I N T R O D U C
T I O N
Most
of us are no
strangers to
infections. Just
about everybody has
had colds and coughs
and infected cuts,
the flu or chicken
pox. Some people
have had first-hand
experience with
infections that are
even more
serious—pneumonia
and meningitis.
Usually, we expect
to recover quickly
from an infection.
We count on our
body’s immune
defenses (sometimes
with the help of
antibiotics) to get
rid of any germs
that cause
infection, and to
protect us against
new germs in the
future.
Some people,
however, are born
with an immune
defense system that
is faulty. They are
missing some or, in
the worst cases,
almost all of the
body’s immune
defense weapons.
Such people are said
to have a primary
immunodeficiency
(PI).
There are over 70
different types of
PIs. Each type has
somewhat different
symptoms, depending
on which parts of
the immune defense
system are
deficient. Some
deficiencies are
deadly, while some
are mild. But they
all have one thing
in common: they may
open the door to
multiple infections.
Individuals with
PI—many of them
infants and
children—get one
infection after
another. Ear, sinus,
and other infections
may not improve with
treatment as
expected, but keep
coming back or
occurring with less
common but severe
infections, such as
recurrent pneumonia.
Besides being
painful,
frightening, and
frustrating, these
constant infections
can cause permanent
damage to the ears
or to the lungs.
In the more severe
forms of PI, germs
which cause only
mild infections in
people with healthy
immune systems may
cause severe or
life-threatening
infections.
Although infections
are the hallmark of
PIs, they are not
always the only
health problem, or
even the main one.
Some PIs are
associated with
other immune system
disorders, such as
anemia, arthritis,
or autoimmune
diseases. Other PIs
involve more than
the immune system;
some, for instance,
are associated with
symptoms involving
the heart, digestive
tract, or the
nervous system. Some
PIs retard growth
and increase the
risk of cancer.
Today, thanks to
rapid advances in
medicine, many PI
diseases can be
successfully treated
or even cured. With
proper treatment,
most people with PIs
are not only
surviving
once-deadly
diseases, they are
usually able to lead
normal lives.
Children usually can
go to school, mix
with playmates, and
take part in sports.
Most adults with PI
are leading
productive lives in
their communities.
Successfully
combatting PI,
however, depends on
prompt detection.
Physicians, parents,
and adult patients
alike need to
recognize when
infections are more
than "ordinary," so
that treatment can
be started in time
to prevent permanent
damage or
life-threatening
complications.
This booklet is
designed to make PIs
easier to recognize,
and to cope with, by
making them more
familiar. It
describes how these
diseases arise, how
they affect health,
and how they can be
treated. It also
reports on promising
areas of research,
and suggests sources
of help for patients
and their families.
It is not intended
as a substitute for
professional medical
care. You should
consult your
pediatrician or
family physician for
specific information
on the diagnosis,
treatment, and
clinical care of
patients with PI.
Top
W H A T I S P
R I M A R Y I M M
U N O D E F I C I E
N C Y ?
API
disease results
whenever one or more
essential parts of
the immune system is
missing or not
working properly at
birth because of a
genetic defect.
Since the immune
system is
tremendously
complex, hundreds of
things can go wrong
during development
and sometimes the
backup systems
cannot compensate
for the defects.
(See section on
The Immune Defenses)
A variety of
developmental errors
in the immune system
create different
types of PIs. They
make people
susceptible to
different kinds of
germs and create
different sets of
symptoms.
|
THE
IMMUNE
DEFENSE
SYSTEM
IS A
BODY-WIDE
NETWORK
OF
ORGANS,
TISSUES,
CELLS,
AND
PROTEIN
SUBSTANCES
THAT
WORK
TOGETHER
TO
DEFEND
THE BODY
AGAINST
ATTACKS
BY
"FOREIGN"
INVADERS. |
PI diseases were
once thought to be
rare, mostly because
only the more severe
forms were
recognized. Today
physicians realize
that PIs are not
uncommon. They are
sometimes relatively
mild, and they can
occur in teenagers
and adults as often
as in infants and
children.
Very serious
inherited
immunodeficiencies
become apparent
almost as soon as a
baby is born. Many
more are discovered
during the baby’s
first year of life.
Others—usually the
milder forms—may not
show up until people
reach their twenties
and thirties. There
are even some
inherited immune
deficiencies that
never produce
symptoms.
