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Sarcoidosis

What Is Vitamin B12 Deficiency Anemia? V itamin B12 deficiency anemia is a megaloblastic anemia that is characterized by defective DNA synthesis of red blood cells due to a lack of vitamin B12. Vitamin B12 is… 

Peripheral Neuropathy 

Microscopic Slide of Lymphocytic Colitis. Courtesy Quizlet.com
Microscopic  Slide of Biopsy Sample Showing Lymphocytic Colitis. Courtesy Quizlet.com

What Is Lymphocytic Colitis?

L ymphocytic colitis is a microscopic inflammation of the large intestinal mucosa with infiltration of lymphocytes (IELs)  that is characterized by non-bloody secretory diarrhea.

Secretory diarrhea describes bowel movements that consist of a large volume of liquid stool.

Q: What are IELs?

A: IELs is an abbreviation for intraepithelial lymphocytes, which are white blood cells that infiltrate within epithelial cells or between them. Epithelial cells form the surface mucosa of the large intestine also called the colon.

The histopathological criteria (biopsy) for lymphocytic colitis are a density of at least 20 IELs per 100 surface epithelial cells; chronic inflammatory infiltrate of mononuclear cells in the lamina propria; epithelial damage; and a subepithelial collagen layer of less than 10 µm. The increased collagen band consists basically of collagen type I and III, which are the subtypes produced by repair functions, indicating a reactive origin.1That is, the mucosa is reacting to some irritative substance.

Up to 10% of adults undergoing colonoscopy for investigation of chronic diarrhea and having visibily normal appearing mucosa may have lymphocytic colitis.2

Bile acid malabsorption has been shown to coexist in 60% of patients with lymphocytic colitis.1

Lymphocytic colitis (LC) is categorized as primary or secondary.  Primary LC is a clinical and histopathological disease of unknown cause. Secondary LC may develop as the result of iritating factors acting on the colon such as smoking or many medications.  In one study, the most common drug treatments as a percentage of the study group were corticosteroids (32.1%), proton pump inhibitors (26.0%), antidepressant drugs, specifically selective serotonin reuptake inhibitors (21.4%), angiotensin-converting enzyme inhibitors or angiotensin II receptor antagonists (18.3%), statins (17.6%), thyroid hormones (17.6%), and beta-blockers (16.0%).3

Secondary lymphocytic colitis is associated with several concomitant diseases including celiac disease. This is why lymphocytic changes must be interpreted with caution before considering them as a separate entity of autoimmune origin, instead of secondary reactions to ischemia and toxic stimulants. Efforts must be made to better classify and diagnose patients with real, primary lymphocytic colitis to avoid over-prescription of corticosteroids for treatment.3

What Is Lymphocytic Colitis In Celiac Disease and/or Gluten Sensitivity?

Sources:
  1. Ohlsson B. New insights and challenges in microscopic colitis. Therap Adv Gastroenterol. 2015 Jan;8(1):37-47. doi: 10.1177/1756283X14550134. [↩] [↩]
  2. Abdo AA, Urbanski SJ, Beck PL. Lymphotcytic and collagenous colitis: the emerging entity of microscopic colitis. An update on pathophysiology, diagnosis and management. Canadian Journal of Gastroenterology. Jul 2003;17(7):425-32. [↩]
  3. Roth B, Manjer J, Ohlsson B. Drug Target Insights. 2013 Aug 11;7:19-25. doi: 10.4137/DTI.S12109. [↩] [↩]

Autism and Learning Disabilities

Malignant lymphoma high grade B-cell. Courtesy Wikimedia
Malignant lymphoma high grade B-cell. Courtesy Wikimedia

What Is B-Cell Non-Hodgkin’s Lymphoma?

B cell non-Hodgkin’s lymphoma is a malignant, monoclonal (arising from a single cell) proliferation of lymphocytes that is preceded by lymphadenopathy and characterized by varying, less predictable spread than Hodgkin’s disease.

Lymphadenopathy is enlargement of lymph nodes greater than 1.5 cm caused by activation and increased production of lymphocytes and phagocytes (type of white blood cell that engulfs pathogens during infection) or invasion by a tumor.

Q: How does this type of lymphoma develop?

A: 80% to 85% of non-Hodgkin’s lymphoma arise from B-lymphocytes (B-cells).

