Pediatric Chronic Abdominal Pain

John F. Pohl MD Professor of Pediatrics Primary Children’s Medical Center University of Utah Salt Lake City, Utah

Disclosure: INSPPIRE to Study Acute Recurrent and Chronic Pancreatitis in Children, NIH R21 Grant, NIDDK

Learning Objectives

   Understand the physiology and differential diagnosis of chronic abdominal pain in children.

Understand the testing (laboratory, radiographic, endoscopic) available for the treatment of chronic abdominal pain in children.

Understand the treatment options for chronic abdominal pain, including treatment for recurrent abdominal pain of childhood and irritable bowel syndrome.

Somatic Complaints in Our Practice

     IBS Chronic pelvic pain Interstitial cystitis Fibromyalgia Certain headache presentations

38-60% of visits to the primary care office practice!

Kroenke, et al. Am J Med (1989): Only 16% of 1000 general medical outpatients had an organic cause to somatic complaints.

Somatic Complaints in Our Practice

 Just because no organic source for a complaint is found, this does not rule out neurobiological alterations.



Regardless, many of us feel this way:

“A patient has irritable bowel syndrome if your stomach hurts after you leave the patient’s room…”

How Common in Pediatric Abdominal Pain?

    Survey of 500 adolescents in a community clinic.

13-17% experienced weekly abdominal pain 20% of these cases severe enough to affect daily activities.

Need to consider medical, social, cultural, familial, and emotional factors during evaluation.

Thiessen. Recurrent abdominal pain.

PIR

, 2002; Vol. 23: pp. 39-45.

IBS -- History

  

1.

2.

3.

4.

First described by Cummings in 1849 (

London Med Gazette

).

Various terms used: Spastic colon, nervous colon, irritable colon, “colitis” Defined by the Rome criteria:

12

week (or more) history in a pain that cannot be explained by structural / biochemical abnormalities.

12

month period of time of abdominal Pain is relieved with defecation.

Pain is associated with BM frequency change.

Pain is associated with BM form change.

Need 2 of 3 features.

Separate like nuts Sausage shaped but lumpy Like a sausage but with cracks Like a snake, smooth and soft Soft blobs with clear cut edges Fluffy with ragged edges This is the only scale validated for determining

diarrhea

in a toilet (6 or 7)

In children, the presentation of IBS can appear differently AND all functional abdominal pain may not be IBS!

Diagnosis

 History and physical examination are the cornerstone to establishing a clear diagnosis!!!

 Can take at least

1 hour

to completely work-up childhood abdominal pain.

  Therefore, many children are sent to the pediatric gastroenterolgist due to PCP time restraints.

BUT most causes can be determined by the primary care provider.

Diagnosis

Most referrals to the pediatric gastroenterologist: 1.

Symptomatic for 12 months or less.

2.

3.

Multiple diagnostic tests (laboratory and radiographic) have already been performed by PCP.

Large number of negative tests reinforces parental / patient anxiety as to cause of abdominal pain (

Glass-half full vs. Glass-half empty

).

Pathophysiology of IBS…Potential Pathway

Psychosocial factor?

Hypothesis:

Motility Disturbance?

1.

2.

3.

Neurotransmitter imbalance Infection Inflammation

Visceral Hypersensitivity?

Horwitz and Fisher,

NEJM

(2001)

Pathophysiology of IBS…Potential Pathway

Psychosocial factor?

Motility Disturbance?

1.

2.

3.

Neurotransmitter imbalance Infection Inflammation

CNS defect?

MRI / PET changes at thalamus and anterior cingulate cortex Visceral Hypersensitivity?

Rectal balloon distention of IBS patients Horwitz and Fisher,

NEJM

(2001)

CNS Defect Mechanism?

Ascending Aminergic System EMOTIONAL MOTOR SYSTEM

Neuroendocrine Pain Modulation Autonomic

Bowel Motility Alteration?

