Page 1052 - Clinical Immunology_ Principles and Practice ( PDFDrive )

CHaPter 75 Immunological Diseases of the Gastrointestinal Tract 1015

treated with a recommended course of conventional antibiotics, (especially Salmonella spp. and C. difficile) occurs in CGD, an
including those positive for the C. difficile toxin. SIBO should be idiopathic CGD-associated IBD also develops: In the mouth,
treated, and recurrent SIBO may need cycling antibiotic regimens. granulomatous stomatitis and dental abscesses cause pain and
The treatment of the idiopathic enteropathy is very challenging. difficulty eating; in the esophagus, dysphagia, chest pain, and
Although this seems to be a late complication in a subset of vomiting may result from narrowing by strictures or stenosis
patients, it can be fatal. In the early stages, it may be responsive and dysmotility related to granulomatous inflammation and
to a short course of oral corticosteroids, either prednisone or fibrosis; in the stomach, loss of motility and capacity caused by
budesonide. Case reports attest to the efficacy of infliximab, but thickened walls and narrowed lumen leads to vomiting, epigastric
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this cannot be routinely advised. It is possible that immunosup- pain, and weight loss as a result of feeding difficulty; in the small
pressants may be used to control the inflammatory response and large intestines, diarrhea (including protein losing enter-
underlying the small-bowel mucosal damage, but this should opathy), bowel obstruction (large granulomata compromising
only be done in a closely observed clinical setting, with monitoring the size of the lumen), rectal bleeding, and tenesmus may result
for infections. At all times the patient’s nutritional status should from active colitis/enteritis with mucosal ulceration, anal fissures,
be maintained, initially using the oral route but administering and perianal abscesses. In addition, because of the transmural
parenteral nutrition to compliment oral nutrition and when nature of the granulomatous inflammation, penetrating complica-
oral feedings are not adequately absorbed and exacerbating the tions, such as fistulae and abscesses, can occur. Feeding difficulties
diarrhea. and the chronic inflammatory state itself predispose to growth
Portal hypertension may complicate CVID, typically from delay that often affects pediatric patients with CGD.
the nodular regenerative hyperplasia of the liver; however, little Hepatic abscesses represent another frequent complication
78
fibrosis occurs. It needs to be clarified in individual patients in CGD, occurring in up to 45% of patients. These patients
with splenomegaly (≈20%) that portal hypertension is not caused most often present with fever as well as abdominal pain, fatigue,
by excessive splenic vein flow associated with splenomegaly and, less often, abdominal tenderness and hepatomegaly on
(induced by antibody-mediated autoimmune cytopenias) that examination. The erythrocyte sedimentation rate (ESR) and the
might be ameliorated by splenectomy. In any scenario, the alkaline phosphatase level are elevated in half the affected
management of such late complications requires an especially individuals. However, a high level of suspicion, especially in the
experienced team of internists, surgeons, and nutritionists. setting of fever with or without abdominal pain, should instigate
a search for hepatic abscesses.
KeY COnCePts Immune Pathophysiology
Common Variable Immunodeficiency (CVID) Given the defects in ability to kill intracellular bacteria and fungi,
pathogens, and possibly commensals alike, it is thought that the
• The majority of gastrointestinal (GI) complications of CVID are infectious
and generally do not respond to intravenous or subcutaneous immu- exuberant granulomatous response is caused by delayed antigenic
noglobulin (IV/SCIG) therapy (compared with sinopulmonary suppurative clearance or persistent infection. In this way, granulomata continue
infections). to multiply and grow while other inflammatory pathways that
• CVID enteropathy is a rare immune-mediated complication of CVID normally deal with the microbes or are induced by cytokines
that also does not respond to IV/SCIG. are activated. The end results of granulomatous inflammation
• CVID enteropathy is often confused with celiac disease because of are most evident in tissues rich in macrophages and reticuloen-
similar villus damage on biopsy, but additional features (lack of plasma dothelial cells, such as the gut lamina propria, liver, lymph nodes,
cells, increased epithelial apoptosis, absence of celiac gene risk alleles)
can help differentiate them. and spleen.
• CVID enteropathy has no established therapy though judicious use
of short courses of oral steroids, or conventional immunosuppression Diagnosis
may relieve the malabsorption and diarrhea temporarily. The symptoms and signs will dictate the initial diagnostic
examinations. For diarrheal complaints, stool culture and
examination for C. difficile toxin are required; in the setting of
Chronic Granulomatous Disease hypoalbuminemia, fractional fecal excretion of α 1 antitrypsin
CGD results from defects in the nicotinamide adenine dinucleotide can detect protein-losing enteropathy (>50 mg/24 hour) as a
phosphate (NADPH)–oxidase complex that impair the ability result of either diffuse mucosal inflammation or lymphangiectasia.
of phagocytic cells to produce the reactive oxygen species required For complaints of dysphagia, vomiting, or epigastric pain, upper
to kill bacteria and fungi within intracellular phagolysosomes endoscopy can help document macroscopic and microscopic
(Chapter 22). Patients with CGD have recurrent infections of involvement with granulomatous inflammation. Radiological
the skin, lungs, liver, and bone, and nearly half develop gut studies using oral contrast may be helpful in showing a narrowed
inflammatory complications affecting areas anywhere from the lumen, stricturing, and motility and mucosal abnormalities of
mouth to the anus. Interestingly, the frequency of GI disease in the esophagus and stomach but cannot provide histological
CGD is higher in the X-linked gp91 phox defect, but the most confirmation. However, radiological imaging studies may be the
recently described p40 phox defect occurred in a young male patient primary diagnostic tools to evaluate obstructive symptoms from
who presented with granulomatous colitis alone. 75-77 the small intestine, including barium small-bowel studies and
CT or magnetic resonance enterography. Images can show lumen
Presentation narrowing; bowel wall thickening; mucosal abnormalities, includ-
The most typical GI complaints in patients with CGD are ing ulceration; and penetrating complications, such as fistulization.
abdominal pain and diarrhea (with or without rectal bleeding). Finally, to evaluate lower abdominal and perianal pain and rectal
GI symptoms usually begin in the first decade of life, sometimes bleeding, anoscopy, colonoscopy, and pelvic CT or magnetic
preceding the diagnosis of CGD. Although infectious diarrhea resonance imaging (MRI) will help diagnose granulomatous