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Integrating the Functional, Psychodynamic, and Immunologic Matrix: New Adventures in Delayed Food Sensitivity Testing - IMMH Brazil 2015

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In this presentation (here represented in English before translation) Dr. Cady deconstructs the curious and sometimes perplexing manifestations of delayed sensitivity food allergy testing, supporting it with citations from the peer-reviewed medical literature and extensive bibliographic references. The importance of understanding the potential immunologic contribution to a patient's mental state is reviewed.

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Integrating the Functional, Psychodynamic, and Immunologic Matrix: New Adventures in Delayed Food Sensitivity Testing - IMMH Brazil 2015

  1. 1. Integrating the Functional, Psychodynamic, and Immunologic Matrix: New Adventures in Delayed Food Sensitivity Testing Louis Cady, MD CEO, Founder – Cady Wellness Institute Newburgh, Indiana (US) Indiana School of Medicine, Dept. of Psychiatry Brazil, 2015
  2. 2. “There are two objects of medical education: to heal the sick and to advance the science.” - Dr. Charles H. Mayo, MD “The glory of medicine is that it is always moving forward, that there is always more to learn.” - Dr. William J. Mayo
  3. 3. CURRENT PRACTICE OF MEDICINE: What a patient had to say about her “specialists”: “They just monitor my degeneration.”
  4. 4. Triadic model of thinking about diagnosis or treatment puzzles • PSYCHODYNAMIC - what makes a patient the way he/she is? – (what makes them act &/or respond as they do?) • FUNCTIONAL - what are some of the underlying physiologic processes which may be pathogenic? • IMMUNOLOGIC - what are the subtle manifestations of food allergies & sensitivities?
  5. 5. “If you can only read one article in your entire career at Mayo on psychotherapy, read this one.” - John Graf, MD “If you can only read one article in your entire career at Mayo on psychotherapy, read this one.” - John Graf, MD Greben, S. Can Psychiatr. Assoc Journ. Vol 22 (1977): 371-380 “On Being Therapeutic” “On Being Therapeutic”
  6. 6. Stanley E. Greben, MD • Some therapists stand out as uniquely effective. • Academics are no better. • “Every potential therapist must have a floor and a ceiling to his therapeutic capacity.” • Some gifted therapists are able to say why they succeed; others can’t explain it. “A great deal of what they do ‘right’ is intuitive.” “On Being Therapeutic” [Canadian Psychiatric Association Journal. Vol. 22(1977) 371-380.
  7. 7. Greben’s “Seven Habits” • Empathy & concern • Warmth • Interaction • Ability to arouse hope • Expectation of improvement • “Not to despair” • Reliability & Friendliness *Requires clinical depth and breadth of knowledge *
  8. 8. Psychodynamics 101 • Patients can be vexing. • Diagnostic impasses provoke narcissistic angst. • Frustrated clinicians do not relate well with patients. • The more tools and capabilities one has, the greater the freedom, the options, and the ability to positively impact the patient. • The greater the success, the better the patient feels, the doctor feels, and the doctor-patient relationship feels. • The converse, worrisomely, also exists.
  9. 9. IMMUNOLOGY The forgotten component of “workups”
  10. 10. "What is food for one, is to others bitter poison.” Lucretius – 099? B.C. – 055? A.D. De rerum natura.
  11. 11. “The Three Little Ig’s & Three Stories” •Ig E •Ig G •Ig xciting- emocionante oing along – indo junto Norant -ignorante
  12. 12. IgE Antibodies: catastrophic reactions vs. sneezes and itching (checked via skin tests or RAST) http://pathmicro.med.sc.edu/ghaffar/skintest.jpg
  13. 13. http://users.rcn.com/jkimball.ma.ultranet/B iologyPages/M/MastCell.gif www.souzaoenterprises.com/A llergiescomp.jpg CELLULAR immunity
  14. 14. This model of human IgG1 was created by E. A. Padlan -- "Anatomy of the Antibody Molecule." Molecular Immunology 31:169 (1994) HUMORAL Immunity “Globulin molecules capable of attacking the invading agent.” [Guyton]
  15. 15. Actions and downstream effects • Direct action of antibodies: – Agglutination, precipitation, neutralization, lysis • Downstream effects: complement activation: – Lysis, opsonization/phagocytosis, chemotaxis, agglutination, neutralization of viruses, INFLAMMATORY EFFECTS
  16. 16. ADHD Diagnosis - DSM-IV or 5 – Symptoms present before age 7 years (12 years in DSM 5) – Impairment from symptoms present in 2 or more settings – Significant social, academic, or occupational impairment – Exclude other mental disorders
  17. 17. From: www.patientmedia.com (used with permission of William Esteb) A sua vida é indo a lugar nenhum ?
