Celiac Disease: Pathophysiology, Clinical Manifestations, and Associated Autoimmune Conditions
Section snippets
Clinical presentation
The clinical presentation of celiac disease is remarkably varied and depends on age (Table 1) [2], [3], [4], [5]. The classic presentation with a failure to thrive, malnutrition, diarrhea, abdominal pain, and distension within the first few years of life represents the tip of what is commonly referred to as the “celiac disease iceberg.”
In contrast to the dramatic presentation noted typically in younger children, many patients with celiac disease present at a later age with subtle symptoms, and
Extraintestinal manifestations
In this article, the phrase “extraintestinal manifestations” of celiac disease is used to refer to conditions that are associated with celiac disease and are at least partially responsive to a gluten-free diet (see Table 1). The distinction from conditions that are associated with celiac disease can be difficult, and categorization is not necessarily exact.
Arthritis involving the peripheral and axial skeletal has been reported in as many as 25% of patients presenting with celiac disease [10].
Pathophysiology
Celiac disease is unique from other autoimmune diseases in that a clearly identified environmental trigger (gluten) and a dominant HLA contribution are required for disease to occur (DQ2 or DQ8). Autoantibodies against TG are detectable in over 95% of individuals with celiac disease.
Multiple proposed pathways involved in the pathogenesis of celiac disease lead to enterocyte destruction and subsequent villous atrophy, all of which are related to dietary gluten, the major storage protein of
Epidemiology
The understanding of the epidemiology of celiac disease has evolved over the last several decades with the advent of serologic tests as screening tools (Table 2). Celiac disease was initially thought to be relatively rare, with prevalence rates of approximately 1 in 5000 [23]. These rates were based on the classic presentation of the disease, which is now recognized to be only one form of celiac disease. The previously reported prevalence rates represent the tip of the celiac disease iceberg,
Serologic testing
Serologic testing can be performed in subjects in whom the diagnosis of celiac disease is entertained, such as those with malabsorption and vitamin or mineral deficiencies, osteoporosis/osteopenia, infertility, or other clinical symptoms. It can also be used to screen individuals considered to be at high risk for celiac disease, such as those with type 1 diabetes or first-degree relatives of an affected individual. Serologic testing can also be used to monitor therapy, because antibody levels
Diagnosis
The diagnosis of celiac disease is usually first suggested by the presence of TG autoantibodies but is established by biopsy of the small intestine by upper intestinal endoscopy (Fig. 2A, B) [6], [37]. Histology will show some degree of villous atrophy and crypt hyperplasia. Intraepithelial lymphocytes are typically seen in celiac disease lesions, but their presence alone is insufficient to diagnose celiac disease. Histologic grading is based on the Marsh scoring system. Normal intestinal
Treatment
The clear and established treatment for celiac disease is lifelong avoidance of gluten found in wheat, rye, and barley. Although some controversy exists as to whether oats are safe in individuals with celiac disease, most evidence supports the safety of oats in a celiac diet provided there is no cross-contamination with gluten [43]. It might be wise to establish a positive response to a strict gluten-free diet before allowing the careful addition of oats. Consultation with a dietician for
Complications of celiac disease
Celiac disease has been associated with an increased risk for fracture and osteoporosis, although the degree of the association varies from strong (odds ratio for fractures, 5–7) [46] to relatively minor (odds ratio for fractures, 1.9) when compared with controls [23], [47]. Bone mineral density is noted to be decreased in patients with celiac disease, and there is at least some improvement in bone mineral density with institution of a gluten-free diet. Nevertheless, a gluten-free diet
Associated conditions
The term associated conditions refers to conditions that are found at increased frequency in celiac disease but are not thought to be due to gluten ingestion (see Table 1). Dermatitis herpetiformis is a skin lesion associated with celiac disease characterized by the presence of symmetric papulovesicular lesions on the arms, legs, buttocks, trunk and neck and scale. Histology reveals immunofluorescence with granular deposits of IgA. Dermatitis herpetiformis often responds to a gluten-free diet.
Summary
The clinical spectrum of celiac disease continues to evolve. What was once thought to be a rare disorder affecting young children is now recognized to be very common with a range of symptoms from asymptomatic disease to severely affected persons. Screening for celiac disease has become relatively easily with reliable antibodies against self-antigens (TG) and modified environmental antigens (DGP). Diagnosis is confirmed by small intestinal biopsy with characteristic changes graded by the Marsh
References (65)
Clinical presentation of celiac disease in the pediatric population
Gastroenterology
(2005)- et al.
