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Gluten Sensitive Enteropathy (Active Celiac Disease)

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. [↩]

Dry Eyes, Chronic

Microscopic View of a Liver Granuloma. Courtesy pathology.med.umich.edu/greensonlab.
Microscopic View of a Liver Granuloma. Courtesy pathology.med.umich.edu/greensonlab.

What Is Hepatic Granulomatous Disease?

H epatic granulomatous disease is an infiltrative chronic liver disorder characterized by growth of small granulomas.

Rather than being a final diagnosis, the presence of hepatic granulomas entails the need for further investigations towards identifying the underlying etiology, with a pathologist being at the center of the diagnostic process.1

Q: What are hepatic granulomas?

A: Hepatic granulomas are unique inflammatory formations that require liver biopsy for diagnosis.2

Hepatic granulomas develop through the interactions of T lymphocytes and macrophages, with the integral involvement of T-helper (T(H)) 1 or T(H)2 pathways or both, depending on the specific granulomatous disease.

Hepatic granulomas may be detected clinically by elevated levels of serum alkaline phosphatase and g-glutamyltransferase enzymes, damage to specific structures (e.g., intrahepatic bile ducts in primary biliary cirrhosis), or infrequently, progressive liver disease with portal hypertension and cirrhosis (e.g., sarcoidosis).

Systemic immunologic disorders, infectious diseases, drug hepatotoxicity, and reaction to neoplastic disease are the major causative factors responsible for granulomas in the liver.3

What Is Hepatic Granulomatous Disease In Celiac Disease and/or Gluten Sensitivity?

Sources:
  1. Turhan N, Kurt M, Ozderin YO, Kurt OK. Hepatic granulomas: a clinicopathologic analysis of 86 cases. Pathol Res Pract. 2011 Jun 15;207(6):359-65. doi: 10.1016/j.prp.2011.03.003. Epub 2011 Apr 30. [↩]
  2. Bhardwaj SS, Saxena R, Kwo PY. Granulomatous liver disease. Curr Gastroenterol Rep. 2009 Feb;11(1):42-9. [↩]
  3. Lagana SM1, Moreira RK, Lefkowitch JH. Hepatic granulomas: pathogenesis and differential diagnosis. Clin Liver Dis. 2010 Nov;14(4):605-17. doi: 10.1016/j.cld.2010.07.005. [↩]

Cataracts

Glucose Meter Reading Showing Hypoglycemia. Courtesy Abbott.
Glucose Meter Reading.Courtesy Abbott.

What Is Diabetic Instability?

D iabetic instability, also called brittle diabetes, is poor control of blood sugar characterized by frequent rise (hyperglycemia) and fall (hypoglycemia). These fluctuations can be life-threatening and cause unnecessary complications.

Q: What are complications in diabetes?

A: Complications of diabetes include any/all of the following:

  • Peripheral neuropathy that causes burning, numbness, or tingling in the extremities.
  • Skin infections and ulcers that do not heal and can lead to amputation of toes, feet or legs.
  • Damage to retina that can progress to blindness.
  • Cataracts and glaucoma that impair vision and can cause blindness.
  • Increased susceptibility to serious infections of the genitourinary tract, lung and upper respiratory tract that can become systemic and life-threatening.
  • Kidney disease that can lead to kidney failure.
  • Heart disease that can lead to heart failure.
  • Vascular disease that can lead to stroke.
  • Impaired motility in digestive tract that can lead to dyspepsia and constipation.
  • Pregnancy complications.
  • Shortened life expectancy.

The main causes of brittleness include malabsorption, certain drugs (alcohol, antipsychotics), defective insulin absorption or degradation, defect of hyperglycemic hormones especially glucocorticoid and glucagon, and above all delayed gastric emptying as a result of autonomic neuropathy.1

What Is Diabetic Instability In Celiac Disease and/or Gluten Sensitivity?

Sources:
  1. Vantyghem MC, Press M. Management strategies for brittle diabetes. Ann Endocrinol (Paris). 2006 Sep;67(4):287-96. [↩]

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?

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?

Miscarriage (Spontaneous Abortion)

Pitting edema. Right photo shows that indent remains from pressing. Courtesy wikimedia.
Pitting edema. Right photo shows that indent remains from pressing. Courtesy wikimedia.

What Is Edema?

