Inflammatory Bowel Disease

Overview

Inflammatory bowel disease (IBD) is a chronic immune-mediated disorder of the digestive tract in which the body inappropriately attacks its intestines. Symptoms vary depending on the location and extent of inflamed bowel but usually include chronic diarrhea that is sometimes bloody, abdominal pain, and weight loss. Extraintestinal conditions may involve the mouth, skin, joints, liver, or eyes. IBD has the potential to affect nutrition, growth, and puberty. This resource provides guidance to primary care clinicians to care for children and teens with IBD.
The term IBD covers 2 disease entities that can have significant clinical overlap: ulcerative colitis (UC), in which inflammation affects mostly the large intestine, and Crohn’s disease (CD), where any portion of the digestive tract from mouth to anus can be affected. Children with IBD who do not fit either category (≈15%) are diagnosed with “indeterminate colitis” or inflammatory bowel disease unclassified type (IBD-U).

Other Names & Coding

Crohn’s disease Indeterminate colitis Regional enteritis Ulcerative colitis

ICD-10 coding

K50, Crohn's disease [regional enteritis]

K51, Ulcerative colitis

K52, Other and unspecified noninfective gastroenteritis and colitis

Multiple digits indicating the primary location of inflammation can be used with codes K50, K51, and K52. See ICD-10 for Noninfective Enteritis and Colitis (icd10data.com) for coding details.

Prevalence

The prevalence of ulcerative colitis and Crohn’s disease in children younger than 20 years is 1:2,326 and 1:3,571, respectively. [Kappelman: 2007] IBD peaks around age 20 and again at age 60; nearly 25% of patients with IBD present before the age of 20. [Wong: 2008] The peak incidence of IBD occurs in patients between 15 and 30 years. [Johnston: 2008]
There is a very early-onset form of IBD (VEO-IBD) in children ≤6 years of age and constituting 4-10% of pediatric IBD, also known as monogenic IBD. [Moran: 2017] Approximately 5-10% of patients develop IBD during childhood or adolescence; the incidence of pediatric IBD appears to be increasing.

Genetics

Though the DNA of patients with IBD has been extensively studied, no causative genes have been found. However, twin studies suggest a genetic component: [Halme: 2006]

In identical twins, 20-50% will both get Crohn’s disease; 15% will both get ulcerative colitis.
In non-identical twins, 5-10% will both get Crohn’s; 5% will both get ulcerative colitis
In non-twin siblings, 5-10% will both get IBD.

Prognosis

The inability to absorb adequate calories and nutrients can lead to malnutrition, growth retardation, abnormal sexual maturation, and vitamin and micronutrient deficiencies. Chronic inflammation leads to anemia and, in Crohn's disease, to abscess, stricture, and fistula formation. Both Crohn’s disease and ulcerative colitis carry an increased risk for colorectal cancers, particularly when disease has been present for many years. Significant limitations in school, sports, and other activities occur with flares or with poorly controlled disease. The social stigma associated with fecal urgency or surgical ostomy can be extreme. Some children develop comorbid anxiety and depression.

Practice Guidelines

Ruemmele FM, Veres G, Kolho KL, Griffiths A, Levine A, Escher JC, Amil Dias J, Barabino A, Braegger CP, Bronsky J, Buderus S, Martín-de-Carpi J, De Ridder L, Fagerberg UL, Hugot JP, Kierkus J, Kolacek S, Koletzko S, Lionetti P, Miele E, Navas López VM, Paerregaard A, Russell RK, Serban DE, Shaoul R, Van Rheenen P, Veereman G, Weiss B, Wilson D, Dignass A, Eliakim A, Winter H, Turner D.
Consensus guidelines of ECCO/ESPGHAN on the medical management of pediatric Crohn's disease.
J Crohns Colitis. 2014;8(10):1179-207. PubMed abstract / Full Text

Critch J, Day AS, Otley A, King-Moore C, Teitelbaum JE, Shashidhar H.
Use of enteral nutrition for the control of intestinal inflammation in pediatric Crohn disease.
J Pediatr Gastroenterol Nutr. 2012;54(2):298-305. PubMed abstract

Roles of the Medical Home

The medical home should:

Monitor for signs of ongoing disease and exacerbation.
Monitor for side effects of medications.
Help ensure adequate catch-up growth.
Monitor for appropriate pubertal development.
Screen for physical findings of vitamin and mineral deficiencies.
Screen for comorbid depression and anxiety.
Evaluate illnesses in patients on immune-modulating medications.
Work with the patient and family to encourage therapeutic compliance.
Perform routine health screening and immunizations.
Assist family in establishing care with a behavioral therapist.
Assist family with eventual transition to adult care.

Ongoing collaboration with pediatric gastroenterology may optimize outcomes for patients. Follow-up with the subspecialist varies from patient to patient and with response to medications but generally occurs every 1–2 months following initial diagnosis and every 6–12 months in patients with remission. Development of a 504 Plan may include immediate/discreet access to a bathroom, stop-the-clock testing, access to healthy snacks and beverages, plans for unintended late arrivals to school, and alternative activities for physical education class. School Accommodations: IEPs & 504s has tips for collaborating with school personnel to help ensure appropriate education-related services.

