OUTLINE

1. OUTLINE Case Presentation Narrowing differentials Short term management Long term follow up Integrative care Psychologic care

2. JR 11 y/o boy with his mom C/o blurry vision, fatique, foot pain.

3. 1. Vision Vision loss R lateral field this am Bruise on eye from hitting himself last week Lasted just under an hour, then resolved completely First time Was rubbing eye just before it happened. Had headache last night.

4. 2. Fatigue Tired a lot Gets through school ok, too tired to play Several months Noticeably worsening over last 1 1/2 weeks

5. 3. Foot pain Feet hurting since June/July, now getting better Woke 1 day w/ sore joints in his feet, was seen here and recommended ice, rest. Sometimes joints in feet feel swollen, especially 1st and 2nd mcp, pip, heal. Never look red/swollen or feel warm. No trouble with any other joints.

6. HISTORY - Mom I keep getting told these things are all probably normal, so I’ve tried not to worry about it, but something is not right with him.

7. HISTORY - chart Different provider each visit since EMR No contact with PCP Comes infrequently Few complaints at WCC Asthma - occasionally uses Xopenex Hit by car as pedestrian - broke jaw Acute sore throat, bronchitis, pneumonia

8. Nate Harmon Considered iron defic anemia 2nd to chronic blood loss - considered GI source. See note 12/21/06. Discussed case with pedi GI - Dr. Inglesia, He was not convinced MCV or anemia due to GI bleed, especially if not active bleeding. CBC and guiac x3 in 8 weeks. If recurrence, refer to pedi GI.

9. Over a year later No more BRBPR Guiac neg. Dropped off stool samples - never heard about results - assumed they were normal. Lead, mono, lyme negative No longer taking iron. Is taking flintstones w/ iron (16mg)

10. Family Hx Colonic polyposis + colon CA -both MGP, PGP Dad - heartburn, lactose intol Mom - migraines, asthma Lots of eczema, psoriasis Thyroid CA, hypothyroid. Don’t know of any autoimmune, bleeding, joint dieseases.

11. ROS No fever/chills/weight loss. Sleeps well. Recent drop in weight on growth curve - not well plotted. Sore throat off/on. Glands often get big, especially around Christmas. No chest pain/pressure, SOB, PND, orthopnea, palpitations. No dib/cough/wheeze other than in hpi

12. ROS Occasional tummy ache in morning. Appetite good. Eats a lot. No diff swallowing/heartburn/nausea/vomitting/constipation/diarrhea/black/red/white bms/hemorroids.

13. ROS No polyuria/polydipsea. Cold a lot when others seem warm. No skin changes/rashes/dryness/hair change or loss. No bumps on leg. No easy bruising / bleeding. No hx clotting abnormalities. No neuro sx. No psych. Outgoing kid. Does well and likes school. Stable mood. MS - foot.

14. PE Pale Slender, not skinny. Very intelligent, answers questions for himself. His mom lets him, filling in details only when necessary

15. HEENT PERRLA, EOMI, AT, Sclera clear, Conjunctiva pale. Fundus normal - no edema/hem. Ears - TMs clear Nasal - mucosa nml, no d/c Oral - mucosa healthy, moist, pink, 2-3 mucosal tags, tonsils mildly edematous and erythematous, no PND, exudate. Mild b/l cla, no thyroid mass/nodules/bruit.

17. H, L, A, E H Rapid at 122, reg, no M/R/C/G C clear Abd - ND, nml BS, soft, nontender, no guard/rebound/masses. Spleen not palp, liver just at costal margin. Ext - No ed/er/cyanosis. +Clubbing. No inguinal LA. 2+ pulses. Skin - no rashes/bruises/petechiae.

18. RECTAL ?

19. LABS

20. LABS CBC w/ diff CMP MONOSPOT TSH w/ reflex T4 ESR Rheumatoid / immune survey

21. DDx

22. Differential Anemia Mono Hyperthyroid Lead JRA or other autoimmune Leukemia Celiac Other gut

23. Anemia

24. Results WBC 14.4 RBC 2.86 (4.5 - 5.3) Hg 4.2 (13-16) Hct 15 (37-49) MCV 52 (78-98) MCH 15 (27-31) MCHC 28 (33-37) RDW 19.8 (11.5 - 14.5)

