Thoracic Imaging 2003 - Society of Thoracic Radiology

The Spectrum of Pulmonary Infection in the
Immunocompromised Child
Richard I. Markowitz, M.D.
The Children’s Hospital of Philadelphia & University of Pennsylvania School of Medicine
Although respiratory infection is one of the most common
childhood illnesses, it can be a signal of an underlying abnormality
of the immune system. A high frequency of infection, an
infection of unusual severity ,or an infection by an organism
usually not pathogenic in a healthy individual should arouse
suspicion of an immunodeficiency.1
However, the radiologic and pathologic patterns of disease in
imrnunodeficient children are not different from the patterns of
infection found in normal individuals.2 These pathologic patterns
differ according to the distribution and extent of pulmonary
infection and include bronchopneumonia, interstitial
pneumonia, lobar pneumonia, lung abscess, empyema,
bronchiectasis, and overwhelming pneumonia. Examples of
these patterns will be shown demonstrating the wide and variable
spectrum of pulmonary infection in the immunocompromi
sed child.
The most common immune defects in children are not due to
rare genetic mutations, but are secondary to common systemic
problems such as severe malnutrition,3 debilitating chronic illness,
or immaturity of the immune system.. Iatrogenic immunodeficiency
is a common side effect of steroids, chemotherapy,
and radiation predisposing these children to serious infection.
Infants are especially vulnerable to infection because of the
immaturity of their immune system, although they do obtain
passive immunity from their mothers.
Host Defenses
Much has been learned concerning the factors and mechanisms
that comprise the immune system. Cellular, humoral, and
mechanical factors work in concert to prevent microorganisms
from literally “eating us alive.” T-lymphocytes, B-lymphocytes,
natural killer cells, granulocytes, complement, and antibodies as
well as a wide variety of receptors and polypeptide mediators
known as cytokines interact in complex ways. The first barrier
to infection is the skin and mucous membranes which afford
mechanical protection. When these mechanical defenses are
impaired as in cystic fibrosis or immotile cilia syndrome ,chronic
infection can lead to irreversible tissue destruction, i.e.
bronchiectasis.
Primary 1mm unodeficiency Disorders
Primary immunodeficiency disorders are inherited diseases
which affect one or more specific parts of the immune system.
Although they have been classified by which cell type is predominantly
affected, there is a large overlap in the ways these
disorders cause disease.4 First, we will consider T-cell (cellular)
immune deficiency, then B-cell (humoral) immune deficiency,
and then combined T and B cell deficiency syndromes. Finally,
we will discuss some disorders of phagocytic function and complement
deficiencies. Although all of these disorders result in
increased susceptibility to pathogens, humoral defects, such as
Bruton’ s agammaglobulinemia, predispose patents to bacterial
infections, while cellular or T-cell defects make the individual
more prone to viral, fungal, and parasitic diseases.
Disorders of cellular immunity
The prototype genetic defect of T-cell immunity is DiGeorge
syndrome or congenital thymic hypoplasia. This disease derives
from a deletion at the chromosome 22q11 site which inhibits
normal development of structures derived from the third and
forth pharyngeal pouches. Partial or complete absence of
thymic lymphoid tissue results in varying degrees of T-cell deficiency;
absence of the parathyroid glands causes hypocalcemia
which can lead to tetany; and cardiac and aortic arch anomalies
are frequent.5 These patients present in early infancy, and their
course is often complicated by severe viral and fungal infections.
Radiologic recognition of the absent thymus is a valuable
clue in the first day or two of life, but becomes more difficult
thereafter because severe stress in infants with other illnesses
can cause rapid thymic involution.
Disorders of humoral immunity
X-linked agammaglobulinemia (Bruton) is a prime example
of a defect in humoral immunity caused by a failure of development
of B-cell precursors into mature B-cells. This genetic
defect of B-cell maturation results from a mutation on the long
arm of the X chromosome responsible for the production of a
specific tyrosine kinase (Bruton tyrosine kinase or btk) which is
necessary for pro B-cells and pre-B-cells to properly develop
into mature B-cells capable of producing biologically active
gamma-globulin.6 Because of the location on the X chromosome,
this X-linked recessive disease presents only in the sons
of maternal carriers. Clinical manifestations include absent germinal
centers of lymph nodes; underdeveloped tonsils, adenoids,
and hilar lymph nodes; absent plasma cells; and severely diminished
serum gamma-globulin. Recurrent bacterial infections of
the respiratory tract due to Streptococcus pneumoniae,
Staphylococcus aureus, and Haemophi/us influenzae are common
and may lead to bronchitis, pneumonia, bronchiectasis ,
and empyema. Radiologic signs of this disease include a paucity
of the normal lymphoid structures surrounding the upper airway,
i.e. absent tonsils and adenoids, as well as recognition of an
increased frequency and severity of infections with common
pyogenic organisms. Immunoglobulin replacement is standard
treatment.
Selective or isolated IgA deficiency is common occurring in
approximately 1 in 600 people.7 Both serum and secretory IgA
are absent due to a failure of maturation of fgA-positive B-cells.
It can be a familial defect or acquired following a viral infection.
Most individuals are asymptomatic, but are prone to variable
bacterial infections of the sinuses, respiratory tract, and
gastrointestinal tract.
The term “common variable agammaglobulinemia” denotes
a heterogeneous group of disorders characterized by defective
B-cell function and frequent bacterial sinus and pulmonary
infections. Bronchitis and bronchiectasis may lead to chronic
respiratory failure.7 Non-caseating granulomas are often found
as well. Gastrointestinal infections are also common.
Hyperimmunoglobulin E syndrome, sometimes referred to as
Job’s syndrome, is a rare inherited disorder which manifests
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