- Clinical science
Celiac disease, also referred to as celiac sprue or nontropical sprue, is a common condition characterized by a maladaptive immune response to gluten, a protein found in many grains (e.g., wheat). The disease often occurs in patients with other autoimmune illnesses, as both are associated with HLA variants (human leukocyte antigens, which encode immunoregulatory proteins) that cause pathologically increased immune responses. The underlying pathophysiology is believed to be a combination of gluten intolerance, which triggers an autoimmune reaction, and production of autoantibodies that target tissue transglutaminase, specifically within the proximal small intestine. Typical findings include changes in bowel habits and symptoms associated with malabsorption (e.g., fatigue, weight loss, vitamin deficiencies). Diagnostic tests include the detection of various antibodies. To confirm the diagnosis, an endoscopic biopsy from the small intestine is needed. Histopathological findings often include villous atrophy and crypt hyperplasia. A definitive diagnosis is necessary, as therapy involves a lifelong commitment to a gluten-free diet. If patients comply with this diet, the prognosis is generally very good and the increased risk of celiac-associated malignancies (e.g., intestinal lymphoma) is mitigated.
- Sex: ♀ > ♂
- Age of onset:
- Prevalence: in the US ∼ 1:3000
- More common in individuals of northern European descent
Epidemiological data refers to the US, unless otherwise specified.
- Genetic predisposition with association to HLA antigens
- Consuming gliadin from grains such as wheat, rye, and barley leads to an autoimmune reaction within the small intestinal wall.
- Commonly associated with autoimmune diseases (see “Clinical features” below)
- Consumption of food containing gluten → tissue transglutaminase is released → modifies gliadin; from gluten proteins → pathogenic T cells react ; to and are activated by modified gliadin → mediate chronic intestinal inflammation → epithelial damage resulting in villous atrophy, crypt hyperplasia; , and loss of brush border → impaired resorption of nutrients in the small intestine (especially in the distal duodenum and proximal jejunum) → malabsorption symptoms
- Chronic or recurring diarrhea: steatorrhea
- Flatulence, abdominal bloating, and pain
- Lack of appetite
- Constipation (rarely)
Extraintestinal symptoms and associations
- symptoms: fatigue, weight loss, , , osteoporosis, hypocalcemia
- In children: failure to thrive, growth failure, delayed puberty
- Dermatologic associations:
- Neuropsychiatric symptoms: peripheral neuropathies (numbness, burning and tingling of the hands and feet) , headache, ataxia, depression, irritability
- Gynecological associations: reduced fertility or infertility
- Endocrine associations: autoimmune thyroid disease, type 1 diabetes mellitus
- Associated chromosomal syndromes: Turner syndrome, Down syndrome
- Other associated conditions: autoimmune hepatitis, inflammatory bowel disease, rheumatoid arthritis, sarcoidosis, selective IgA deficiency 
In both children and adults, mild or asymptomatic cases are more common than the classic presentation of the disease.
General principles 
- Celiac disease is an underdiagnosed condition that requires a high index of suspicion.
- Diagnosis is based on serology (initial testing) and EGD with duodenal biopsy (confirmation).
- Common indications for testing include:
- Symptoms of malabsorption (e.g., steatorrhea) 
- First-degree relatives with celiac disease 
- Iron deficiency anemia unresponsive to treatment 
- Elevated liver enzymes with no discernable cause 
- Type 1 diabetes mellitus 
- Signs of osteoporosis (e.g., repeated, unexplained fractures) 
- Workup of other autoimmune disorders (e.g., thyroiditis, hepatitis) 
Laboratory studies 
- IgA tissue transglutaminase antibody (tTG IgA): initial test
- Total IgA
- IgG-based testing: indicated in IgA deficiency or discordant biopsy and serology
- HLA testing: second-line testing after unclear initial evaluation
- Anti-endomysial antibody (EMA): Potential second-line confirmatory test (high-specificity) 
EGD with small intestine biopsy (confirmatory test) 
- Indications: positive serology or high clinical suspicion despite negative serology
- At least five duodenal biopsies should be taken (with ≥ 1 from the duodenal bulb). 
