Primary immunodeficiency Flashcards
When recurrent infections signal something more
Most common causes of recurrent infections?
Allergies
Immunodeficiencies
Incidence of PIs (Primary immunodeficiencies)
1:2000 live births
What are PIs
Inherited disorders affecting the functioning of the imnune system, predisposing pt to infection, autoimmune disease, aberrant inflammatory response and malignancy
3 main types of PIs
- Humoral (antibody) deficiency
- Cellular deficiency
- Combination humoral + cellular deficiencies
Key presenting feature of PIs
Increased susceptibility to infection
Specific types of PIs
- B-cell immunodeficiencies (50%)
- Combined T-cell and B-cell immunodeficiencies (20%)
- Phagocyte immunodeficiencies (18%)
- T-cell immunodeficiencies (10%)
- Complement immunodeficiencies (2%)
Warning signs (1-5/10) 2 or +, further assess
- 4 or more new ear infections/year
- 2 or more serious sinus infections/year
- 2 or more months on antibiotics with little effect
- 2 or more Pneumonias/year
- Failure of an infant to gain weight or grow normally
Warning signs (6-10/10) 2 or +, further assess
- Recurrent, deep skin or organ abscesses
- Persistent thrush in mouth or fungal infection on skin
- Need for IV antibiotics to clear infections
- 2 or more deep seated infections, including septicemia
- Family Hx PIs
B cell disorders (common)
- Selective IgA deficiency: recurrent sinopulmonary infection, GI disorders, Allergy, Cancer, autoimmune disease
- IgG2 subclass/selective deficiency: same, some Pts: recurrent bacterial infections
- Transient Hypogammaglobulinemia of infancy: upper or lower respiratory tract infections
B cell disorders (uncommon)
- X-linked agammaglobulinemia (XLA): inf begin at 4-6 mo, pyogenic inf PROMINENT, viral inf possible, susceptibility to encapsulated bacteria, Sinusitis, Otitis Media, Pneumonia
- Common variable immunodeficiency (CVID): Recurrent upper or lower resp tract inf, Bronchiectasis, Enteropathy, Autoimmune manifestions, Malignancy
T cell disorders (common)
DiGeorge anomaly (partial): presents in the first few days of life, dysmorphic facies, Hypocalcemia, Depressed T cell immunity, congenital heart disease
T cell disorders (uncommon)
DiGeorge anomaly (complete): thymic aplasia, susc to infection, susc to graft vs host disease (GVHD)
Severe combined immunodeficiencies (uncommon)
Severe combined immunodeficiency (SCID), Wiskott-Aldrich syndrome, Ataxia Telangiectasia, Chronic granulomatous disease, Leukocyte adhesion deficiency, Complement component disorders
Severe combined immunodeficiency (SCID)
FTT, onset of inf neonatal period, opportunistic infections, chronic or recurrent thrush, chronic rash, chronic or recurrent diarrhea, paucity of lymphoid tissue
Wiskott-Aldrich syndrome
Eczema, thrombocytopenia, bacterial infection
Ataxia Telangiectasia
Vascular malformations, Neurologic defects, Tumors and immunodeficiency
Chronic granulomatous disease
Recurrent infections to catalase + organisms (Staph aureus, Aspergillus, Nocardia, Serratia marcescens, E Coli, Burholderia Cepacia)
Granulomas: skin, liver, lungs, lymph nodes
Leukocyte adhesion deficiency
Recurrent ST infections
Delayed umbilical cord separation
Severe periodontal disease
Complement component disorders
Recurrent pyogenic infection and connective tissue disease
Recurrent infections due to Neisseria sp
How do you Dx PI
Using a stepwise approach (4 stages)
Stage 1 work up
Hx and PE
CBC + diff
Quantitative Immunoglobulin levels related to age (IgG, IgM, IgA)
Stage 2 work up
Specific antibody responses (Tetanus, Diphtheria)
Response to pneumococcal vaccine (before and after) for children 3 y and older
IgG subclass analysis
Stage 3 work up
Tetanus and candida skin tests
Lymphocyte surface markers CD3, CD4, CD8, CD19, CD16 , CD56
Mononuclear lymphocyte proliferation studies, using mitogen and antigen stimulation
Stage 4 work up
Complement screening: C3, C4, CH50 Enzyme measurements (adenosine deaminase, purine nucleoside phosphorylase) Phagocyte studies (surface glycoproteins, mobility, phagocytosis) Natural killer citotoxicity studies Further complement studies AH50 Neoantigen to test antibody production Other surface/cytoplasmic production Cytokine receptor studies Family/genetic studies
CBC and/or quantitative Ig levels abnormal?
Repeat to make sure it was not a lab error, if it remains abnormal (stage 1) further testing indicated (going after stage 1) –> refer to Allergist or Immunologist, they need to evaluate for allergies in addition to immunodeficiencies
Why is early Dx of PI critical?
To avoid chronic problems, LT adverse effects and severe morbidity (e.g. Bronchiectasis)
Because they can be candidates for bone marrow transplantation (BMT), the younger the better
Tx PI
Immunoglobulin therapy: IV (clinic) or SQ (home)
BMT for severe cases
SQ Immunoglobulin Tx advantages
Improved QOL, lower cost, lower systemic adverse effects
SQ Immunoglobulin Tx disadvantages
More frequent treatments, local reaction at infusion site
What are the considerations for transplantation?
Early intervention is preferable before chronic illness and disability sets in
For hematopoietic stem cell transp, matched-related donor is better than matched-unrelated (registry) donor
For some smaller Pts (<10 kg), cord blood stem cell Tx may be possible
You can find study protocols, including gene therapy in www.clinicaltrials.gov
IV immunoglobulin therapy, standard protocol
For those with antibody deficiency
400-600 mg/kg infusion q 4 wk
Adjust doses and/or interval (poss to q 2-3 wk) depending on clinical response
Cons trough (pretreatment) level +300 mg/dl for those starting with a higher serum IgG level
Follow clinical response, not just the #s
Consider SQ Tx to eliminate trough levels
btw… common causes of secondary immunodeficiency?
Viral infections, malignancy, malnutrition, drugs (CS, immunosuppresive therapy, etc)
