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    Scott Adams

    Exploring Other Causes of Villous Atrophy Beyond Celiac Disease

    Reviewed and edited by a celiac disease expert.

    Shedding light on various health conditions that may present with similar histological changes in the small intestine.

    Exploring Other Causes of Villous Atrophy Beyond Celiac Disease - Golden reflections by Peggy2012CREATIVELENZ is licensed under CC BY 2.0.
    Caption:

    Celiac.com 02/10/2024 - Villous atrophy, a condition marked by the blunting or flattening of the microscopic structures called villi in the small intestine, is most commonly associated with celiac disease. However, emerging research and clinical observations have unveiled a spectrum of diverse conditions beyond celiac disease that can lead to villous atrophy. This article explores the lesser-known contributors to villous atrophy, shedding light on various health conditions that may present with similar histological changes in the small intestine. While celiac disease remains a prominent cause, understanding these alternative pathways to villous atrophy is crucial for accurate diagnosis, appropriate management, and a comprehensive approach to gastrointestinal health. From autoimmune disorders to infections and drug-induced reactions, exploring the multifaceted nature of villous atrophy enhances our grasp of gastrointestinal pathology and guides clinicians toward more nuanced and personalized patient care.

    Other Conditions Associated with Villous Atrophy

    In the following sections, we delve into a comprehensive exploration of diverse health conditions intricately linked to villous atrophy, shedding light on their unique associations and implications for gastrointestinal health.

    Eosinophilic Enteritis

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    Eosinophilic enteritis is an inflammatory disorder characterized by an increased presence of eosinophils in the gastrointestinal tract. Eosinophils are a type of white blood cell involved in the immune response. In eosinophilic enteritis, these cells infiltrate the walls of the intestines, causing inflammation and damage. This inflammatory process can lead to various symptoms, including abdominal pain, diarrhea, and malabsorption. In some cases, the inflammation may result in villous atrophy, affecting the absorptive capacity of the small intestine. Diagnosis often involves endoscopic procedures with tissue biopsy to evaluate the extent of inflammation and associated damage.

    Crohn's Disease

    Crohn's disease is a chronic inflammatory bowel disease that can affect any part of the gastrointestinal tract, from the mouth to the anus. In the small intestine, Crohn's disease can cause inflammation and damage to the intestinal lining, leading to complications such as strictures and fistulas. In some cases, individuals with Crohn's disease may experience villous atrophy, particularly in areas of the small intestine affected by inflammation. The severity of villous atrophy can vary among patients with Crohn's disease, and its presence may contribute to malabsorption issues and nutritional deficiencies. Management often involves anti-inflammatory medications, immunosuppressants, and, in severe cases, surgical intervention to address complications.

    Giardiasis

    Giardiasis is an intestinal infection caused by the parasite Giardia lamblia. This parasitic infection can lead to symptoms such as diarrhea, abdominal cramps, and bloating. In addition to the acute phase of the infection, chronic giardiasis has been associated with villous atrophy in some cases. The mechanisms by which Giardia lamblia causes villous atrophy are not fully understood, but it is believed to involve both direct damage to the intestinal lining and an immune response triggered by the presence of the parasite. Diagnosis typically involves stool tests to detect the parasite, and treatment includes antiparasitic medications.

    Common Variable Immunodeficiency (CVID)

    Common Variable Immunodeficiency (CVID) is a primary immunodeficiency disorder characterized by impaired antibody production, leading to increased susceptibility to infections. Some individuals with CVID may experience gastrointestinal symptoms, including chronic diarrhea and malabsorption. In severe cases, villous atrophy can occur, impacting the absorption of nutrients in the small intestine. The association between CVID and villous atrophy underscores the complex interplay between the immune system and the intestinal mucosa. Management involves immunoglobulin replacement therapy to address the immune deficiency and supportive measures for gastrointestinal symptoms.