  18. 18. Food Allergies and ADHD in the Literature • Get “THE THINKER” illustration•Food allergies presumed to be related to ADHD •Before 1976 – No known relationship between FA and ADD •1976 – IgE reactivity + food allergies = decreased IQ •1985 – d/c of antigenic foods = ADHD improvement •1993 – more confirmation •1994 – some kids that got better on diet did NOT have IgE reactivity •2003 – evidence mounting for non-IgE sensitivities related to food allergies] •2002 – 2011 Pelsser LM et al – SIX published papers (European and Dutch literature, cf: www.pubmed.gov). •66 papers – 8/19/2011 •82 papers – 8/30/2015 !
  19. 19. Millman, et al – the groundbreaking article • “Allergy & Learning Disabilities in Children” – Annals of Allergy, 1976 [36:3, 149-160.] • “The allergic tension-fatigue syndrome observed by Speer” – “A symptom complex accepted by many allergists.” • Food allergies established by scratch testing or intradermal injections • Positive correlation between [IgE] food allergies and IQ scores. –The more the food allergies, the lower the IQ scores.
  20. 20. Oligoantigenic diet (w/o testing) • “Controlled trial of oligoantigenic treatment in the Hyperkinetic Syndrome.” Egger et al. Lancet, March 9, 1985, 540-545. • No testing performed • Children empirically placed on restrictive diet. – Two meats, two carb sources, two fruits, one vegetable, water, calcium, vitamins. • No food allergy symptoms were provoked; ADHD improved.
  21. 21. The crossover study – no distinguishing between IgE and IgG • “Effects of a few foods diet on ADD.” Carter et al, Archives of Disease in Childhood, 1993;69:564-568. • “Few foods” elimination diet – 59 of 78 children improved. • “This trial indicates that diet can contribute to behavior disorders in children and that this effect can be shown in a double blind, placebo controlled trial.” • “The ways in which [this] diet worked remain unclear. Toxic pharmacological, or allergic mechanisms could be involved, and the physiological effects of different foods may vary.”
  22. 22. Profound cautions • “Effects of a few foods diet on ADD.” Carter et al, Archives of Disease in Childhood, 1993;69:564-568 (cont.) • “The treatment, as applied in this study, has disadvantages. It is a difficult and exacting regimen, which puts a considerable strain on the whole family. It is not yet clear whether modified diets can also be effective…. It may therefore be possible to devise a less restricted diet with similar levels of success.” • Cady impression: “Shooting in the dark is dangerous.”
  23. 23. The appearance of IgG • “Foods and additives are common causes of ADHD in children.” Boris, et. al. Annals of Allergy, vol.. 72, 1994, 462-468. • “DBPCF” - “double blind placebo controlled food challenge test” • 4/19 children who showed improvement with removal of offending foods were non- atopic.
  24. 24. “IgE and Non IgE Food Allergy” • Sabra, et al. Annals of Allergy, Asthma, and Immunology 2003;90 (Suppl 3)71-76. • “The gastrointestinal tract serves not only a nutritive function but also is a major immunologic organ. Although previously thought to be triggered primarily by an IgE mediated mechanism of injury, considerable evidence now suggests that non- IgE mechanisms may also be involved in the pathogenesis of FA (“food allergy”).