What Is B Cell Non-Hodgkin’s Lymphoma In Celiac Disease and/or Gluten Sensitivity?

Multiple Sclerosis

canstockphoto17997339What Is Gluten Sensitive Enteropathy?

Gluten sensitive enteropathy is active celiac disease characterized by inflammation of the small intestinal mucosa that results from an inherited immunologic intolerance to ingested gluten.

Q: What does the inflammation do to the mucosa in the small intestine?

A: Inflammation is a cell level immune response to gluten that has these effects on the mucosa:

  • Damages the barely visible villi (multitudinous finger-like structures) by causing atrophy or loss.
  • Likely affects the structural support and microcirculation of the villus, leading to collapse of the villus.
  • Elongates the crypts between villi. The thickening of the crypt is not so much a response to loss of surface enterocytes but represents inflammation of the mucosa.1
  • Increases round cells in the lamina propria and surface epithelial cells leaving few, irregular microvilli (brush border) on the surface of villi.
  • Damage is most intense in the duodenum and decreases toward the large intestine.
  • The extent of the damage to the intestine determines the malabsorptive consequences of the disease. Both gastric and small intestinal permeability are disrupted in patients with celiac disease.2
  • Relationship between active celiac disease and intestinal permeability: There is a clear association between degree of mucosal damage and the intestinal-permeability ratio, and a normal ratio generally implies near-normal small intestinal structure. A raised intestinal permeability of the mucosal lining (leaky gut) could predispose to a high absorption of gluten and exacerbate an existing lesion and hence convert a latent to an overt enteropathy.3
  • Relationship between active celiac disease and tight junction proteins: A study of intestinal permeability showed that the expression of all junction proteins of the small intestinal lining (occludin, claudin 3, zonula occludens 1, and E-cadherin) was already decreased in early stage celiac disease when compared with non-celiac controls, showing leaky gut and confirming the above earlier study by Johnston et al. Junction protein expression correlated positively with mucosal villus structure and negatively with the number of intraepithelial lymphocytes (IELs), the intensity of small-intestinal autoantibody deposits, and serum autoantibodies. The expression of claudin 3 showed a negative correlation with diarrheal score.4
  • Relationship between active celiac disease and inflammation. In celiac disease there is an over production of inflammatory interleukin-15 (IL-15) which inhibits the correct removal of damaged intraepithelial lymphocytes caused by the reaction to gluten. Serum levels of IL-15 are directly correlated with the seriousness of tissue damage.5

  • Relationship between active celiac disease and gut microbiota. Results of a study investigating intestinal microbiota (normal bacterial residents) in patients with celiac disease suggest that with lower levels of the genus bifidobacteria, celiac patients have an imbalance in the intestinal microbiota even while on a gluten-free diet. This fact could favor the pathological process of the disorder. The concentration of bifidobacteria per gram of feces was significantly higher in healthy subjects (2.5 ± 1.5 x107 CFU/g) when compared to celiac patients (1.5 ± 0.63 x108 CFU/g).6

  • Relationship between active celiac disease and endoscopy technique. The most severe degree of villous atrophy was detected when distal duodenal biopsy specimens were taken in addition to a duodenal bulb biopsy specimen from either the 9- or 12-o’clock position (96.4% sensitivity; 95% CI, 79.7%-100%). The difference between the 12-o’clock position biopsy and the 3-o’clock position biopsy in detecting the most severe villous atrophy was 92% (24/26 patients) versus 65% (17/26 patients).7
  • Relationship between active celiac disease and diet adherence. Patients with consistent gluten free diet adherence experience symptomatic responses to dietary gluten (SRDG) faster and more severe in comparison to their prior gluten exposure possibly demonstrating an adept immunological response. Anxiety and depression also enhance the speed of symptom onset and co-existing visceral hypersensitivity is a risk factor for severe reactions to dietary gluten.8
  • Relationship between active celiac disease and atrial fibrillation: Patients with celiac disease, verified by intestinal biopsy, are at increased risk of atrial fibrillation. This observation is consistent with previous findings that elevation of inflammatory markers predicts atrial fibrillation.9

How Prevalent Is Gluten Sensitive Enteropathy?

