Skip to content

Tuberculosis – Increased Susceptibility 

Bacteria that causes tuberculosis. Courtesy Wikimedia.
Bacteria that causes tuberculosis. Courtesy Wikimedia.

What Is Increased Susceptibility To Tuberculosis?

[dropcap]T[/dropcap]uberculosis (TB), is an infectious disease caused by a bacteria called mycobacterium tuberculosis. It is characterized by chronic bacterial infection most commonly affecting lungs that develops in stages.

Increased susceptibility to tuberculosis menas the person’s defense mechanisms against developing infection are inadequate. Tuberculosis may be dormant or active.

Q: What happens in active tuberculosis?

A: Active tuberculosis  produces inflammation and formation of tubercles, necrosis (death of tissues), abcess, fibrosis, and calcification. Calcification is the body’s action to encapsulate the bacterial invasion. Active tuberculosis is life-threatening and may result in death.

About one third of the world’s population is infected with tuberculosis bacteria. In 2012 the number reached a staggering 8.6 million people. Of these, 1.3 million people died from tuberulosis.  About 95% of tuberulosis deaths occur in low- and middle-income countries and it is among the top three causes of death among women aged 15 to 44.1

People with weakened immune systems have a much greater risk of falling ill from tuberculosis. For example, a person living with HIV is about 20 to 30 times more likely to develop active tuberculosis.2 The combination of tuberculosis, HIV coinfection, and malnutrition has been commonly termed as “triple trouble.”3

What Is Increased Susceptibility To Tuberculosis In Celiac Disease and/or Gluten Sensitivity?

Sources:
  1. http://www.who.int/features/factfiles/tb_facts/en/index.html [↩]
  2. http://www.who.int/features/factfiles/tuberculosis/en/ [↩]
  3. Steinbrenner H, Al-Quraishy S, Dkhil MA, Wunderlich F, Sies H. Dietary selenium in adjuvant therapy of viral and bacterial infections. Adv Nutr. 2015 Jan 15;6(1):73-82. doi: 10.3945/an.114.007575. Print 2015 Jan. [↩]

Osteoporosis

Woman with long standing osteoporosis. Courtesy of Wikimedia.
Woman with long standing osteoporosis. Courtesy of Wikimedia.

What Is Osteoporosis?

[dropcap]O[/dropcap]steoporosis 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:
  1. 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. [↩]
  2. Grace-Farfaglia P. Bones of Contention: Bone Mineral Density Recovery in Celiac Disease-A Systematic Review. Nutrients. 2015 May 7;7(5):3347-3369. [↩]

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. [↩]

Iron Deficiency

ferritinWhat Is Iron?

[dropcap]I[/dropcap]ron 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.

Q: How are iron stores regulated?

A:Iron stores are regulated by intestinal iron absorption.1That is, whenever iron is needed, more iron is absorbed than when iron is sufficient. This mechanism prevents excess iron in the body which is harmful.

In the brain, iron is necessary to ensure oxygenation and to produce energy in the cerebral parenchyma (via cytochrome oxid. ase), and for the synthesis of neurotransmitters and myelin.

Iron concentrations in the umbilical artery are critical during the development of the fetus, and in relation with the IQ in the child.2

What Is Iron Deficiency In Celiac Disease and/or Gluten Sensitivity?

Sources:
  1. http://ods.od.nih.gov/factsheets/Iron-HealthProfessional accessed 12/11/12 [↩]
  2. Bourre JM. Effects of nutrients (in food) on the structure and function of the nervous system: update on dietary requirements for brain. Part 1: micronutrients. J Nutr Health Aging. 2006 Sep-Oct; 10(5):377-85. [↩]

Autism and Learning Disabilities

Child with autism stacking cans. Courtesy Wikimedia.
Child with autism stacking cans. Courtesy Wikimedia.

What Is Autism and Learning Disabilities?

[dropcap]A[/dropcap]utism and learning disabilities constititute a non-progressive psychiatric syndrome appearing in childhood characterized by withdrawal from communication with others often accompanied by repetitive or primitive behaviors.

Primary gastrointestinal pathology may play an important role in the inception and clinical expression of autism.