  25. 25. The patient: “Billy” • 8/1998 – 4 yo Eastern European adopted child – “ADD & behavioral problems, destructive.” – First 3 years of life in orphanage • Fam Psych Hx: – Dad – “substance induced paranoid psychosis” – Mother – “recurrent schizophrenic decompensations”
  26. 26. Billy’s symptoms • “Mercurial” – easy to get along with (except for hyperactivity) then one week at a time will be glowering, sullen, terrible mood, knock brothers over, throw food from table, etc. • MSE – very hyper. Not able to focus on Nintendo (!) Found standing on top of a box in my video room, supervised by his Dad. DSM-IV: 5/6 • Previous trial of Rx: mixed amphetamine salts 5 mg up to 10 mg. Made him much worse • ….started on methylphenidate and clonidine
  27. 27. Billy, cont. • Some improvement • 3/1999 – increasingly vile temper. Sad, dysphoric. “Back to square one.” – Sertraline added. – Methylphenidate only lasting 1 ½ hours • 5/1999 - 4 ½ yoa. Rehab Center testing: – Auditory comprehension = 2 y 11 mo’s – Total language = 2 y 11 mo’s • 6/1999 – Flaxseed oil, L-tyrosine, Pediactive tabs added. In constant trouble Dad getting depressed.
  28. 28. Billy, cont – 1999 - 2000 • Ritalin and Adderall not working • Temper to the point of clawing at his face. Sniffing. Now urinating in bed. • 12/1999 – started on risperidone – 1mg in a.m. and ½ mg later in day • 2/2000 – Psych testing – IQ 78 – ADHD – Borderline intelligence – Processing problems – “r/o childhood psychosis”
  29. 29. Billy, cont. • 3/2000 – Valproate added to risperidond for temper and “bipolar” feel. Now doing even worse. Staggering some. – DSM IV 6/7 – risperidone, guanfacine, sertraline, valproate, methylphenidate SR (@ 6 yoa!) • Summer – OROS MPH tried. Seemed to respond, then “downhill trend before school started.” • 10/2000 – “staring spells.” Cleared by neurologist. Negative EEG. • Mayo suggested; insurance wouldn’t pay.
  30. 30. Billy, late 2000 • Fall 2000: – Bit and stabbed his teacher with a pencil, kicked chair, wall, and desk, spat on floor and teacher. Obsessively lining up his cars in his room, tongue thrusting and smacking (? Tardive dyskinesia?) • On risperidone, valproate, and OROS methylphenidate. • 8/2001 – 2002 some better but still unpredictable. Meltdowns. Valproate increased. Olanzapine added. • 8/2002 – throwing things against windows. Valproate not working. Mood cycling.
  31. 31. May 2002: 9th Annual IFM Conference
  32. 32. Billy, 2003 • Ongoing unpredictability until ziprasidone started. – Less hyper – Dry in a.m. – Clearer speech and better eye contact. • July 2003 – IgG food allergy testing ordered
  33. 33. Billy – IgG Food Sensitvities July 2003 • 21 + IgG reactions.. Of these….. – Cheese (3+) – Cow’s milk (3+) – Goat’s milk (2+) – Brewer’s yeast (3+) – Millet (+1) – Lettuce (!) (+1) Reviewed labs with internet savvy Mom (who did NOTHING).
  34. 34. Billy, 2003 - 2004 • Variable. Food sensitivity diet not really followed. • 9/2003 “absolutely cannot sit still. Moods are flipping. Gets angry and aggressive really fast.” • 12/2003 – no better – On valproate, ziprasidone, OROS Methylphenidate, Clonidine – 1/2004 – VPA level 122 ug/ml; {50 – 100} • 3/2004 - “An incredibly nice kid when he’s doing what he wants to do; an asshole when it comes to relating.” (per Dad)
  35. 35. Radical interventions/ workup • June 2004 – Lithium added – Made him briefly toxic but symptoms improved. – Worked on getting him inpatient tx. • Fatty acid panel ordered. • Told Mom to GET SERIOUS about food allergies/sensitivities
  36. 36. Clinical manifestations of EFAD • Dermatitis • Increased appetite and caloric intake in infants (adults?!) • Failure of wound healing • Irritability • Alopecia, dry hair, dandruff • Brittle nails • Increased susceptibility of infections • Thirst, polydipsia, polyuria • Liver fatty infiltration • Increased capillary fragility • RBC fragility • Increased Cholesterol/HDL ratio
  37. 37. Essential Fatty Acid findings Value Reference range EPA 3 (L) 20 - 80 DHA 32 (L) 70 - 150
  38. 38. Billy – May 3, 2005 • Stable. Has stopped sneaking food. • IgG restrictions: wheat, gluten*, cow’s milk, processed sugar. (Able to tolerate unprocessed cane sugar.) All forms of chocolate and caffeine. • Drinks: homemade lemonade, soy or rice milk • Doing a music program at school. “Learning songs he never could before.” • MEDS: Levocarn; 72 mg OROS methylphenidate, “DHA heavy” fish oil; 20 mg ziprasidone (1/2 the previous) – Eliminated: Lithium, risperidone, and valproate • Prognosis: excellent. Still with cognitive challenges, but making progress at school and beginning to catch up. Behavior is stable. No more mood swings or rages. * Note – not originally seen on testing.