    Autoimmune Enteropathy

    Autoimmune enteropathy is a rare autoimmune disorder that primarily affects the small intestine. In this condition, the immune system mistakenly attacks the cells of the intestinal lining, leading to severe inflammation and damage. Villous atrophy is a characteristic feature of autoimmune enteropathy, affecting the absorptive surface area of the small intestine. Individuals with autoimmune enteropathy often present with persistent diarrhea, malabsorption, and failure to thrive. Diagnosis requires extensive evaluation, including endoscopic procedures and tissue biopsy. Treatment involves immunosuppressive medications to modulate the autoimmune response and manage symptoms.

    Human Immunodeficiency Virus (HIV)

    Advanced Human Immunodeficiency Virus (HIV) infection can result in various gastrointestinal complications, affecting both the upper and lower parts of the digestive tract. HIV-associated enteropathy may involve villous atrophy, contributing to malabsorption and nutritional deficiencies. The mechanisms leading to villous atrophy in HIV infection are multifactorial, involving both direct viral effects and immune-mediated processes. Additionally, opportunistic infections and other HIV-related complications can further impact the gastrointestinal mucosa. Management includes antiretroviral therapy to control HIV replication and supportive measures to address nutritional deficiencies and associated symptoms. Regular monitoring and a multidisciplinary approach are crucial in the care of individuals with HIV-associated gastrointestinal conditions.

    Dermatitis Herpetiformis (DH)

    Dermatitis herpetiformis is a chronic skin condition characterized by intensely itchy, blistering skin lesions. While DH primarily manifests as a skin disorder, its connection to celiac disease is well-established. Both conditions share a common trigger: gluten ingestion. DH is considered the skin manifestation of celiac disease, and individuals with DH often have underlying gluten sensitivity. The immune response triggered by gluten in susceptible individuals leads to the formation of IgA antibodies, which deposit in the skin, causing the characteristic skin lesions. While DH predominantly affects the skin, it is crucial to recognize its association with celiac disease, as individuals with DH may also experience villous atrophy in the small intestine. Therefore, a gluten-free diet is not only essential for managing skin symptoms but also for addressing the underlying celiac disease and preventing intestinal damage. Diagnosis involves skin biopsy for characteristic IgA deposits and, in some cases, intestinal biopsy to assess the extent of villous atrophy. Treatment primarily revolves around strict adherence to a gluten-free diet, often complemented by medications to control skin symptoms. Managing DH effectively requires a multidisciplinary approach, involving dermatologists, gastroenterologists, and dietitians to address both the skin manifestations and the underlying celiac disease.

    Idiopathic Sprue

    Idiopathic sprue is a term used for cases of sprue (malabsorption syndrome) where the cause is unknown. It may include cases that do not fit the criteria for celiac disease or other known causes of malabsorption. It shares some features with celiac disease, such as malabsorption and damage to the small intestine, but it lacks specific diagnostic markers for celiac disease. Diagnosis may involve excluding other causes of malabsorption, and it may be considered when typical celiac disease markers are absent.

    Tropical Sprue

    Tropical sprue is a malabsorption syndrome that occurs in tropical regions, and its exact cause is not fully understood. It is thought to be associated with infections or environmental factors. It presents with symptoms of malabsorption, such as diarrhea, weight loss, and nutritional deficiencies. It is more commonly observed in tropical regions but can occur in non-tropical areas as well.

    Collagenous Sprue

    Collagenous sprue is a rare disorder characterized by collagen deposition in the small intestine. The cause is not well-established. It leads to malabsorption and features similar to celiac disease but is distinguished by the characteristic collagen band in the intestinal lining. Diagnosis involves histological examination of small intestinal biopsies. The management of collagenous sprue may involve a combination of treatments, including a gluten-free diet and immunosuppressive medications. Corticosteroids or other immunosuppressants may be prescribed.

    Peptic Duodenitis

    Peptic duodenitis, a condition characterized by inflammation of the duodenal lining due to exposure to stomach acid, shares a commonality with celiac disease in its potential to induce villous atrophy. In peptic duodenitis, the inflammatory response triggered by gastric acid can extend into the duodenum, disrupting the delicate balance of the intestinal mucosa. This sustained inflammation may lead to changes in the architecture of the small intestine, including the villi, finger-like projections crucial for nutrient absorption. The damage incurred can result in villous atrophy, akin to the characteristic intestinal changes observed in celiac disease.