Sources:
  1. Murray JA, the widening spectrum of celiac disease. American Journal of Clinical Nutrition. Mar 1999; 69(3):354-365. [↩]
  2. Murray JA, the widening spectrum of celiac disease. American Journal of Clinical Nutrition. Mar 1999; 69(3):354-365. [↩]
  3. Johnston SD, Smye M, Watson RGP. Intestinal permeability and morphometric recovery in coeliac disease. Lancet. Jul 28, 2001;358(9278):259, 2p. [↩]
  4. Rauhavirta T, Lindfors K, Koskinen O, Laurila K, Kurppa K, Saavalainen P, Mäki M, Collin P, Kaukinen K. Impaired epithelial integrity in the duodenal mucosa in early stages of celiac disease. Transl Res. 2014 Sep;164(3):223-31. doi: 10.1016/j.trsl.2014.02.006 [↩]
  5. Stazi AV, Trinti B. Selenium status and over-expression of interleukin-15 in celiac disease and autoimmune thyroid diseases. Ann Ist Super Sanita. 2010;46(4):389-99.DOI: 10.4415/ANN_10_04_06. [↩]
  6. Golfetto L, de Senna FD, Hermes J, Beserra BT, França Fda S, Martinello F. Lower bifidobacteria counts in adult patients with celiac disease on a gluten-free diet. Arq Gastroenterol. 2014 Apr-Jun;51(2):139-43. [↩]
  7. Kurien M, Evans KE, Hopper AD, Hale MF, Cross SS, Sanders DS. Duodenal bulb biopsies for diagnosing adult celiac disease: is there an optimal biopsy site? Gastrointest Endosc. 2012 Jun;75(6):1190-6. doi: 10.1016/j.gie.2012.02.025. [↩]
  8. Barratt SM, Leeds JS, Sanders DS. Factors influencing the type, timing and severity of symptomatic responses to dietary gluten in patients with biopsy-proven coeliac disease. J Gastrointestin Liver Dis. 2013 Dec;22(4):391-6. [↩]
  9. Emilsson L, Smith JG, West J, Melander O, Ludvigsson JF. Increased risk of atrial fibrillation in patients with coeliac disease: a nationwide cohort study. Eur Heart J. 2011 Oct;32(19):2430-7. doi: 10.1093/eurheartj/ehr167. [↩]

Developmental Delay

EATL of Jejunum.Courtesy pubcan.org
EATL of Jejunum with Thickening And Yellowish Ulcers Visible. Courtesy pubcan.org

What Is Enteropathy-Associated T-Cell Lymphoma?

E nteropathy associated T-cell lymphoma (EATL), although rare, is a tumor of intraepithelial lymphocytes. It is the most common primary gastrointestinal T-cell lymphoma and is characterized by its aggressive course and poor prognosis.

Primary means this malignancy starts out in the intestinal wall rather than spreading to it from a tumor somewhere else in the  body.

EATL usually affects the jejunum and grossly (visible to the eye) appears as multiple ulcers causing circumferential thickening of affected bowel wall without the formation of definite tumor masses most commonly in the proximal small bowel. As such, patients may present with intestinal perforation, obstruction or hemorrhage.1

Mesenteric lymph nodes in the abdomen are commonly involved.2

Q: How is EATL diagnosed?

A: Work-up of EATL must include immunohistology, T-cell flow cytometry, T-cell rearrangement and adequate imaging with CT and PET scanning.3

Management of EATL requires a combination of early diagnosis and treatment by surgical resection followed by chemotherapy to achieve treatment success. Overall however, the treatment completion rate remains at 50% and EATL carries a poor prognosis with a 5-year survival rate of <20%.4

What Is Enteropathy-Associated T-Cell Lymphoma In Celiac Disease and/or Gluten Sensitivity?