The exact number of
persons with PI is
not known. It is
estimated that each
year about 400
children are born in
the United States
with a serious PI.
The number of
Americans now living
with a primary
immunodeficiency is
estimated to be
between 25,000 and
50,000.
As new laboratory
tests become more
widely available,
more cases of PIs
are being
recognized. At the
same time, new types
of PI are being
discovered and
described.
Currently, the World
Health Organization
lists over 70 PIs
and the numbers are
increasing.
Among the rarest
forms of immune
deficiency is Severe
Combined Immune
Deficiency (SCID).
SCID has been
reported in small
numbers, while some
deficiencies, like
DiGeorge Anomaly,
are diagnosed more
commonly.
At the other
extreme, an immune
disorder called
Selective IgA
Deficiency may occur
in as many as one in
every 300 persons.
This figure is an
estimate, based on
studies of blood
from blood donors,
since most people
with IgA deficiency
are healthy and
never realize they
have this disorder.
W H E R
E D O
P R I M
A R Y I
M M U N
O D E F
I C I E
N C Y
D I S E
A S E S
C O M E
F R O M
? |
PI
diseases
are
usually
inherited.
Like
anything
that is
inherited,
these
diseases
are the
result
of
altered
or
mutated
genes
that can
be
passed
on from
parent
to child
or can
arise as
genes
are
being
copied.
(See box
on
DNA,
Genes
and
Chromosomes.)
One
or both
parents,
usually
healthy
themselves,
may
carry a
gene (or
genes)
that is
somehow
defective
or
mutated,
so that
it no
longer
produces
the
right
protein
product.
If their
child
inherits
a
defective
gene and
does not
have a
normal
gene to
compensate,
the
child
may show
signs of
immunodeficiency.
The loss
of just
one
small
molecule,
if it is
an
important
one, can
impair
the
body’s
immune
system. |
Sometimes
close
relatives—brothers,
sisters,
cousins—also
inherit
the
defective
gene. If
they do
not
inherit
a normal
gene
copy
they may
also
have
immunodeficiency.
In some
PIs,
some
relatives
may have
only
mild
symptoms,
while
others
may have
no
symptoms
at all.
It is
also
possible
to
develop,
or
acquire,
an
immunodeficiency
disorder
during
one’s
lifetime.
This can
be the
result
of
immune
system
damage
due to
an
infection,
as is
the case
with
AIDS—the
acquired
immune
deficiency
syndrome.
AIDS is
caused
by
infection
with
HIV, the
human
immunodeficiency
virus,
which
infects
immune
cells
and
destroys
the
immune
system.
When |
HIV is
transmitted
from the
mother
to the
baby,
congenital
AIDS may
occur;
but the
disease
is viral
and not
inherited.
An
immunodeficiency
can also
develop
as the
unintended
side-effect
of
certain
drug or
radiation
treatments,
such as
those
given to
cancer
or
transplant
patients.
The
focus of
this
booklet
is
primary
immunodeficiency
disease
that is
heritable.
It is
carried
through
the
genes;
you
cannot
"catch
it" like
a cold. |
Top
T H E I M M U
N E D E F E N S E
S
The
immune defense
system is a
body-wide network of
organs, tissues,
cells, and protein
substances that work
together to defend
the body against
attacks by "foreign"
invaders. Those
invaders are
primarily
germs—tiny,
infection-causing
organisms such as
bacteria and
viruses, parasites
and fungi. (See box
on Germs)
The immune system is
amazingly complex.
It can recognize
millions of
different enemies,
and it can enlist
specialized cells
and secretions to
seek out and destroy
each of them.
(Substances
recognized as
foreign that provoke
an immune response
are called
antigens.)
The organs of the
immune system are
known as lymphoid
organs because they
are home to
lymphocytes, small
white blood cells
that are key
components of the
immune defenses.
Bone marrow is soft
tissue in the hollow
center of bones, and
it is the original
source of all blood
cells. The thymus is
an organ that lies
behind the
breastbone; that is
where some
lymphocytes mature.
The spleen, located
in the upper left of
the abdomen, serves
as headquarters for
many immune system
activities.
|
T Y P E
S O F
W H I T
E B L
O O D C
E L L S |
Immune
cells,
once
alerted
to
danger,
undergo
important
changes.
They
begin to
produce
powerful
chemicals
that
allow
the
cells to
grow and
multiply,
and to
attract
and
direct
their
fellow
cells.
