OUTLINE

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OUTLINE

• Case Presentation
• Narrowing differentials
• Short term management
• Long term follow up
• Integrative care
• Psychologic care

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JR

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

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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.

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2. Fatigue

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

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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.

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HISTORY - Mom

• I keep getting told these things are all probably
  normal, so Ive tried not to worry about it, but
  something is not right with him.

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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

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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.

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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)

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Family Hx

• Colonic polyposis colon CA
• -both MGP, PGP
• Dad - heartburn, lactose intol
• Mom - migraines, asthma
• Lots of eczema, psoriasis
• Thyroid CA, hypothyroid.
• Dont know of any autoimmune, bleeding, joint
  dieseases.

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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

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ROS

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

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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.

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PE

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

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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.

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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.

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RECTAL

• ?

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LABS
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LABS

• CBC w/ diff
• CMP
• MONOSPOT
• TSH w/ reflex T4
• ESR
• Rheumatoid / immune survey

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DDx
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Differential

• Anemia
• Mono
• Hyperthyroid
• Lead
• JRA or other autoimmune
• Leukemia
• Celiac
• Other gut

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Anemia

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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)

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Results

• Platelets 616 (400)
• Poly 76
• Lymph 12
• Mono 11
• Eos 1
• Baso 0

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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

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ER

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

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Results

• TP 6.6
• IgG 1670 (700 - 1600)
• IgA 475 (70 - 400)
• IgM 94
• C3 131
• C4 29.5
• Rh F lt11

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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)

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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

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Heme / Onc

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

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GI

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

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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

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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

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Diagnosis

• Suspicion
• Exclusion of others
• Differentiation between UC and Crohns
• Localization of region
• Identify extraintestinal manifestations

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Presenting Symptoms

• Kids under 10
• Abdom pain (95)
• Weight loss (80)
• Diarrhea (77)
• Hematochezia (60)
• Growth Failure (30)
• Extraintestinal (20)

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Growth Failure

• Fall in height percentile gt0.3 sd/year
• Velocity lt 5cm/year
• Decrease in velocity gt 2cm prev yr.
• Worse in Crohns, 50 untreated short stature
• Begin before GI symptoms.

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Growth Failure

• Decreased calorie intake (33) rather than
  decreased absorption
• Pro inflammatory cytokines
• Inflamm stomach, esophagus, duodenum
• Delayed gastric emptying

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Oral

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

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• Hydrocortisone and sulfacrate

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Extraintestinal Manifestations

• Arthritis
• Erythema Nodosum
• Aphthous stomatitis
• Pyoderma gangrenosum
• Noninfectious pneumonia
• Metastatic crohns

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Treatment

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

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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

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Aminosalicylates

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

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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)

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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

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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

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Methotrexate

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

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Antibiotics

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

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Other

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

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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

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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

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• Episcleritis

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• Ant uveitis - injection of the sclera and opacity
  of ant chamber

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Short term follow up

• Weekly until stable, then 1-3 months
• Pediatric Crohns disease activity index
• -abdom pain, stools, activity
• -Hct, ESR, Albumin
• Score inactive, mild, mod - severe
• Clinical response to treatment.
• IMPACT 35

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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

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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

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Vaccines

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

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Psyco Social

• Crohns and Colitis Foundation of America
• www.ccfa.org
• 25 teens w/ mod - severe depression
• Small, delayed puberty, NG tubes, colostomy,
  absent.
• Financial
• Huge consequences.

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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.

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Arthropathy

• Type I - peripheral, acute, lt6 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

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Integrative Approach

• Omega 3 gt 3000mg/day
• -EPA, DHA, other
• -Renew Life, Nordic Naturals
• Anti-Inflammatory Diet
• Probiotics
• gt 20 billion cfus/bid-tid.
• Lactobacillus sp.
• Allergy Testing vs elimination diets.

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• 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-1ALPHA
  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-1ALPHA 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-1ALPHA 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

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Other approaches

• Traditional Chinese Medicine
• Homeopathy
• OMT
• -mitigate complications
• -supports and integrates healing response.
• -help develop trust in bodys ability to heal.

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Take home

• Dont ignore warning signs
• Specialists are not always right
• Follow up
• Continuity of care