Diarrhea, Chronic

What Is Chronic Diarrhea?

Chronic diarrhea is an intestinal motility disorder characterized by 1) alteration in stool formation causing loose to fluid movements and quantity of movements with or without abdominal pain and 2) interference with normal carbohydrate salvage by the intestinal microbe population.

The severity of diarrhea is determined by the frequency and quantity of fluid lost.

Q: What is carbohydrate salvage by microbes in the colon?

A: Carbohydrate salvage in the colon is the necessary process whereby billions of microbes normally present in the colon work to breakdown undigestible carbohydrate foodstuffs such as fiber that continually arrive from the small intestine.

The microbial action releases energy to the body that would otherwise be lost with defecation, generates short-chain fatty acids, and stimulates sodium and fluid absorption. In this important process, butyrate and proprionate are produced which nourish the colonocytes (cells that line the colon), and acetate is produced for the liver.

While diarrhea may be a common symptom of small bowel mucosal disease, the consequent malabsorption can lead to substantial malnutrition and nutrient deficiencies. The small intestine, unlike the colon, has been relatively inaccessible, and systematic evaluation is often necessary to identify and treat small intestinal mucosal diseases that lead to diarrhea. All patients with severe diarrhea or diarrhea associated with features suggestive of malabsorption may have a disease of the small intestinal mucosa that requires careful evaluation and targeted management.1

What Is Chronic Diarrhea In Celiac Disease and/or Gluten Sensitivity?

• Chronic diarrhea is a classic symptom in patients with untreated celiac disease which indicates extensive damage to small intestinal mucosa.2
• Patients with partial villous atrophy presented with similar diarrhea characteristics as did patients with severe villous atrophy meaning the severity of diarrhea does not depend on the severity of intestinal damage.3
• Diarrhea is one of the clinical manifestations of zinc deficiency and has been isolated in infants with celiac disease and diarrhea.4
• After treatment with a gluten free diet, chronic diarrhea persists in a substantial percentage of patients. Athough ongoing gluten ingestion is one possible cause, other causes may be more frequent. Other causes include microscopic colitis, steatorrhea secondary to pancreatic insufficiency, dietary lactose malabsorption, anal sphincter dysfunction causing fecal incontinence, and the irritable bowel syndrome. Therefore, a diagnostic evaluation of diarrhea in celiac disease after treatment seems warranted.5
• In diarrhea persisting despite being on a gluten-free diet, study results from 259 patients with diarrhea show that low elastase (a pancreatic enzyme) in stool samples is common in patients with celiac disease and chronic diarrhea, suggesting exocrine pancreatic insufficiency. In this group of patients, pancreatic enzyme supplementation may provide symptomatic benefit.6
• Celiac disease screening tests are needed in chronic diarrhea for any ethnicity patients.7

How Prevalent Is Chronic Diarrhea In Celiac Disease and/or Gluten Sensitivity?

• Chronic diarrhea is the most frequent symptom of patients with untreated celiac disease.8
• In the USA, 79% of patients experienced diarrhea before treatment, and 17% had chronic diarrhea (of lesser severity) after treatment.5
• In Canada, 71.7% reported diarrhea at diagnosis, and 71.6% reported recovery from diarrhea after 5 years on a gluten free diet.9
• In India, diarrhea as the presenting symptom was seen in 74 % of children and 58.7% of adolescent/adults.10
• In Ireland, diarrhea in was seen in 45% of 106 consecutive adult patients.11
• In gluten sensitivity, a significantly higher proportion of patients with positive IgA gliadin antibodies reported unexplained diarrhea attacks.12,13
• A retrospective study in India of 381 consecutive children diagnosed with celiac disease observed a prevalence of 48.2% for classic diarrheal celiac disease. 51.8% had non-diarrheal celiac disease.14
• Diarrhea was found in 73% of the children with gluten sensitivity. Histology revealed normal to mildly inflamed mucosa (Marsh stage 0-1) in these children with gluten sensitivity.15

What Are The Symptoms Of Chronic Diarrhea?

• Chronic diarrhea is marked by passage of bulky, frequent fluid or unformed stool, with or without abdominal pain.

