Page 345 - Clinical Immunology_ Principles and Practice ( PDFDrive )

CHaPtEr 22 Phagocyte Deficiencies 325

diminished levels of Kell blood group antigens. Patients may Pulmonary aspergillosis remains a major cause of death in
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eventually develop progressive neurodegenerative symptoms, CGD. Aspergillus fumigatus is the most commonly isolated
such as areflexia, dystonia, and choreiform movements. In patients fungus, but it is now easily and successfully treated with azole
with McLeod syndrome, anti-Kx and anti-Km antibodies are antifungals. In contrast, A. nidulans and A. viridinutans, species
formed when transfusions are given, making future transfusions with low pathogenicity in the normal host, cause severe disease in
extremely difficult. Deletions centromeric from CYBB may cause CGD. 34,35 Surgical resection of these infections is often required.
ornithine decarboxylase deficiency along with CGD. 28 Aspergillus infections in CGD are often unaccompanied by fever
34
and leukocytosis. Acute diffuse pulmonary fungal infection in
Autosomal Recessive CGD CGD is referred to as “mulch pneumonitis,” characterized by fever,
Mutations in p47 phox (NCF1, located at 7q11.23) cause the majority hypoxia, and diffuse pulmonary infiltrates caused by inhalation
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of the recessive cases of CGD, around 25%, usually caused by of fungi, typically during mulching, leaf raking, or gardening.
homozygous deletions of the canonical GT splice site at the start This syndrome can be the initial presentation of CGD in older
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of exon 2. p22 phox (CYBA, located at 16q24) and p67 phox (NCF2, children and adults and is important to recognize, since it best
located at 1q25) are responsible for less than 5% of CGD cases responds to a combination of antifungals and steroids.
each. p40 phox (NCF4, located at 22q13.1) deficiency has been Septicemia is relatively uncommon but may occur with B.
reported in a boy with early-onset severe granulomatous fistulizing cepacia complex and Chromobacterium violaceum. Granulibacter
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colitis without a significant infectious phenotype. No autosomal bethesdensis is a pathognomonic gram-negative rod that causes
dominant cases of CGD have been identified. chronic necrotic lymph node and spleen involvement in CGD. 37
Inflammatory granuloma formation is one of the hallmarks
Clinical Manifestations of CGD of CGD. Pyloric outlet obstruction, bladder outlet obstruction,
The first severe infection usually occurs in infancy or childhood and ureteral obstruction are common. Crohn-like IBD affects
but can also occur in adulthood. Later diagnoses usually are between 30–50% of patients, predominantly X-linked, and may
seen in patients with residual superoxide production, either involve the esophagus (Fig. 22.6), jejunum, ileum, cecum, rectum,
38
hypomorphic gp91 phox or p47 phox deficiency. 23,31 The constellation and perirectal area. GI manifestations can include diarrhea,
of signs and symptoms that suggest CGD range from failure to
thrive, to IBD, to visceral abscesses, to recurrent sinopulmonary
infections, to characteristic infections. Infections are most com-
monly pneumonia, lymphadenitis, liver abscess, skin abscess,
perianal abscess, and osteomyelitis. As in other neutrophil defects,
the most common pathogen is S. aureus. Characteristic infections
are caused by catalase-positive organisms such as S. aureus,
Burkholderia cepacia complex, Serratia marcescens, Nocardia spp.,
and Aspergillus spp. (Fig. 22.5).
Staphylococcal liver abscesses in CGD are dense and necrotic
and cause significant morbidity. Their fibrocaseous consistency
means that percutaneous drainage was rarely successful, and
open surgery was required. However, combined steroid and
antibiotic therapy of CGD liver abscess has now become the
32
preferred approach in many centers. Liver involvement leading
to portal hypertension is the likely cause of the splenomegaly
commonly seen in CGD and is also closely tied to mortality. 33

FIG 22.5 Computed Tomography (CT) Scan of the Lungs of
a Patient With Chronic Granulomatous Disease (CGD) and FIG 22.6 Esophageal Involvement in Chronic Granulomatous
Aspergillus Pneumonia. Aspergillus pneumonia is often a Disease (CGD). Esophageal strictures caused by granuloma
peripheral consolidation in the lung parenchyma. formation as shown by barium swallow.