Table 18.1 Nomenclature of bone tumors

EPIDEMIOLOGY & DEMOGRAPHICS
• Estimates of the incidence and prevalence of celiac sprue in the U.S. range from 50 to 550 cases/100,000 persons; it is highest in whites of northern European ancestry (1 in 300).
• Incidence is highest during infancy and the initial 36 months (secondary to the introduction of foods containing gluten), in the third decade (frequently associated with pregnancy and severe anemia during pregnancy), and in the seventh decade.
• There is a slight female predominance.
Clinical Features
The fully developed disease presents with severe diarrhea, significant weight loss, general weakness, and typical features of nutritional deficiencies that clearly point to the diagnosis. In this situation the diagnosis is quickly confirmed by specific investigations. In patients with a short history and severe disease the clinical differential includes underlying malignancy. The further differential diagnosis of celiac disease includes Crohn disease, hyperthyroidism, anorexia nervosa, severe laxative abuse, and Addison disease.
Atypical and occult presentations of celiac disease are up to 10 times more frequent than that of the fully developed clinical picture. Patients often present with mono- or oligosymptomatic disease. The diagnosis is often delayed in those with isolated iron deficiency anemia or osteomalacia until malabsorption is considered and appropriate investigations performed. In 5−10% of patients with celiac disease diarrhea is absent. There may even be a tendency to constipation. The most important complication of untreated celiac disease is the increased risk of intestinal malignancy, in particular T-cell lymphoma. This risk is particularly high in patients with refractory sprue, ulcerative jejunitis, and the rare collagenous sprue; all conditions that do not respond to the gluten-free diet.
In severe disease, physical examination may reveal, in addition to cachexia, a bloated “doughy” abdomen, peripheral edema, hypotonia, and increased skin pigmentation (without mucosal pigmentation in contrast to Addison disease). These findings are absent when the disease is controlled.
PHYSICAL FINDINGS & CLINICAL PRESENTATION
• Physical examination may be entirely within normal limits.
• Weight loss, dyspepsia, short stature, and failure to thrive are noted in children and infants.
• Weight loss, fatigue, and diarrhea are common in adults.
• Abdominal pain, nausea, and vomiting are unusual.
• Pallor as a result of iron deficiency anemia is common.
• Manifestations of calcium deficiency, such as tetany and seizures, are rare and can be exacerbated by coexistent magnesium deficiency.
• Angular cheilitis, aphthous ulcers, atopic dermatitis, and dermatitis herpetiformis are frequently associated with celiac disease.
ETIOLOGY
• Celiac sprue results from an inappropriate T-cell-mediated immune response against ingested gluten in genetically predisposed people. There is sensitivity to gliadin, a protein fraction of gluten found in wheat, rye, barley, and oats.
• Recently a peptide that resists degradation by proteases in the small bowel was identified as the potential triggering molecule.
DIAGNOSIS
The diagnosis of celiac disease is suggested by serological tests and confirmed by small bowel biopsy (Fig. 7.11). IgA and IgG antigliadin antibodies do not have sufficient specificity or sensitivity for diagnosis, indeed antigliadin IgA antibodies can be detected in up to 90% of healthy, elderly individuals. In contrast antiendomysial antibodies offer high diagnostic accuracy. The antigenic target for antiendomysial antibodies was recently discovered to be the enzyme tissue transglutaminase. The detection of specific IgA and IgG transglutaminase antibodies further increase the specificity and sensitivity of serological tests.

Celiac disease

BASIC INFORMATION
DEFINITION
Celiac disease in adults and children is caused by a gluten-sensitive, immune-mediated enteropathy (gluten or gliadin is a protein found in cereal crops, including wheat, barley, and rye). In certain individuals (genetic predisposition) the presence of gluten in the diet triggers immune-mediated mucosal damage in the small bowel. This is usually reversible after exclusion of gluten from the diet. New methods of screening in Europe have shown that celiac disease is one of the most common genetic diseases with a prevalence of between 1:130 and 1:300. The probability that first degree relatives are affected lies between 10−20%. The disease affects both sexes with equal frequency and presents most commonly in middle age, with a tendency to abrupt changes in clinical course (e. g., occult to overt disease).
SYNONYMS
Gluten-sensitive enteropathy
Celiac sprue

Fig. 7.11 Small bowel histology a Normal; b Untreated celiac disease; there is villou atrophy and increased intraepithelial lymphocytes.

DIFFERENTIAL DIAGNOSIS
• IBD
• Laxative abuse
• Intestinal parasitic infestations
• Other: irritable bowel syndrome, tropical sprue, chronic pancreatitis, Zollinger-Ellison syndrome, cystic fibrosis (children), lymphoma, eosinophilic gastroenteritis, short bowel syndrome, Whipple’s disease
WORKUP
Initial evaluation consists of laboratory tests followed by radiographic studies and upper GI endoscopy with biopsy of duodenum or proximal jejunum.
LABORATORY TESTS
• Iron deficiency anemia
• Folic acid deficiency
• Vitamin B12 deficiency, hypomagnesemia, hypocalcemia
• Antigliadin IgA and IgG antibodies are elevated in >95% of patients; however, they are nonspecific. IgA endomysial antibodies are more specific for celiac sprue and are the best screening test for celiac disease, except in the case of patients with IgA deficiency. Tissue transglutinase autoantibody by ELISA is a newer serologic test for celiac sprue.
• Biopsy of the small bowel is generally recommended to establish the diagnosis. It reveals absence or shortening of villi, intraepithelial lymphocytes, and crypt lengthening and hyperplasia. Several biopsy specimens should be obtained for proper diagnosis.
• Tests for malabsorption are abnormal: fecal fat estimation for 72 hours is elevated (>7 g/day),D-xylose testing reveals malabsorption of sugar.
IMAGING STUDIES
• Barium studies are usually unnecessary. Typical radiologic features include dilation of the small intestine with thickening or obliteration of the mucosal folds.
• Capsule endoscopy can also be used to evaluate the small intestinal mucosa, especially if future innovations will allow mucosal biopsy.
TREATMENT
NONPHARMACOLOGIC THERAPY
Patients should be instructed on gluten-free diet (avoidance of wheat, rye, and barley). Recent studies show that oats do not damage the mucosa in celiac disease.
ACUTE GENERAL Rx
• Correct nutritional deficiencies with iron, folic acid, calcium, vitamin B12 as needed.
• Prednisone 20 to 60 mg qd gradually tapered is useful in refractory cases.
CHRONIC Rx
• Lifelong gluten-free diet is necessary.
• Repeat small bowel biopsy following treatment generally reveals significant improvement. It is also useful to evaluate for increased risk of small bowel T-cell lymphoma in these patients (10%), especially in untreated patients.
DISPOSITION
• Prognosis is good with adherence to gluten-free diet. Rapid improvement is usually seen within a few days of treatment.
• Serial antigliadin or antiendomysial antibody tests can be used to monitor the patient’s adherence to a gluten-free diet.