How Does Chronic Diarrhea Develop In Celiac Disease and/or Gluten Sensitivity?

• Chronic diarrhea results from any of these factors:

• Undigested nutrients from the small intestine act to pull large amounts of water out of tissues into the intestine.
• Dysbiosis or unhealthy microbe population normally present in the gut.
• Altered motility or peristalsis (normal wave-like muscle movement) of the intestine.
• Zinc deficiency in celiac disease.

• Importantly, diarrhea causes loss of potassium, which in turn, alters bowel motility, encourages anorexia, and can introduce a cycle of bowel distress.16
• Refractory celiac disease is a cause of chronic diarrhea due to continual inflammation and malabsorption.
• Enteropathy-associated T-cell lymphoma (EATL) which is a complication of celiac disease, is a cause of chronic diarrhea.

Does Chronic Diarrhea Respond To Gluten-Free Diet?

Yes. Celiac disease-related chronic diarrhea responds to gluten free diet within days for most patients. Correction of low vitamin A and zinc is important for healing.17

Response to gluten free diet is similar for patients with partial villous atrophy and severe villous atrophy.3

Low fecal elastase (a pancreatic enzyme) is common in patients with celiac disease and chronic diarrhea, suggesting exocrine pancreatic insufficiency. In this group of patients, pancreatic enzyme supplementation may provide symptomatic benefit.6

6 Steps To Improve Chronic Diarrhea In Celiac Disease and/or Gluten Sensitivity:

• 1Remove the Trigger. Maintain a Strict, Nutritious Gluten Free Diet:

• 2 Reduce Inflammation. Foods to Eat and Foods Not to Eat:

Because gluten is inflammatory, eliminate OTHER inflammatory foods from your diet to reduce an additive effect to gluten. At the same time, try to eat foods that reduce inflammation (anti-inflammatory).

• 3 Information Sheet You Can Take to Your Doctor or Other Health Professional:

Click here.

• 4 Manage Your Medications Safely:

• 5Nutritional Supplements To Help Correct Deficiencies:

• 6Manage Natural Remedies: 

What Do Medical Research Studies Tell About Chronic Diarrhea In Celiac Disease and/or Gluten Sensitivity?

RESEARCH STUDY SUMMARIES

“Clinical, serologic, and histologic features of gluten sensitivity in children.”  This study seeking to describe the clinical, serologic, and histologic characteristics of children with gluten sensitivity demonstrated findings that support the existence of gluten sensitivity in children across all ages with clinical, serologic, genetic, and histologic features similar to those of adults. Diarrhea was found in 73% of the children with gluten sensitivity.

 Subjects were 15 children (10 males and 5 females; mean age, 9.6 ± 3.9 years) with gluten sensitivity who were diagnosed based on a clear-cut relationship between wheat consumption and development of symptoms, after excluding celiac disease and wheat allergy, along with 15 children with active celiac disease (5 males and 10 females; mean age, 9.1 ± 3.1 years) and 15 controls with a functional gastrointestinal disorder (6 males and 9 females; mean age, 8.6 ± 2.7 years). All children underwent celiac disease panel testing (native antigliadin antibodies IgG and IgA, anti-tissue transglutaminase antibody IgA and IgG, and anti-endomysial antibody IgA), hematologic assessment (hemoglobin, iron, ferritin, aspartate aminotransferase, erythrocyte sedimentation rate), HLA typing, and small intestinal biopsy (on a voluntary basis in the children with gluten sensitivity).

Abdominal pain was the most prevalent symptom in the children with gluten sensitivity (80%), followed by chronic diarrhea in (73%), tiredness (33%), bloating (26%), limb pain, vomiting, constipation, headache (20%), and failure to thrive (13%). Native antigliadin antibodies IgG was positive in 66% of the children with gluten sensitivity. No differences in nutritional, biochemical, or inflammatory markers were found between the children with gluten sensitivity and controls. HLA-DQ2 was found in 7 children with gluten sensitivity. Histology revealed normal to mildly inflamed mucosa (Marsh stage 0-1) in the children with gluten sensitivity.20

“Clinical features and symptom recovery on a gluten-free diet in Canadian adults with celiac disease.” This study investigating the clinical features and symptom recovery on a gluten-free diet in a Canadian adult celiac population found that many patients report continuing symptoms despite adhering to a gluten-free diet for more than 5 years, with women experiencing more symptoms and a lower recovery rate than men. 71.7% reported diarrhea at diagnosis; 71.6% reported recovery from diarrhea after 5 years on a gluten free diet.

