Celiac Disease and Malabsorptive Disorders

Celiac Disease and Malabsorptive Disorders



Jamilé Wakim-Fleming



DEFINITION


Celiac disease (CD) is an immune-mediated disorder that develops in genetically susceptible persons when gluten, a major protein found in wheat, barley, and rye is ingested in the diet. Also called nontropical sprue, celiac sprue, or gluten-sensitive enteropathy, CD is primarily an enteropathy characterized by inflammation of the small bowel mucosa and atrophy of the villi, resulting in nutrient malabsorption, wasting, and diarrhea. These symptoms define the classic or typical symptoms of CD (Table 1).



Table 1 Types of Celiac Disease

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Any organ system may be involved in CD, and patients can develop extraintestinal manifestations—also called atypical manifestations—such as anemia, bone disease, infertility, unfavorable outcomes of pregnancy, lymphoma, and liver disease. The clinical presentation can include a wide range of symptoms, or even lack of symptoms as in silent CD, but patients can have abnormal celiac serology (endomysial [EMA] and tissue transglutaminase [tTG] antibodies) and varying degrees of small bowel involvement on biopsy. A definition of the various forms of CD based on clinical, pathologic and serologic findings is listed in Table 1.


Genetic susceptibility defines persons who possess the gene pair encoding the major histocompatibility complex class II HLA DQ2 or DQ8. These genes are virtually required for CD to occur, and lack of these genes makes CD very unlikely.



PREVALENCE AND EPIDEMIOLOGY


Availability of highly sensitive and specific serologic tests such as endomysial and tissue transglutaminase antibodies (EMA and tTG) has made it possible to assess the true prevalence of CD. Epidemiologic studies using such tests along with small bowel biopsies report a higher prevalence of CD than previously thought. Prevalence in Western Europeans and in the United States is reported to range between 1 in 250 and 1 in 133, and it is higher in relatives of persons with CD, occurring in 1 in 22 first-degree relatives and in 1 in 39 second-degree relatives. It is rarely, if ever, reported in people with pure ethnic backgrounds from Africa, the Caribbean, China, and Japan. Women are affected more commonly than men, but there is no age predilection.


Other than persons who have relatives with CD, persons at increased risk include those with Down syndrome, Turner syndrome, type 1 diabetes mellitus, thyroid disease, lymphocytic colitis, and autoimmune disorders (Box 1).



Box 1 Patients Who Are at Risk for Celiac Disease and Should Be Tested



• Patients with gastrointestinal and classic symptoms: diarrhea, weight loss, abdominal distention, failure to thrive

• Patients with autoimmune diseases, type 1 diabetes, thyroid disorders, Sjögren’s syndrome, microscopic colitis, inflammatory bowel disease

• First-degree relatives

• Patients with elevated liver enzymes

• Patients with Down syndrome

• Patients with Williams syndrome

• Patients with iron deficiency anemia

• Patients with osteoporosis

• Patients with delayed puberty

• Infertile patients

• Patients with irritable bowel syndrome


PATHOPHYSIOLOGY


Celiac disease is a multifactorial and a multisystem disorder involving a genetic predisposition, environmental exposure of the small bowel mucosa to gluten, and an immunologic response to gluten.



Genetic


The majority (>90%) of persons with CD possess the HLA DQ2 haplotype, and 5% to 10% possess the DQ8 haplotype, conferring a negative predictive value greater than 98%. These haplotypes are encoded within the HLA class II region of the major histocompatibility complex on chromosome 6p. However, about 40% of the general population carry these haplotypes without having the disease, which makes their presence necessary but not sufficient for its development. Other non-HLA genes have been proposed, but their role in influencing the disease has not been clearly defined.



Environmental


It was a serendipitous observation that children with CD improved during World War II when cereals used to make bread were scarce, and they relapsed after the war when the supply of these cereals was reinstituted. Risk for developing CD is increased with the introduction of gluten in the diet of infants before the age of 4 months. Grains that activate the disease contain proteins that can form gluten (prolamins: glutenins and gliadins) and include wheat, barley, and rye. Grains that do not activate the disease include rice, corn, sorghum, and millet. Oats contain a very small proportion of prolamins and should be avoided initially.



