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Dr. Alexander Shikhman MD PhD FACR
Institute for Specialized Medicine
Gluten-Free Remedies
ifsmed.com | glutenfreeremedies.com
May 2014
Content Available
Slides available: slideshare.com/ifsmed
Video available: youtube.com/ifsmed
Case Study
 42 y.o. woman presumable fibromyalgia diagnosis
 Developed severe eye, mouth and vaginal dryness
 Consulted by a rheumatologist and diagnosed with ankylosing
spondylitis
 Started anti-inflammatory drugs and then intravenous
infusions of Remicade
 Drugs discontinued after 6 months
 Seeking second opinion regarding the nature and management
of her pain
Case Study
Main complaints during initial consultation included:
 Generalized muscle pain
 Fatigue
 Morning stiffness
 Eye, mouth and vaginal dryness
 Osteoporosis
 Frequent migraine headaches
 Irregular bowel movements with a predominant
constipation
 Bloating
Case Study
Her family history was pertinent
for:
•Osteoporosis
•Irritable bowel syndrome
•Sjogren’s syndrome
•Hypothyroidism
Physical examination was pertinent
for:
•Skin rash over shoulders
•Eye and mouth dryness
•Mild abdominal tenderness
•Generalized muscle tenderness
Lab test results:
•Mild anemia
•Low level of vitamin D
•Positive genetics for celiac
disease
Her endoscopy was requested and
small intestinal biopsy was negative for
celiac disease
Case Study
 Patient went on gluten-free diet
 Started oral iron and vitamin D supplementations
 One month after initiation of the diet, pain subsided by 40-50%
 In three months she became pain-free
 Accidental consumption of gluten resulted in near complete reproduction
of her pain
 Six months after diet, noticed improvement of mucosal dryness
 Two years after initiation of the diet, the patient is still symptom free
Gut and Rheumatic Disease
The gastrointestinal system is the main entry for foreign materials (foods) into the
human body and the main transitory route for an enormous mass of microorganisms
and products of their activity in the form of feces.
 In an average person, the absorptive surface area of the small intestine is roughly
2700 square feet - the size of a tennis court
 The total alveolar area of the lungs is equal to 1700 square feet
 In comparison, the average skin surface area is only 17 square feet
Gut and Rheumatic Disease
 Food and microbial products are the main stimulants
of the immune system and the main external
regulator of various metabolic pathways
 Accordingly, composition of the consumed food can
influence immune responses and inflammatory
processes leading to the development of distinct
forms of rheumatic diseases
Focus on Gluten Intolerance
 Most common food-driven autoimmune disease affecting
humans
 10 to 35% of general population are genetically predisposed
 The mortality rate in patients with gluten intolerance exceeds
the general population by a factor of 1·9–3·8
 After 1–5 years on a gluten-free diet, the reduction in excess
mortality suggests diet is protective against malignant diseases
in patients with gluten intolerance
Dietary Grains and Proteins that Trigger
Gluten Intolerance
GRAIN PATHOGENIC PROTEINS
WHEAT GLIADINS
RYE SEKALINS
BARLEY HORDEINS
DURUM
GLIADIN-LIKE PROTEINS
SPELT
TRITICALE
KAMUT
EINCORN
Gluten Intolerance—a disease that
goes against the grain
Gluten intolerance is a permanent, genetically based intolerance
to ingested gluten that results in chronic inflammation and
systemic autoimmune responses
Why Gluten?
 Human digestive enzymes cannot completely digest gluten in the
gastrointestinal tract
 Consumption results in formation of large protein fragments
stimulating inflammatory reaction within the intestinal wall
 Gluten peptides can penetrate in systemic circulation and trigger
immune responses in internal organs distant from the intestine
(thyroid gland, salivary glands, brain etc)
 Gluten peptides can be detected in breast milk and can trigger
various undesirable reaction in breast-fed infants
Genetics of Gluten Intolerance
 Patients with gluten intolerance demonstrate a strong
association with specific HLA class II genotypes
 If people genetically predisposed to gluten intolerance do
not ingest gluten, the illness will not manifest
Genetics of Gluten Intolerance
Approximately 95% of
patients with gluten
intolerance have a
particular type of HLA DQ
alpha and beta chain
encoded by two genes,
HLA-DQ2 (85-90%), and
HLA-DQ8 (5-10%)
Immunology of Gluten Intolerance
 T lymphocytes invariably
recognize gluten peptides
that are presented by
HLA-DQ2 orDQ8
molecules.