Dental enamel defects in celiac patients
Oral Surg Oral Med Oral Pathol Oral Radiol Endod
(1997) - et al.
Hypertransaminasemia in pediatric celiac disease patients and its prevalence as a diagnostic clue
Am J Gastroenterol
(2002) Neurologic presentation of celiac disease
Gastroenterology
(2005)- et al.
Interleukin 15: a key to disrupted intraepithelial lymphocyte homeostasis and lymphoma genesis in celiac disease
Gastroenterology
(2003) - et al.
Interleukin 15 mediates epithelial changes in celiac disease
Gastroenterology
(2000) - et al.
Coordinated induction by IL15 of a TCR-independent NKG2D signaling pathway converts CTL into lymphokine-activated killer cells in celiac disease
Immunity
(2004) - et al.
A prospective study of the incidence of childhood celiac disease
J Pediatr
(2003) - et al.
One third of HLA DQ2 homozygous patients with type 1 diabetes express celiac disease associated transglutaminase autoantibodies
J Autoimmun
(1999) - et al.
Celiac disease in children with autoimmune thyroid disease
J Pediatr
(2001)
Fluctuating transglutaminase autoantibodies are related to histologic features of celiac disease
Clin Gastroenterol Hepatol
Antibodies against synthetic deamidated gliadin peptides and tissue transglutaminase for the identification of childhood celiac disease
Clin Gastroenterol Hepatol
Role of human-tissue transglutaminase IgG and anti-gliadin IgG antibodies in the diagnosis of coeliac disease in patients with selective immunoglobulin A deficiency
Dig Liver Dis
HLA types in celiac disease patients not carrying the DQA1*05-DQB1*02 (DQ2) heterodimer: results from the European genetics cluster on celiac disease
Hum Immunol
HLA susceptibility genes in celiac disease: genetic mapping and role in pathogenesis
Gastroenterology
Combination enzyme therapy for gastric digestion of dietary gluten in patients with celiac sprue
Gastroenterology
Fracture risk in people with celiac disease: a population-based cohort study
Gastroenterology
Fertility and pregnancy-related events in women with celiac disease: a population-based cohort study
Gastroenterology
Celiac disease and risk of adverse fetal outcome: a population-based cohort study
Gastroenterology
Risk of malignancy in patients with celiac disease
Am J Med
Impact of celiac autoimmunity on children with type 1 diabetes
J Pediatr
Part I. Clinical practice guidelines for children with Down syndrome from birth to 12 years
J Pediatr Health Care
Part II. Clinical practice guidelines for adolescents and young adults with Down syndrome: 12 to 21 years
J Pediatr Health Care
Identification of tissue transglutaminase as the autoantigen of celiac disease
Nat Med
Prevalence of celiac disease in at-risk and not-at-risk groups in the United States: a large multicenter study
Arch Intern Med
Celiac sprue
N Engl J Med
Celiac disease
N Engl J Med
NIH consensus development conference on celiac disease
NIH Consens State Sci Statements
Short stature and the probability of coeliac disease, in the absence of gastrointestinal symptoms
Arch Dis Child
Celiac disease as a cause of growth retardation in childhood
Curr Opin Pediatr
Clinical features of children with screening-identified evidence of celiac disease
Pediatrics
The arthritis of coeliac disease: prevalence and pattern in 200 adult patients
Br J Rheumatol
Cited by (150)
Celiac disease: A rare cause of cirrhotic portal hypertension - A case report
2024, Gastroenterology and EndoscopySulfated polysaccharides accelerate gliadin digestion and reduce its toxicity
2024, Biochemical and Biophysical Research CommunicationsPathophysiology and immunogenetics of celiac disease
2022, Clinica Chimica ActaPrevalence of medically unsupervised activated charcoal use a cause for concern in celiac disease?
2022, Journal of the American Pharmacists AssociationExtracellular vesicle microRNAs in celiac disease patients under a gluten-free diet, and in lactose intolerant individuals
2022, BBA AdvancesCitation Excerpt :Celiac disease (CD) affects around 1% of the world's population and is caused by the presentation of gluten peptides by major histocompatibility complex molecules to the effector immunological response, injuring intestinal mucosa in genetically predisposed individuals [2,27].
Work by Dr. Barker is supported by Juvenile Diabetes Research Foundation grant 11-2005-15 and work by Dr. Liu by NIH grant K08064605.