infectious mononucleosis, hepatitis B or C, human immunodeficiency virus, cytomegalorvirus infection, typhoid
- Bone marrow infiltration with malignancy
- Aplastic anaemia
- Vitamin B12 or folate or iron deficiency
- Chemotherapy – cytotoxics and immunosuppressants
- Exposure to chemical agents e.g. Benzene, organophosphate, radiotherapy
[*] Management (neutrophil count of <1.0 x10^9)
- Treat suspected neutropenic sepsis as an acute medical emergency and offer empiric antibiotic therapy immediately
- Assess patient’s risk of septic complications
Describe the presentation and management of the Asplenic/Splenectomised patient
[*] The Asplenic/Splenectomised Patient
Presentation:
- Increased susceptibility to encapsulated bacteria (most invasive, difficult to get rid of – can only be phagocytosed if opsonized) e.g. Haemophilus influenzae, Streptococcus pneumoniae and Neisseria Meningitidis
- OPSI (overwhelming post-splenectomy infection) => sepsis and meningitis: 0.25-5% splenectomised individuals per year, 5% lifetime risk; 40-70% mortality (low risk but risk of mortality is high)
Management:
- Penicillin prophylaxis (life-long)
- Immunisation against encapsulated bacteria (at least two weeks before splenectomy if possible)
- Patient information; Medic Alert bracelet
Why is the spleen so important?
- Largest lymphoid organ
- Blood borne pathogens – capable of dealing with encapsulated bacteria!
- Antibody production: (acute response: IgM production which activates complement; long term protection: IgG production (best antibody weapon)
- Splenic macrophages – removal of opsonized microbes and immune complexes
Describe the presentation and management of patients with phagocyte deficiencies
[*] Presentation of patients with phagocyte deficiencies
- Prolonged and reuccrent infections
- Skin and mucous membranes (ulcers)
- Osteomyelitis
- Deep abscesses
- Commonly staphylococcal (catalase +ve)
- Invasive Aspergillosis (fungal opportunistic infection – most common cause of death in patients with a phagocyte defect)
- Inflammatory problems (granuloma)
- Will leave noticeable scars
[*] Management of patients with phagocyte deficiencies
- Prophylactic antibiotics/ anti-fungal agents / Immunization
- Surgical management
- Interferon-gamma (CGD)
- Steroids (CGD)
- Stem cell / bone marrow transplantation (ultimate resort)
Describe the presentation and management of DiGeorge Syndrome
[*] DiGeorge Syndrome Management:
- Neonatal cardiac surgery (depending on nature and severity of cardiac abnormality)
- Supplement to correct hypocalcaemia
- Immune defect variable (only 20% of DiGeorge have immunodeficiency -?) (low T cell number)
If <0.4x10^9/L, Pneumocystis Pneumonia (PCP) prophylaxis with antibiotics
Bone marrow transplantation (severe forms)
- Use only X-irradiated and CMV(-) – blood
- No live vaccines (BCG, MMR, oral polio) – because of the possibility of replication and becoming pathogenic