Sources:
  1. Pun AH, Kasmeridis H, Rieger N, Loganathan A. Enteropathy associated T-cell lymphoma presenting with multiple episodes of small bowel hemorrhage and perforation. J Surg Case Rep. 2014 Mar 20;2014(3). pii: rju013. doi: 10.1093/jscr/rju013. [↩]
  2. Yang DH, Myung SJ, Chang HS, et al. A case of enteropathy-associated T-cell lymphoma presenting with recurrent hematochezia. Korean Journal of Gastroenterology = Taehan Sohwagi Hakhoe Chi. Dec 2003;42(6):527-32. [↩]
  3. Meijer JWR, Mulder CJJ, Goerres MG, Boot H, Schweizer JJ. Coeliac disease and (extra)intestinal T-cell lymphomas: definition, diagnosis and treatment. Scandanavian Journal of Gastroenterology. Dec 2004;39(Suppl 241):78,7p. [↩]
  4. Pun AH, Kasmeridis H, Rieger N, Loganathan  Enteropathy associated T-cell lymphoma presenting with multiple episodes of small bowel hemorrhage and perforation.A. J Surg Case Rep. 2014 Mar 20;2014(3). pii: rju013. doi: 10.1093/jscr/rju013. [↩]

Osteomalacic Myopathy

IMG_1007a stomach body normalWhat Is Lymphocytic Gastritis?

L ymphocytic gastritis is an inflammatory stomach disorder that is characterized by superficial inflammation of the stomach lining (mucosa) that mainly involves the gastric antrum in children.

Lymphocytic gastritis is defined by the recognition of more than 25 intraepithelial lymphocytes (IEL) per 100 surface epithelial cells lining the stomach wall.

Q: What are intraepithelial lymphocytes?

A: Intraepithelial lymphocytes in lymphocytic gastritis are a unique T-cell population  of white blood cells that are interspersed between epithelial cells in the mucosa.

What Is Lymphocytic Gastritis In Celiac Disease and/or Gluten Sensitivity?

Autoimmune Disorders In Celiac Disease

Lipase Enzyme. Courtesy johnsonmatthey.
Lipase Enzyme. Courtesy Johnson Matthey Catalysts.

What Is Macrolipasemia?

M acrolipasemia is a rare enzyme disorder characterized by altered molecules of lipase, a pancreatic enzyme needed to digest fats, that are abnormally bound with serum antibody proteins. These antibodies are commonly immunoglobulin G (IgG) and/or less likely immunoglobulin A (IgA).

Q: What happens when lipase is bound to immunoglobulins (IgA and/or IgG)?

A: The resulting molecule is too large to be filtered by the kidneys and excreted in the urine, consequently these abnormal molecules build up in the plasma causing sustained elevation of lipase levels called macrolipasemia.

Macrolipasemia occurs with or without macroamylasemia, which is the binding of immunoglobulin A and/or G to amylase, a pancreatic enzyme needed to digest starches.1

What Is Macrolipasemia In Celiac Disease and/or Gluten Sensitivity?

Sources:
  1. La Villa G, Pantaleo P, Tarquini R, Cirami L, Perfetto F, Mancuso F, Laffi G. Multiple immune disorders in unrecognized celiac disease: a case report. World J Gastroenterol. 2003;9(6):1377-1380, Available at: http://www.wjgnet.com/1007-9327/9/1377.asp. Accessed Jan 3, 2005. [↩]

Inability to Concentrate 

Invagination_Schema[1]What Is Small Bowel Intussusception?

S mall bowel intussusception is a bowel derangement that is characterized by the slipping of one section of intestine into another, leading to bowel obstruction.

Acute bowel intussusception is a rare manifestation in adults, which mainly involves the small intestine.1

What Is Small Bowel Intussusception In Celiac Disease and/or Gluten Sensitivity?

Sources:
  1. Grados A, Bernard F, Coquet-Reinier B, Rossi P, Bagneres D, Demoux AL, Marciano S, Frances Y, Granel B. Acute bowel intussusception revealing celiac disease a new case and literature review. Rev Med Interne. 2011 Oct;32(10):628-32. doi: 10.1016/j.revmed.2011.03.334 [↩]

Anxiety, Chronic

Fermentation of Grain by Yeast Releases Carbon Dioxide Which rises the Dough. Courtesy Johnson Mathey Catalyst
Bread is a Major Source of Maltose. Courtesy Johnson Mathey Catalyst

What Is Maltose Intolerance?

M altose intolerance is an enzymopathy (enzyme failure) characterized by inability of the gut to properly break down maltose sugar molecules in food due to low maltase enzyme activity of the small intestinal lining.

Q: What is maltose and maltase?