Immunologic


Exposure of the upper small bowel mucosa to gluten in susceptible persons precipitates an inflammatory reaction characterized by infiltration of the lamina propria and the epithelium with inflammatory cells, which eventually leads to destruction and atrophy of the mucosa.


Ingestion of gluten induces the antigen-precipitating cells, which express HLA DQ2/DQ8, in lamina propria to sensitize T lymphocytes in both lamina propria and in epithelium. Activated T lymphocytes, particularly CD8+ intraepithelial lymphocytes expressing γ/δ receptors, become abundant and their numbers increase about sixfold. These in turn activate B lymphocytes and other lymphocytes to secrete immunoglobulins, cytokines, interferons, tumor necrosis factor, and other inflammatory mediators, notably interleukin (IL)-15, and cause damage to the enterocytes, resulting in villous atrophy. Additionally, tTG, a ubiquitous enzyme that is released by inflammatory and endothelial cells, deamidates glutamine residues in gluten to glutamic acid, which is negatively charged and in turn facilitates further reactivation of more lymphocytes and potentially affects more organ systems in the body.



CLINICAL MANIFESTATIONS


Celiac disease exhibits a spectrum of clinical and pathologic manifestations. Left untreated, CD can progress to involve multiple organ systems with severe complications and nutritional deficiencies.


Symptoms can manifest in infancy and as early as cereals are introduced in the diet. Crampy abdominal pain, steatorrhea, failure to thrive, apathy and irritability, muscle wasting, and hypotonia are described. Any of these symptoms should trigger a diagnostic workup. Catch-up growth is well documented once a gluten free-diet is introduced.


In adults, the clinical symptoms are variable and not specific. The classic symptoms of malabsorption are less and less encountered since testing with serological antibodies has become available, and diagnosis is recognized before the full-blown clinical wasting occurs. On the other hand, atypical presentations are increasingly recognized and becoming more common.


Patients with CD can exhibit weakness, fatigue, and dyspnea as a result of vitamin B12, folate, and iron deficiency; bone fractures, muscular atrophy, and tetany as a result of osteoporosis and osteopenia due to vitamin D and calcium deficiencies; peripheral neuropathy and ataxia as a result of cerebellar and posterior column inflammatory damage; and secondary hyperparathyroidism, edema, petechiae, and dermatitis herpetiformis. Infertility is observed in men and women. Amenorrhea, intrauterine growth retardation, and unfavorable outcomes of pregnancy have been reported. Liver enzyme abnormalities and nonspecific hepatitis have been incidentally recognized in patients with CD, and advanced liver disease and cirrhosis have been reported, with improvement of the liver disease upon withdrawal of gluten from the diet. It is generally accepted that patients with abnormal elevation of liver enzymes should be tested for celiac disease.


Dermatitis herpetiformis may be the clinical presentation of a latent CD. It is characterized by a papulovesicular rash that is intensely pruritic and affects the buttocks and the extensor surfaces of elbows and knees. It is characterized by granular immunoglobulin (Ig)A deposits in the dermo-epidermal junction. Most patients have abnormalities of the intestinal mucosa. Treatment consists of withdrawing gluten from the diet. If skin lesions do not improve, dapsone may be added at 1 to 2 mg /day.


Other manifestations of CD include weight gain and obesity, gastroesophageal reflux disease, irritable bowel syndrome with abdominal pain and constipation, pancreatitis, myocarditis, aphthous ulcers of the oral mucosa, lymphocytic and collagenous colitis, hyposplenism, and asymptomatic IgA nephropathy. There is a slightly higher risk for gastrointestinal malignancies and lymphomas in CD patients than in the general population.

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Jul 18, 2017 | Posted by in GENERAL SURGERY | Comments Off on Celiac Disease and Malabsorptive Disorders

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