Editor’s note: Promising research published January 8, 2007 shows that adequate levels of vitamin D in the elderly are important to maintain cognitive function or thinking skills that include use of language, awareness, social skills, math ability, memory, reasoning, judgment, intellect, learning, and imagination. This study is called a retrospective review because the researchers did not actually examine anyone. Instead they reviewed data from records of 32 older adults who had been examined for memory
Osteomalacia is common in celiac disease. Osteomalacia can occur at any age. It children, it is called rickets. It is a metabolic bone disorder that involves slow loss of minerals from bone tissue throughout the skeleton, stemming from inadequate absorption of vitamin D. As minerals are dissolved from bone tissue to provide for essential functions elsewhere in the body, bones gradually lose their hardness.
Consequently, pronounced softening of the bones characterizes osteomalacia. Soft bones become deformed, especially bones of the arms, legs, spine, thorax and pelvis. The softer bones have a normal amount of collagen, a strong fibrous protein in the bone matrix (osteoid) that gives bone its structure and tensile capacity, but there is not sufficient calcium and phosphate minerals available to properly mineralize or be deposited in the osteoid to give it necessary hardness.
H ypoprothrombinemia is a deficiency of prothrombin (clotting factor II) in the blood that is characterized by impaired hemostasis in response to trauma or a laceration.
Q: What is hemostasis and how is it altered by a deficiency of prothrombin?
A: Hemostasis encompasses the tightly regulated processes of blood clotting, platelet activation, and blood vessel repair.1
Prothrombin is a protein clotting factor present in blood that is involved in the first part of hemostasis, which is blood clotting or coagulation. Vitamin K is required for prothrombin production.
When a laceration or wound is sustained, prothrombin is converted to the enzyme thrombin. Thrombin in turn acts on fibrinogen to convert it to fibrin which then forms the framework of a clot to stop bleeding. Deficiency of prothrombin prevents this series of events and bleeding is not properly stopped.
After the clotting process of hemostasis would come the second part, platelet activation. Eventually, coagulation and platelet activation are switched off by blood-borne inhibitors.
What Is Hypoprothrombinemia In Celiac Disease and/or Gluten Sensitivity?
Sources:
Versteeg HH, Heemskerk JWM, Levi M, Reitsma PH. New Fundamentals in Hemostasis. Physiological Reviews Published 1 January 2013Vol. 93no. 327-358DOI: 10.1152/physrev.00016.2011 [↩]
E czema, or atopic dermatitis, is a chronic recurring inflammatory skin disorder characterized by itching, eczematous plaques and a defective epidermal barrier (surface layer of skin cells) that fails to hold moisture, with affected areas becoming dry then inflamed.
Q: Why does eczema develop?
A: Patients with atopic dermatitis have genetically determined risk factors that affect the barrier function of the skin and immune responses that interact with environmental factors.1
Atopic eczema is associated both with an abnormal skin matrix and impaired systemic immune response. Therefore, isolated topical treatment may have suboptimal effect.2
Atopic eczema is a common presentation of immune response towards food proteins in infancy.3
Global evidences reflect a marked increase in prevalence, which has tripled since 1960. In the United States, the current prevalence rates range from 10% to 20% in children and 1 to 3% in adults.4
What Is Eczema In Celiac Disease and/or Gluten Sensitivity?
Sources:
Mesquita Kde C, Igreja AC, Costa IM. Atopic dermatitis and vitamin D: facts and controversies. An Bras Dermatol. 2013 Nov-Dec;88(6):945-53. doi: 10.1590/abd1806-4841.20132660. [↩]
Caffarelli C, Santamaria F, Vottero A, Bernasconi S. Progress in Pediatrics in 2012: choices in allergy, endocrinology, gastroenterology, hematology, infectious diseases, neurology, nutrition and respiratory tract illnesses. Ital J Pediatr. 2013 May 8;39(1):26. [↩]
Ho MH, Wong WH, Chang C. Clinical Spectrum of Food Allergies: a Comprehensive Review. Clin Rev Allergy Immunol. 2012 Nov 16. [↩]
Mesquita Kde C, Igreja AC, Costa IM. Atopic dermatitis and vitamin D: facts and controversies. An Bras Dermatol. 2013 Nov-Dec;88(6):945-53. doi: 10.1590/abd1806-4841.20132660. [↩]
Woman with long standing osteoporosis. Courtesy of Wikimedia.
What Is Osteoporosis?
Osteoporosis is a metabolic bone disorder characterized by diminished bone mass (density) with normal cell appearance but fragile bone strength that prediposes to broken bones, and with high bone turnover.
This condition usually goes undetected until late when loss of height or a bone fracture occurs. In fact, each year 1.5 million fractures mainly of the hip, spine and wrist are attributed to osteoporosis. Compression fractures of vertebrae bones are the most common, accounting for 700,000 cases.
Bone is composed of specialized connective tissue called osseous tissue. Osseous tissue is made up of living bone cells (osteocytes) that are embedded in a hard matrix (framework) of calcified substance.
Bone matrix contains collagen fibers and the minerals calcium phosphate and calcium carbonate, which provide strength to bone. The copper enzyme, lysyl oxidase, is involved in the cross-linking of collagen in forming the framework for depositing calcium and other minerals to build and repair bone.
Q: How do osteocytes function in bone?
