Page 1053 - Clinical Immunology_ Principles and Practice ( PDFDrive )

1016 Part seven Organ-Specific Inflammatory Disease

inflammation of the colon and its complications, including the most frequent isolate, S. aureus) is generally appropriate
perirectal and perianal abscesses. In the case of hepatic abscess although percutaneous aspiration of hepatic abscesses maybe
detection (generally 1–6 cm), CT, MRI, and ultrasonography helpful. 83
have similar sensitivity (≈60%). Active abscesses appear to be
solid, hypoechoic lesions on ultrasonography or postcontrast
ring–enhancing lesions on CT and MRI. KeY COnCePts
The GI histological diagnosis hinges on the presence of Chronic Granulomatous Disease (CGD)
noncaseating granulomata, both gross and microscopic. These
granulomata are often seen against a background of acute • Half of patients with CGD develop gastrointestinal (GI) involvement
inflammation (acute focal colitis, crypt abscesses, cryptitis) as with granulomatous inflammation.
well as chronic inflammation (lymphocytic infiltrate, Paneth • Symptoms are caused by both obstructive complications of stricture
formation and mucosal inflammation.
cell metaplasia in the colon) that can be mild to severe. The • A resemblance to Crohn disease is suggested by granulomatous
histological picture may resemble Crohn disease except that the inflammation, transmural bowel involvement, and underlying innate
granulomata of CGD are well defined, often large collections of immune defect, but unlike in Crohn disease, there are also prominent
epithelioid histiocytes that can expand the mucosa (and even skin and lung infections and periodic acid-Schiff–positive lipid-laden
deform the overlying epithelium to make it look flattened in the macrophages in the lamina propria.
case of the villous mucosa of the small intestine). Like Crohn • Complicated hepatic abscesses require specialized medical
intervention.
disease, the inflammation can affect the three layers of the gut
wall, but unlike in Crohn disease, CGD biopsy specimens also
show prominent lipid-laden macrophages that have periodic
acid-Schiff (PAS)–positive cytoplasmic granules. GI Complications Occurring in Other Primary
Immunodeficiency States
Treatment Severe combined immunodeficiency (SCID) covers a wide
Current clinical practice for CGD includes using prophylactic phenotype of low-to-absent T cells, NK cells, and dysfunctional
antimicrobials to prevent infections, typically trimethoprim- B cells reflecting the mechanisms of the genetic defect (Chapter
sulfamethoxazole for bacterial and itraconazole for fungal 35). Recurrent infectious diarrhea and thrush are typical GI
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infections. Some clinicians also use IFN-γ (subcutaneous, three- conditions before a diagnosis of SCID in newborns and neonates.
times-weekly dosing) to prevent infections, although this is not After allogeneic hematopoietic stem cell transplantation (HSCT),
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a universal practice. Obviously, discovery of infectious etiologies GI graft-versus-host disease (GvHD) is a possibility. For many
of diarrhea should be treated appropriately. of the monogenic immunodeficiency diseases that confer sus-
Once infections are ruled out and granulomatous inflammation ceptibility to GI inflammation, the success of HSCT to correct
of the GI tract is established, with or without complications, the secondary effect on the GI tract will depend entirely on
such as stricturing of the bowel, treatment with corticosteroids whether the gene defect affects the myeloid or lymphoid cells
is indicated; beginning doses up to 1 mg/kg/day tapering over primarily. If the gut stromal or epithelial cells also depend on
12–20 weeks to maintenance doses of 2.5–5 mg every other day normal function of the defective gene, then bone marrow
has been reported to induce rapid alleviation of symptoms. Use transplantation will not likely relieve the GI effects.
of sulfasalazine for colitis may have limited benefit in some The rare X-linked recessive Wiskott-Aldrich syndrome
patients. Isolated reports of successful use of cyclosporine and (Chapter 35) results from Wiskott-Aldrich syndrome (WAS) gene
infliximab have indicated that these agents are best reserved for mutations, a signaling protein largely restricted to hematopoietic
refractory cases because of the potential for infectious side effects. cells, and leads to a syndrome of eczema, thrombocytopenia,
Similarly both granulocyte–colony-stimulating factor (G-CSF) and infections related to combined immunodeficiency (impaired
and granulocyte macrophage–colony-stimulating factor (GM-CSF) antibody responses and T-cell function). An interesting aspect
have been used with therapeutic benefit in GI complications of of the gut complication in this immunodeficiency is that patients
CGD because of their success in the granulomatous colitis of may develop a noninfectious colitis resembling UC (confluent
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glycogen-1-β storage disease. Although there are no data to mucosal inflammation with ulceration, crypt abscesses, and no
suggest that IFN-γ worsens established disease, it also may not granulomata) with the bleeding exacerbated by the thrombo-
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prevent it as >40% of one cohort developed GI manifestations cytopenia. Patients may respond to mesalamine drugs, but use
of granulomatous inflammation after starting it; in contrast, of steroids and immunosuppressive must be done cautiously
isolated reports have attributed alleviation of GI inflammation because of exacerbating infection risk. Successful bone marrow
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to IFN-γ. IL-1 receptor blockade, based on preclinical efficacy transplantation can treat the colitis as well.
data in CGD, may offer limited success. 82 Early-onset IBD is a severe complication of rare mutations
Finally, it cannot be overstated that surgical drainage of that affect IL-10 production or the IL-10 receptor. Patients present
complicating abscesses and resection of fibrotic or refractory with colitis within weeks of birth that has features of Crohn
strictures need to be pursued, when indicated. Although there disease. Diagnosis is made by genetic testing as well as by assay
can be considerable postoperative complications because of of peripheral blood mononuclear cells for absence of IL-10
ongoing fistula formation and wound breakdown, these problems production or absent IL-10 signaling demonstrated by decreased/
can be managed by administration of corticosteroids. In addition, absent induction of phospho-STAT3 following the addition of
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judicious use of endoscopic therapy to dilate narrowed esophageal IL-10. The only cure is with HSCT.
or pyloric regions is an option for symptomatic strictures. The hyper-IgM syndrome (type 1) (Chapter 34) is an X-linked
Treatment of hepatic abscesses has been shown to be amenable condition resulting from mutations in CD40 ligand leading
to nonsurgical management by adding corticosteroids to the to defective antibody class switching (hence high [or normal]
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antibiotic regimen. Empiric antibiotic coverage (at least to cover IgM with low IgA and IgG) and NK- and T-cell cytotoxicity.