Pediatrics [IMMUNODEFICIENCY]

Introduction
For a quick review, our adaptive immune system takes time to crank- Cellular Humoral
up but provides “specific” protection against targets. Our innate Adaptive T-cells B-cells, Antibodies (Ig)
immune system acts as first responders and provides “general” Innate NK, Macrophages Complement
protection against targets. See the table for what’s what.

In any child with recurrent infections, prolonged infections, infections General rules for immunodeficiency
with unusual pathogens, or severe infections with typical pathogens, - Earlier age of onset ~ Increased severity
immunodeficiency should be suspected. There may also be symptoms - B-cells require functioning T-cells to work
such as diarrhea and failure to thrive. See how the age of patient can - 6-9 months? Look for T-cell defects
help with diagnosis. - 6-12 months? Look for B-cell +/- T-cell defects
- Over 12 months? Look for B-cell defects
Initial testing depends on what’s suspected. A good general first test is
quantitative immunoglobulins (QIGs) and CBC with differential.
This will give antibody numbers and cell types that are present. Of note, Initial Testing by Suspected Defect
defects pertaining to antibody production can be masked in the first 6- Humoral QIGs, Vaccine-associated
9 months of life due to presence of maternal antibodies, so checking antibodies
QIGs is probably not helpful. While the basic sciences tell us that Cellular Lymphocyte count, HIV testing
certain cells are designed to fight certain infections (B cells Bacteria, Complement C3, C4, CH50
T cells fungus), there’s little correlation with the bug infecting and the Phagocytosis Phagocytic morphology and count
underlying diagnosis.

Defects in Humoral Immunity (Antibody Production)

X-Linked (Bruton’s) Agammaglobulinemia (XLA)

It’s an X-linked disorder (only boys get it) of a B-cell deficiency. Generally, for humoral immunity defects:
Presents with recurrent “normal” infections (sinusitis / otitis / - Think “mucosal infections” (sinopulmonary, GI)
pneumonia) that are frequent. Get the immunoglobulin levels; this - Treat with scheduled IVIG
disease will be apparent as all immunoglobulins are deficient (A, G,
M, and E). Flow cytometry will show absence of B-cells; confirm with
genetic testing for BTK gene. Patients will need scheduled IVIG. Use
of prophylactic antibiotics is debatable.

Hyper-IgM Syndrome
When immunoglobulin levels are obtained due to immunodeficiency
suspicion, there’ll be low levels of IgA and IgG but with a normal to
high IgM. Differentiation (class-switching) doesn’t occur but the body
is still able to do some defending with the less selective IgM. Treat with
scheduled IVIG.

Selective IgA Deficiency

This is the most common primary immunodeficiency and typically
benign. IgA protects against the mucosal barrier so patients may have
respiratory or GI infections. However, IgM still works so these
patients may never be diagnosed at all. The big red flag is a patient who
gets an anaphylactic reaction after blood transfusion from exposure
to the new (and foreign) IgA. Included here as there may be some
common genetic basis with CVID.

Common Variable Immunodeficiency (CVID)

This can present in adults as well as children (though in mid to late
childhood). Seen in both males and females. CVID is less severe but
has similar infection types when compared to XLA. Check
immunoglobulin levels – need deficiencies in at least 2 out of 3 (IgA,
IgG, IgM). As expected, treat with scheduled IVIG. Use of
prophylactic antibiotics is debatable.

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 Pediatrics [IMMUNODEFICIENCY]

Defects in Cellular Immunity

22q11.2 Deletion (DiGeorge) Syndrome

The thymus and facial structures come from the 3rd and 4th
pharyngeal pouch. There will be micrognathia, wide-spaced eyes,
low-set ears, and absent thymic shadow (the syndrome). However,
there’s a broad spectrum of presentation given the variable deletions at
22q11.2. This disease can be suspected on the baby’s physical
appearance but any fungal or Pneumocystis pneumonia should be a
huge red flag. There may be an underlying cardiac defect that has to
be identified. Start by giving prophylaxis against PCP (TMP/SMX)
and scheduled IVIG if the immunodeficiency is severe enough. Cure
by giving the baby a thymic transplant. If the facial structures lead to
thinking about DiGeorge, pay close attention to the calcium as absent
parathyroid glands can lead to hypocalcemia (and seizures).