25. Results Platelets 616 (400) Poly 76% Lymph 12% Mono 11% Eos 1% Baso 0%

26. Results Na 135 K 3.5 Cl 97 (98-112) CO2 26.3 BUN 8 Cr 0.6 TP 7.0 Albumin 2.1 (3.8-5.4) ALT 25 AST 15 Bili 0.1

28. ER Rectal Exam - no fissures/sores, brown, faint heme + Iron Studies Transfused 2uPRBCs Refered to Pedi Heme / Onc

29. Results TP 6.6 IgG 1670 (700 - 1600) IgA 475 (70 - 400) IgM 94 C3 131 C4 29.5 Rh F <11

30. Results ANA Positive ANA Titer 1/160 Pattern nucleolar DNA negative CRP 4.3 (0-0.9) ESR 92 (0-10) Albumin 2.76 (3.5 - 4.8)

31. Results Mono neg TSH 1.64 Lyme neg Iron 4 (35-150) TIBC 280 %sat 1% (15-50) Retic 3.47% (.5 - 1.5) cRetic 1.12%

32. Heme / Onc Chronic GI blood loss most common Wait for colonoscopy Dec platelets secondary to low iron, as WBC okay.

33. GI Crohns Ulcerative Colitis Chronic H. Pylori Frequent NSAID use Celiac Sprue (anemia, guiac +, ESR, mouth ulcers, poor recent weight gain, dec albumin)

34. Endoscopy & Colonoscopy Active esophagitis w/ ulceration Focal active gastritis (- H. Pylori) Nml duodenum (no celiac) Sigmoid w/ active colitis Rectum w/ focal active proctitis But no granulomas

36. Crohns Disease Immune mediated inflammatory disease of any portion of intestinal tract from mouth to anus. -localized to illeum, cecum, colon -30% have upper Incidence 5-10 / 100 000 / year 20 -25% are in kids

37. Diagnosis Suspicion Exclusion of others Differentiation between UC and Crohns Localization of region Identify extraintestinal manifestations

38. Presenting Symptoms Kids under 10 Abdom pain (95%) Weight loss (80%) Diarrhea (77%) Hematochezia (60%) Growth Failure (30%) Extraintestinal (20%)

39. Growth Failure Fall in height percentile >0.3 sd/year Velocity < 5cm/year Decrease in velocity > 2cm prev yr. Worse in Crohns, 50% untreated short stature Begin before GI symptoms.

40. Growth Failure Decreased calorie intake (33%) rather than decreased absorption Pro inflammatory cytokines Inflamm stomach, esophagus, duodenum Delayed gastric emptying

41. Oral May precede GI by years - granulomas on biopsy Mucogingivitis Mucosal tags Deep ulceration Cobblestoning Lip swelling Pyostomatitis

42. Hydrocortisone and sulfacrate

45. Extraintestinal Manifestations Arthritis Erythema Nodosum Aphthous stomatitis Pyoderma gangrenosum Noninfectious pneumonia Metastatic crohns

48. Treatment Location important b/c action of drugs Severity Complications perianal fistula - antibiotic / immunosupp intraabdom - surgery growth failure - steroid sparring

51. Initial Corticosteroids -prednisone -budesonide high 1st pass met - dec systemic sx limited to illeum and ascending colon. -80% in remission in 30 days -30% become steroid dependent Corticosteroids + purine dec steroids, dec relapse, inc comp. Nutritional therapy - elemental (vivonex) or polymeric diet (ensure) 50-80%

52. Aminosalicylates 5-ASA inhibits syn of PG an LT Pentasa and Asacol - small intestine Suppositories - rectum Sulfasalazine, Colazal - colon

53. Thiopurine 6-Mercaptopurine (6 MP) and azathioprine (AZA) Inhibit lymphocyte proliferation by impairing DNA synthesis 70-80% remission in 3-6 mo. Check thiopurine methyltransferase (TPMT activity)

54. Thiopurines SE: myelosuppression, infections, pancreatitis, hepatitis, possibly lymphoma. Monitor CBC, ALT, AST bl, then 2,4,8,12 wks, then q 3 mo or 2-3 weeks after change in dose. 6-thioguanine nucleotide levels

55. Infliximab Monoclonal antibody to TNFa Approved in kids 2006 Refractory to steroids and 6MP Closes perianal fistulas Infusion rxn - 15-35% -pretreat w/ steriods, adalimumab Hepatosplenic T cell lymphoma -demyelinating disease, liver failure, infxn

56. Methotrexate Moderately effective (80,24) SQ to oral Myelosuppression, oral ulcers, infection, pulmonary abnormalities, hepatitis Folic acid 1mg daily. CBC, liver enzymes.

57. Antibiotics Infectious complications Mild active CD Cipro, metronidazole C diff, tendon rupture, metalic taste, peripherial neuropathy.