To
work
well,
most
immune
cells
need the
help of
other
immune
cells.
Sometimes
immune
cells
communicate
with one
another
by
direct
physical
contact,
sometimes
by
releasing
chemical
messengers.
Each
type of
immune
cell has
its
special
role. B
cells
work
chiefly
by
making
plasma
cells
that
secrete
antibodies.
Antibodies
are
large
molecules
that
attach
to
invading
germs
(and
other
foreign
particles)
and mark
them for
destruction.
T
cells
contribute
to the
immune
defenses
in two
major
ways.
Helper T
cells
and
cytotoxic
T cells
secrete
powerful
chemicals
(cytokines)
that
allow
them to
control
the
immune
responses,
including
the work
of B
cells.
Natural
killer
cells
directly
attack
cells
that
have
been
infected
by
viruses.
Phagocytes
are
large
white
blood
cells
that act
as
scavengers.
They
roam
through
the
body,
engulfing
germs
and
destroying
them.
Neutrophils
and
monocytes
are
phagocytes
that
contain
bags of
potent
chemicals
that
help
destroy
the
germs
they
engulf. |
Antibodies
are
blood
proteins
known as
immunoglobulins.
They are
produced
by B
cells.
Different
types,
or
classes,
of
immunoglobulins
play
different
roles in
immune
defenses.
As an
immune
response
unfolds,
B cells
gradually
switch
from
making
one type
of
immunoglobulin
to
another.
-
Immunoglobulin
M
(IgM)
is
the
first
to
respond
to
an
invading
germ.
IgM
antibodies
tend
to
stay
in
the
bloodstream,
where
they
aid
in
killing
bacteria.
-
Immunoglobulin
G
(IgG)
follows
on
the
heels
of
IgM.
It
is
the
main
immunoglobulin
working
in
the
blood
and
tissues.
IgG
antibodies
coat
germs
so
that
immune
cells
have
an
easier
time
of
engulfing
them.
-
Immunoglobulin
A
(IgA)
is
produced
along
surface
linings
of
the
body
and
secreted
in
body
fluids
such
as
tears,
saliva,
and
mucus,
where
it
protects
the
entrances
to
the
body—mouth,
nose,
lungs,
and
intestines.
It
is
also
present
in
breast
milk
and
provides
important
protection
against
bacteria
in
the
intestines
of
newborns.
|
-
Immunoglobulin
E
(IgE)
which
is
normally
present
only
in
trace
amounts,
is
an
important
component
of
allergic
reactions.
Another
important
component
of the
immune
defenses
is the
complement
system.
The
complement
system
is
composed
of a
series
of more
than 20
blood
proteins
that,
when
activated,
work
closely
together
in a
step-wise
fashion.
Complement
helps
antibodies
and
phagocytes
destroy
bacteria
and acts
as a
signal
for
recruiting
phagocytes
to sites
of
infections.
Although
the
immune
system
is
designed
to
recognize
and
attack
foreign
invaders,
its
recognition
program
sometimes
breaks
down.
Then the
body
begins
to make
T cells
and
antibodies
directed
against
its own
cells
and
organs.
These
misguided
T cells
and
these
autoantibodies,
as they
are
known,
contribute
to
"autoimmune"
diseases.
For
instance,
T cells
that
attack
pancreatic
islet
cells
contribute
to
diabetes,
while
certain
autoantibodies
are
common
in
persons
with
rheumatoid
arthritis. |
Lymphocytes can
travel throughout
the body, using the
blood vessels or a
system of lymphatic
vessels. The
lymphatic vessels
carry a clear fluid
known as lymph.
Scattered along the
lymphatic vessels
are small,
bean-shaped lymph
nodes, where immune
cells gather and
interact.
Clumps of lymphoid
tissue are found in
many parts of the
body, especially in
the linings of the
digestive tract and
the airways and
lungs—areas that
protect gateways
into the body. These
tissues include the
tonsils, adenoids,
and appendix.
The immune system
makes use of many
types of white blood
cells. These include
two main kinds of
lymphocytes, T
lymphocytes (T
cells) and B
lymphocytes (B
cells); and a class
of cytotoxic
lymphocytes called
natural killer (NK)
cells. Additionally,
there are large
white blood cells
known as phagocytes
(neutrophil and
monocyte).