All adult members (n=10,693) of the two national celiac support organizations, the Canadian Celiac Association and Fondation québécoise de la maladie coeliaque, were surveyed using a questionnaire.

A total of 5912 individuals (18 years of age or older) with biopsy-confirmed celiac disease and⁄or dermatitis herpetiformis completed the survey. The female to male ratio was 3:1. Mean time to diagnosis after onset of symptoms was 12.0 ± 14.4 years. In addition to diarrhea, symptoms of abdominal pain and bloating (84.9%), tiredness (74.2%), and anemia (67.8%) were the most commonly reported at the time of diagnosis. Sex differences were reported in clinical features before diagnosis, recovery after being on gluten-free diet and perceived quality of life, with women experiencing more difficulties than men.

Delays in diagnosis of celiac disease in Canada remain unacceptably long despite wider availability of serological screening tests. Awareness of celiac disease needs improvement, and follow-up with a physician and a dietitian is essential for all patients with celiac disease.9

“Celiac disease presentation in a tertiary referral center in India: current scenario.” This retrospective study comparing the clinical spectrum of non-diarrheal celiac disease (NDCeliac Disease) with that of diarrheal/classical celiac disease (CCeliac Disease) found the number of patients with a Marsh score IIIb and above of duodenal biopsy was significantly more in the CCeliac Disease group. A total of 381 consecutive patients were diagnosed with Celiac Disease during the study period. NDCeliac Disease was present in 192 (51.8 %). NDCeliac Disease had higher mean age at presentation (5.8 ± 2.8 vs. 6.9 ± 2.9 years respectively) and longer duration of symptoms prior to diagnosis (2.9 ± 1.7 years vs. 3.6 ± 2.2 years) as compared to CCeliac Disease.

In the NDCeliac Disease group, the most frequent gastrointestinal (GI) symptoms were recurrent abdominal pain [122 (63.5 %)] and abdominal distension [102 (53.1 %)] followed by constipation [48 (25 %)], vomiting [76 (39.6 %)] and recurrent oral ulcers [89 (46.4 %)].21

“Adult celiac disease in Ireland: a case series.” This retrospective study investigating files from a patient database to analyse the presenting symptoms, associated conditions and complications in a consecutive series of patients with adult celiac disease found a prevalence of diarrhea in 44 patients (45%).

One hundred and six patients (69 females to 37 males, mean age: 46, range: 23-95 years) were included. The modes of presentation were diarrhea in 44 patients (45%), weight loss in 41 (42%), anemia in 37 (38%), abdominal pain in 15 (15%), fatigue in 8 (8%), hypocalcaemia in 4 (4%) and steatorrhoea in 4 (4%). Associated conditions included thyroid disorders in 7 patients (7%), bipolar affective disorder in 4 (4%), major depression in 3 (3%), rheumatoid disease in 3 (3%), inflammatory bowel disease in 4 (4%) and type I diabetes mellitus in 2 (2%). Malignancy emerged as a major complication in 15 patients (15%).22

“Adult celiac disease with severe or partial villous atrophy: a comparative study.” This retrospective study investigating the impact of partial villous atrophy on the clinical presentation of adult celiac disease (ACD) versus patients with severe villous atrophy found partial villous atrophy in 21% of patients with ACD. Patients with partial villous atrophy presented with similar clinical, biological and immune characteristics and outcomes as did patients with severe villous atrophy. Diarrhea, malabsorption syndrome and osteopenia were independent of the degree of villous atrophy meaning the extent of these conditions does not depend on the severity of intestinal damage.