    Bowel motility is altered with stress.

May increase / decrease colon contraction.

Fasting (anorexia?) 

loss

IBS patients.

of MMC complexes in

Increased

patients.

contraction after high-fat meal in IBS

ARM

ARM

Internal sphincter External sphincter

ARM

ARM

 Visceral Hypersensitivity?

Balloon distention of rectum  IBS patients experience pain with smaller balloon volumes compared to controls.

 1.

2.

WHY? Two ideas: Are the pain receptors in this region “primed” by infection, lumen contents, etc?

Are there inherent pain modulation differences in nociceptor regions in these patients (i.e., genetic predisposition)?

Visceral Hypersensitivity?

Faure and Wieckowska.

J Peds

(2007): Looked at children with IBS, FAP, Functional dyspepsia, and no symptoms.

Noted significantly decreased threshold for pain sensation with polyvinyl bag.

Visceral Hypersensitivity?

P<0.002 compared to controls No difference

Psychosocial factors

   Stress affects bowel motility.

Patients with IBS  disease.

higher rate of psychiatric Childhood history of abuse  symptoms.

↑ severity of IBS  Noxious stimuli after birth (gastric suctioning)?

Anand KJS, Runeson B, Jacobson B. “Gastric Suction at Birth Associated with Long-Term Risk for Functional Intestinal Disorders in Later Life.”

The Journal of Pediatrics

, 2004; Vol. 144, pp. 449-454.

Neurotransmitter Imbalance?

  95% of body serotonin in the GI tract.

Serotonin enhances intestinal secretion, peristalsis (nausea, vomiting, abdominal pain, etc.).

 Other transmitters involved?

Acetylcholine Substance P Nitric oxide Vasoactive intestinal peptide etc…

Anxiety and Sensorimotor Function

  Geeraerts, et al. (

Gastroenterology

2005): Took 14 patients and placed them in an anxious emotional state (anxious face + 10 minute audiotape of stressful event).

 Evaluated gastric sensitivity and accommodation.

Gerrarets, et al. “Influence of Experimentally Induced Anxiety on Gastric Sensorimotor Function in Humans.” Gastro 2005; 129: 1437-1444.

Anxiety and Sensorimotor Function

During anxiety induction:  Gastric compliance was decreased compared to controls.

 Balloon volume to cause gastric discomfort decreased compared to controls.

 Suggests a psychological component for pain.

Gerrarets, et al. “Influence of Experimentally Induced Anxiety on Gastric Sensorimotor Function in Humans.” Gastro 2005; 129: 1437-1444.

Infection / Inflammation?

   Inflammatory mediators  ↑ intestinal motility ?infectious enteritis  ↑ risk of developing IBS Increased risk of IBS in patients with IBD (Crohn’s, Ulcerative colitis).

Infection / Inflammation?

  Mearin ,et al.

Gastroenterology



Shigella enteritidis

persons).

2005; 129: 98-104.

outbreak occurred in Catalonia, Spain (1243 Prospective evaluation of IBS symptoms in these people over time.

Followed for one year (controls vs. infected patients): 1.

2.

3.

Dyspepsia incidence ↑’d in affected patients.

IBS (diarrhea-type) ↑’d in affected patients.

Is this an immune response?

1. Genetic tendency?

2. ↑ IL-1 (pro-inflammatory)?

3.

 IL-10 (antiinflammatory)?

4.

Also, patients who were treated with antibiotics had a higher rate of post infectious IBS… The reason for this is unknown.

Infection / Inflammation?

Do pediatric patients with IBS have specificmicrobiomes?

Ruminococcus-like microbe seen in pediatric patients using metagenomic PhyloChip DNA hybridization Saulnier, et al.

Gastroenterology

2011 Do antibiotics work for IBS (diarrhea type) Example: Rifaximin Krause, et al.

NEJM

2011

Diagnosis of IBS

1.

Rule out the “Red Flags” of the History 2.