Top
G E N E S A N
D P I
In
the past few years,
scientists have
succeeded in
identifying the
genes that are
responsible for many
PI diseases. These
include X-Linked
Agammaglobulinemia,
X-linked Hyper-IgM
Syndrome,
Wiskott-Aldrich
Syndrome, Ataxia
Telangiectasia, four
forms of Chronic
Granulomatous
Disease, and several
forms of SCID. The
search for other
genes that cause PI
is under way and
more are being
discovered.
Sometimes the same,
or nearly the same,
symptoms can be the
product of different
defective genes on
different
chromosomes. For
example, SCID can be
caused by mutations
in different genes.
One genetic defect
blocks activation of
B cells and T cells.
Another genetic
defect prevents
immune cells from
getting rid of toxic
chemicals. In every
case, however, the
end result is the
same: major immune
defenses are
non-functional.
Once researchers
have identified the
defective gene, they
try to find out what
it normally does,
what protein it
makes, and how that
protein contributes
to the immune
response. Some
proteins, for
example, relay
signals that tell
immune cells to
multiply and mature.
Other proteins help
the immune system to
eliminate excess or
unwanted cells.
The next step is to
ascertain what
happens when the
protein is missing
or distorted and how
the faulty protein
causes disease.
Learning about a
disease-causing gene
and its protein
product raises the
exciting prospect of
finding a cure for
the disease.
|
G E R M
S |
-
Bacteria
are
tiny
living
organisms.
Each
bacterium
consists
of a
single
cell,
but
bacteria
often
live
in
colonies.
Most
are
harmless
or
even
beneficial,
but
some
can
cause
illness
and
death.
Bacteria
are
responsible
for many
respiratory,
skin,
and bone
infections.
Examples
of
infection-causing
bacteria
include
"strep"
(Streptococcus)
and
"staph"
(Staphylococcus).
-
Viruses
consist
of
the
barest
essentials:
a
strand
of
genetic
material,
either
DNA
or
RNA,
surrounded
by a
protein
coat.
Some
viruses
also
have
an
outer
envelope.
Viruses
are
so
simple
that,
in
order
to
reproduce,
they
need
to
invade
a
living
cell
and
use
the
cell’s
machinery.
Different
types of
viruses
target
different
types of
cells.
Some
viruses
kill the
cell
they
invade.
Others
permanently
change
the way
the cell
behaves. |
Viruses
cause
the flu
(or
influenza,
a highly
contagious
respiratory
infection),
colds,
polio,
hepatitis
(liver
inflammation),
and
measles.
A single
virus
family,
Herpes
viruses,
causes
everything
from
cold
sores to
chicken
pox.
-
Parasites
live,
grow,
and
feed
on
other
organisms,
which
serve
as
their
"hosts."
Parasites
come
in
many
shapes
and
sizes,
and
they
cause
a
wide
range
of
diseases.
Microscopic
one-cell
parasites
known as
Cryptosporidium
and
Giardia
lamblia
cause
diarrhea
and
inflammation
of the
digestive
system.
Pneumocystis
carinii
can
cause
pneumonia,
and
Toxoplasma
gondii
can
produce
brain
inflammation.
-
Mycoplasma
are
simpler
than
bacteria
but
more
complex
than
viruses.
They
are
the
smallest
known
organisms
that
can
live
without
a
host.
Mycoplasma
can
cause
pneumonia
and
a
type
of
arthritis.
|
-
Fungi,
which
are
primitive
plant
forms,
include
yeasts
and
molds.
As a
cause
of
disease,
they
are
especially
dangerous
for
persons
with
impaired
immunity.
A
fungus
called
Candida
albicans
causes
thrush,
which
commonly
forms a
white
mat
coating
on the
inside
of the
mouth in
severely
immunodeficient
people.
This
fungus
may also
cause
esophagitis,
a type
of
diaper
rash, or
a blood
infection.
Cryptococcus
can
cause
meningitis,
an
inflammation
of the
membranes
surrounding
the
brain
and
spinal
cord.
Aspergillus,
an
ordinarily
harmless
mold,
can
cause
severe
infections
in those
with PI,
especially
infections
of the
lung. |
One possibility
might be to replace
a mutated gene
through gene
therapy. Another way
might be to supply
the missing protein
as a medicine.
Top
S I G N S A N
D S Y M P T O M S
The
most common problem
in PI disease is an
increased
susceptibility to
infection. For
people with PI,
infections may be
common, severe,
lasting, or hard to
cure.