Medical files of 48 patients with ACD diagnosed between 1992 and 2003 were retrospectively studied. The diagnosis was based on the presence of intestinal villous atrophy, with increases in intraepithelial lymphocytes and circulating celiac specific antibodies. Villous atrophy was classified as severe (subtotal and total) or partial. Symptoms, biological signs of malabsorption, immune markers, bone mineral density at diagnosis and response to gluten-free diet were recorded.

At diagnosis, ten patients (four M/six F) had partial villous atrophy and 38 patients (five M/33 F) had severe villous atrophy, with a median age of 54 and 33 years, respectively. Positivity for specific antibodies, HLA typing and frequency of autoimmune disease at diagnosis were similar in both groups, as was their response to gluten-free diet.23

“Is exocrine pancreatic insufficiency in adult celiac disease a cause of persisting symptoms?” This study investigating whether exocrine pancreatic insufficiency causes persisting symptoms compared with controls, we determined whether pancreatic enzyme supplementation provided symptomatic benefit in celiac patients with chronic diarrhea. Results show that low fecal elastase is common in patients with celiac disease and chronic diarrhea, suggesting exocrine pancreatic insufficiency. In this group of patients, pancreatic enzyme supplementation may provide symptomatic benefit.

Subjects: 259 were subdivided into four groups: (a) 57 new celiac disease, (b) 86 celiac disease patients on a gluten-free diet without gastrointestinal symptoms, (c) 66 celiac disease patients on a gluten-free diet with chronic diarrhea and (d) 50 patients with chronic diarrhea without celiac disease. Stool frequency and weight, before and after treatment with pancreatic enzyme supplementation were recorded.

The prevalence of a low fecal elastase-1 within the groups was: group (A) six of 57 (11%), group (B) five of 86 (6%), group (C) 20 of 66 (30%) and group (D) two of 50 (4%). Low fecal elastase-1 was more frequent in celiac disease patients with chronic diarrhea vs. other subgroups of celiac disease and controls. In 18 of 20 stool frequency reduced following pancreatic enzyme supplementation from four per day to one. No weight increase was observed.6

“Effect of a gluten-free diet on gastrointestinal symptoms in celiac disease.” This study investigating the effect of a gluten free diet on GI symptoms revealed that steatorrhea occurred in only 1/5th of celiac disease patients.24

“Antigliadin antibodies in the absence of celiac disease.” This study measuring IgG and IgA isotypes and IgG subclasses observed that a significantly higher proportion of patients with positive IgA gliadin antibodies reported unexplained diarrhea attacks.13

The prevalence and causes of chronic diarrhea in patients with celiac sprue treated with a gluten-free diet.” This study demonstrated that after treatment with a gluten free diet, chronic diarrhea persists in a substantial percentage of patients. Athough ongoing gluten ingestion is one possible cause, other causes may be more frequent. Other causes include microscopic colitis, steatorrhea secondary to pancreatic insufficiency, dietary lactose malabsorption, anal sphincter dysfunction causing fecal incontinence, and the irritable bowel syndrome. Therefore, a diagnostic evaluation of diarrhea in celiac disease after treatment seems warranted.5

“Do adults with high gliadin antibody concentrations have subclinical gluten intolerance?” This study measuring IgG and IgA isotypes and IgG subclasses observed that a significantly higher proportion of patients with positive IgA gliadin antibodies reported unexplained diarrhea attacks.12

CASE REPORT SUMMARIES

“A rare but potentially fatal cause of diarrhoea and weight loss: enteropathy-associated T-cell lymphoma.“ This case report describes finding celiac disease and enteropathy-associated T-cell lymphoma (EATL) in a patient who presented to the physician with diarrhea and weight loss.  EATL commonly presents with abdominal pain, diarrhea and weight loss, but can also present with complications such as bowel obstruction and perforation. It is the most common neoplastic complication of celiac disease, but can occur with no prior diagnosis of celiac disease.

