Case 17- Immunodeficiency Flashcards
Primary immunodeficiency
Due to an inherited genetic mutation, for example; severe combined immunodeficiency disorder (SCID). Rare, intrinsic, usually inherited immune disorders usually present at birth and diagnosed in childhood. Potentially life threatening. Its more common in males
Secondary immunodeficiencies
Acquired immunodeficiencies as a result of disease or environmental factors i.e. HIV. More common then primary, manifests at any age
Treatment of secondary immunodeficiencies
Treatment of primary condition usually leads to resolution of the immunodeficiency
Causes of secondary immunodeficiency
Malnutrition is the biggest cause, other causes:
• Drug effects- chemotherapy, immunosuppressive drugs
• Chronic infections- HIV/AIDs, Malaria, Measles
• Malignancy- Leukaemia, Lymphoma and Myeloma
• Radiation exposure
• Extremes of age- prematurity
Immunodeficiency disorder
Partial or full impairment of the immune system which leaves patients unable to resolve infections. Can lead to infections or cancer
The clinical features of immunodeficiency
SPURR:
• Severe – increased severity of infection and unexpected complications
• Persistent – increased duration of infection
• Unusual - unusual manifestations of infection and non-infectious manifestations
• Recurrent – increased frequency
• Runs in the family (PIDs)
Symptoms of immunodeficiency
1) _ Increased frequency, severity and duration of infection
2) Infections with organisms of low pathogenicity (opportunistic infections)
3) You get non-infectious manifestations in gastrointestinal, endocrinological and haematological organ systems. Such as auto-immunity, inflammatory disorders, fevers, rashes, bowel problems and swollen joints
Clinical findings of immunodefiency in children
- > 4 ear infections in 1 year
- > 2 sinus infections in 1 year
- > 2 months on antibiotics
- > 2 pneumonias in 1 year
- Failure to thrive
- Recurrent Abscesses
- Persistent fungal infections
- IV antibiotics needed
- > 2 deep seated infections
- Family history
Immunodeficiency diagnosis
• History- infections, other symptoms of immunodeficiency, Family history
• Physical examination
• Baseline blood tests
Once diagnosed you would perform a complete blood count and Immunoglobulin levels to determine the type of immunodeficiency. You’d want to rule out a severe cause like antibody deficiency, neutropenia, SCID and AID’s.
Further tests for immunodeficiency
• Lymphocyte proliferation • B cell maturation • Phagocyte function • Complement components Where possible do genetic testing so you can definitively diagnose the immunodeficiency disorder.
Autobody immunodeficiencies
1) Most common cause of Primary immunodeficiency (PID). 2) Can occur in SID due to a T cell deficiency
3) Antibodies are part of the humoral response and protect our extracellular space
4) Commonly causes bacterial infections such as Otitis, Pneumonia, Sinusitis, GI tract disturbances and Autoimmunity i.e. coeliac disease.
5) Infectious organisms include Pneumococcus and H.influenzae.
6) Diagnosed with low immunoglobulins and B cell abnormalities. Untreated patients can develop bronchiectasis.
Treatment for antibody immunodeficiencies
Immunoglobulin replacement (IgG)
Examples of antibody immunodeficiencies
1) Transient physiological agammaglobulinaemia of the neonate
2) X-linked agammaglobulinemia of Bruton (Bruton’s disease)
3) Common variable hypogammaglobulinemia (CVID)
4) Selective IgA deficiency
Transient physiological agammaglobulinemia of the neonate
Neonates dont have a fully developed immune system at birth but rely on maternal transfer in utero. There is delayed IgG production till 3 months. If the baby is premature then this condition is exaggerated as the mother produced more IgG in the last trimester
X-linked agammaglobulinemia of Bruton (Bruton’s disease)
X linked recessive disorder which causes defective B cell maturation. Causing an antibody deficit, more common in males. Recurrent pyogenic infections i.e. streptococci and staphylococci, seen at 6 months
Common variable hypogammaglobulinaemia
Heterogeneous group of conditions with normal B cell numbers but abnormal function. Deficit in IgG and at least one other immunoglobulin. Late onset 15-35 years, presents with recurrent pyogenic infections i.e. streptococci and staphylococci
Selective IgA deficiency
Deficiency in just IgA, most common tyoe. More common in caucasians. Can be asymptomatic or cause recurrent infections of the respiratory and gastrointestinal tract. IgA is mostly found in mucosal secretions i.e. tears, saliva or secretions. In mucosal secretions its known as secretory IgA. Affects 1 in 400-1000, unknown genetic cause but often familial.
Example of secondary antibody deficiencies
Chronic Lymphocytic Leukaemia (CLL)- affects the ability of B cells to differentiate into plasma cells.
Multiple Myeloma- cancer of plasma cells producing abnormal antibodies.
The different presentations of selective IgA deficiency
- Asymptomatic- majority, diagnosed incidentally. May have some IgM or IgG in the secretions which partially compensate. May go on to become symptomatic
- Recurrent infection of mucosal surfaces- about half of symptomatic patients. Infections in sinus, ear, lungs and GI tract. Can have partial IgG deficiency but will have normal blood levels
- Allergies- 10-15% of symptomatic patients. For example, allergic asthma or food allergies
- Autoimmunity- 25-33% of symptomatic patients. Get rheumatoid arthirits, lupus and coeliac disease
Diagnosis of selective IgA deficiency
Blood IgA <0.5-0.7 mg/L, other Ig levels normal. Normal B and T cell number and function. Can coexist with an IgG deficiency but changes diagnosis to CVID.
Treatment for selective IgA deficiency
No specific treatment, you treat infections as they arise and use long term prophylaxis. Patients with severe infections may be offered immunoglobulin (IgG) replacement therapy but doesn’t always work.