 This results in the
lymphocyte activation and
initiation of the
inflammatory reaction and
autoimmune responses
Genetics of Gluten Intolerance
MYO9B (myosin IXB) gene
polymorphisms is
associated with celiac
disease, ulcerative colitis,
SLE and RA susceptibility,
presumably through
alteration of the intestinal
permeability
Spectrum of Gluten Intolerance
35-40% will develop
gluten intolerance
during their lifetime
60-70%
will be
affected
by
rheumatic
diseases
Celiac disease
3-5%
Gluten intolerance
without celiac disease
30-35%
Latent gluten intolerance
HLA DQ2 or DQ8 +
without clinical symptoms
60-70%
Gastrointestinal Involvement in Gluten
Intolerance
Metabolic Problems Associated
with Gluten Intolerance
 Malabsorbtion of vitamins (vitamin D, A, E, K, B1, B6),
macroelements (iron, calcium, magnesium) and
microelements (zinc, copper selenium)
 Leaky gut syndrome
 Pernicious anemia (vitamin B12 deficiency due to autoimmune
damage of gastric parietal cells)
 Osteoporosis
 Disbacteriosis
Rheumatic Diseases Commonly
Associated with Gluten Intolerance
GLUTEN
INTOLERANCE
SJOGREN’S SYNDROME
FIBROMYALGIA
PSEUDOGOUT
OSTEOPOROSIS
SACROILIITIS
DERMATOMYOSITIS
PSORIASIS/PSORIATIC
ARTHRITIS
Sjogren’s Syndrome
Main symptoms are:
 Dry eyes –burning or itching, sandy feeling, blurry vision,
light sensitivity
 Dry mouth –chalky or cotton like, difficulty swallowing,
speaking, or tasting, dental decay (cavities) and mouth
infections.
Sjogren’s Syndrome
Effects other parts of the body:
 joint and muscle pain
 prolonged dry skin
 skin rashes on the extremities
 chronic dry cough
 vaginal dryness
 numbness or tingling in the
extremities
 prolonged fatigue
Fibromyalgia Core features of the
disorder include:
 debilitating fatigue
 sleep disturbance
 joint stiffness
 difficulty with swallowing
 bowel and bladder abnormalities
 difficulty breathing
 diffuse sensations of numbness and
tingling
 abnormal motor activity
 cognitive dysfunction
Osteoporosis
 Bone mineral density is reduced
 Bone microarchitecture is disrupted
 Non-collagenous proteins in bone is
altered
 No specific symptoms
 Increased risk of bone fractures.
 Gluten intolerance increases risk of
osteoporosis due to malabsorbption
of vitamins (vitamin D in particular),
minerals and microelements
Pseudogout
Calcium Pyrophosphate Deposition Disease
 An inflammatory body reaction to the
crystal deposits of calcium pyrophosphate
 Severe episodes of localized pain and
swelling
 Chronic arthritis that mimics osteoarthritis
or rheumatoid arthritis
 Knees wrists, shoulders, ankles, elbows
 Vitamin D deficiency causing secondary
hyperparathyroidism
Rheumatic Diseases Less Commonly
Associated with Gluten Intolerance
 Scleroderma
 Rheumatoid Arthritis
 Systemic Lupus Erythematosus (SLE)
 Juvenile Rheumatoid Arthritis
Nonrheumatic Diseases Commonly
Associated with Gluten Intolerance
IRRITABLE
BOWEL
SYNDROME
DERMATITIS
HERPETIFORMIS
CELIAC
DISEASE
AUTISM
BIPOLAR
DISORDER
SECONDARY
HYPERPARATHYROIDISM
ADHD
PERIPHERAL
NEUROPATHY
SEIZURE DISORDER SCHIZOPHRENIA
CHRONIC FATIGUE
SYNDROME
Indicators of Gluten Intolerance
Medical History
 Thyroid disorders
 Irritable bowel syndrome
 Iron deficiency
 Osteoporosis
 Sjogren’s syndrome
 Asthma
Indicators of Gluten Intolerance
Skin Conditions
KERATOSIS
PILARIS
PERIUNGUAL
ERYTHEMA
DERMATITIS
HERPETIFORMIS
Laboratory Findings Suspicious for
Gluten-Driven Autoimmune Process
 Low levels of vitamin D1 or D3
 Elevated PTH
 Positive anti-neuronal antibodies
 Positive anti-SSA/SSB antibodies
 Positive anti-cardiolipin antibodies
 Hyperprolactinemia
 Persistently elevated b2-microglobulin
 Positive anti-TPO antibodies
 Low level of vitamin A or retinol
How to Diagnose Gluten Intolerance
 Genetic testing
 Immunologic testing
 Blood
 Feces
 Intestinal / colon biopsy
 Elimination diet with subsequent gluten challenge
Treatment of Gluten Intolerance
ELIMINATION OF
GLUTEN
CORRECTION
OF