  39. 39. Billy – June 23, 2009 • Stable. Teenager. “Doing well except when his will is crossed.” • IgG restrictions: wheat, gluten, cow’s milk, processed sugar. (Able to tolerate unprocessed cane sugar.) All forms of chocolate and caffeine. • More verbal: of CWI therapy pet, he comments, “This dog doesn’t growl; he likes people.” • MEDS: – “DHA heavy” fish oil twice daily – MVI in a.m – Lis-dexamfetamine 70 mg, booster methlphenidate in the afternoon; risperidone 0.5 mg twice daily, valproate 500 mg ER twice daily . • ADHD symptoms: – zero – inattentive symptoms – ONE – hyperactive/impulsive symptom
  40. 40. Status: August 17 2011 • “He’s doing great.” • Failed attempts to wean off of IgG food allergies. – Apples have been added occasionally – Still can’t do dairy, gluten, citrus, or bananas. • H.S. sophomore– one year behind (in special ed.) classroom. • Getting along well with siblings; has not progressed past 1st grade academically, but visual spatial talents excellent. • Landscaped the entire back yard. Moved 8 tons of rock
  41. 41. FROM HYPERNESS TO HEADACHES …and joint pains, migraines, brain fog, irritable bowel syndrome, asthma, fatigue, misc. aches and pains
  42. 42. www.pubmed.com search August 30, 2015 Correlations found between food allergy & : • Depression • Anxiety • Acute psychoses • Autism • Schizophrenia
  43. 43. Gluten – one of the ultimate “bad boys” in food sensitivities • Headaches • Tearing up your gut • Depression • Suicide* – * Untreated celiac disease and attempted suicide. Lancet, September 1995. Pelligrino et al
  44. 44. Gluten and neurologic disease • “More recent studies have emphasized that a wider spectrum of neurologic syndromes may be the presenting extraintestinal manifestation of gluten sensitivity with or without intestinal pathology.” – -Bushara, KO. Neurologic presentation of celiac disease – Gastroenterology. 2005 Apr; 128(4 Suppl 1):592-7.
  45. 45. “UBO’s on MRI” – the gluten connection • 10 patients – had headaches. – MRI – UBO’s • 6 – unsteady, 4 gait ataxia • 90% response rate to gluten free diet.
  46. 46. What to be looking for… • Obvious GI problems • Atypical presentations • KNOWN associations (autism) • Symptoms varying with diet • Excess ABX use (candida) • Lack of normal progression in treatment
  47. 47. Classic “atypical presentation” • 43 year old aerobically fit MWM competitive cyclist/ pharmaceutical rep. Drinks protein shakes (whey). Exhausted/fatigued with multiple vague symptoms for 3 years. Taking naps in car in afternoon. – Intermittently nauseated for last two years. MD ignored him. • Also: at 41 yoa – dx’ed with Rocky Mountain Spotty Fever. Tx’ed with Doxycycline – Ulcer dx by GI doc, with + h. pylori. • Rx: Macrodantin + Flagyl. – “Pins & needles sensation under skin began – May 2009 (Antihistamine tried – didn’t work. )
  48. 48. Dx, Interventions and Trial Tx • Sleep study – non revealing • IgE food allergy possibility per dermatologist. Anti- histamine used. Sxs would stop then come back. • Soreness – consulted pain management doctor. No help. • Transdermal testosterone tried (low normal T) – no help. • Cholecystectomy – Sept 2009 • Severe constipation Dec 2009 – went days without bowel movement • Colonoscopy – benign. Possible “small bowel bacterial overgrowth.” ABX used. • Dx’ed with possible Lyme’s – more ABX.