Rule out the “Red Flags” of the Physical Exam Thiessen,

Peds in Review

, 2002

Red Flags

during the History

      Pain LOCALIZES away from the umbilicus.

Pain associated with bowel habit changes.

Pain with nighttime wakening.

Repetitive emesis (esp. bloody / bilious) Constitutional symptoms: fever, weight loss Emesis with unusual headaches (occipital) Thiessen,

Peds in Review

, 2002

Where is the Pain?

4 1 7 5 .

2 3 6 1. RUQ 2. Epigastric 3. LUQ 4. RLQ 5. Peri-umbilical 6. LLQ 7. Suprapubic

Where is the Pain?

       RUQ – gallstones, liver disease Epigastric – ulcer, pancreatitis LUQ – renal (UPJ obstruction) RLQ – appendicitis, infectious enteritis Periumbilical – RAP LLQ – constipation, colitis, proctitis Suprapubic – UTI

Red Flags

during the P.E.

       Loss of weight / decreased height velocity Organomegaly / abdominal mass Localized abdominal tenderness away from umbilicus.

Peri-rectal changes Joint swelling or tenderness Unusual rash Pale mucosa / conjunctivae Thiessen,

Peds in Review

, 2002

Pertinent Tests

     

Laboratory tests:

 CBC, ESR Liver panel, GGT Amylase, lipase UA, urine culture  -HCG T4 / TSH Anti-endomysial Antibody  Tissue transglutaminase Antibody (celiac testing)  

Radiographic tests:

 Abdominal flat plate  Abdominal US Abdominal CT UGI ± SBFT

Pertinent Tests

     

Laboratory tests:

 CBC, ESR Liver panel, GGT Amylase, lipase UA, urine culture  -HCG T4 / TSH Anti-endomysial Ab  Tissue transglutaminase Ab  

Radiographic tests:

 Abdominal flat plate  Abdominal US Abdominal CT UGI ± SBFT

ENDOSCOPY WITH BIOPSY?

What other functional abdominal pain disorders exist in children?

+

Functional Pain (“irritable bowel syndrome”)

Keep in Mind:

 In 90-95% of children, no cause for abdominal pain is ever found (

functional pain

).

 Is the pain RAP or IBS?

IBS RAP

Functional Pain (“irritable bowel syndrome”)

   

Is this RAP?

Recurrent abdominal pain

Apley (1958) had 1 st (RAP) description.

  Defined as 3 episodes of pain that interfere with activity in a period ≧ 3 months.

Incidence: 10-15% of children Slightly increased prevalence in girls.

Functional Pain (“irritable bowel syndrome”)

    Study of 1000 school children: RAP: Boys = girls until 9 years of age.

After 9 years of age, girls > boys (1.5 : 1) RAP rare before age 5.

RAP

      No organic cause Usually peri-umbilical Self-limited Rarely related to meals Rarely awakens child from sleep.

“Organicity of pain is inversely proportional to the number of school absences.”

Irritable Bowel Syndrome (IBS)

   1.

2.

3.

4.

5.

6.

RAP may develop into IBS.

Some children develop IBS without RAP.

Criteria for IBS: Abd. pain relieved with defecation.

↑d stooling at onset of pain.

But can see constipation or a “mixed type.”

Alteration of stool form at time of pain Passage of mucus Associated bloating / abdominal distention No pathological cause (pain fiber dysfunction?)

Functional Pain (“irritable bowel syndrome”)

Organic disease (

10-15

%) Psychological Stressors (family, home)

PAIN

Inherent stress of child (controversial) “Functional” pain (no clear cause)

Imaging in IBS

Constipation

Malrotation

Small Bowel Follow Through

Ileal stricture

Ileocecal Thickening Abdominal CT

Peri-Rectal Abscess

Irritable Bowel Syndrome

H. Pylori

Gastritis

Duodenum

Lymphoid aggregate Increased inflammatory cells in crypt region

Shortened villi

Okay, you think the patient has IBS…

  Treatment options: Depends on the type of IBS…

IBS

“Mixed” Diarrhea type Predominantly pain Constipation type

IBS Treatment

Placebo effect:

 Can improve IBS symptoms in 20-50% of IBS patients  Thus, careful clinical trials are needed

Psychotherapy:

 Good for recognizing triggers of IBS.