METABOLIC
DISORDERS
CORRECTION
OF
IMMUNE
RESPONSES
TUMOR
SURVEILLANCE
Elimination of Gluten
Gluten-Free
Diet
Management of
Gluten
Contamination
Desorption of
Gluten from
Intestinal
Lining
Elimination of Gluten
Gluten-containing grains to avoid
Wheat Bulgar Filler
Wheat Bran Couscous Triticale
Wheat Starch Durum Kamut
Wheat Germ Einkorn Matzo
Flour/Meal Emmer Barley
Semolina Faro BarleyMalt/Extract
Spelt Rye Graham Flour
Elimination of Gluten
Obvious Sources Potential Sources
 Bread
 Bagels
 Cakes
 Cookies
 Pasta/noodles
 Cereal
 Patries/pies
 Rolls
 Candy
 Communion wafers
 Cured pork products
 Drink mixes
 Gravy
 Imitation meat/seafood
 Sauce
 Self-basting turkeys
 Soy sauce
Elimination of Gluten
 Lipstick/gloss/balms
 Mouthwash/toothpaste
 Play dough
 Stamp and envelope glues
 Prescription or OTC medications
 Vitamin, herbal and mineral preparations
Elimination of Gluten
 Only 50% of Americans with a chronic illness adhere to
their treatment including:
 Diet
 Exercise
 Medication
Correction of Metabolic Disorders
 Management of malabsorption and leaky gut syndrome
 Therapy of hormonal imbalance
 Management of osteopenia and osteoporosis
Correction of Metabolic Disorders
 Low Iron
 Low Folate
 Low Vitamin B12
 Low Vitamins ADEK
 Low Thiamine
 Low B6 (rare)
 Low Beta-carotene
 Low Zinc
 Essential fatty acid
deficiency
 Low Niacine
Correction of Immune Responses
 Therapy of autoimmune disorders
 Normalization of gastrointestinal ecology
Tumor Surveillance
 Biochemical markers
 Physical surveillance
Slides available: slideshare.com/ifsmed
Video available: youtube.com/ifsmed
CONTENT AVAILABLE

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Gluten intolerance and rheumatic diseases 5.2.14

  • 1. Dr. Alexander Shikhman MD PhD FACR Institute for Specialized Medicine Gluten-Free Remedies ifsmed.com | glutenfreeremedies.com May 2014
  • 2. Content Available Slides available: slideshare.com/ifsmed Video available: youtube.com/ifsmed
  • 3. Case Study  42 y.o. woman presumable fibromyalgia diagnosis  Developed severe eye, mouth and vaginal dryness  Consulted by a rheumatologist and diagnosed with ankylosing spondylitis  Started anti-inflammatory drugs and then intravenous infusions of Remicade  Drugs discontinued after 6 months  Seeking second opinion regarding the nature and management of her pain
  • 4. Case Study Main complaints during initial consultation included:  Generalized muscle pain  Fatigue  Morning stiffness  Eye, mouth and vaginal dryness  Osteoporosis  Frequent migraine headaches  Irregular bowel movements with a predominant constipation  Bloating
  • 5. Case Study Her family history was pertinent for: •Osteoporosis •Irritable bowel syndrome •Sjogren’s syndrome •Hypothyroidism Physical examination was pertinent for: •Skin rash over shoulders •Eye and mouth dryness •Mild abdominal tenderness •Generalized muscle tenderness Lab test results: •Mild anemia •Low level of vitamin D •Positive genetics for celiac disease Her endoscopy was requested and small intestinal biopsy was negative for celiac disease
  • 6. Case Study  Patient went on gluten-free diet  Started oral iron and vitamin D supplementations  One month after initiation of the diet, pain subsided by 40-50%  In three months she became pain-free  Accidental consumption of gluten resulted in near complete reproduction of her pain  Six months after diet, noticed improvement of mucosal dryness  Two years after initiation of the diet, the patient is still symptom free
  • 7. Gut and Rheumatic Disease The gastrointestinal system is the main entry for foreign materials (foods) into the human body and the main transitory route for an enormous mass of microorganisms and products of their activity in the form of feces.  In an average person, the absorptive surface area of the small intestine is roughly 2700 square feet - the size of a tennis court  The total alveolar area of the lungs is equal to 1700 square feet  In comparison, the average skin surface area is only 17 square feet
