Celiac Sprue 

Celiac sprue, also known as celiac disease or gluten-sensitive enteropathy, is a chronic disease of the digestive tract that interferes with the digestion and absorption of food nutrients. People with celiac sprue cannot tolerate gliadin, the alcohol-soluble fraction of gluten. Gluten is a protein commonly found in wheat, rye, and barley. Most patients with celiac disease tolerate oats, but they should be monitored closely. When people with celiac sprue ingest gliadin, the mucosa of their intestines is damaged by an immunologically mediated inflammatory response, resulting in maldigestion and malabsorption. Patients with celiac disease can present with failure to thrive and diarrhea (the classical form). However, some patients have only subtle symptoms (atypical celiac disease) or are asymptomatic (silent celiac disease).^[1]

Celiac sprue has a strong hereditary component. The prevalence of the condition in first-degree relatives is approximately 10%.

A strong association exists between celiac sprue and two human leukocyte antigen (HLA) haplotypes (DQ2 and DQ8). Damage to the intestinal mucosa is seen with the presentation of gluten-derived peptide gliadin, consisting of 33 amino acids, by the HLA molecules to helper T cells. Helper T cells mediate the inflammatory response. Endogenous tissue transglutaminase deamidates gliadin into a negatively charged protein, increasing its immunogenicity. Absence of intestinal villi and lengthening of intestinal crypts characterize mucosal lesions in untreated celiac sprue. More lymphocytes infiltrate the epithelium (intraepithelial lymphocytes). Destruction of the absorptive surface of the intestine leads to a maldigestive and malabsorption syndrome.^[2]

Frequency

United States

The frequency of celiac sprue in the United States is relatively low, about 1 case in 3000 persons. Estimates suggest that approximately 1% of the population is affected. Celiac disease is underdiagnosed in most affected people.

Because the historical prevalence and long-term outcome of undiagnosed celiac disease were unknown, Rubio-Tapia et al collected serologic information on 3 cohorts^[3] : 9,133 healthy young adults from whom sera were collected between 1948 and 1954, and 12,768 gender-matched subjects from 2 recent cohorts, 1 whose years of birth were similar to those of members of the first cohort, and 1 in whom age at sampling was similar.

The sera were first tested for tissue transglutaminase, then, if abnormal, for endomysial antibodies. During 45 years of follow-up in the older cohort, all-cause mortality was nearly 4-fold greater in persons with undiagnosed celiac disease than among those who were seronegative (hazard ratio = 3.9; 95% confidence interval, 2.0-7.5; P < 0.001).^[3] Comparison of the older and more recent cohorts suggested that undiagnosed celiac disease in the United States has increased dramatically in the past half century: 0.2% of the older cohort had undiagnosed celiac disease compared with 0.8% of the cohort with similar years of birth and 0.9% of those with similar age at sampling (P ≤ .0001).^[3]

International

Approximately 3 million people in Europe and another 3 million people in the United States are estimated to be affected by celiac sprue. Celiac sprue is prevalent in European countries with temperate climates. The highest prevalence of celiac sprue is in Ireland and Finland and in places to which Europeans emigrated, notably North America and Australia. In these populations, celiac sprue affects approximately 1 in 100 individuals. The incidence of celiac sprue is increasing among certain populations in Africa (Saharawui population), Asia (India),^{[4, 5]} and the Middle East.

Mortality/Morbidity

Although rarely lethal, celiac sprue is a significant and often debilitating maldigestive and malabsorption syndrome affecting multiple organ systems.

• Patients with celiac sprue are at increased risk for complications, such as lymphomas and adenocarcinomas of the intestinal tract.
• Untreated pregnant women are at risk of miscarriage and at risk of having a baby with a congenital malformation.
• Short stature often results when celiac sprue prevents nutrient absorption during the childhood years when nutrition is critical to growth and development.
• Symptoms of celiac sprue malabsorption can include one or more of the following (see History):

  • Chronic diarrhea
  • Steatorrhea
  • Abdominal bloating or cramps
  • Flatulence
  • Weight loss
  • Fatigue
  • Anemia
  • Bleeding diathesis
  • Osteopenia
  • Seizure disorders
  • Stunted growth

Race

Celiac sprue is most prevalent in Western Europe and the United States. The incidence is increasing in Africa and Asia.

Sex

Incidence of celiac sprue is slightly higher in females than in males.

Age

The age distribution of patients with celiac disease is bimodal, the first at 8-12 months and the second in the third to fourth decades. The mean age at diagnosis is 8.4 years (range, 1-17 y).

• Celiac disease might become apparent in infants when gluten ingestion begins. Symptoms of celiac disease might persist throughout childhood if untreated but usually diminish in adolescence. Symptoms often reappear in early adulthood, between the third and fourth decades of life.
• Approximately 20% of patients with celiac disease are older than 60 years.^[6]
• Adolescents with celiac sprue frequently present with extraintestinal manifestations, including short stature, behavioral problems, fatigue, and skin problems. The diagnosis of celiac sprue is often not established until middle age or old age.