Page 1050 - Clinical Immunology_ Principles and Practice ( PDFDrive )

CHaPter 75 Immunological Diseases of the Gastrointestinal Tract 1013

may need colectomy and ileostomy to manage refractory symp- been described in EoE, contributing more to dysphagia than to
toms or drug intolerance. strictures. 64
The pathogenesis of EoE seems to be linked to allergen
Eosinophilic Esophagitis hypersensitivity. Given a familial association of EoE, atopy, and
Eosinophilic esophagitis (EoE) is a more recently recognized food allergy, a genetic component may be contributing to disease
disease defined by symptomatic idiopathic eosinophilic inflam- susceptibility. Several candidate disease susceptibility gene/gene
mation in the absence of other known causes, especially chronic loci in EoE include the 3’ untranslated region of eotaxin (CCL26),
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gastroesophageal reflux disease (GERD). Although its etiopathol- the TGF-β 1 promoter, a filaggrin (FLG) exon, and a thymic stromal
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ogy is unclear, there are gene associations (FLG for epithelial lymphopoietin (TSLP) intron and TSLP receptor (CRLF2) exon.
barrier effects and eotaxin-3 and TSLP for immune response These associations are biologically plausible, since eotaxin is
effects), and data from animal models and human disease have excessively expressed in EoE mucosae, filaggrin is a structural
implicated central roles for loss of tolerance to food antigens skin protein that helps maintain barrier function (and is down-
involving Th2 cytokines IL-5 and IL-13. EoE is being recognized regulated by IL-13), and TSLP has been shown to stimulate IL-13
with increasing frequency against a background of increased production by innate helper cells in the lamina propria. Moreover,
incidence of inflammatory allergic diseases. the inflammation in EoE is characterized by increased IL-13 and
EoE is estimated to occur at 4–5 cases/10 000 children, has a IL-5 production; animal models of aeroallergen induction of an
male predominance (up to 70%), and peak incidence in neonates EoE-like lesion is blocked in both IL-13–deficient and signal
to 3-year-olds. Symptoms include failure to thrive and feeding transducer and activator of transcription 6 (STAT6)–deficient
difficulty in infants (e.g., food refusal, limited variety diet, (an intracellular molecule important for IL-13 receptor α 1 signal-
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prolonged feeding times) and abdominal pain and vomiting in ing) animals. These data suggest that IL-13 secretion induces
older children and adolescents. In adults, the primary symptom production of eotaxin from epithelial cells, which, together with
is typically intermittent dysphagia, with the first presentation IL-5, drives the local eosinophilic infiltration. Finally, the associa-
possibly being an acute food impaction in the esophagus. Adult tion with food allergy has led to successful therapy of EoE by
patients may report GERD symptoms that do not respond to using strict elimination diets (sometimes informed by skin testing)
adequate acid-suppression therapy. Patients report a high rate or even the use of elemental diet tube feedings.
(>50%) of atopy (rhinoconjunctivitis, wheezing, or family history Given the strong association with food allergies, strict elimina-
of atopy) as well as food allergies (including positive skin prick tion of suspect foods or those identified by in vitro or skin prick
test, allergen-specific IgE test, or anaphylactic response to a testing may be restricted first. Lack of improvement in symptoms
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dietary allergen). There is also an association of esophageal would lead to a trial of amino acid–based elemental liquid diet
disease (strictures or EoE) in the parents of up to 10% of necessitating nasogastric (or later percutaneous gastrostomy)
patients. placement, but this can be uncomfortable, impractical, and
The diagnosis of EoE requires endoscopic biopsy of the expensive. If this dietary approach is successful, then after
esophagus, since increased eosinophils in the esophageal epithe- several weeks, individual foods may be added back every 5–7
lium must be measured. The endoscopic appearance of the days. For patients not responding to dietary therapy or with
esophagus can show multiple thin rings (“feline esophagus”), no identifiable dietary allergens, corticosteroid treatment has
with linear longitudinal furrows and whitish papules that represent been used successfully. Both systemic oral and swallowed topical
eosinophilic microabscesses at the surface of the squamous corticosteroids (e.g., fluticasone propionate metered dose inhalers)
epithelium. Biopsy should show an infiltrate of eosinophils in for 4–6 weeks have been shown to relieve symptoms and resolve
the epithelium of at least 15—20 eosinophils/high-power field histological inflammation; one or the other may be more or
(hpf). These often concentrate just under the epithelial surface less effective based on body weight, dose, steroid resistance, or
and also form microabscesses in groups of ≥4 eosinophils. It is severity of the EoE. However, relapse rates are high over the
important to take at least three biopsy specimens, since involve- year following a course of steroids. Lastly, endoscopic therapy to
ment may be variable and patchy; in addition, it is advisable to treat strictures using dilation may incur higher risk of mucosal
take biopsy specimens from the distal and mid-to-upper esophagus tears so that conservative treatment (smaller dilators, assessment
(to help differentiate changes seen in GERD that can be limited for tears during the procedure before proceeding further) is
to the distal esophagus) and specimens from the gastric and encouraged.
duodenal mucosae (to show that the eosinophilic infiltration is Eosinophilic gastroenteritis encompasses an additional group
limited to the esophagus and does not represent a diffuse process, of infrequent conditions that link increased intestinal eosinophilia
such as that found in eosinophilic gastroenteritis or hypereo- (from mucosal to full-thickness intestinal wall infiltration) and
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sinophilic syndrome). Systemic eosinophilia can be seen in over symptoms, such as abdominal pain, diarrhea, and malabsorption.
70% of patients with EoE. These are assumed to be primary inflammatory responses,
In terms of GERD, it is important to make sure that any although exclusion of parasitic infections, especially with hel-
excessive acid reflux is treated and controlled; persistent symptoms minths, is a necessary part of the workup.
(and persistent biopsy abnormalities) may prompt a 24-hour
ambulatory pH study of the distal esophagus to ensure that the GASTROINTESTINAL COMPLICATIONS OF
acid-suppression treatment results in a normal acid-contact time. PRIMARY IMMUNODEFICIENCIES
In fact, there seems to be a form of EoE that, while seeming to
be without excess exposure to gastric acid, does, in fact, respond Certain primary immunodeficiency diseases increase the risk
well to PPI treatment; this may be attributed to the non–acid- for GI complications. These complications fall into three main
suppressive effects of a drug, such as omeprazole, that can suppress categories: infectious, idiopathic inflammatory/autoimmune,
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eotaxin-3 secretion from squamous mucosae. Multiple types and neoplastic. Common variable immunodeficiency (CVID)
of esophageal dysmotility, often reversible with treatment, have and chronic granulomatous disease (CGD) have some of the