  • 8. Gut and Rheumatic Disease  Food and microbial products are the main stimulants of the immune system and the main external regulator of various metabolic pathways  Accordingly, composition of the consumed food can influence immune responses and inflammatory processes leading to the development of distinct forms of rheumatic diseases
  • 9. Focus on Gluten Intolerance  Most common food-driven autoimmune disease affecting humans  10 to 35% of general population are genetically predisposed  The mortality rate in patients with gluten intolerance exceeds the general population by a factor of 1·9–3·8  After 1–5 years on a gluten-free diet, the reduction in excess mortality suggests diet is protective against malignant diseases in patients with gluten intolerance
  • 10. Dietary Grains and Proteins that Trigger Gluten Intolerance GRAIN PATHOGENIC PROTEINS WHEAT GLIADINS RYE SEKALINS BARLEY HORDEINS DURUM GLIADIN-LIKE PROTEINS SPELT TRITICALE KAMUT EINCORN
  • 11. Gluten Intolerance—a disease that goes against the grain Gluten intolerance is a permanent, genetically based intolerance to ingested gluten that results in chronic inflammation and systemic autoimmune responses
  • 12. Why Gluten?  Human digestive enzymes cannot completely digest gluten in the gastrointestinal tract  Consumption results in formation of large protein fragments stimulating inflammatory reaction within the intestinal wall  Gluten peptides can penetrate in systemic circulation and trigger immune responses in internal organs distant from the intestine (thyroid gland, salivary glands, brain etc)  Gluten peptides can be detected in breast milk and can trigger various undesirable reaction in breast-fed infants
  • 13. Genetics of Gluten Intolerance  Patients with gluten intolerance demonstrate a strong association with specific HLA class II genotypes  If people genetically predisposed to gluten intolerance do not ingest gluten, the illness will not manifest
  • 14. Genetics of Gluten Intolerance Approximately 95% of patients with gluten intolerance have a particular type of HLA DQ alpha and beta chain encoded by two genes, HLA-DQ2 (85-90%), and HLA-DQ8 (5-10%)
  • 15. Immunology of Gluten Intolerance  T lymphocytes invariably recognize gluten peptides that are presented by HLA-DQ2 orDQ8 molecules.  This results in the lymphocyte activation and initiation of the inflammatory reaction and autoimmune responses
  • 16. Genetics of Gluten Intolerance MYO9B (myosin IXB) gene polymorphisms is associated with celiac disease, ulcerative colitis, SLE and RA susceptibility, presumably through alteration of the intestinal permeability
  • 17. Spectrum of Gluten Intolerance 35-40% will develop gluten intolerance during their lifetime 60-70% will be affected by rheumatic diseases Celiac disease 3-5% Gluten intolerance without celiac disease 30-35% Latent gluten intolerance HLA DQ2 or DQ8 + without clinical symptoms 60-70%
  • 18. Gastrointestinal Involvement in Gluten Intolerance
  • 19. Metabolic Problems Associated with Gluten Intolerance  Malabsorbtion of vitamins (vitamin D, A, E, K, B1, B6), macroelements (iron, calcium, magnesium) and microelements (zinc, copper selenium)  Leaky gut syndrome  Pernicious anemia (vitamin B12 deficiency due to autoimmune damage of gastric parietal cells)  Osteoporosis  Disbacteriosis
  • 20. Rheumatic Diseases Commonly Associated with Gluten Intolerance GLUTEN INTOLERANCE SJOGREN’S SYNDROME FIBROMYALGIA PSEUDOGOUT OSTEOPOROSIS SACROILIITIS DERMATOMYOSITIS PSORIASIS/PSORIATIC ARTHRITIS
  • 21. Sjogren’s Syndrome Main symptoms are:  Dry eyes –burning or itching, sandy feeling, blurry vision, light sensitivity  Dry mouth –chalky or cotton like, difficulty swallowing, speaking, or tasting, dental decay (cavities) and mouth infections.
