Page 547 - Clinical Immunology_ Principles and Practice ( PDFDrive )

CHaPtEr 37 Infections in the Immunocompromised Host 525

requires rapid assessment, with particular focus on physical
examination of areas with high bacterial colonization, such as PRIMARY CELLULAR AND COMBINED
the oral cavity and perianal region, as well as sites of indwelling IMMUNODEFICIENCIES (Chapter 35)
intravenous catheters. Empiric broad-spectrum antibiotics after
obtaining appropriate cultures are often prudent. Severe Combined Immunodeficiency
Monocytopenia has been described in GATA2 deficiency and Severe combined immunodeficiency (SCID) results from a severe
associated with disseminated Bacille Calmette-Guérin (BCG) deficiency in the number or function of T cells. Depending on
with interferon (IFN) regulatory factor 8 (IRF8) deficiency. 11,12 the genetic defect, B and/or natural killer (NK) cells are affected
The described spectrum of GATA2 deficiency is increasing and as well. Presentation is typically very early in life, with significant
includes MonoMAC syndrome, Emberger syndrome with compromise within the first few months of life. In recent years,
lymphedema and myelodysplasia, familial leukemia, aplastic there has been more recognition of “leaky” forms of SCID, in
11
anemia, and childhood-onset neutropenia. The predominant which the defects are not complete and presentation can be later
clinical findings are disseminated mycobacteria; fungal infections, and more variable. 16
such as disseminated histoplasmosis; warts with cervical and SCID is associated with recurrent and persistent viral, bacterial,
vulvar dysplasia; pulmonary alveolar proteinosis (PAP); myelo- and fungal infections. PJP frequently occurs in early infancy,
dysplasia; and leukemia. Onset is typically in later childhood and prophylaxis should be provided. Chronic mucocutaneous
and adulthood, and in addition to monocytopenia, lymphocy- candidiasis (CMC) is frequent and may require antifungal sup-
topenia may be present. When the patient is symptomatic, pressive therapy. Diarrhea from viral and other etiologies fre-
treatment is typically with HSCT. quently leads to failure to thrive. Severe respiratory viral infections
and CMV also occur. In countries where BCG vaccine is given,
HUMORAL IMMUNODEFICIENCIES (Chapter 34) disseminated infection may result; transplantation may lead to
an immune reconstitution syndrome in which sites of BCG
Humoral immunodeficiencies are characterized by absent or infection become inflamed and abscesses may form.
defective B cells with resultant lack of specific antibody responses,
leading predominantly to infections with encapsulated bacteria. DiGeorge Syndrome
There is a spectrum of severity with X-linked agammaglobulin- Immune deficiency in DiGeorge syndrome results from varying
17
emia (XLA) characterized by a total absence of B cells and degrees of thymic hypoplasia or aplasia. Other manifestations
presentation in the first years of life and the later presentations include congenital heart disease, characteristic facies and palate
of common variable immunodeficiency (CVID). 13 anomalies, hypocalcemia, and learning disabilities. With the
Humoral immunodeficiencies are characterized by recurrent exception of severe cases in which there is thymic aplasia and
ear, sinus, and lung infections, with typical bacterial etiologies severe T-cell lymphopenia, opportunistic infections (OIs) are
being Streptococcus pneumoniae and Haemophilus influenzae. infrequent. Upper respiratory tract infections predominate, and
Despite immunoglobulin (Ig) replacement, bronchiectasis may prophylactic antibiotics may not be necessary. With the more
occur, and with it, the spectrum of pulmonary infections may mild defects, live viral vaccination may be considered safe. 18
broaden requiring careful microbiological monitoring. Neutro-
penia may occur with XLA and CD40 ligand deficiency, frequently Autosomal Dominant Hyper-IgE Syndrome
when replacement Ig is not provided, and may be associated (Job’s Syndrome)
with a broader spectrum of infection, with more severe S. aureus Autosomal dominant hyper-IgE syndrome (Job’s syndrome;
and Pseudomonas infections. Chronic Mycoplasma and Ureaplasma AD-HIES), resulting from STAT3 mutations, has been frequently
spp. infections can occur leading to lung disease and arthritis. characterized as a phagocytic defect. However, in recent years,
Giardia can be a source of GI disease. In severe humoral defects, it has been recognized that the immune defects center around
such as XLA, persistent Helicobacter, Flexispira, and Campylobacter the failure of T-helper 17 (Th17) cell differentiation and a decrease
spp. infections are infrequent and are characterized by ulcerative in memory T and B cells. 19,20 A lack of Th17 cells resulting in
skin lesions. 14,15 These infections require a high index of suspicion impaired interleukin-17 (IL-17) and IL-22 signaling and dimin-
to be identified, as special microbiology media with longer lengths ished antimicrobial peptide upregulation appears to at least
of incubation may be required. Eradication of infection, even explain some of the infection susceptibility.
with a combination of intravenous antibiotics, is often difficult. AD-HIES is characterized by recurrent skin and lung bacterial
Severe meningoencephalitis with enteroviral infections may occur infections, CMC, eczema, and a variety of connective tissue,
20
and can be quite devastating and difficult to treat. Replacement skeletal, and vascular abnormalities. S. aureus skin abscesses
Ig therapy, given intravenously or subcutaneously, is used to start early in life, and S. aureus colonization appears to drive the
minimize the recurrent encapsulated bacterial infections and eczema. S. aureus, S. pneumoniae, and H. influenzae pneumonias
diminish the risk of enterovirus infection. The role of prophylactic typically start in the first few years of life, and prophylactic
antibiotics is not well studied and varies among centers. antimicrobials, such as TMP-SMX, can be useful in reducing
CD40 ligand deficiency (X-linked hyper-IgM) is the most the frequency. Healing of pneumonias appears aberrant, and
13
common of the Ig class switch defects. Sinopulmonary infections bronchiectasis and pneumatoceles frequently result. The lung
similar to XLA typically arise in early childhood. However, as with these parenchymal abnormalities is then predisposed to
opposed to XLA, Pneumocystis jiroveci pneumonia (PJP) occurs mold infections (most frequently Aspergillus and Scedosporium
and may be the initial infection. Other infections indicative of spp.) and gram-negative infections, such as with Pseudomonas
T-cell defects occur as well, including cytomegalovirus (CMV) aeruginosa and nontuberculous mycobacteria (Fig. 37.2). These
infection, toxoplasmosis, and cryptosporidiosis. Cryptosporidial secondary infections can be quite difficult to eradicate. CMC is
infection can be a chronic and severe problem and may lead to the most frequent fungal infection. PJP is much less frequent,
sclerosing cholangitis. typically occurring in infancy, potentially as the first pneumonia.