  49. 49. Other dx/tx procedures: - CT brain – normal - CT abdomen – normal - HIDA scan – abnormal - Gallbladder – removed - MRI – lower lumbar – essentially normal but with slightly bulging disc - MRI – thoracic and cervical – good - Colonoscopy & sigmoidoscopy – benign. - Muscle biopsy – “nerve damage” - Stress EKG and Stress Echocardiogram – wnl
  50. 50. Symptoms at presentation • Mind and emotions: – Depression – Difficulty with memory, attention, – Short attention span – Weakness, fatigue, loss of energy • Miscellaneous: – Fatigue – Apathy/lethargy – Sleep apnea (previously reviewed) – Difficulty getting out of bed in the a.m. • Recurrent apthous ulcers
  51. 51. More symptoms at presentation • dry/brittle skin; puffy wrinkled skin • dark circles under eyes • persistent rash with pins and needles sensations on skin • “heaviness” in legs; shortness of breath • exhaustion with minor exertion • certain foods cause ill feelings • difficulty losing weight • Needs to drink coffee to get going in a.m. • Tired 1 – 3 hours after eating • Feels faint or weak. • Rates self as overweight
  52. 52. Most relevant labs (ordered before appointment):
  53. 53. What you can do with an integrated approach in 15 months: RX: dairy free diet (+IgG test); D3 5000 IU/d; Armour thyroid, Testosterone cypionate 100 mg IM q wk, MVI, Zinc, DHEA 50 mg SR, CoQ10 400mg (photo shot 15 months after tx) (permission granted to use photos & data)
  54. 54. Just one more: Joey - 6/28/11 • 11 year old male 5th grader with dx of ADHD and Speech Apraxia; problems with reading, writing, oral expressive language, math, sequencing • Medical: – Hx of “lazy bowel” • “He doesn’t go more than once in two weeks.” • Dietary: likes cheese, chicken nuggets, ice cream, Coke, pizza. Used to like cottage cheese. – GI sxs refractory to pediatric interventions • Dx 1: ADD: 6/9 sxs of inattentiveness ON RX. • Dx 2:“Probable severe IgG food sensitivity with obvious stool retention problems”
  55. 55. Dairy IgG sensitivity suspected. Testing/Results: • Pediatrician ordered IgE RAST = NEGATIVE • 7/25/11 – no change. 2 BM’s in one month. – IgG Testing previously ordered. (Mom resistant and delayed due to cost. Finally done after this appt). RESULTS: • Milk – SEVERE • Mild: green peas, pinto beans, corn, garlic, tomato, wheat • 8/15/11 - constipation and fecal retention totally eliminated.
  56. 56. What I learned; what we can learn • Think about “the matrix” first. • Functional and immunologic inquiry and stabilization is a prerequisite for improvement in some cases. – (“You can’t tell by looking.”) • Psychodynamic errors (“blaming the patient”) can sabotage miraculous progress. • The human body has marvelous ability to heal itself naturally if given the breathing room to do so.
  57. 57. Diagnostic challenges & IgG food sensitivities - opportunities exist • “Tough cases” • Weird, multiple symptoms • Headaches • GI symptoms, food cravings, or both • ADHD and “bipolar” type symptoms • Processing issues (no pills available!) • Headaches resistant to standard chiropractic and medical tx • Fatigue, “brain fog”, temper fits
  58. 58. Personal collection - Louis B. Cady, M.D.
