Peds Immuno Flashcards
X-linked (Bruton) agammaglobulinemia
An X-linked recessive B-cell deficiency found only in boys
Symptoms begin after 6 months of age with recurrent sinopulmonary, GI, and urinary tract infections with encapsulated organisms (Haemophilus influenzae, Streptococcus pneumoniae, Neisseria meningitidis, Pseudomonas
B cells are ↓ in Bruton (whereas those in THI are normal)
Dx: Quantitative Ig levels: if low, confirm with B- and T-cell subsets (B cells are absent; T cells are often high)
Absent tonsils and other lymphoid tissue may provide a clue
Tx: prophylactic antibiotics and IVIG
Common variable immunodeficiency (CVID)
Usually a combined B- and T-cell defect All Ig levels are low (in the 20s and 30s) Normal B-cell numbers; ↓ plasma cells Symptoms usually present later in life (15–35 years of age, men & women) Encapsulated organisms (Haemophilus influenzae, Streptococcus pneumoniae, Neisseria meningitidis)
↑ Pyogenic upper and lower respiratory infections
↑ Risk for lymphoma and auto- immune disease
Dx: Quantitative Ig levels; confirm with B- and T-cell subsets
Tx: IVIG
IgA deficiency
Mild; the most common immunodeficiency
↓ IgA levels only
Usually asymptomatic; patients may develop recurrent respiratory or GI infections (Giardia)
Anaphylactic transfusion reaction caused by anti-IgA antibodies is a common presentation
Dx: Quantitative IgA levels; treat infections
Tx: Be careful giving IVIG, as it can lead to the production of anti-IgA antibodies and cause severe allergic reactions; if IVIG is necessary, give IgA-depleted IVIG
Hyper-IgM syndrome
Absence of CD40 ligand that allows class-switching from IgM to other Ig classes
↑ IgM levels, low levels of all other Ig, and normal numbers of lymphocytes
Severe, recurrent sinopulmonary infections caused by impaired Ig
Treat with antibiotic prophylaxis and IVIG
Thymic aplasia (DiGeorge syndrome)
See the mnemonic CATCH 22
Presents with tetany (2° to hypocalcemia) in the first days of life
Autosomal dominant
Variable risk for infection
↑↑↑ Infections with viruses, fungi, and pneumocystis pneumonia (PCP)
X-ray may show absent thymic shadow
Dx: Absolute T-lymphocyte count; mitogen stimulation response; delayed hypersensitivity skin testing
Tx: bone marrow transplantation, IVIG for antibody deficiency; give PCP prophylaxis
Ataxia-telangiectasia
Progressive cerebellar ataxia and oculocutaneous telangiectasias
Caused by an autosomal recessive mutation in gene responsible for repair of dsDNA breaks
↑ Incidence of malignancies, including non-Hodgkin lymphoma, leukemia, and gastric carcinoma
No specific treatment; may require IVIG depending on the severity of the Ig deficiency
Severe combined immunodeficiency
Most commonly X-linked recessive
Severe lack of B and T cells caused by a defect in stem cell maturation and ↓ adenosine deaminase
Severe, frequent bacterial infections; chronic candidiasis; opportunistic organisms
Tx: bone marrow or stem cell transplantation and IVIG, PCP prophylaxis
Wiskott-Aldrich syndrome
An X-linked recessive disorder seen only in male patients
Symptoms usually present at birth Patients have ↑ IgE/IgA, ↓ IgM, and
thrombocytopenia
The classic presentation involves bleeding, eczema, and recurrent otitis media
mnemonic WIPE:
Wiskott-Aldrich Infections Purpura (thrombocytopenic) Eczema
↑↑ Risk for atopic disorders, lymphoma/leukemia, and infection from S pneumoniae, S aureus, and H influenzae type b (encapsulated organisms)
Treatment is supportive (IVIG and antibiotics)
Patients are at ↑ risk for developing autoimmune diseases and malignancies
Patients rarely survive to adulthood
Patients with severe infections may be treated with BMT
Chronic granulomatous disease (CGD)
X-linked (2/3) or autosomal- recessive (1/3) disease with deficient superoxide production by polymorphonuclear leukocytes and macrophages
Anemia, lymphadenopathy, and hypergammaglobulinemia may be present
Chronic skin, lymph node, pul- monary, GI, and urinary tract infections; osteomyelitis and hepatitis
Infecting organisms are catalase ⊕ (S aureus, Escherichia coli, Candida, Klebsiella, Pseudo- monas, Aspergillus)
May have granulomas of the skin and GI/GU tracts
Dx:
Absolute neutrophil count with neutrophil assays
The dihydrorhodamine (DHR) test is diagnostic for CGD; nitroblue tetrazolium test is the previous gold standard and still occasionally used
Tx: daily TMP-SMX; make judicious use of antibiotics during infections IFN-γ can ↓ the incidence of serious infection
Leukocyte adhesion deficiency
Defect in the chemotaxis of leukocytes
↓ Phagocytic activity
Recurrent skin, mucosal, and pulmonary infections
May present as omphalitis in the newborn period with delayed separation of the umbilical cord (> 14 days post-birth)
No pus with minimal inflammation in wounds (caused by a chemotaxis defect)
Lab: High WBCs in blood
BMT is curative
Chédiak-Higashi syndrome
An autosomal recessive disorder that leads to a defect in neutrophil chemotaxis / microtubule polymerization
The syndrome includes partial oculocutaneous albinism, peripheral neuropathy, and neutropenia
↑↑ Incidence of overwhelming pyogenic infections with S pyogenes, S aureus, and Pneumococcus species
Look for giant granules in neutrophils
BMT is the treatment of choice
Job syndrome (Hyperimmunoglobulin E syndrome)
A defect in neutrophil chemotaxis
Remember the mnemonic FATED: Coarse Facies, Abscesses (S aureus), Retained primary Teeth, Hyper-IgE (eosinophilia), Dermatologic (severe eczema)
Recurrent S aureus infections and abscesses
Treat with penicillinase-resistant antibiotics and IVIG
C1 esterase inhibitor defi- ciency (hereditary angioedema)
An autosomal dominant disorder with recurrent episodes of angioedema lasting 2–72 hours and provoked by stress or trauma
Can lead to life-threatening airway edema
Evaluation: Total hemolytic complement (CH50) to assess the quantity and function of complement
Management: Purified C1 inhibitor (C1INH) concentrate and FFP can be used before surgery
Terminal comple- ment deficiency (C5–C9)
Inability to form membrane attack complex
Recurrent Neisseria infections, meningococcal or gonococcal
Rarely, lupus or glomerulonephritis
Management: Meningococcal vaccine and appropriate antibiotics