Even healthy
youngsters may get
frequent colds,
coughs, and
earaches. For
example, many
infants and young
children with normal
immunity have one to
three ear infections
per year. Children
with PI, however,
can get one
infection after
another. Or they get
two or three
infections at a
time. Weakened by
infection, the child
may fail to gain
weight or fall
behind in growth and
development.
Despite the usual
antibiotics, the
infections of PI
often drag on and
on, or they keep
coming back—that is,
they become chronic.
One common problem
is chronic sinusitis
(infection and
inflammation of the
sinuses, air
passages in bones of
the cheeks,
forehead, and jaw).
Another common
problem is chronic
bronchitis
(infection and
inflammation of the
airways leading to
the lungs).
|
D N A ,
G E N E
S , A
N D C H
R O M O
S O M E
S |
All our
traits—height,
eye
color,
foot
size—are
determined
by the
genes
that we
inherit
from our
parents.
A gene
is a
working
subunit
of
DNA.
DNA is
like a
huge
database,
made up
of
millions
of
chemical
building
blocks.
DNA
resides
in the
core of
every
cell,
and it
carries
a
complete
set of
instructions,
or
blueprint,
for
making
everything
the cell
will
ever
need.
The
DNA in
each
human
cell
contains
about
100,000
genes.
Each
gene
encodes
the
instructions
that
allow
the cell
to make
one
specific
product—for
example,
a
protein
such as
an
enzyme.
(Proteins
are
major
components
of all
cells.
Enzymes
are
proteins
which
help
carry
out
chemical
reactions.) |
When
genes
are
working
properly,
our
bodies
develop
correctly
and work
well.
But
small
changes,
or
mutations,
in just
one gene
sometimes
can have
huge
effects,
leading
to birth
defects
and
other
diseases.
DNA is
packaged
in
structures
known as
chromosomes.
Chromosomes
come in
pairs,
and a
normal
human
cell
contains
46
chromosomes.
These
consist
of 22
pairs of
"autosomes"
and two
"sex
chromosomes,"
X and Y.
A female
has two
X
chromosomes
while a
male has
one X
and one
Y.
|
We
inherit
one
chromosome
of each
pair
from our
mother
and the
other
from our
father.
Since
genes
are
lined up
on the
chromosomes,
we thus
inherit
two
copies
of most
genes,
one from
each of
our
parents.
If
one copy
of a
gene is
not
working
properly,
its
partner
from the
other
parent
can
often
compensate.
However,
this is
not
possible
if both
copies
of the
gene are
defective
or, in
the case
of an X
chromosome
gene
defect
in a
boy,
where
there is
only one
X
chromosome. |
Serious infections,
especially bacterial
infections, may
cause a youngster to
be hospitalized
repeatedly.
Pneumonia is an
infection of the
smallest airways and
airsacs in the
lungs, which
prevents oxygen from
reaching the blood
and makes breathing
hard. Meningitis, an
infection of the
membranes that
surround the brain
and spinal cord,
causes fever and
severe headache, and
can lead to
seizures, coma, and
even death.
Osteomyelitis is an
infection that
invades and destroys
bones. Cellulitis is
a serious infection
of connective
tissues just beneath
the skin.
Some people with PI
develop blood
poisoning, an
infection that
flourishes in the
bloodstream and
spreads rapidly
through the body.
Some people may
develop deep
abscesses, pockets
of pus that form
around infections in
the skin or in body
organs.
Some children with
PI are infected with
germs that a healthy
immune system would
hold in check. These
are known as
"opportunistic"
infections because
the germs take
advantage of the
opportunity afforded
by a weakened immune
system. Such an
unusual infection
may be the tip-off
to an
immunodeficiency.
For example,
Pneumocystis carinii
is a microscopic
parasite that
infects many healthy
people without
making them sick.
But when the immune
system is
compromised,
Pneumocystis can
produce a severe
form of pneumonia.
Toxoplasma is
another widespread
parasite that
usually produces no
disease. In persons
with a weakened
immune system, it
causes
toxoplasmosis, which
can be a
life-threatening
infection of the
brain that can cause
confusion,
headaches, fever,
paralysis, seizures,
and coma.
|
P A T T
E R N S
O F I N
H E R I
T A N C
E |
Scientists
studying
inherited
diseases
group
them
according
to the
way in
which
the
disease-causing
gene is
passed
on. In
general,
"recessive"
diseases
occur
when
there is
no
normal
copy of
a gene
to
compensate
for a
defective
one,
while
"dominant"
diseases
are
manifest
even
with one
normal
and one
abnormal
gene
copy.
