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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?

[dropcap]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?

[dropcap]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?

Nails, Horizontal Ridges (Beau’s Lines), Fragile

Photo showing resolving deep bruise on the thigh.
Photo showing resolving deep bruise on the thigh.

What Is Easy Bruising?

[dropcap]E cchymosis, or easy bruising, is a feature of impaired secondary hemostasis (blood clotting) characterized by subcutaneous bleeding (under the skin) in response to light trauma.

Q: What causes easy bruising?

A: Easy bruising is the direct result of vitamin K deficiency that develops from inadequate diet, malabsorption, dysbiosis, and vitamin K depleting medications.

What Is Easy Bruising In Celiac Disease and/or Gluten Sensitivity?

Koilonychia (Washboard Nails)

Epistaxis1[1]What Is Epistaxis?

[dropcap]E pistaxis, or nosebleed, is a feature of secondary hemostasis (blood clotting) characterized by fragility of a plexus of blood vessels in the antero-inferior septum (just inside nostril) and/or abnormal blood coagulation.

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

Nails, Splinter Hemorrhages In

Grade_1_hypertension[1]What Is Reversible Hypertension?

[dropcap]R eversible hypertension is a pressure disorder of arteries associated with increased systemic (body wide) blood vessel resistance to blood flow due to endothelial (cell) dysfunction of arterial blood vessels that can improve with nutritional treatment.

Hypertension itself is defined as a systolic blood pressure (SBP) of 140 mm Hg (mercury) or greater and/or diastolic blood pressure (DBP) of 90 mm Hg or greater.

Q: What is blood vessel (vascular) resistance to blood flow?

A: Vascular resistance to blood flow means the arteries carrying blood away from the heart cannot relax or dilate when needed to lower blood pressure but stay constricted, which in turn, keeps the pressure high.

Here’s an analogy: if you replace your garden hose having a one inch inside diameter with one that has a smaller half inch diameter and open the water valve as usual, the result would be water shooting out with more force.

What Is Reversible Hypertension In Celiac Disease and/or Gluten Sensitivity?

Nails, White Spots And White Bands

Cardiomegaly-Heart-frontWhat Is Cardiomegaly?

[dropcap]C ardiomegaly is a non-inflammatory disorder of the myocardium (heart muscle) causing the heart to enlarge.

Q: What happens when the heart enlarges?

A:The heart enlarges because excessive growth of muscle tissue (hypertrophy) thickens the heart walls which in turn reduces the size of the lower chambers (ventricles) and impairs the filling of the heart chambers with blood. In consequence, the heartbeat quickens.

Also, the enlarging heart encroaches on lung space which impairs their ability to expand with inspiration of air.

Cardiomegaly can result in heart failure because of inability to pump sufficient blood for the needs of the body and ventricular arrhythmias (irregular or missed beats) that can stop the heart. An echocardiogram, which is a test that uses sound waves to produce a picture of the heart, is used to detect and diagnose cardiomegaly.

What Is Cardiomegaly 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?

[dropcap]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. [↩]

Cancer Predisposition In Children 

Mesenteric Lymph Node Cavitation. Courtesy
Mesenteric Lymph Node Cavitation.  Courtesy McBride OM, Skipworth RJ, Leitch D, Yalamarthi S.

What Is Mesenteric Lymph Node Cavitation And Hyposplenism?

[dropcap]M esenteric lymph node cavitation and hyposplenism combination is a rare lymphatic entity. It is characterized by involution (degeneration) of a mesenteric lymph node (abdominal) and absence of functional spleen tissue.

Q: What is happening to the lymph nodes?

A: Lymph nodes are enlarged with central, partly cystic degeneration. When cut open either at surgery or autopsy, milky fluid exudes from the cut surface.

In regards to absent spleen function, the body is highly susceptible to bacterial invasion such as pneumonia because tissues of the spleen, called the pulp, produce specialized white blood cells that protect the body against bacterial invasion and trap foreign antigens.

What Is Mesenteric Lymph Node Cavitation And Hyposplenism In Celiac Disease and/or Gluten Sensitivity?

Osteomalacic Myopathy

IMG_1007a stomach body normalWhat Is Lymphocytic Gastritis?

[dropcap]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?