A: Maltose is a double sugar made up of two molecules of glucose and is derived from starch. Maltase is the enzyme required to digest or release glucose from maltose. Maltase is produced in the microscopic brush border (microvilli) at the base of villi.

Here’s what happens when maltose is not digested:

  • Undigested maltose cannot be absorbed into the body but remains inside the small intestine where it acts osmotically to draw an unnatural amount of water from the body into the intestine which produces diarrhea.
  • Additionally, normal gut bacteria ferment the abnormal abundance of unabsorbed maltose, thereby generating an abundance of short-chain fatty acids and hydrogen gas which result in bloating and pain.1
  • Positive response to a breath hydrogen test (BHT), involving 1 – 3 hours of time post ingestion of maltose test dose, signifies malabsorption in the small intestine and fermentation in the colon. If BHT is positive before 60 minutes, the result implies bacteria is abnormally present in the small intestine, causing fermentation there.

What Is Maltose Intolerance In Celiac Disease and/or Gluten Sensitivity?

Sources:
  1. Krause’s Food, Nutrition, & Diet Therapy. 10th Edition. Kathleen Mahan, Sylvia Escott-Stump. 2000. W.B. Saunders Company. [↩]

Bitot’s Spots 

 

Jaundice, or yellowing of the skin and sclera of eyes.
Jaundice, or yellowing of the skin and sclera of eyes, is a symptom of autoimmune hepatitis.

What Is Autoimmune Hepatitis?

A utoimmune hepatitis is an autoimmune attack against liver cells that is characterized by inflammation and results in chronic liver disease which includes low blood albumin and cirrhosis.

Autoimmune hepatitis is diagnosed by detection of autoantibodies in blood and liver biopsy.

Q: What is cirrhosis?

A: Cirrhosis is a degenerative process of the liver that can be fatal. Normal lobular liver structure is distorted and replaced with nodules of regenerating liver cells separated by bands of fibrous tissue that cannot properly carry out liver function and block the necessary flow of blood through the liver, ending in liver failure.

The liver is the largest organ within the body and lies mostly in the upper part of the abdomen on the right side just under the diaphragm. About 70% of liver tissue is made up of cube shaped cells called hepatocytes that do the main work of the liver. Other cells form structure and are arranged in single layers around blood vessels, sinusoids, and bile ducts.

Bile ducts carry bile, a greenish brown liquid made by the liver, to the gall bladder for storage until needed to aid in the digestion and absorption of fat from the small intestine. Bile emulsifies fat eaten in the diet so that the pancreatic enzyme called lipase can break it down into its fatty acid and glycerol components.

The liver is a very busy organ, carrying out over 500 metabolic processes! Nutritionally, it is the first to receive all the blood carrying nutrients freshly absorbed from the digestive tract. Hepatocytes then convert the nutrients to provide the body with energy, a host of amino acids as building blocks for numerous cell activities, and proteins such as albumin and fibrinogen. In fact, hepatocytes build the structural proteins for the liver itself. Imagine the array of nutrients the liver uses and keeps at its disposal for its metabolic functions. Included in liver storage are vital vitamins and minerals such as vitamin A and vitamin B12.

As a detoxifier, Kupffer cells located in the sinusoids act like amoebas to engulf and digest unwanted matter. As a blood cleanser, the liver removes waste products produced by normal metabolism and toxic substances and rids it by preparing these substances for elimination in urine, such as ammonia converted to urea, and/or excreting them in bile for eventual elimination in stool. Bile is continually made by the liver from phospholipids salt, cholesterol, aging blood cells it removes from circulation.

Autoimmune hepatitis is classified into several types. Type 1 autoimmune hepatitis is the most common form in North America. Type 1 can occur at any age; however, it most often starts in adolescence or young adulthood. People with type 1 autoimmune hepatitis commonly have other autoimmune disorders (see listed below).

Type 2 autoimmune hepatitis is less common and occurs more often in children than adults. People with type 2 can also have any of the autoimmune disorders (see listed below).

Both types of autoimmune hepatitis are treated with prednisone, a corticosteroid hormone to control inflammation and reduce the body’s immune activity against the liver.1

What Is Autoimmune Hepatitis In Celiac Disease and/or Gluten Sensitivity?

Sources:
  1. National Digestive Diseases Information Clearinghouse [↩]