  59. 59. Perhaps the ability not only to acquire the confidence of the patient, but to deserve it, to see what the patient desires and needs, comes through the sixth sense we call intuition, which in turn comes from wide experience and deep sympathy for and devotion to the patient, giving to the possessor remarkable ability to achieve results. ...William J. Mayo, 1935
  60. 60. Contact information and slide resources Louis B. Cady, MD Cady Wellness Institute 4727 Rosebud Lane – Suite F Newburgh, IN 47630 USA Office (812) 429-0772 info@cadywellness.com Available on Apple “app store” and Google Android store. www.slideshare.net/lcadymd
  61. 61. Extra slides for further background follow in appendix Contact info: Louis B. Cady, M.D. www.cadywellness.com info@cadywellness.com Office: 812-429-0772
  62. 62. Background notions – Greben (appendix) • “The practice of psychotherapy [& medicine!] is, and always will be, in large measure an art” • “Psychotherapy must have a theoretical base…” • “Those elements which are therapeutic in any one form of psychotherapy [or healing encounter with physician – Cady] are likely to be present in any other forms of psychotherapy [encounter] to a significant degree.” “On Being Therapeutic” [Canadian Psychiatric Association Journal. Vol. 22(1977) 371-380.
  63. 63. Greben’s conclusions: • Not learned techniques but reflections of the personality and character and values of the therapist. • “a spectrum exists” • “All can improve through understanding… which increases the likelihood of good therapeutic effect.” All of this is relevant for the astute clinician physician to improve the communication/ relationship with the patient!
  64. 64. 121 children with multiple food allergies studied -44 had immediate reactions -Of this 44, 41 also had delayed reactions -77 children had delayed reactions ONLY -That means 118/121 total children had IgG rxns!
  65. 65. Nutrition and ADHD • “There is increasing evidence that many children with behavioral problems are sensitive to one or more food components that can negatively impact their behavior…In general, diet modification plays a major role in the management of ADHD and should be considered as part of the treatment protocol.” • Schnoll, et al. Appl Psychophysiol Biofeedback. 2003 Mar;28(1):63-75
  66. 66. 236 refs July 2005; 315 refs June 23, 2009 329 refs Aug 17, 2011 390 refs August 30, 2015 August 30, 2015
  67. 67. Fibro, IgG deposits, and "neurogenic inflammation"
  68. 68. Shooting in the dark with milk - 1986... or: "What do you do if you don't have a test?!"
  69. 69. IgG Food Sensitivities - in "IBS" • 100% of twenty IBS patients with confirmed IgG sensitivities treated with elimination diet and rotation had significant improvement – Improvement continued out one year at follow-up. – They had FAILED “standard medical therapies in a tertiary care clinic.” • Drisko et al. Treating irritable bowel syndrome with a food elimination diet followed by food challenge and probiotics. J Am Coll Nutr. 2006 Dec;25(6):514-22 University of Kansas Medical Center – 150 outpatients – different study - “Food elimination based on IgG antibodies may be effective in reducing IBS symptoms and is worthy of further biomedical research.” • Atkinson, et al. Food elimination based on IgG antibodies in IBS: a randomized control trial. Gut. 2004 Oct;53(10):1459-64.
  70. 70. 43 refs July 2005 58 on 6/23/2009 66 on 8/18/2011 83 citations – August 30, 2015
  71. 71. Observant pediatricians and depressed parents – with celiac dz
  72. 72. Corvaglia, et al 1999 • 3 adult patients found with undiagnosed/untreated celiac disease • Found by pediatricians who noted family history when child’s medical history obtained. • Celiac disease diagnosis was MADE in childhood, but diet was stopped due to no more GI symptoms. • In all three patients, depressive symptoms improved with gluten free diet.
  73. 73. Does it have to be celiac/gluten to mess up your head? Answer: NO! -Migraine has high prevalence – 18% -Allergen-specific IgG in serum of patients REFRACTORY TO TRADITIONAL TREATMENT examined. -IgG antibodies obtained to 108 food allergens measured in 56 patients with migraine and a control group. -Statistically significant differences found between migraine group and control group in number of food allergies. -CONCLUSIONS: “ACCORDING TO THE RESULTS OBTAINED, serum IgG Antibodies to common food should be investigated in patients with migraine.”

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