Diseases
caused
by
defects
in a
single
gene
fall
into one
of the
following
categories:
-
X-linked
recessive
diseases
are
caused
by
genes
located
on
the
X
chromosome.
Although
we
have
two
copies
of
most
genes,
men
have
only
one
X
chromosome
and
only
one
copy
of
genes
on
that
X
chromosome.
If a
man
inherits
a
disease-causing
gene
mutation
that
is
on
the
X
chromosome,
he
has
no
backup
normal
X
gene,
and
he
will
likely
develop
the
disease.
A
woman
will not
usually
develop
an
X-linked
recessive
disease
because
she has
two X
chromosomes,
but she
can be a
"carrier."
She
remains
healthy
because
the
normal
gene on
one X
chromosome
continues
to
function,
even
though
she
carries
the
mutated
gene,
and can
pass it
on to
her
children.
With
each and
every
pregnancy,
there is
an equal
chance
that the
baby
will be
a boy
with the
disease,
a
healthy
girl who
is a
carrier,
a
healthy
boy, or
a
healthy
girl who
is not a
carrier. |
For
some
X-linked
recessive
immunodeficiency
diseases,
carriers
can be
identified
by
laboratory
tests.
With
others,
a woman
is
discovered
to be a
carrier
only
after
she
gives
birth to
a child
with the
disease.
-
Autosomal
recessive
diseases
occur
when
a
person
inherits
two
faulty
recessive
genes
located
on
autosomes
(non-sex
chromosomes),
one
from
each
parent;
both
parents
are
healthy
carriers.
These
diseases
are
as
likely
to
affect
girls
as
boys.
With
every
pregnancy,
there
is
one
chance
in
four
that
the
baby
will
have
the
disease,
two
chances
in
four
that
the
baby
will
be
healthy
but
a
carrier,
and
one
chance
in
four
that
the
child
will
be
healthy
and
not
carry
a
defective
copy
of
the
gene.
-
Autosomal
dominant
disorders
are
caused
by a
single
dominant
gene.
One
of
the
parents
is
not
just
a
carrier,
but
has
the
disease.
Each
child
in
the
family
has
a
50-50
chance
of
inheriting
the
defective
gene
and
the
disorder.
-
New
mutations
may
cause
diseases.
In
some
cases,
neither
parent
has
the
disease-causing
mutation.
This
may
occur
because
the
mutation
in
the
gene
occurred
in
the
parents’
germ
cells
(sperm
or
egg)
but
not
other
cells
of
their
body.
New
mutations
account
for
a
substantial
proportion
(up
to
one-third)
of
X-linked
immunodeficiency
diseases.
|
Although
many PI
diseases
can be
traced
to a
single
gene,
others
cannot.
No
family
pattern
is
evident,
and they
are said
to occur
"sporadically."
A
sporadic
disorder
might be
the
result
of
several
disabled
genes
interacting,
interactions
between
particular
forms of
genes,
and
environmental
influences.
It might
develop
from
gene
changes
that
occur
during a
person’s
lifetime.
Or it
might be
due to
new
mutations
in germ
cells or
an
inheritance
pattern
that has
not been
recognized
yet.
Some
PIs are
X-linked,
others
autosomal
recessive.
At least
one is
autosomal
dominant.
Some PIs
have
more
than one
pattern
of
inheritance.
For
example,
a group
of
diseases
known as
Common
Variable
Immunodeficiency
(CVID)
can be
inherited
as
autosomal
recessive,
autosomal
dominant,
or
X-linked.
Most
cases of
CVID,
however,
are
sporadic. |
Besides all the
infections, some
immunodeficiency
diseases produce
other immune system
problems, including
autoimmune
disorders.
Autoimmune disorders
develop when the
immune system gets
out of control and
mistakenly attacks
the body’s own
organs and tissues.
In some autoimmune
disorders, the
faulty immune system
targets a single
type of cell or
tissue. For example,
an immune attack on
blood cells can lead
to anemia (a
debilitating loss of
red blood cells). An
attack on islet
cells of the
pancreas can lead to
diabetes (a disorder
caused by
insufficient amounts
of insulin, a
pancreatic hormone
that helps the body
convert digested
food into energy).