 Cognitive behavioral therapy, relaxation therapy, hypnotherapy, etc.

 Mainly effects pain and diarrhea, not constipation.

IBS Treatment – Constipation

Fiber supplementation:  Fiber  colonic bacteria utilization gas/fluid  soft and wet stools  increases  End-result: Increases peristalsis and decreases pain of defecation.

# grams of fiber daily = Age + 5 (to max of 20-25 grams daily)

IBS Treatment – Constipation

Osmotic laxatives

– best to use if fiber is not helping or is causing bloating.

 1.

Long-term use of osmotic laxatives are safe.

Milk of Magnesia ™ 2.

3.

4.

Mineral oil (CAREFUL: aspiration pneumonia) Lactulose Miralax ™ (Polyethylene glycol powder 3350) tbsp (17g) in 8 ounces water/juice – One  Can be given as scheduled dosing or prn.

IBS Treatment – Constipation

 Miralax: Pediatric dosing?

 Average long term effective dose (avg. 8.4 months) has been determined to be

0.7 g/kg/day to 1 g/kg/day).

 Biggest issue  Under-dosing or not using long enough.

Pashankar,

et al

. Long-term efficacy of polyethylene glycol 3350 for the treatment of chronic constipation in children with and without encopresis.

Clin Pediatr

2003; 42: 815-819.

Pashanker,

et al

. Efficacy and optimal dose of daily polyethylene glycol 3350 for treatment of constipatoin and encopresis in children.

JPGN

2001; 139: 428 432.

IBS Treatment – Constipation

Stimulants

(senna, bisacodyl)   I rarely use these… Side effects: severe cramping, “dependence”, tachyphylaxis.

 Animal models  possible permanent disruption of enteric nervous system.

Bottom line…stick with osmotic laxatives.

IBS Treatment – Constipation

IBS Treatment – Diarrhea

 

Opiate analogues work great!

 Loperamide controls diarrhea symptoms but does NOT control pain.

 No prescription needed.

Given as scheduled or prn.

Cholestyramine  good for refractory diarrhea Careful of fat-soluble vitamin malabsorption!

 Antibiotics? (metronidazole, rifaximin, gentamicin)

IBS Treatment – Pain

 

Antispasmodics:

 Usually anticholinergic agents.

 Also, can be Ca antagonists.

++ -channel blockers, opiate Good for post-prandial increased contractility.

Studies for these agents show good results (many studies lack blinding and are short duration).

IBS Treatment – Pain

Antispasmodics (Anticholinergics):

 Often given 30 minutes prior to a meal or every 4 hours prn.

 Side effects: 1.

2.

3.

Dry mouth Constipation Blurred vision 4.

5.

6.

Fatigue Urination difficulty Narrow-angle glaucoma and urine retention are contraindications.

Sedative aspects of combining antispasmodics with sedatives or BZDs may decrease anxiety aspects of IBS.

Antispasmodic Agents Single agents:      Belladona Hyoscyamine (Levsin ®) Glycopyrrolate (Robinul ®) Dicyclomine (Bentyl ®) Clidinium Combined agents:  Clidinium + chlordiazepoxide (Librax ®)  Hyoscyamine + atropine + phenobarbital (Donnatal ®)

with unpleasant effects of high-dose anticholinergics.

.

Tricyclic Antidepressants   Ex. Amitriptyline, nortriptyline     Effective at low doses for migraine, neuropathic pain,noncardiac chest pain, IBS.

May ↑ visceral pain threshold Effects takes 1-2 weeks.