Autistic children often manifest complex biochemical and immunological abnormalities.1 Following are four  main features involving the digestive tract:

1) Brain dysfunction from an abnormal gut. Common characteristics of hepatic encephalopathy (brain dysfunction caused by liver disease) and a form of autism associated with developmental regression and immune caused gastrointestinal pathology (abnormal) in an apparently healthy child, have led to the proposal that there may be similar mechanisms of toxic brain dysfunction caused by gluten and casein proteins.

Gluten in wheat and casein in cow milk are called exomorphines because they act like morphine (opioid) in the brain. Aberrations in opioid biochemistry are common in autism.

2) Characteristic intestinal pathology. Many autistic children with gut symptoms have ileocolonoic lymphoid nodular hyperplasia and inflammation of the intestinal lining. The colon lesion consisting of a mucosal infiltrate of yo T cells and Celiac Disease8+ T cells and crypt cell proliferation is enhanced significantly, and the basement membrane is thicker than in normal or disease groups. Neutrophil and eosinophil mucosal infiltration and absence on colonic epithelium of HLA-DR antigen suggests a T-helper -2 dominated immune response.

The corresponding small intestinal lesion also shows a distinct inflammatory reaction in which immune-mediated epithelial cell damage is predominant and blood anitibodies of the IgG type colonizes with complement. 

3) Intestinal permeability abnormalities. A subset of children with autism were found to display increased immune reactivity to gluten, the mechanism of which appears to be distinct from that in celiac disease. The increased anti-gliadin antibody response and its association with gastrointestinal symptoms points to a potential mechanism involving immunologic and/or intestinal permeability abnormalities in affected children.2

4) Secondary dysbiosis. Anaerobic dysbiosis develops in the colon caused by fermentation of the overload of undigested food arriving from the small intestine. Billions of microbes in the colon normally breakdown undigested food, however,  in autism, the process is dysfunctional and produces byproducts that are toxic to the brain resulting in encephalopathy.

What Is Autism and Learning Disabilities In Celiac Disease and/or Gluten Sensitivity?

Sources:
  1. Wakefield AJ, Puleston M, Montgomery SM, Anthony A, O’Leary JJ, Murch SH. Review Article: the concept of entero-colonic encephalopathy, autism, and opioid receptor ligands. Aliment Parmacol Ther. 2002; 16:663-674. [↩]
  2. Lau NM, Green PH, Taylor AK, Hellberg D, Ajamian M, Tan CZ, Kosofsky BE, Higgins JJ, Rajadhyaksha AM, Alaedini A. Markers of Celiac Disease and Gluten Sensitivity in Children with Autism. PLoS One. 2013 Jun 18;8(6):e66155. Print 2013. [↩]

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

Beaus lines in thin nails (The tiny brown streak is a splinter hemorrhage.)
Beau”s lines in a thin nail. (The tiny brown streaks are splinter hemorrhages due to vitamin C deficiency.)

What Are Horizontal Ridges In Fragile Nails?

Horizontal ridges, also called “beau’s lines,” are abnormalities of the nail plate that appear as rumpling from the base to the tips of nails and are characterized by poor nail structure of both fingernails and toenails.

The nail plate is the hard keratin cover of the finger tip and toe tip which we ordinarily call “nails.” The nail plate is produced by the nail matrix. 

Q: Why do Beau’s lines develop in nails?

A: Beau’s lines occur due to temporary cessation of proliferation (growth) of proximal nail matrix at the nail base. As the finger nail grows at the rate of 0.1 mm/day, the time course of the illness can be estimated from the position of the Beau’s line from proximal nail fold.1

Nail Anatomy. Nail Anatomy. A. Nail plate; B. lunula; C. root; D. sinus; E. matrix; F. nail bed; G. hyponychium; H. free margin. Courtesy Wikipedia.org.

A. Nail plate; B. lunula; C. root; D. sinus; E. matrix; F. nail bed; G. hyponychium; H. free margin. Courtesy Wikipedia.

Beau’s lines are frequently seen in nutritional deficiency states, bacterial illness, acute stress, and systemic disease. The conditions where Beau’s lines have been described include severe systemic illness, chemotherapy, malnutrition, zinc deficiency, trauma, paronychia, pemphigus, and Kawasaki disease.2 Beau’s lines are commonly seen in patients undergoing chemotherapy.3

 This condition of nails was named after Joseph Honoré Simon Beau (1806-1865).