58. Other Cyclosporine - acute fistulizing dz Thalidomide - inhibit TNF, angiogenesis Tacrolimus Adalimumab - TNF Natalizumab - progressive mulifocal leukoencephalopahy, just reintroduced Mycophenolic acid

59. Surgery Complications 46% req surgery for growth, bowel perf, fistula, hemmorrhage before immunomodulators, 2.8yrs Limited region of disease -rapid improvement 2-5yrs -catch up growth and puberty

60. What about his eyes? Referal to opthalmology Mom missed appt. Took him to corner vision store IOP huge Beginning cataracts from steroids Thick cornea No iritis / uveitis

61. Episcleritis

62. Ant uveitis - injection of the sclera and opacity of ant chamber

63. Short term follow up Weekly until stable, then 1-3 months Pediatric Crohn’s disease activity index -abdom pain, stools, activity -Hct, ESR, Albumin Score inactive, mild, mod - severe Clinical response to treatment. IMPACT 35

64. Nutrition followup Initial, then annual eval of: Folate B12 25-hydroxyvitamin D (30) Iron - H/H and iron studies Zinc, Selenium Calcium (1500mg), Phosphorus Iodine

65. Long term follow up Growth Dexa at time of diagnosis, repeat if long treatment with steroids (30% ki Colonoscopy 8-10 yrs after dx, then every 1-3 yrs Opthalmology at time of dx, then annual. TB test before therapy

66. Vaccines Avoid live vaccines: Polio and Rubella Get Influenza, meningococcus, pneumonia important if immunosuppressed Titers/repeat: Measles and varicella.

67. Psyco Social Crohn’s and Colitis Foundation of America www.ccfa.org 25% teens w/ mod - severe depression Small, delayed puberty, NG tubes, colostomy, absent. Financial Huge consequences.

68. What about his feet? Arthritis associated w/ crohns Hands swollen in the morning - stiff for hour or so. -got better w/ prednisone, now worse as he is weaning. Waiting for Rheumatology consult.

69. Arthropathy Type I - peripheral, acute, <6 joints, assoc w/ flares of bowel disease, self limiting, no deformaties, knee, before bowel sx, 5%. HLA B27 Type II - Polyarticular, mcp, migratory arthritis (50%), active synovitis for months, recur repeatedly independent of bowels, 3-4%, rarely preceeds dx. HLA B-44

70. Integrative Approach Omega 3 > 3000mg/day -EPA, DHA, other -Renew Life, Nordic Naturals Anti-Inflammatory Diet Probiotics > 20 billion cfu’s/bid-tid. Lactobacillus sp. Allergy Testing vs elimination diets.

72. Eicosanoid Major Site(s) of Synthesis Major Biological Activities PGD2 mast cells inhibits platelet and leukocyte aggregation, decreases T-cell proliferation and lymphocyte migration and secretion of IL-1&ALPHA; and IL-2; induces vasodilation and production of cAMP PGE2 kidney, spleen, heart increases vasodilation and cAMP production, enhancement of the effects of bradykinin and histamine, induction of uterine contractions and of platelet aggregation; decreases T-cell proliferation and lymphocyte migration and secretion of IL-1&ALPHA; and IL-2 PGF2a kidney, spleen, heart increases vasoconstriction, bronchoconstriction and smooth muscle contraction PGH2 many sites a short-lived precursor to thromboxanes A2 and B2, induction of platelet aggregation and vasoconstriction PGI2 heart, vascular endothelial cells inhibits platelet and leukocyte aggregation, decreases T-cell proliferation and lymphocyte migration and secretion of IL-1&ALPHA; and IL-2; induces vasodilation and production of cAMP TXA2 platelets induces platelet aggregation, vasoconstriction, lymphocyte proliferation and bronchoconstriction TXB2 platelets induces vasoconstriction LTB4 immune cells* induces leukocyte chemotaxis and aggregation, vascular permeability, T-cell proliferation and secretion of INF-? , IL-1 and IL-2 LTC4 immune cells* component of SRS-A**, induces vasodilation, vascular permeability and bronchoconstriction and secretion of INF-? LTD4 immune cells* predominant component of SRS-A, induces vasodilation, vascular permeability and bronchoconstriction and secretion of INF-? LTE4 mast cells and basophils component of SRS-A**, induces vasodilation and bronchoconstriction * mainly from immune cells, such as monocytes, basophils, alveolar macrophages, neutrophils, eosinophils, mast cells, epithelial cells; ** SRS-A = slow-reactive substance of anaphylaxi

73. Other approaches Traditional Chinese Medicine Homeopathy OMT -mitigate complications -supports and integrates healing response. -help develop trust in body’s ability to heal.

74. Take home Don’t ignore warning signs Specialists are not always right Follow up Continuity of care