.

At low dosing, no anti-depressant effects noted.

Effect may be anticholinergic. Serotonergic effects unknown.

 May work best for diarrhea-predominant IBS.

Tricyclic Antidepressants  1.

2.

3.

4.

5.

 Side effects: Fatigue Somnolence Dry mouth Urinary retention Rare: cardiac arrhythmia, lowered seizure threshold.

Start at low dosing (ex. Amitriptyline 10-20 mg nightly).

I get a baseline EKG.

Selective Serotonin-Reuptake Inhibitors (SSRIs)    Tried for IBS but mixed results.

Treats depression well; minimal effect on visceral pain threshold.

Best case scenario  disorder.

IBS + underlying mood

Serotonin-3-Receptor Antagonists

  Serotonin-3 receptors: ↑ secretion, sensation.

Antagonist  IBS.

Good for intestinal motility,

diarrhea

-predominant

Alosetron (Lotronex ®)

 2 large studies in

ADULT

females: good for diarrhea-predominant IBS at 1 mg bid.

 Side effect: Ischemic colitis (1:700). Removed from market.

 2002: FDA allowed drug back in market with strict guidelines.

Serotonin-4-Receptor Agonists

 Serotonin-4 receptors: Increase peristalsis, increase gastric emptying.

 

Tegaserod (Zelnorm ®)

 3 large

ADULT

studies  effective for constipation-predominant IBS for up to 12 weeks.

2 & 6 mg tabs; 6 mg po bid.

$$$. So, consider laxatives or fiber first.

Other Agents:

 Linaclotide: Activates guanylate cyclase-C (stimulating cGMP production  fluid secretion). Contraindicated in children less than 6 years old (killed mice pups).

 Lubiprostone: Activates chloride channel activation increasing fluid secretion.

Other Agents:  Herbal mixtures (standardized 20+ Chinese herbs)  Slight improvement in pain?

 Peppermint oil: Works as an antispasmodic but also  LES sphincter tone (GERD?)  Leuprolide (gonadotropin-releasing-hormone antagonist): studied for menstrual-related IBS in women.

 Buspirone: Helpful for non-ulcer dyspepsia

Probiotics?

    O’Mahony, et al.,

Gastroenterology

541-551.

  2005; 128: Gave 77 patients (adults) with IBS either

Lactobacillus salivarius

or

Bifidobacterium infantis

.

B. infantis

 improved pain, bloating, dyschezia.

No change in bowel frequency.

IL-10 / IL-12 ratio improved on therapy ( ↑IL-10 protective;  IL-12 protective).

Treatment for IBS?

Data for children?

“Lactobacillus

and

Bifidobacterium

in Irritable Bowel Syndrome Symptom Response and Relationship to Cytokine Profiles”

Gastro

205; 128: 541-551.

Functional Pain (“irritable bowel syndrome”)

Treatment:

 Exercise  Fiber (age + 5 = # of grams daily) IBS w/o change in BMs

1.

Anti-spasmodic 2.

TCA 3.

SSRI

IBS with constipation IBS with diarrhea

2.

1.

Anti-spasmodic / TCA Miralax™ (polyethylene glycol) 4.

3.

Lactulose Tegaserod™ (Zelnorm) 1.

2.

Anti-spasmodic / TCA Loperamide 3.

Antibiotics

Endoscopy?

Cases

1.

2.

3.

5 year old male with 6 week history of peri umbilical pain that does not awaken at night with recent social stress.

19 year old female with 10 year history of constipation, diffuse abdominal pain, worsening now that she lives in a dorm.

17 year old male with abdominal pain in a “band”, diarrhea, and pain relief with defecation.

Cases

1.

2.

3.

Counseling regarding stress, PPI?, antispasmodic, supportive care due to limited nature of disorder. Osmotic laxative, fiber, tegaserod?

Anti-spasmotic, tricyclic, loperamide.

Thank you!