This case demonstrates the difficulties that can be faced in diagnosing this disorder, particularly when there is no preceding history of celiac disease. Early diagnosis is of utmost importance in order to start treatment before the effects of malnutrition increase the risk of complications from chemotherapy. Hence awareness of the condition among general medical physicians, to whom it will often present first, is essential. However, even with prompt diagnosis, outcomes for this condition remain poor.25

“Tetany caused by chronic diarrhea in a child with celiac disease: A case report.” There is no awareness about celiac disease in Mexico. A 2.9 year old mestizo boy was admitted to a Mexican hospital with muscle cramps and fine tremors. He suffered chronic diarrhea, abdominal distention, hypotrophic limbs, stunting and wasting, and presented hypocalcemia, anemia and high titers of serological markers. Diagnosis of celiac disease was confirmed by a duodenal biopsy. After replacement of calcium and a gluten-free diet, the symptoms resolved within 6 weeks. After 2-months, serum analyses, anthropometric data as well as antibodies titers were normal after 4 years. Celiac disease screening tests are needed in chronic diarrhea for any ethnicity patients.26

1. Murray JA1, Rubio-Tapia A. Diarrhoea due to small bowel diseases. Best Pract Res Clin Gastroenterol. 2012 Oct;26(5):581-600. doi: 10.1016/j.bpg.2012.11.013. [↩]
2. Murray JA, the widening spectrum of celiac disease. American Journal of Clinical Nutrition. Mar 1999; 69(3):354-365. [↩]
3. Malamut G, Matysiak-Budnik T, Grosdider E, Jais JP, Morales E, Damotte D, Caillat-Zucman S, Brousse N, Cerf-Bensussan N, Jian R, Cellier C. Adult celiac disease with severe or partial villous atrophy: a comparative study. Gastroenterol Clin Biol. 2008 Mar;32(3):236-42. doi: 10.1016/j.gcb.2008.02.011. [↩] [↩]
4. Giorgi PL, Catassi C, Guerrieri A. Zinc and chronic enteropathies. La Pediatria Medica e Chirurgica: Medical and Surgical Pediatrics. Sep-Oct 1984;; 6(5):625-36. [↩]
5. Fine KD, Meyer RL, Lee EL. The prevalence and causes of chronic diarrhea in patients with celiac sprue treated with a gluten-free diet. Gastroenterology. Jun 1997;112(6);1830-8. [↩] [↩] [↩]
6. Leeds JS, Hopper AD, Hurlstone DP, Edwards SJ, McAlindon ME, Lobo AJ, Donnelly MT, Morley S, Sanders DS. Is exocrine pancreatic insufficiency in adult celiac disease a cause of persisting symptoms? Aliment Pharmacol Ther. 2007 Feb 1;25(3):265-71. [↩] [↩] [↩]
7. Hurtado-Valenzuela JG, Sotelo-Cruz N, López-Cervantes G, de la Barca AM. Tetany caused by chronic diarrhea in a child with celiac disease: A case report. Cases J. 2008 Sep 23;1(1):176. doi: 10.1186/1757-1626-1-176. [↩]
8. Murray JA, Watson T, Clearman B, Mitros F. Effect of a gluten-free diet on gastrointestinal symptoms in celiac disease. American Journal of Clinical Nutrition. Apr 2004; 79(4):669-73. [↩]
9. Pulido O, Zarkadas M, Dubois S, Macisaac K, Cantin I, La Vieille S, Godefroy S, Rashid M. Clinical features and symptom recovery on a gluten-free diet in Canadian adults with celiac disease. Can J Gastroenterol. 2013 Aug;27(8):449-53. [↩] [↩]
10. Kochhar R, Jain K, Thapa BR, Rawal P, Khaliq A, Kochhar R, Bhadada S, Vaiphei K, Varma S, Dutta U, Nain CK, Prasad KK, Singh K. Clinical presentation of celiac disease among pediatric compared to adolescent and adult patients. Indian J Gastroenterol. 2012 Jun;31(3):116-20. doi: 10.1007/s12664-012-0198-9. [↩]