E dema is an abnormal swollen condition of the skin characterized by excess extracellular fluid volume, meaning there is an increase of the fluid that normally surrounds cells. Edema may be hardly noticeable or it can become extensive.

Edema can have various appearances and can develop from various causes.

Q: What are the appearances and causes of edema?

A: Here are the appearances of edema:

  • Pitting edema. It is called pitting edema if when the skin is pressed with a finger, the indent remains. This edema results from fluid leaking out of the bloodstream into the surrounding tissues. Pitting edema can be a feature of many disorders including heart disease, kidney disease, vascular disease, cancer, and malnutrition.
  • Myxedema is a firm swelling or thickening of subcutaneous skin that does not pit, as seen in thyroid disease.

Here are causes of edema:

  • Local edema as a response to trauma or infection.
  • Lower extremity edema from poor circulation and malnutrition.
  • Edema in the lungs from right sided heart disease.
  • Abdominal edema from liver disease, intestinal disease.
  • Body wide edema from heart disease, kidney disease, thyroid disease.

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

Lymphoma, Enteropathy-Associated T-Cell (EATL) 

A real photomicrograph of carcinoma of the esophagus. Panorama of 6 photos of a slide at 40x through the microscope. Some areas may appear blurry due to shallow DOF.
A real photomicrograph of carcinoma of the esophagus. Panorama of 6 photos of a slide at 40x through the microscope. Some areas may appear blurry due to shallow DOF.

What Is Cancer Of The Esophagus?

C ancer of the esophagus is a malignancy arising in the stratified squamous cell lining of any part of the esophagus and having a poor prognosis.

This tumor first invades the deeper layers of the esophagus which includes the layer beneath the mucosa (submucosa) and muscle before it may invade structures close to it including the aorta and trachea. Later, it may spread to organs further away such as the liver, lungs and bones.

Q: What is the stratified squamous cell lining of the esophagus?

A: Stratified squamous cells are flat epithelial cells that are composed of several layers, called the epithelium. This type of epithelium forms the surface mucosa that lines the inside of the esophagus.

The esophagus itself is a muscular tube that transports swallowed substances to the stomach. It begins at the cricoid cartilage (Adam’s apple) as a continuation of the pharynx in the throat and ends at the lower esophageal sphincter (LES).

The LES is a circular muscle surrounding the junction of the esophagus and stomach. The LES opens to allow swallowed food and liquids to enter the stomach and closes to prevent their travelling back into the esophagus.

Who is Affected in the General Population?

Esophageal cancer is the fifth leading cause of death in men from cancer worldwide.1

What Is Cancer Of The Esophagus In Celiac Disease and/or Gluten Sensitivity?

Sources:
  1. Feldman M, Friedman LS, Brandt LJ. Sleisenger & Fordtran’s Gastrointestinal and Liver Disease. ed 9. Philadelphia: Saunders; 2010. pp. 745–767. [↩]

Diarrhea, Chronic

chronic diarrhea gluten celiac disease symptomWhat 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?

Sources:
  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. [↩]

Cancer Of The Pharynx 

Areas of the Pharynx Where Cancer May Occur. Courtesy Wikimedia.
Areas of the Pharynx Where Cancer May Occur. Courtesy Wikimedia.

What Is Cancer Of The Pharynx?

Cancer of the pharynx is a malignant growth of stratified squamous cells that line the pharynx, or throat.

Q: What are stratified squamous cells that line the pharynx?

A: Stratified squamous cells are thin, flat epithelial cells consisting of several layers forming the surface mucosa that protects underlying layers of the pharynx. These cells lie very close together and have no blood vessels.

The pharynx is the upper passageway of the throat where swallowing food and fluids from the mouth first pass on the way to the esophagus and breathing air passes from the nose and mouth to and from the lungs.

The pharynx provides for speech production, adequate taste reception, and proper hearing through equalization of air pressure in the eustachian tubes.

The pharynx has three areas and pharyngeal cancer can occur in any of them: the nasopharynx behind the nose, the oropharynx behind the mouth, and the hypopharynx or laryngopharynx, just above the larynx. Tonsils, adenoids, and other lymph tissue lie at the back of the throat.

Unfortunately, cancers of the pharynx tend not to be detected until late in their course when symptoms become evident. This makes the prognosis poor. See symptom below.

What Is Cancer Of The Pharynx In Celiac Disease and/or Gluten Sensitivity?