    Helicobacter Pylori

    Helicobacter pylori, a bacterium known for its association with gastric ulcers and gastritis, has been implicated in gastrointestinal conditions that extend beyond the stomach, including potential involvement in villous atrophy akin to celiac disease. The presence of H. pylori in the duodenum and small intestine has been linked to chronic inflammation and alterations in mucosal architecture. The bacterium's ability to induce immune responses may contribute to the damage of the intestinal villi, compromising their structure and functionality. This shared consequence of villous atrophy highlights the interconnectedness of various gastrointestinal disorders and underscores the need for comprehensive investigations to discern the specific triggers and mechanisms at play. While celiac disease and H. pylori-related duodenal changes differ in their etiology, understanding the potential overlap in their impact on intestinal health is crucial for accurate diagnosis and tailored therapeutic interventions.

    Small Intestinal Bacterial Overgrowth (SIBO)

    Small intestinal bacterial overgrowth (SIBO) is recognized for its capacity to disrupt the normal balance of microorganisms in the small intestine, leading to various gastrointestinal manifestations. In some cases, SIBO has been associated with mucosal damage, mirroring the villous atrophy observed in conditions like celiac disease. The overgrowth of bacteria in the small intestine can interfere with nutrient absorption and trigger an inflammatory response, potentially contributing to the erosion of the intestinal villi. While the mechanisms differ from those in celiac disease, the shared outcome of villous atrophy underscores the intricate relationship between dysbiosis and intestinal health. 

    Lymphoma

    Lymphoma, a form of cancer that originates in the lymphatic system, can exhibit parallels with celiac disease in terms of inducing villous atrophy. In some cases, individuals with longstanding untreated celiac disease may face an elevated risk of developing enteropathy-associated T-cell lymphoma (EATL), a rare but serious complication. EATL is characterized by the infiltration of malignant T lymphocytes into the intestinal mucosa, leading to structural changes reminiscent of villous atrophy. While lymphoma and celiac disease differ fundamentally, the shared manifestation of villous atrophy underscores the intricate interplay between chronic inflammation and the potential oncogenic transformations within the gastrointestinal milieu. 

    Thiamine (Vitamin B1) Deficiency

    There is some old research that indicates that prolonged low thiamine (vitamin B1) may cause thinning of the microvillus membrane.

    While these conditions may share some clinical features with celiac disease, the differences in their etiology, histopathology, and diagnostic criteria make them distinct entities. Accurate diagnosis and differentiation often require a thorough clinical evaluation, including serological tests, histopathological examination, and consideration of geographic or idiopathic factors. Consulting with a gastroenterologist or healthcare professional is essential for proper diagnosis and management.

    Drug-Associated Enteropathy: Medications Associated with Villous Atrophy

    Understanding the intricate interplay between medications and intestinal well-being is paramount for individuals managing chronic health conditions. While medications play a pivotal role in alleviating symptoms and improving overall health, certain drugs may harbor the potential to influence the delicate environment of the small intestine. This section delves into the impact of various medications on the intestinal villi, focusing on conditions that may lead to villous atrophy. From common pain relievers to immunosuppressive drugs, the discussion aims to shed light on the nuanced relationship between medications and gastrointestinal health. It underscores the importance of informed healthcare decisions, proactive monitoring, and open communication between patients and healthcare providers to mitigate potential complications and ensure optimal intestinal function during the course of medical treatments.

    Non-Steroidal Anti-Inflammatory Drugs (NSAIDs)

    Non-Steroidal Anti-Inflammatory Drugs (NSAIDs) are commonly used to alleviate pain and inflammation, but prolonged and excessive use has been associated with adverse effects on the gastrointestinal (GI) tract. NSAIDs can cause irritation and inflammation in the small intestine, potentially leading to villous atrophy. The mechanism involves the inhibition of cyclooxygenase enzymes, which play a role in maintaining the integrity of the GI mucosa. Individuals relying on NSAIDs for chronic pain management should be cautious and work closely with healthcare providers to monitor and mitigate potential GI complications.

