Partially responsive celiac disease resulting from small intestinal bacterial overgrowth and lactose intolerance
© Ghoshal et al; licensee BioMed Central Ltd. 2004
Received: 24 December 2003
Accepted: 22 May 2004
Published: 22 May 2004
Celiac disease is a common cause of chronic diarrhea and malabsorption syndrome all over the world. Though it was considered uncommon in India in past, it is being described frequently recently. Some patients with celiac disease do not improve despite gluten free diet (GFD). A study described 15 cases of celiac disease unresponsive to GFD in whom small intestinal bacterial overgrowth (SIBO) or lactose intolerance was the cause for unresponsiveness.
During a three-year period, 12 adult patients with celiac disease were seen in the Luminal Gastroenterology Clinic in a tertiary referral center in northern India. Two of these 12 patients (16.6%), who did not fully respond to GFD initially, are presented here. Unresponsiveness resulted from SIBO in one and lactose intolerance in the other. The former patient responded to antibiotics and the latter to lactose withdrawal in addition to standard GFD.
In patients with celiac disease partially responsive or unresponsive to GFD, SIBO and lactose intolerance should be suspected; appropriate investigations and treatment for these may result in complete recovery.
Celiac disease is a common cause of chronic diarrhea and malabsorption syndrome (MAS) all over the world. Though it was considered uncommon in India in past, it is being described frequently recently [1, 2]. Some patients with celiac disease do not improve despite gluten free diet (GFD). Tursi et al described 15 cases of celiac disease unresponsive to GFD in whom small intestinal bacterial overgrowth (SIBO) or lactose intolerance was the cause of unresponsiveness . We describe two adult patients with celiac disease only partially responsive to GFD; unresponsiveness resulted from SIBO in one and lactose intolerance in the other.
During a 3-y period from July 2000 to July 2003, 12 adult patients with celiac disease diagnosed using standard criteria  were seen in the Luminal Gastroenterology Clinic of the Department of Gastroenterology in a tertiary referral center in northern India. All except two (16.6%) of them responded clinically to GFD. The data of the two patients, who were initially unresponsive to standard GFD is presented below.
Discussion and conclusion
Diagnosis of celiac disease in both the patients was established on standard criteria . We have earlier shown that half of patients with MAS resulting from various causes including celiac disease may have SIBO . In patients with tropical sprue it resulted from small intestinal stasis as evidenced by prolonged OCTT . Similar mechanisms may operate in patients with MAS due to other causes; the patient with celiac disease with SIBO in this report had prolonged OCTT. Prolonged OCTT has been reported by other workers in patients with celiac disease, which normalized after GFD . Unabsorbed foods within the intestinal lumen may also promote growth of bacteria in small intestinal lumen. We believe that SIBO in patients with MAS due to another cause may have following clinical significances, (1) a response to antibiotics may lead to a fallacious diagnosis of tropical sprue as response to antibiotics has been considered to be an important criterion for diagnosis of this disease ; (2) it may be a cause for inadequate response or refractory state despite GFD as occurred in our first patient and as has been reported by Tursi et al . Lactose intolerance could be another cause for such inadequate response to GFD. Lactase deficiency causing intolerance to lactose is known to be either primary or secondary; though in our patient, whether it was primary or secondary is a matter of conjecture, the latter is more likely as degenerated intestinal epithelial cells in patients with celiac disease are often found to have sparse endoplasmic reticulum, reflecting low level of digestive enzymes including lactase ; primary lactase deficiency is somewhat uncommon too . However, a definite diagnosis of lactose intolerance is important as a firm diagnosis helps the clinician as well as the patient to completely withdraw lactose containing foods, compliance to which may not be so easy for a patient with celiac disease already on significant dietary restriction without a definite diagnosis, particularly if the patient is vegetarian. The second patient continued to have diarrhea despite improvement in D-xylose test and duodenal biopsy, which led us to suspect a predominantly osmotic factor as the cause of diarrhea. Therefore, we investigated for lactose intolerance contributing to osmotic diarrhea. Normal result of D-xylose test was helpful as it suggested normalization of intestinal mucosa; D-xylose test has a high sensitivity to detect abnormal mucosa causing MAS . In fact, serial tests of intestinal permeability, which are based on a principle similar to D-xylose test, have been used successfully to non-invasively predict normalization of intestinal mucosa before undertaking invasive tests like endoscopic duodenal biopsy .
Small intestinal bacterial overgrowth in patients with celiac disease may lead to persistent diarrhea due to disturbances in luminal digestion and alteration of mucosal function, albeit minor . Bacteria in small intestine in patients with SIBO causes deconjugation of bile acids, which causes watery diarrhea due to stimulation of colonic secretion and steatorrhea due to depletion of bile acid pool . Lactose intolerance results in persistence of diarrhea mainly due to osmotic effect of unabsorbed lactose and flatulence due to production of gas from fermentation of unabsorbed lactose.
Refractory celiac sprue is defined as an initial (primary) or subsequent (secondary) failure of a strict GFD to restore normal intestinal structure and function and may result from several mechanisms . It is important to keep all these causes of refractory celiac sprue in mind and to investigate and treat for all these factors . Though SIBO and secondary lactose intolerance are expected and known to be common in celiac disease, until recently [3, 15], only a few reports have been published on this issue [16, 17]. Though normalization of duodenal histology may take long time up to one to two years, clinical response such as reduction in diarrhea and weight gain occurs within weeks . Failure of normalization of duodenal histology has been proposed as a criterion for diagnosis of refractory sprue . Persistent symptoms despite normalization of duodenal histology may suggest causes other than refractory sprue such as SIBO and lactose intolerance.
In conclusion, we believe that if diarrhea persists in a patient with celiac disease despite improvement in duodenal biopsy and D-xylose absorption, lactose intolerance and SIBO should be suspected; appropriate investigations and treatment for these may result in complete recovery.
List of abbreviations
gluten free diet
small intestinal bacterial overgrowth
enzyme linked immunosorbant assay
colony forming units
glucose 'hydrogen breath test
parts per million
orocecal transit time
body mass index
high power field
partial villous atrophy
lactose hydrogen breath test
lactose tolerance test
We thank the patients who are presented in this report for giving us written consent for publishing their data.
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