Page 1043 - Clinical Immunology_ Principles and Practice ( PDFDrive )

1006 Part seven Organ-Specific Inflammatory Disease

only in a minority of patients and does not necessarily reverse the On tHe HOrIZOn
intestinal metaplasia. Histologically, this form of atrophic gastritis
is differentiated from primary autoimmune atrophic gastritis by Gastritis
the presence of H. pylori organisms in the specimen (and concur- • Development of an ultimate Helicobacter pylori eradication treatment
rent involvement of the antrum). Specific immunohistochemical with easy global implementation yet without significant adverse effects
methods for detecting H. pylori are required when organisms or antibiotic resistance issues.
are not seen on hematoxylin and eosin staining, when intestinal
metaplasia occurs widely (H. pylori does not colonize intestinal
metaplasia heavily), or when confirming H. pylori eradication CELIAC DISEASE
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after antibiotic treatment. Although there are many pieces of
evidence to support immune mechanisms for the persistence of Celiac disease (also known as gluten enteropathy) is the most
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HP infection in the stomach, data suggest that pro-regulatory prevalent immune-mediated disease of the human GI tract. Gluten
effects of H. pylori infection, including local IL-10 production, peptide–specific T cells drive specific autoantibody formation,
increases in regulatory T cells (Tregs) in the gastric mucosa and small intestinal villus atrophy, and malabsorption caused by
increased antigen-presenting cell (APC) phagocytosis of apoptotic subsequent intestinal surface injury. The identification of the
cells all contribute to persistence of chronic H. pylori gastritis. 9-11 specific antigen-presenting human leukocyte antigen (HLA)
The indications for diagnosis and treatment of active H. pylori molecules and the gluten peptide cognate ligands that activate the
infection include active gastroduodenal ulcer disease, gastric MALT T cells have advanced the understanding of the pathophysiology
lymphoma, and, in highly endemic areas, dyspepsia symptoms and genetics of celiac disease and are driving innovative therapies.
(upper abdominal pain, bloating, early satiety, and nausea). Active
disease can be diagnosed with endoscopic biopsy, which has Presentation
high sensitivity and specificity, while simultaneously assessing The classic clinical presentation of celiac disease—chronic
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peptic and malignant complications. Noninvasive testing for diarrhea, weight loss, and abdominal bloating—results from
H. pylori infection includes serum antibody detection (best used defective nutrient absorption by the small intestine as a result
in highly endemic areas to predict active infection), urea breath of inflammatory injury. However, patients with celiac disease
testing (limited by expense and possible false-positive results), are more likely to present with complications of nutrient
and fecal antigen testing (which has potential advantages in the deficiency (anemia, osteoporosis, failure to thrive in children)
setting of intestinal metaplasia and after antibiotic treatment). without overt GI complaints. Celiac disease can also present
Once H. pylori infection is diagnosed, there are many effective with a gluten-reactive skin eruption (dermatitis herpetiformis),
eradication therapies that need to be tailored to patients’ drug cerebellar ataxia, infertility and miscarriage, chronic fatigue, and
tolerance and allergy history as well as local antibiotic resistance associated autoimmune disorders, such as diabetes and thyroiditis,
patterns. In general, a 14-day course with a proton pump inhibitor Addison disease, Sjögren syndrome, autoimmune hepatitis, and
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(histamine 2 [H2] blockers may be substituted) and two antibiot- primary biliary cirrhosis. A high frequency of nonspecific GI
ics (clarithromycin with amoxicillin or metronidazole) is recom- symptoms, such as abdominal pain and constipation, reported in
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mended as first-line treatment. Alternative regimens, including over one-fifth of newly diagnosed subjects, complicates targeted
bismuth or sequential therapy, may be needed in cases of antibiotic disease screening. The variations of celiac disease presentation
resistance. Eradication of infection can be confirmed by either may reflect several features: (i) celiac disease severity follows
invasive or noninvasive (but not serum antibody) methods. In a dose effect of risk alleles; (ii) the actual occurrence of celiac
addition to the cure of recurrent gastroduodenal ulcer disease, disease requires genetic and environmental factors in addition to
eradication of H. pylori can cause regression of gastric MALT the well-characterized HLA molecules; (iii) celiac disease expres-
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lymphoma in a majority of coinfected patients. Investigation sion depends on the quantity and quality of gluten exposure;
continues into enhancing eradication or preventing chronic and (iv) celiac disease complications reflect the severity of the
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infection through targeting molecules critical for H. pylori survival inflammation and the length of involved bowel. The concept of
in the gastric environment as well as vaccine strategies. a vast subclinical celiac disease prevalence has led to an “iceberg
model,” where the visible tip is the group with symptomatic GI
disease and the characteristic gut mucosal lesion, and below the
KeY COnCePts surface are those with silent disease (no overt symptoms but gut
Gastritis mucosal lesions) and latent disease (no symptoms or mucosal
lesions but genetic susceptibility possibly with positive serology).
• Atrophic gastritis/Pernicious anemia results from loss of the acid- The key to diagnosing celiac disease is simply to consider it
producing cells of the gastric body and is associated with antiparietal in the differential diagnosis of classic gut malabsorption as well
cell antibodies, an intact antral gastric mucosa, and no evidence of as subtle manifestations of malabsorption (e.g., unexplained iron
Helicobacter pylori infection. deficiency anemia). Conversely, the differential diagnosis of villus
• However, H. pylori infection has been linked to atrophic gastritis/perni- blunting or intraepithelial lymphocytosis includes small-intestinal
cious anemia via increased rates of antigastric antibodies, autoantibodies
to H -K -adenosine triphosphatase (ATPase), and gastric mucosal CD4 bacterial overgrowth, tropical sprue, autoimmune enteropathy,
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T cells with cross-reactivity to H -K -ATPase and H. pylori antigens. common variable immunodeficiency (CVID) enteropathy, and
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• H. pylori infection of the stomach is chronic because of metabolic H. pylori gastritis, emphasizing that celiac disease is also not
and immune adaptations by the pathogen that allow persistence in solely a histological diagnosis.
the acidic gastric environment.
• H. pylori infection is a leading cause of peptic ulcer disease and a Immune Pathophysiology
World Health Organization (WHO) class I carcinogen because of its
link to gastric adenocarcinoma. Celiac disease results from the activation of T cells by gluten
peptide–MHC complexes on APCs in the lamina propria of the