    Immunosuppressive Drugs

    Immunosuppressive drugs, such as methotrexate and mycophenolate mofetil, are crucial in managing autoimmune conditions and preventing organ rejection after transplantation. While these medications target the immune system to curb excessive responses, they may also impact the gastrointestinal lining. Long-term use could lead to intestinal complications, including villous atrophy. Healthcare providers prescribing immunosuppressive drugs carefully assess the risk-benefit profile for each patient and monitor closely for potential adverse effects on the GI tract.

    Chemotherapy Drugs

    Chemotherapy, a cornerstone in cancer treatment, aims to eradicate rapidly dividing cells, including cancerous ones. However, the impact isn't limited to tumors, and normal, healthy cells may also be affected. The rapidly renewing cells in the small intestine are particularly susceptible, potentially resulting in damage to the villi and compromising the absorptive capacity of the intestines. Individuals undergoing chemotherapy should discuss potential gastrointestinal side effects with their oncologist to address and manage any complications that may arise.

    Some Antibiotics

    Certain antibiotics, such as tetracycline and ampicillin, may disrupt the balance of the gut microbiota, leading to gastrointestinal disturbances. While these antibiotics target harmful bacteria, they can also affect beneficial microbes, influencing the overall health of the intestinal lining. The intricate relationship between antibiotics and the gut underscores the importance of judicious antibiotic use and, when necessary, the simultaneous administration of probiotics to support a healthy gut environment.

    Proton Pump Inhibitors (PPIs)

    Proton Pump Inhibitors (PPIs), commonly prescribed for acid reflux and gastroesophageal reflux disease (GERD), reduce stomach acid production. Prolonged use of PPIs has been linked to changes in the small intestine, potentially impacting the structure and function of the villi. Individuals relying on PPIs for an extended period should collaborate with healthcare providers to assess the necessity of continued use and explore alternative approaches to manage acid-related conditions.

    Opioid Pain Medications

    Opioid pain medications, including morphine and oxycodone, are known for their analgesic properties but are also associated with side effects such as constipation. Chronic use of opioids may lead to intestinal issues, affecting the normal functioning of the small intestine. It is crucial for healthcare providers to carefully manage opioid prescriptions, considering the potential impact on the gastrointestinal tract, and to explore alternative pain management strategies whenever possible. Patients should communicate openly with their healthcare team about any digestive issues experienced during opioid therapy to ensure timely intervention and support.

    Conclusion

    In conclusion, the journey through conditions associated with villous atrophy extends far beyond the realms of celiac disease. This exploration has highlighted the intricate interplay of various factors that can impact the health of the small intestine, leading to structural changes in the form of villous atrophy. Recognizing these diverse contributors is pivotal for healthcare professionals navigating the complexities of gastrointestinal disorders. As we deepen our understanding of the nuanced manifestations of villous atrophy, we pave the way for improved diagnostic accuracy and tailored treatment strategies. The heterogeneity of conditions linked to villous atrophy underscores the need for a holistic and individualized approach to patient care, ensuring that the intricacies of each case are addressed with precision and empathy. Through continued research and clinical vigilance, we strive to unravel the mysteries of these conditions and enhance the well-being of individuals facing the challenges of villous atrophy.

    Further reading on the topic of other causes of villous atrophy:



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    Recommended Comments

    Auldtwa

    is it safe to say that if your bloodwork has the indicators for celiac AND you have the atrophy, the atrophy is due to celiac?

    I'm interested because I have a different eosinophilic disease, thankfully in remission for forever (pulmonary eosinophilic granuloma, now know as Pulmonary Langerhan's disease.) If you have one problem with eosinophils do you get others?  Who knows?

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    Scott Adams

    Yes, if you have a positive celiac disease blood test AND a villous atrophy the cause is almost certainly celiac disease. A follow up biopsy and blood test 6 months to a year after going gluten-free would verify this--antibodies that drop, and villi regrowth.

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    Auldtwa

    Thanks

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    normagain

     I am scheduled for endoscopy the end of May and concerned about small intestinal bacterial overgrowth's affect on villous atrophy. I would rather not go on a strict gluten free diet if sibo and not gluten is the culprit. I have had candida overgrowth trouble for many years even though the doctor pooh poohed it my very first office visit. Is it automatically assumed that celiac is present if villi are atrophied even though in reality the atrophy may be caused by the sibo? I am having trouble digesting all this (no pun intended) so any help would be appreciated. 