Xerophthalmia

Parathyroid gland anatomyWhat Is Idiopathic Hypoparathyroidism?

I diopathic hypoparathyroidism is a metabolic condition that results from reduced secretion or impaired action of parathyroid hormone (PTH) which results in a combination of low calcium and elevated phosphorus levels in the body.

Calcium and phosphorus are minerals that act in opposition to each other in the body. Idiopathic means the cause is not known.

Parathyroid hormone is produced by the four pea sized parathyroid glands that are located on the thyroid gland in the front of the neck. Partly because the thyroid and parathyroid glands share the same anatomic place in the body and partly because they have similar names, they are often confused although they have completely different actions.

Q: What does parathyroid hormone do in the body?

A: This vital hormone maintains a correct balance of calcium and phosphorous in the bloodstream and ultimately has an effect on all organs because of the complexity of intracellular calcium physiology.1 

Parathyroid hormone is required to sustain life, therefore undetected or misdiagnosed hypoparathyroidism may pose a significant threat to health outcomes, as its presence may increase disease and mortality in affected individuals.

The clinical consequences of parathyroid hormone deficiency or impaired receptor action involve many body functions. In some patients, however, its manifestation may be non-specific, and in these cases the correct diagnosis may be easily missed.

Digestive manifestations of hypoparathyroidism are few and consist mainly of steatorrhea due to insufficient meal-stimulated cholecystokinin secretion by the duodenal mucosa.2

Laboratory measurements show hypocalcemia (low blood calcium level), hyperphosphatemia (high blood phosphate level), and inappropriately low or undetectable parathyroid hormone levels. Treatment consists of oral calcium supplementation and vitamin D derivatives.3

Idiopathic hypoparathyroidism is rare, although there is a growing incidence of the autoimmune form of hypoparathyroidism, which may occur in combination with other autoimmune diseases such as celiac disease.

What Is Idiopathic Hypoparathyroidism In Celiac Disease and/or Gluten Sensitivity?

Sources:
  1. Abboud B, Daher R, Boujaoude J. Digestive manifestations of parathyroid disorders. World J Gastroenterol. 2011 Sep 28;17(36):4063-6. doi: 10.3748/wjg.v17.i36.4063. [↩]
  2. Abboud B, Daher R, Boujaoude J. Digestive manifestations of parathyroid disorders. World J Gastroenterol. 2011 Sep 28;17(36):4063-6. doi: 10.3748/wjg.v17.i36.4063. [↩]
  3. Krysiak R, Handzlik-Orlik G, Kedzia A, Machnik G, Okopień B. Hypoparathyroidism: the present state of art. Wiad Lek. 2013;66(1):18-29. [↩]

Seborrhea Dermatitis

Swollen Tongue Causing Tooth Indentations. GFW
Swollen Tongue Causing Tooth Indentations. Notice the Accompanying Denuded Area Due to Riboflavin Deficiency and Mild Candida Overgrowth. GFW

What Is A Pale, Smooth, Burning Tongue?

A pale, smooth, burning tongue is an alteration in tongue tissue characteristic of iron deficiency. The tongue is also swollen.1

Additionally, the sore tongue surface may be invaded by candida yeast which takes advantage of the sore tissue.

Iron deficiency itself increases susceptibility to infection.

Q: What is iron deficiency?

A: Iron deficiency results when the level within cells is too low to meet metabolic needs of the body for this mineral.

Deficiency is characterized by impaired red blood cell formation, free-radical disposal, oxygenation of cells, immune response to infection, enzyme activity, cognitive performance, digestion, nail structure, and fetal health.2

Iron is an essential mineral that is required for normal body function. Almost two-thirds of iron in the body is found in hemoglobin, the protein in red blood cells that carries oxygen to tissues. Smaller amounts of iron are found in myoglobin, a protein that helps supply oxygen to muscle, and in enzymes that assist biochemical reactions.

Iron is also found in proteins that store iron for future needs and that transport iron in blood. Iron stores are regulated by intestinal iron absorption.3

What Is A Pale, Smooth, Burning Tongue 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. [↩]
  2. Kathleen Mahan and Sylvia Escott-Stump, ed. Krause’s Food, Nutrition & Diet Therapy, 10th Edition. Philadelphia, PA. USA: W.B. Saunders Company, 2000. [↩]
  3. http://ods.od.nih.gov/factsheets/Iron-HealthProfessional accessed 12/11/12 [↩]