In other situations,
the immune system
strikes multiple
cells and tissues,
producing diseases
such as rheumatoid
arthritis or
systemic lupus
erythematosus (SLE).
Rheumatoid arthritis
targets primarily
the joints, but it
can also damage
nerves, lungs, and
skin. Lupus strikes
skin, muscles,
joints, kidneys, and
other organs,
causing rashes,
joint pain, fatigue,
and fever, among
other things.
Finally, an
immunodeficiency can
be just one part of
a complex syndrome,
with a telltale
combination of signs
and symptoms. For
example, children
with DiGeorge
Anomaly not only
have an
underdeveloped
thymus gland (and a
corresponding lack
of T cells), they
typically have
congenital heart
disease,
malfunctioning, or
underdeveloped
parathyroid glands,
and characteristic
facial features.
Young boys with
Wiskott-Aldrich
Syndrome, in
addition to being
prone to infections,
develop bleeding
problems and a skin
rash.
T H E 1
0 W A R
N I N G
S I G N
S O F
P R I M
A R Y
I M M U
N O D E
F I C I
E N C Y
*
-
Eight
or
more
new
ear
infections
within
a
year.
-
Two
or
more
serious
sinus
infections
within
a
year.
-
Two
or
more
months
on
antibiotics
with
little
effect.
-
Two
or
more
pneumonias
within
a
year.
-
Failure
of
an
infant
to
gain
weight
or
grow
normally.
-
Recurrent
deep
abscesses
in
the
skin
or
organs.
-
Persistent
thrush
in
mouth
or
on
skin,
after
age
one.
-
Need
for
intravenous
antibiotics
to
clear
infections.
-
Two
or
more
deep-seated
infections
such
as
meningitis,
osteomyelitis,
cellulitis,
or
sepsis.
-
A
family
history
of
primary
immunodeficiency.
*Courtesy
of The
Jeffrey
Modell
Foundation
and the
American
Red
Cross. |
Top
D I A G N O S I
N G P I
Sometimes
the signs and
symptoms of a PI are
so severe, or so
characteristic, that
the diagnosis is
obvious. In most
cases, it is not
clear if a long
string of illnesses
are just "ordinary"
infections, or if
they are the result
of an
immunodeficiency.
Many conditions can
produce an
immunodeficiency, at
least temporarily,
and most children
who seem to have
"too many"
infections are not,
in fact, suffering
from an
immunodeficiency.
Experts estimate
that half of the
children who see a
doctor for frequent
infections are
normal. Another 30
percent may have
allergies, and 10
percent have some
other type of
serious disorder.
Just 10 percent turn
out to have a
primary or secondary
immunodeficiency.
T H E B A S I C S
When a pattern of
frequent infections
suggests an
immunodeficiency,
the doctor begins by
exploring the
patient’s "history"
and the family’s
history, and then
conducts a physical
examination.
-
The patient’s
history.
What infections
has the patient
had in the past,
or has now? Have
they been
unusually
frequent, or
severe, or
long-lasting?
Have they failed
to respond to
standard
treatments? When
a child who is
immunologically
normal develops
a string of
infections, they
are usually mild
and short-lived,
and between
infections the
child recovers
completely.
What, besides a PI,
might explain the
high rate of
infections? Normal
immune responses can
be suppressed by
many factors,
including
malnutrition,
injuries such as
burns, and certain
types of drugs
(corticosteroids,
for instance).
Immune responses can
also be muted by
some diseases, such
as leukemia, and
some infections,
including:
infectious
mononucleosis
(mono), measles,
chicken pox, and
AIDS. In fact,
almost every serious
illness impairs the
immune responses.
-
Physical
examination:
Is the child
well-nourished
and growing
well? A severely
immunodeficient
child is likely
to look sickly
and pale. Very
often the child
is underweight
and lags behind
in growth and
development.
The child may be shy
or quiet. An active,
robust,
healthy-looking
child is less likely
to have a serious
immune deficiency.
The doctor will
listen for changes
in the lungs and
look for rashes,
sores, thrush in the
mouth, an enlarged
spleen or liver, and
swollen joints. Some
immunodeficient
children may lack
palpable tonsils or
lymph nodes in the
neck.
-
Family
history.
Have any family
members or
relatives ever
been diagnosed
with PI or shown
an unusual
susceptibility
to infections?
Have there been
any infant
deaths from
infections? Were
only boys
|