    Serological evidence for celiac disease was present on 3/25 blood test.

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    Scott Adams

    Given that you had a positive blood test for celiac disease, if you also have villous atrophy the likely culprit would definitely be celiac disease, and not SIBO.

    Villous atrophy is a hallmark of celiac disease, but it can also be caused by SIBO and other conditions. Proper diagnosis often requires a multidisciplinary approach involving gastroenterologists, dietitians, and other healthcare professionals to differentiate between these conditions and provide targeted treatment.

    Another way to differentiate between celiac disease and SIBO as causes of villous atrophy is the response to treatment. Celiac disease is primarily treated with a strict gluten-free diet, which should lead to villous healing over time. On the other hand, SIBO is treated with antibiotics and dietary modifications aimed at reducing bacterial overgrowth. Improvement in villous architecture after treating SIBO supports the diagnosis.

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    normagain

    Chances are high that I have both celiac and sibo. The herxheimer reactions over the years pretty much confirm candida overgrowth to me but can not say for sure that it's in the small intestine. 

    Going gluten free will not be easy but something that I could and more than likely would do on its own but sibo clouds the issue. Getting rid of sibo with antibiotics is one thing but severely limiting carbs on top of gluten free is something that I would not attempt at this stage of senior citizenship.

    Many if not most of celiac and sibo symptoms are the same and intertwined. It seems that going gluten free would not heal the villi if sibo is also keeping it down. Am I not seeing this properly or would some sort of partial healing on a gluten free diet provide wellness notwithstanding sibo? Do you think that I should still do endoscopy given the above conflict? Thanks.

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    Auldtwa

    What isn't clear to me is whether an endoscopy would or wouldn't help figure out which issue is causing your problems?  If it would help even slightly, I'd say go for it.  Endoscopies are not particularly grueling.  Someone says "breath deep" and the next minute someone is offering you juice in recovery. Even the diet beforehand is way less of a problem than for colonoscopies.  

    I've been gluten free for about 10 years.  I am diabetic, on insulin.  I also try to adhere to a low oxalate diet due to recurring kidney stones.  I'm almost 80.  It hasn't been all THAT hard to adjust.  Some gluten free products are actually better than regular, if much pricier.  I have a brownie mix that is superb, though the ban on chocolate with the low oxalate diet is now looking to put paid to that.  

    Another benefit.  When I suddenly went vastly anemic the endoscopy showed a mildly bleeding ulcer.  It got removed.  It was only when that didn't FIX the anemia for a year that the doctors turned to celiac. So I had another endoscopy for that diagnosis.  Medicare paid for both.  If the ulcer hadn't been caught, though, things could have been MUCH worse.

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    normagain

    "What isn't clear to me is whether an endoscopy would or wouldn't help figure out which issue is causing your problems?"

    That is exactly what is not clear to me either. I guess I agree with help even slightly that I will probably go for it. Sometimes just talking it out helps clarify the issues. It would have been helpful if I could have done that with my dr but he is not interested at all in sibo.

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    Scott Adams
    3 hours ago, normagain said:

    Going gluten free will not be easy but something that I could and more than likely would do on its own but sibo clouds the issue. Getting rid of sibo with antibiotics is one thing but severely limiting carbs on top of gluten free is something that I would not attempt at this stage of senior citizenship.

    There are plenty of gluten-free carbs you can eat, so that should not be an issue. Corn, potatoes, and everything on this list is safe:

     

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    normagain

    That might be true for a person with a normal appetite but mine is insatiable either because of gluten or candida or both. A sibo/candida diet is all about no carbs. Here is just a sampling of foods that one would never think to be on the list.

    Avoid starchy vegetables such as carrots, sweet potatoes, potatoes, yams, corn, all squash except zucchini, beets, peas, parsnips and all beans except green beans. They all contain sugar and can lead to Candida overgrowth. You should buy your vegetables fresh and eat them raw, steam or grill them.