  • 22. Sjogren’s Syndrome Effects other parts of the body:  joint and muscle pain  prolonged dry skin  skin rashes on the extremities  chronic dry cough  vaginal dryness  numbness or tingling in the extremities  prolonged fatigue
  • 23. Fibromyalgia Core features of the disorder include:  debilitating fatigue  sleep disturbance  joint stiffness  difficulty with swallowing  bowel and bladder abnormalities  difficulty breathing  diffuse sensations of numbness and tingling  abnormal motor activity  cognitive dysfunction
  • 24. Osteoporosis  Bone mineral density is reduced  Bone microarchitecture is disrupted  Non-collagenous proteins in bone is altered  No specific symptoms  Increased risk of bone fractures.  Gluten intolerance increases risk of osteoporosis due to malabsorbption of vitamins (vitamin D in particular), minerals and microelements
  • 25. Pseudogout Calcium Pyrophosphate Deposition Disease  An inflammatory body reaction to the crystal deposits of calcium pyrophosphate  Severe episodes of localized pain and swelling  Chronic arthritis that mimics osteoarthritis or rheumatoid arthritis  Knees wrists, shoulders, ankles, elbows  Vitamin D deficiency causing secondary hyperparathyroidism
  • 26. Rheumatic Diseases Less Commonly Associated with Gluten Intolerance  Scleroderma  Rheumatoid Arthritis  Systemic Lupus Erythematosus (SLE)  Juvenile Rheumatoid Arthritis
  • 27. Nonrheumatic Diseases Commonly Associated with Gluten Intolerance IRRITABLE BOWEL SYNDROME DERMATITIS HERPETIFORMIS CELIAC DISEASE AUTISM BIPOLAR DISORDER SECONDARY HYPERPARATHYROIDISM ADHD PERIPHERAL NEUROPATHY SEIZURE DISORDER SCHIZOPHRENIA CHRONIC FATIGUE SYNDROME
  • 28. Indicators of Gluten Intolerance Medical History  Thyroid disorders  Irritable bowel syndrome  Iron deficiency  Osteoporosis  Sjogren’s syndrome  Asthma
  • 29. Indicators of Gluten Intolerance Skin Conditions KERATOSIS PILARIS PERIUNGUAL ERYTHEMA DERMATITIS HERPETIFORMIS
  • 30. Laboratory Findings Suspicious for Gluten-Driven Autoimmune Process  Low levels of vitamin D1 or D3  Elevated PTH  Positive anti-neuronal antibodies  Positive anti-SSA/SSB antibodies  Positive anti-cardiolipin antibodies  Hyperprolactinemia  Persistently elevated b2-microglobulin  Positive anti-TPO antibodies  Low level of vitamin A or retinol
  • 31. How to Diagnose Gluten Intolerance  Genetic testing  Immunologic testing  Blood  Feces  Intestinal / colon biopsy  Elimination diet with subsequent gluten challenge
  • 32. Treatment of Gluten Intolerance ELIMINATION OF GLUTEN CORRECTION OF METABOLIC DISORDERS CORRECTION OF IMMUNE RESPONSES TUMOR SURVEILLANCE
  • 33. Elimination of Gluten Gluten-Free Diet Management of Gluten Contamination Desorption of Gluten from Intestinal Lining
  • 34. Elimination of Gluten Gluten-containing grains to avoid Wheat Bulgar Filler Wheat Bran Couscous Triticale Wheat Starch Durum Kamut Wheat Germ Einkorn Matzo Flour/Meal Emmer Barley Semolina Faro BarleyMalt/Extract Spelt Rye Graham Flour
  • 35. Elimination of Gluten Obvious Sources Potential Sources  Bread  Bagels  Cakes  Cookies  Pasta/noodles  Cereal  Patries/pies  Rolls  Candy  Communion wafers  Cured pork products  Drink mixes  Gravy  Imitation meat/seafood  Sauce  Self-basting turkeys  Soy sauce
  • 36. Elimination of Gluten  Lipstick/gloss/balms  Mouthwash/toothpaste  Play dough  Stamp and envelope glues  Prescription or OTC medications  Vitamin, herbal and mineral preparations
  • 37. Elimination of Gluten  Only 50% of Americans with a chronic illness adhere to their treatment including:  Diet  Exercise  Medication
  • 38. Correction of Metabolic Disorders  Management of malabsorption and leaky gut syndrome  Therapy of hormonal imbalance  Management of osteopenia and osteoporosis
  • 39. Correction of Metabolic Disorders  Low Iron  Low Folate  Low Vitamin B12  Low Vitamins ADEK  Low Thiamine  Low B6 (rare)  Low Beta-carotene  Low Zinc  Essential fatty acid deficiency  Low Niacine
  • 40. Correction of Immune Responses  Therapy of autoimmune disorders  Normalization of gastrointestinal ecology
  • 41. Tumor Surveillance  Biochemical markers  Physical surveillance
  • 42. Slides available: slideshare.com/ifsmed Video available: youtube.com/ifsmed CONTENT AVAILABLE