- Histological findings: typically ranked by severity according to the Marsh classification 
- Video capsule endoscopy: if EGD is declined or as follow-up if symptoms persist despite treatment 
Diagnosis without endoscopy 
- Adults: diagnosis without biopsy not recommended.
- Children: consider diagnosis without biopsy if all of the following criteria are met (controversial) 
- Nutrient deficiency screening (individualize): indicated in confirmed celiac disease 
- Associated autoimmune disorders: Consider further testing if there are symptoms for thyroiditis, autoimmune hepatitis, and/or diabetes.
Tests for malabsorption: not routinely indicated (low sensitivity and specificity)
- : low urine d-xylose levels (The passive absorption of d-xylose in the proximal small intestine is impaired by the mucosal defect and bacterial overgrowth.)
- Fat malabsorption: quantitative stool fat assays or qualitatively via fat stains (e.g., Sudan III stain)
- See “Diagnostics” in “Malabsorption” for further information.
- Definition: : A disease characterized by chronic diarrhea with subsequent malabsorption in association with a stay in the tropics or subtropics.
- Epidemiology: : occurs in residents of the tropics and subtropics or in travelers returning from these areas (after trips lasting several weeks)
- Etiology: exact cause not known; most likely due to bacterial infection that leads to structural damage of the intestinal mucosa
- Clinical findings
- Blood tests: megaloblastic anemia (due to deficiency of folate and vitamin B12), hypoalbuminemia, hypocalcemia, vitamin D deficiency
- Serology for antibodies to rule out celiac disease (see “Diagnostics” above)
- Stool analysis
- Endoscopy of the small bowel and biopsy
- Treatment: tetracycline in combination with folic acid for 3–6 months
- Definition: :an infectious disease caused by Tropheryma whipplei, an intracellular gram-positive bacteria
- Very rare
- Most commonly occurs in males older than 40 years 
- Intestinal manifestations
- Extraintestinal manifestations
Small intestine biopsies: detection of PAS-positive foamy macrophages in the lamina propria ;
- If gastrointestinal symptoms are absent, biopsies may also be taken from other sites with disease activity
- PCR testing and immunohistochemistry staining
- Imaging may show enlarged mesenteric nodes.
- If neurological complaints occur: Perform a lumbar puncture and CSF analysis and neuroimaging (MRI).
- Small intestine biopsies: detection of PAS-positive foamy macrophages in the lamina propria ;
Anyone who CANT appreciate the foamy, PAStoral rivers of England gets Whipped: the most important features of Whipple disease are Cardiac symptoms, Arthralgias, Neurologic symptoms, Trots (diarrhea), and foamy, PAS-positive macrophages on biopsy.
Whipple disease is lethal if left untreated!
The differential diagnoses listed here are not exhaustive.
Strict, lifelong gluten-free diet
- Abstain from products containing wheat, rye, barley, or spelt.
- Symptoms usually improve quickly 
- Recommended foods: rice, corn, potatoes, soybeans, millet
- Patients with secondary lactase deficiency: Avoid milk products.
- Iron and vitamin supplementation, if there are deficiencies (e.g., iron deficiency anemia) 
- Consider osteoporosis screening in adult patients 
- Refer patients to a dietitian and advise joining support groups. 
Managing celiac disease mainly consists of maintaining a lifelong gluten-free diet.
- See clinical features of
- Secondary lactase deficiency
- Moderately increased risk of malignancies
We list the most important complications. The selection is not exhaustive.
- There is no proven measure to prevent celiac disease.
- With infants, introducing small amounts of wheat (into the supplementary diet) between 4–6 months of age does not increase the risk of developing celiac disease