A: Osteocytes maintain the health of bone by their metabolic activity in regulating normal bone turnover. Bone turnover is the breaking down and removal of old or damaged bone and rebuilding or remodeling of healthy bone that is ongoing throughout life. The bone formation process takes about 3 months to complete.
Osteoporosis develops from failure of the body to maintain health and to provide bone tissue with adequate nutrition for proper function. Risk factors that can be modified include: low calcium intake, sedentary lifestyle, smoking, drinking alcohol excessively, eating a diet with excessive caffeine, protein, and phosphate, and taking certain medications over a long time such as steroids, thyroid preparations, the anti-convulsive drug phenytoin, aspirin, antacids, anticoagulants, some diuretics, and some chemotherapeutic drugs. See below for a fuller description.
In addition to celiac disease, osteoporosis is associated with advancing age, family history, nulliparity (no pregnancies) and post-menopause in females, certain disorders such as hyperthyroidism, hypogonadism, inflammatory bowel disease like Crohn’s disease, multiple myeloma, anorexia nervosa, and Cushing’s disease.
Bone strength is easily measured by testing bone mineral density (BMD). BMD is evaluated by DEXA scan (dual-energy X-ray absorptiometry). DEXA at the femoral neck and lumbar spine is considered the gold standard to confirm the diagnosis of osteoporosis. Results are expressed as T and Z scores. T scores compare the result with a 20 to 40 year old helathy person while Z scores compare the result with persons in the same age group. Both are measured in standard deviations (SD).
According to WHO criteria (World Health Organization), a T-score of -1 SD or greater denotes normal bone, a T-score between −1 to −2.5 SD denotes osteopenia, and a T-score of −2.5 or more denotes osteoporosis.1
Treatment is aimed to preserve and increase bone density, minimize symptoms for better quality of life and reduce risk of bone fractures.
What Is Osteoporosis In Celiac Disease and/or Gluten Sensitivity?
The cumulative effects of gluten-induced inflammation, treatment delay, and malabsorption result in lower bone density and bone fragility.2
Sources:
Pantaleoni S, Luchino M, Adriani A, Pellicano R, Stradella D, Ribaldone DG, Sapone N, Isaia GC, Di Stefano M, Astegiano M. Bone mineral density at diagnosis of celiac disease and after 1 year of gluten-free diet. ScientificWorldJournal. 2014;2014:173082. doi: 10.1155/2014/173082. [↩]
Grace-Farfaglia P. Bones of Contention: Bone Mineral Density Recovery in Celiac Disease-A Systematic Review. Nutrients. 2015 May 7;7(5):3347-3369. [↩]
U rticaria is an immune based skin disorder characterized by multiple eruptions of well-demarcated edematous, intensely pruritic (itchy) plaques that may be small or reach the diameter of many centimeters with surrounding erythema (redness) each lasting less than 24 hours.1
Q: What is the immune reaction in hives?
A: Hives form when, in response to histamine, blood plasma leaks out of small blood vessels in the skin. Histamine is a chemical released from specialized cells along the skin’s blood vessels. Allergic reactions, chemicals in certain foods, insect stings, sunlight exposure, or medications can all cause histamine release.2
In many patients, in spite of extensive investigations, the cause remains elusive. The term idiopathic is often used to denote this category. Now it is known that autoimmunity is the cause of chronic urticaria in 50% of cases.
Treatment is generally started with nonsedating antihistamine in the daytime and sedating antihistamine in the night.3
What Is Chronic Urti caria In Celiac Disease and/or Gluten Sensitivity?
Sources:
Scala E, Giani M, Pirrotta L, Guerra EC, DePita O, Puddu P. Urticaria and adult celiac disease. Allergy. 1999;54:1008-9. [↩]
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:
Murray JA, the widening spectrum of celiac disease. American Journal of Clinical Nutrition. Mar 1999; 69(3):354-365. [↩]
Murray JA, the widening spectrum of celiac disease. American Journal of Clinical Nutrition. Mar 1999; 69(3):354-365. [↩]
Johnston SD, Smye M, Watson RGP. Intestinal permeability and morphometric recovery in coeliac disease. Lancet. Jul 28, 2001;358(9278):259, 2p. [↩]
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 [↩]
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. [↩]
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. [↩]
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. [↩]
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. [↩]
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. [↩]
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?
Lost patch of hair at base of scalp due to alopecia areata. Courtesy Wikimedia,
What Is Alopecia Areata?
A lopecia areata is an autoimmune attack on hair follicles characterized by sudden hair loss involving scalp or beard, although any hairy area may be affected.
Areas of hair loss have a patchy pattern with sharply defined edges.
Q: Can all hair be affected?
A: All body hair may be lost, which is called alopecia universalis although this is uncommon.
In alopecia areata, white blood cells of the immune system attack the rapidly growing cells in the hair follicles. The affected hair follicles become small and drastically slow down hair production. Fortunately, the stem cells that continuously supply the follicle with new cells do not seem to be targeted. So the follicle always has the potential to regrow hair but regrowth is unpredictable.1
What Is Alopecia Areata In Celiac Disease and/or Gluten Sensitivity?
Osteomalacia is common in celiac disease. Osteomalacia can occur at any age. It children, it is called rickets. It is a metabolic bone disorder that involves slow loss of minerals from bone tissue throughout the skeleton, stemming from inadequate absorption of 
