Minor pediatric infectious diseases
Module 3: immune deficiencies
Week 1: Primary immune deficiencies
Primary immunodeficiencies(PID) are inborn errors in the immune system. It has
a very low prevalence(<10% of all immunodeficiency cases) → it’s an abnormal
immunsystem. For instance: SCID. It can lead to live threatening symptoms. The
incidence is 1:500-1:500.000. Most frequent are the humoral deficiencies.
Absence or altered function of one or more gene products→ can lead to infection
(most of those are in the respiratory tract), auto-immunity, malignancy or other.
Secondary immunodeficiencies (90% of all cases) are acquired, abnormalities not within the
immune system itself and this has a high prevalence. For instance: HIV, use of prednisone
and chemotherapy.
Cells Primary ID Secondary ID
B-cells XLA, CVID Loss of protein by gut or kidney
T-cells DiGeorge-syndrome HIV
B- & T-cells SCID, CID Drugs (chemotherapy) or
malignancies
Phagocytes Chronic granulomatous disease, Drugs
Cyclic neutropenia
Complement C2-deficiency Autoimmune disorders
Opportunistic infection: a pathogen that doesn’t give a problem in healthy individuals, but in
immunocompromised patients it can cause major infection. For instance: pneumocystis
jiroveci, cytomegalovirus, candida spp, aspergillus spp, mycobacterium spp, nocardia spp.
When can you think about an immunodeficiency→ the key to detect is to
consider the possibility.
1. >8 upper respiratory tract infections a year
2. >2 severe sinusitis a year
3. >2 pneumonia a year
4. >2 months on AB with little help
5. Recurrent skin or organ abscesses
6. Therapy resistant trust or candida infections
7. 2 or more deep-seated infections including septicemia
8. Failure to gain weight or grow normally
9. Need for IV AB to clear infection
10. Family-history positive for immunodeficiency
11. Opportunistic infections
,Physical examination Immunodeficiency:
Skin and appendages: abnormal hair or teeth, eczema, neonatal erythroderma, albinism,
extensive warts or mollusca, congenital alopecia, vitiligo, petechiae, cold abscesses,
telangiectasia, absence of sweating, nail dystrophy.
Oral cavity: gingivostomatitis, periodontitis, aphthae, giant oral ulcers, thrush, dental
crowding, conical incisors.
Eyes: retinal lesions, telangiectasia
Lymphoid tissue: absence of lymph nodes and tonsils, lymphadenopathy, asplenia,
organomegaly.
Neurological: ataxia, microcephaly, macrocephaly
Other: dysmorphism, stunted growth or disproportional growth
Diagnostic approach PID
1. Recurrent ENT and airway infections→ T en B cell
2. Failure to thrive form early infancy→ T and B cell
3. Recurrent pyogenic infections→ neutrophil
4. Unusual infections or unusually severe course of infections→ T and B-cell
5. Recurrent infections with the same pathogen
6. Autoimmune or chronic inflammatory disease and/or lymphoproliferation
7. Characteristic combinations of features in eponymous syndromes→ T and
B-cell
8. Angioedema→ complement
Opsonization defects Pathogens
IgA-deficiency, IgG subclass deficiency or H. influenzae, S. pneumoniae
defect in specific Ab-production
Agammaglobulinemie H. influenzae, S. pneumoniae, M. pneumoniae,
U. urealyticum
Deficiency C2, C3, C4, MBL H. influenzae, S. pneumoniae, meningococcus
Cellular defects Pathogens
Phagocyte dysfunction, hyper-IgE-syndrome S. Aureus, candida spp, A. fumigatus
T-lymphocyte dysfunction Mycobacterium spp, viruses, candida spp, A.
fumigatus, pneumocystis jiroveci
Hyper-IgM-syndrome Pneumocystis jiroveci
PID relation with clinical presentation:
- recurrent infections of the respiratory tract and the ear-nose-throat (opsonization
defects)
- unusual or opportunistic infections and general malaise, loss of weight and failure to
thrive (t-cell dysfunction)
- Severe recurrent infections of the skin, oral cavity and mucosa and of the internal
organs (lungs and liver) and the skeleton.(granulocyte dysfunction)--> also ENT and
airway.
, - Recurrent meningococcal infections are suggestive for complement deficiencies.
PID what can you investigate:
- Cell differential in peripheral blood
- Lymphocyte subpopulations (T,B,NK), functional tests
- Immunoglobulins
- Phagocytic functional assays
- Complement activation assays
Leukocyte differential and immunoglobulin isotype levels enable detection in most PID
cases. Use age-matched references to avoid misinterpretation of immunological test results.
Treatment:
- Early diagnosis saves lives and improves quality of life.
- Timely recognition of antibody deficiency prevents future organ damage.
- Prevention→ antibiotic prophylaxis, close surveillance.
- Antibiotic treatment of bacterial infections, HSCT
- When PID is suspected in the family, delay live attenuated vaccinations and do not
postpone immunological investigations.
, Week 1: LE immunodiagnostics
Tests: immunofluorescence(light microscopy, antibodies with fluorescence), flow cytometry.