Combined Defects in Humoral and Cellular Immunity

Wiskott-Aldrich
In boys (because it’s X-linked) with “normal bug” infections,
thrombocytopenia, and eczema, think Wiskott-Aldrich. There’ll be Generally, for combined immunity defects:
↑IgE and ↑IgA on immuno-studies. Patients may need bone marrow - Any infection is possible
transplants but they rarely survive to adulthood. Without Bs or Ts the - Treat with bone marrow transplant
body gets eaten by everything. Treat with IVIG, perform splenectomy
(if foregoing bone marrow transplant), and manage eczema and
bleeding.

Ataxia-Telangiectasia
Yeah, you’ll see this. Not. Know “telangiectasias + ataxia, poor DNA
repair, lymphoma, leukemia.” Never suggest this to an attending
unless it’s Dr. House. Pick it on the exam. It’s incredibly rare.
Sinopulmonary infections and absent IgA are associated with it. Avoid
excessive radiation.

SCID
The kid has no immune system. They’re at risk for every single
infection. Knowing that this can be caused by adenosine deaminase
deficiency was required for Step 1. Now, realize that they functionally
have AIDS. Patients become infected with opportunistic infections.
They also need PCP prophylaxis (TMP/SMX) and scheduled IVIG.
Bone marrow transplant will be your ride-or-die but gene and
enzyme replacement have been used.

Defects in Phagocytosis

Chronic Granulomatous Disease

Macrophages can eat but not kill organisms that are catalase . When Generally, for phagocytic defects:
chronic skin or organ abscesses are seen think of this. Pathogens - Think Staph, Staph, Staph
include Staph, Aspergillus, and Serratia. The body knows there’s an - Treat with bone marrow transplant if severe
infection - antibodies are produced (↑IgM and IgG) and cells are
dispatched (↑ WBC) – it’s just that the cells can’t do anything. Confirm
with a negative nitro blue test that reveals an absent respiratory burst.
Organisms that produce their own H2O2 can be killed. Can treat with
prophylactic TMP/SMX and itraconazole but will ultimately require
bone marrow transplant for cure.

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 Pediatrics [IMMUNODEFICIENCY]

Leukocyte Adhesion Deficiency
Neutrophils can’t adhere or get out of the blood vessels. Thusly there’s
no pus despite a massive leukocytosis and high fever (↑ cytokines,
antibodies, and leukocytosis in response to infection). Most common
infection locations are at body vs environment junctions (pulmonary,
GI, genital, skin). An early sign (that will give the diagnosis away in a
vignette) is delayed separation of the cord. Get a bone marrow
transplant.

Chediak-Higashi
It’s an autosomal recessive disorder leading to indiscriminate
lysosomal fusion. It will also show albinism, neuropathy, and
neutropenia. Look for giant granules in neutrophils. Infections
typically involve mucous membranes and skin (Staph aureus). Treat
infections aggressively.

Hyper-IgE (Job) Syndrome

As the name implies, there is (but not always) severely elevated IgE
levels. There can also be peripheral eosinophilia. From an infectious
standpoint, recurrent “cold” abscesses (Staph, H.flu, Strep pneumo) are
typically seen. Additional findings include eczema, retained primary
teeth, fractures, and post-infectious pneumatoceles.

Defects in Complement Cascade

Generally, for complement disorders:
C5-C9 (Terminal Complement Deficiency) - Think encapsulated infections + Neisseria
These complements form a membrane attack complex (MAC) that lyse - Sinopulmonary infections + meningitis common
gram negative bacteria. Neisseria will be most likely cause of infection.

C1 Esterase Deficiency
This is hereditary angioedema. It’s caused by a defect in the C1
inhibitor. This doesn’t contribute to increased susceptibility to
infection. This is here to point out another function of the complement
pathway (and something that will likely be tested). This angioedema is
not IgE-mediated so there is no urticaria and poor response to
antihistamines – use FFP.

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