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    knitty kitty

    @normagain,

    There's a difference between Small Intestinal Bacterial Overgrowth (SIBO) and Candidiasis (Yeast Infection).  It's possible to have one or the other or both.  Celiac Disease causes damage to the small intestine.  The SIBO occurs because the bacteria take advantage of this damage to move in and multiply.  Same with Candida.  

    SIBO is treated with antibiotics, while Candida is treated with antifungal agents.  Both are found in people with diets high in carbohydrates.  Both bacteria and yeast feed on carbohydrates in the intestines.  Yes, the microbiome does communicate with the brain, frequently demanding more carbohydrates be sent down to them.  

    People consuming a high carbohydrate diet need extra Thiamine Vitamin B1 to process the carbohydrates into energy for the body to function.  High Calorie Malnutrition is caused by this overconsumption of carbohydrates without sufficient thiamine to process them.

    Adopting a no carbohydrate diet for several weeks (not forever) can help in starving out and eradicating these organisms.  Carbohydrates can be reintroduced into the diet after the SIBO and Candida have been eliminated. 

    Thiamine influences the bacteria that grow in the intestines, encouraging beneficial bacteria over SIBO bacteria. 

    Thiamine is beneficial in Diabetes as most diabetics are low in Thiamine.  We lose more Thiamine through the kidneys.  

    Riboflavin has been shown to eradicate Candida.  

    Supplementing with vitamins helps boost our ability to absorb these essential vitamins.  

    Talk to your doctors about supplementing vitamins and minerals.  

    Best wishes!

    References:

    Small intestinal bacterial overgrowth among patients with celiac disease unresponsive to a gluten free diet

    https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7759221/

    Dietary Vitamin B1 Intake Influences Gut Microbial Community and the Consequent Production of Short-Chain Fatty Acids

    https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9147846/

    Riboflavin Targets the Cellular Metabolic and Ribosomal Pathways of Candida albicans In Vitro and Exhibits Efficacy against Oropharyngeal Candidiasis

    https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9927497/

    Hiding in Plain Sight: Modern Thiamine Deficiency

    Dr. Chandler Marrs and Dr. Derrick Lonsdale

    https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8533683/

    Thiamine deficiency disorders: a clinical perspective

    https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8451766/

    Thiamine Level in Type I and Type II Diabetes Mellitus Patients: A Comparative Study Focusing on Hematological and Biochemical Evaluations

    https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7282352/

    Communication of gut microbiota and brain via immune and neuroendocrine signaling

    https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9907780/

     

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    normagain

    Thanks Knitty

    Your knowledge of the b vitamin is unreal. I don't recall ever having heard of the riboflavin influence on candida and look forward to a little more help in controlling the beast. Carbs are a problem for me particularly bread, rice and pasta. Worse was my addiction to refined sugar, however, pleased to report that I gave it up for the most part a year and a 1/2 ago and as a result have felt better on a relative basis. I absolutely love sourdough bread which will no longer be on the menu once celiac diet is started if celiac confirmed. Hopefully my appetite and desire for carbs decrease as gut starts to heal.

    Candida and its biofilms are a tough act to beat despite lab findings, at least for people who have had it for decades. The horror stories that I have read about. Some seem to beat it and months later they are back to report that it's back and worse than ever and don't understand why. I, on the other hand, have learned to live with it while trying to control it. 

    Anyway on a happier note I have been taking 50mg of allthiamine in addition to b complex for over a week and feel calmer for it. I'm talking about noticeable calm. I increased to 2 tabs allthiamine couple days ago. So thanks for the heads up.

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    Scott Adams was diagnosed with celiac disease in 1994, and, due to the nearly total lack of information available at that time, was forced to become an expert on the disease in order to recover. In 1995 he launched the site that later became Celiac.com to help as many people as possible with celiac disease get diagnosed so they can begin to live happy, healthy gluten-free lives.  He is co-author of the book Cereal Killers, and founder and publisher of the (formerly paper) newsletter Journal of Gluten Sensitivity. In 1998 he founded The Gluten-Free Mall which he sold in 2014. Celiac.com does not sell any products, and is 100% advertiser supported.


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