What Are Horizontal Nail Ridges In Celiac Disease and/or Gluten Sensitivity?

Sources:
  1. Naik GS1, Harikrishna J. Beau’s lines. Indian J Med Res. 2013 Jan;137(1):220. [↩]
  2. Naik GS1, Harikrishna J. Beau’s lines. Indian J Med Res. 2013 Jan;137(1):220. [↩]
  3. Patel LM, Lambert PJ, Gagna CE, Maghari A, Lambert WC. Cutaneous signs of systemic disease. Clin Dermatol. 2011 Sep-Oct;29(5):511-22. doi: 10.1016/j.clindermatol.2011.01.019. [↩]

Koilonychia (Washboard Nails)

Koilonychia (Hordinsky, Sawaya, and Scher, 2000)

What Is Koilonychia?

[dropcap]K[/dropcap]oilonychia is a feature of an iron deficiency state characterized by abnormally shaped nails, called spoon shaped nails, meaning that the normal downward curve is reversed.

Depending on the inadequacy of iron, nails may simply remain flat or with a slight dip without progressing to a reversed curve.

These nails develop vertical ridges from the base to the nail tip that can become deep, called washboard nails.

Q: Are all nails affected?

A: All nails are affected in varying degrees. The small finger shows the least effect while the thumb shows the greatest change which begins as flattening before scooping upward.

Nail Anatomy. Nail Anatomy. A. Nail plate; B. lunula; C. root; D. sinus; E. matrix; F. nail bed; G. hyponychium; H. free margin. Courtesy Wikipedia.org.

A. Nail plate; B. lunula; C. root; D. sinus; E. matrix; F. nail bed; G. hyponychium; H. free margin. Courtesy Wikipedia.

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

Developmental Delay

developmental delay gluten celiac diseaseWhat Is Developmental Delay?

[dropcap]D[/dropcap]evelopmental delay is failure in infants and young children to meet expected milestones, such as smiling for the first time or taking the first steps, due to an impairment in physical, learning, language, or behavior areas.

These conditions begin during the developmental period, may impact day-to-day functioning, and usually last throughout a person’s lifetime.1

What Is Developmental Delay In Celiac Disease and/or Gluten Sensitivity?

Sources:
  1. Developmental Disabilities: Delivery of Medical Care for Children and Adults. I. Leslie Rubin and Allen C. Crocker. Philadelphia, Pa, Lea & Febiger, 1989. [↩]

Apathy

Apathy celiac disease symptomWhat Is Apathy?

[dropcap]A[/dropcap]pathy is an abnormal emotional state that is characterized by indifference to things which others find interesting, moving or exciting, and diminished motivation to perform regular daily activities.

The neural mechanisms of apathy are postulated to involve the brainstem and forebrain circuits that regulate goal-directed behavior.1

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

Sources:
  1. Marin RS. Apathy: Concept, Syndrome, Neural Mechanisms, and Treatment. Semin Clin Neuropsychiatry. 1996 Oct; 1(4):304-314. [↩]

Anxiety, Chronic

AnxietyWhat Is Anxiety?

[dropcap]A[/dropcap]nxiety or worry is a distressing emotional state of mind or mood that is characterized by a vague uneasiness, unpleasant feelings of apprehension or anticipation of danger and by interference with normal functioning, ranging from mild qualms and easy startling to occasional panic.

Q: What causes anxiety?

A: Anxiety can be a normal response to stress such as making an important decision, illness, divorce, problems at work or preparing for an exam.

In a dangerous situation, profound physiological changes rapidly prepare us for a “fight or flight” response by release of adrenalin hormone. Adrenalin speeds up metabolism to make available quick energy, tightens muscles in readiness, and speeds up the heartbeat and breathing so that more oxygen is made available to the brain and muscles.

Anxiety becomes a maladaptive disorder when it is excessive, unrealistic, or not provoked and impairs the ability to lead a normal life.

Anxiety that is part of a person’s personality is called “trait anxiety.” Anxiety that comes and goes is “state anxiety,” as in state of mind, and is usually due to unresolved stress or an underlying health problem.

What Is Chronic Anxiety in Celiac Disease?