11. Saleem A, Connor HJ, Regan PO. Adult coeliac disease in Ireland: a case series. Ir J Med Sci. 2012 Jun;181(2):225-9. doi: 10.1007/s11845-011-0788-z. [↩]
12. Arnasson JA, Gudjonsson H, Freysdoyyir J, Valdimarsson H. Do adults with high gliadin antibody concentrations have subclinical gluten intolerance? Gut. Feb 1992; 33(2): 194-7. [↩] [↩]
13. Kamaeva OI, Reznikov IuP, Pimenova NS, Dobritsyna LV. Antigliadin antibodies in the absence of celiac disease. Klinicheskaia Meditsina. 1998;76(2):33-5. [↩] [↩]
14. Bhattacharya M, Kapoor S, Dubey AP. Celiac disease presentation in a tertiary referral centre in India: current scenario. Indian J Gastroenterol. 2013 Mar;32(2):98-102. doi: 10.1007/s12664-012-0240-y. [↩]
15. Francavilla R, Cristofori F, Castellaneta S, Polloni C, Albano V, Dellatte S, Indrio F, Cavallo L, Catassi C. Clinical, serologic, and histologic features of gluten sensitivity in children. J Pediatr. 2014 Mar;164(3):463-7.e1. doi: 10.1016/j.jpeds.2013.10.007. [↩]
16. Kathleen Mahan and Sylvia Escott-Stump, ed. Krause’s Food, Nutrition & Diet Therapy, 10th Edition. Philadelphia, PA. USA: W.B. Saunders Company, 2000. [↩]
17. Mehta DI, Lebenthal E, Blecker U. Chronic diarrhea: causes, presentation, and management. Indian Journal of Pediatrics. Jul-Aug 1996;63(4):459-71. [↩]
18. Cummins AG, Thompson FM, Butler RN, et al. Improvement in intestinal permeability precedes morphometric recovery of the small intestine in coeliac disease. Clinical Science. Apr 2001;100(4):379-86. [↩]
19. Farhadi A, Banan A, Fields J, Keshavarzian A. Intestinal barrier: an interface between health and disease. Journal of Gastroenterology and Hepatology. 2003;18:479-91. [↩] [↩] [↩] [↩] [↩] [↩]
20. Francavilla R, Cristofori F, Castellaneta S, Polloni C, Albano V, Dellatte S, Indrio F, Cavallo L, Catassi C. Clinical, serologic, and histologic features of gluten sensitivity in children. J Pediatr. 2014 Mar;164(3):463-7.e1. doi: 10.1016/j.jpeds.2013.10.007. [↩]
21. Bhattacharya M, Kapoor S, Dubey AP. Celiac disease presentation in a tertiary referral center in India: current scenario. Indian J Gastroenterol. 2012 Aug 19. [↩]
22. Saleem A, Connor HJ, Regan PO. Adult coeliac disease in Ireland: a case series. Ir J Med Sci. 2012 Jun;181(2):225-9. doi: 10.1007/s11845-011-0788-z. [↩]
23. Malamut G, Matysiak-Budnik T, Grosdider E, Jais JP, Morales E, Damotte D, Caillat-Zucman S, Brousse N, Cerf-Bensussan N, Jian R, Cellier C. Adult celiac disease with severe or partial villous atrophy: a comparative study. Gastroenterol Clin Biol. 2008 Mar;32(3):236-42. doi: 10.1016/j.gcb.2008.02.011. [↩]
24. Murray JA, Watson T, Clearman B, Mitros F. Effect of a gluten-free diet on gastrointestinal symptoms in celiac disease. American Journal of Clinical Nutrition. Apr 2004;79(4):669-73. [↩]
25. Wali GN, Tyrrell HE, Collins GP, Eagleton HJ. A rare but potentially fatal cause of diarrhoea and weight loss: enteropathy-associated T-cell lymphoma. BMJ Case Rep. 2015 Jan 7;2015. pii: bcr2014204125. doi: 10.1136/bcr-2014-204125. [↩]
26. Hurtado-Valenzuela JG, Sotelo-Cruz N, López-Cervantes G, de la Barca AM. Tetany caused by chronic diarrhea in a child with celiac disease: A case report. Cases J. 2008 Sep 23;1(1):176. doi: 10.1186/1757-1626-1-176. [↩]