Celiac Sprue Clinical Presentation

The manifestations of untreated celiac sprue can be divided into gastrointestinal symptoms and extraintestinal symptoms.

• Gastrointestinal symptoms

  • Diarrhea is the most common symptom in untreated celiac sprue and present in 45-85% of all patients. Diarrhea caused by celiac sprue is due to maldigestion and malabsorption of nutrients. The stools might be watery or semiformed, light tan or gray, and oily or frothy. The stools have a characteristic foul odor. In infants and young children, extensive diarrhea can lead to severe dehydration, electrolyte depletion, and metabolic acidosis.
  • Malabsorption of ingested fat (steatorrhea) results in the delivery of excessive dietary fat to the large bowel. This results in the production of hydroxy fatty acids by bacteria, which causes secretion of fluids into the intestine.
  • Flatulence (28% of patients) and borborygmus (35-72% of patients) results from the release of intestinal gas by the bacterial florae feasting on undigested and unabsorbed food materials and often becomes excessive or even explosive.
  • Weight loss (present in 45% of all patients) is variable because some patients might compensate for the malabsorption by increasing dietary intake. In infants and young children with untreated celiac sprue, failure to thrive and growth retardation are common.
  • Weakness and fatigue (prevalence 78-80%) are usually related to general poor nutrition. In some patients, severe anemia can contribute to fatigue. Occasionally, severe hypokalemia due to the loss of potassium in the stool can cause muscle weakness.
  • Severe abdominal pain (prevalence 34-64%) is unusual in patients with uncomplicated celiac sprue. However, abdominal bloating or cramps with excessive malodorous flatus is a common complaint.
• Extraintestinal symptoms

  • Anemia (10-15% of patients) is usually due to impaired absorption of iron or folate from the proximal small intestine. In severe celiac disease with ileal involvement, absorption of vitamin B-12 might be impaired.
  • A bleeding diathesis is usually caused by prothrombin deficiency due to impaired absorption of fat-soluble vitamin K.
  • Osteopenia and osteoporosis (prevalence 1-34%) might cause bone pain for several reasons, including defective calcium transport by the diseased small intestine, vitamin D deficiency, and binding of luminal calcium and magnesium to unabsorbed dietary fatty acids.
  • Neurologic symptoms (frequency 8-14%) that result from hypocalcemia include motor weakness, paresthesias with sensory loss, and ataxia. Seizures might develop because of cerebral calcifications.^[7]
  • Skin disorders, including dermatitis herpetiformis (a pruritic papulovesicular skin lesion involving the extensor surfaces of the extremities, trunk, buttocks, scalp, and neck), is associated in 10-20% of patients with celiac disease.
  • Hormonal disorders, such as amenorrhea, delayed menarche, and infertility in women and impotence and infertility in men, have been described.

• Abdominal examination shows a protuberant and tympanic abdomen due to distention of intestinal loops with fluids and gas. Ascites occasionally can be detected in patients with severe hypoproteinemia.
• Evidence of weight loss, including muscle wasting or loose skin folds
• Orthostatic hypotension
• Peripheral edema
• Ecchymoses
• Hyperkeratosis or dermatitis herpetiformis
• Cheilosis and glossitis
• Evidence of peripheral neuropathy
• Chvostek sign or Trousseau sign

Celiac sprue results from a combination of immunological responses to an environmental factor (gliadin) and genetic factors.

• Immune mechanisms

  • The interaction of alcohol-soluble gliadin in wheat, barley, and rye products with the mucosa of the small intestine is crucial to the pathogenesis of celiac sprue. Endogenous tissue transglutaminase deamidates glutamine in gliadin, converting it from a neutral to a negatively charged protein. Negatively charged gliadin has been shown to induce interleukin 15 in enteric epithelial cells, stimulating proliferation of natural killer cells and intraepithelial lymphocytes to express NK-G2D, a marker for natural killer T lymphocytes.^[8]
  • Gliadin (a complex mixture of proline- and glutamine-rich polypeptides obtained by alcohol extraction of wheat gluten) can produce symptoms and histological changes in the small intestine when administered to patients with asymptomatic celiac sprue. Antigliadin antibodies can frequently be identified in untreated patients.
  • Immunoglobulin A (IgA) antibodies to smooth muscle endomysium and tissue transglutaminase (the most commonly used test) are used for serological diagnosis. However, 3-5% of all patients with celiac disease are IgA deficient. Therefore, determining total IgA prior to antibody testing is appropriate in patients with celiac disease.
  • Cell-mediated immune responses are also important for the pathogenesis of celiac sprue, as demonstrated by the presence of large numbers of CD8+ T lymphocytes in the intestinal epithelium.
• Genetic factors

  • Genetics play an important role in celiac sprue. The incidence of celiac disease in relatives of patients with celiac sprue is significantly higher than in the general population. The prevalence in first-degree relatives of patients with celiac sprue is approximately 10%. Concordance for the disease in monozygotic twins approaches 75% and is approximately 30% for first-degree relatives.
  • Gliadin binds to HLA-DQ2 heterodimers or HLA-DQ8 heterodimers found in 90-95% and 5-10% of patients with celiac disease, respectively. HLA-DQ2 and HLA-DQ8 are present on the surface of antigen-presenting cells in the lamina propria, and binding of gliadin leads to expression of the proinflammatory cytokine interferon gamma and activation of CD4+ T lymphocytes.