Clinical Assessment

Pearls & Alerts for Assessment

Most abdominal pain in children is not IBD

The child with gassy abdominal pains and bloating, non-focal or periumbilical pain, no diarrhea, no fecal urgency, no nocturnal stooling, and normal growth is unlikely to have IBD, especially if routine bloodwork, including an inflammatory marker (ESR or CRP), is normal. For patients who present with common symptoms of abdominal pain, the most common diagnoses for these are functional abdominal pain (FAP) or constipation. Most hematochezia in children is from constipation, causing external or internal anal fissure, hemorrhoids, etc. [Tabbers: 2014]

Screening

For the Condition

For patients with clinically concerning symptoms (weight loss, diarrhea, blood in stool), screening is performed with serologic testing: CBC, CMP, CRP, ESR. For diarrhea, a fecal calprotectin may be useful for screening as it is a marker of ongoing inflammation in the intestines. The main utility of this test is to aid in diagnosing and monitoring IBD and differentiating it from functional gastrointestinal disorders (FGIDs). [Koninckx: 2021] A recent study shows that it may not be as sensitive a marker for Crohn’s as for UC. [Degraeuwe: 2015] [Henderson: 2014]
Fecal calprotectin levels are better non-invasive screening markers than serology, such as elevated CRP or ESR, at the time of diagnosis. [Levine: 2014]

Of Family Members

Studies have shown that between 1.5% and 28% of people with IBD have a first-degree relative, such as a parent, child, or sibling, who also has one of the diseases. [Crohn’s: 2021]
The genetic risk is greater with Crohn’s disease than ulcerative colitis.
The risk of Crohn’s disease or ulcerative colitis is substantially higher when both parents have IBD.
There is no official recommendation for screening family members, but clinical suspicion should be increased for IBD if family members develop red flag symptoms as discussed in the history and physical section.

For Complications

Patients with IBD on immunosuppressive medications should have bloodwork monitored by their gastroenterologist no less than every 3 months to look for liver damage, pancreatitis, low white blood cell count, and other complications of immunosuppression, including lymphoma. For dysplasia screening, consider a colonoscopy every 5 years after diagnosis.

Presentations

Presentation depends, in part, upon the location and extent of the inflamed bowel. Inflammation in Crohn’s disease may occur anywhere along the GI tract. Most individuals with Crohn’s disease have inflammation in the distal ileum and cecum (~70%). Ulcerative colitis can have variable severity. By definition, the inflammation in those with ulcerative colitis always involves only the large bowel. Either disorder can have associated extraintestinal symptoms. In both conditions, the inflammation manifests primarily as abdominal pain and diarrhea. For this review, patient presentations will be divided into mild intestinal, moderate/severe intestinal, and primarily extraintestinal patterns.
Mild intestinal presentation: Approximately 60% of children with IBD present, typically in an outpatient setting, with mild colonic and distal small bowel symptoms, chronic diarrhea, cramps, and abdominal pains. Mild blood in the stools is more characteristic of ulcerative colitis, but it can present in ~30% of those with Crohn’s disease. Children with mild presentation have normal vital signs, look well, and have unremarkable physical exams.
Moderate/severe intestinal presentation: Approximately 30% of children with IBD present with moderate or severe colonic and distal small bowel symptoms that may include frequent and/or grossly bloody stools, cramps, fecal urgency, fevers, weight loss, and some degree of general systemic illness. Vital sign instability, dehydration, anemia, or pain not controlled by over-the-counter medications may lead to hospitalization. A distended or tender abdomen, particularly with any signs of peritonitis, requires urgent referral for imaging and evaluation by the most experienced team available—ideally, a tertiary care center with a pediatric surgeon. Complications of IBD, such as perforation, obstructive strictures, and toxic megacolon, are surgical emergencies.
Primarily extraintestinal presentation: About 10-50% of children with IBD present with extracolonic symptoms. The most common is growth failure. IBD deserves consideration in an appropriately aged patient with otherwise idiopathic weight loss meeting malnutrition parameters (low weight for age with or without low height for age, or low weight for height) as well as delayed puberty. A pattern of chronic nausea, vomiting, and anorexia is seen in Crohn’s disease with stomach or proximal small bowel involvement. Some children with Crohn’s disease present with just perianal disease. Additional symptoms may include any combination of fatigue, malaise, oligoarthritis arthritis or arthralgia, recurrent oral aphthous ulceration, erythema nodosum, pyoderma gangrenosum, anemia, hepatitis, and digital clubbing.
Patients with other primary autoimmune disorders such as celiac disease, juvenile inflammatory arthritis, vasculitis, for example, can have an increased lifetime risk of developing IBD as well.

Diagnostic Criteria

Diagnosis is usually made by a pediatric gastroenterologist and pathologist. It is based on endoscopic and histologic data, with a suggestive history and physical exam, and after exclusion of infectious etiology. Definitive diagnosis requires all 3 of the following:

Clinical symptoms (diarrhea, rectal bleeding, abdominal pain, weight loss or growth disturbance, complicated perianal disease, and/or fevers)
Appropriate time course (symptoms on 2 or more occasions separated by at least 8 weeks, or ongoing symptoms for at least 6 weeks)
Objective evidence of inflammation on endoscopy, radiology, and/or histology

Abnormal CBC, CRP, ESR, and albumin can suggest the need for further workup but cannot alone make or exclude the diagnosis (see Laboratory Testing, below). The best radiographic study to support diagnosis is magnetic resonance enterography (MRE) because it provides real-time information on luminal inflammation and peristalsis and can better characterize strictures in addition to detecting bowel wall inflammation with additional benefit of no radiation. If MRE is not available, computed tomography enterography with contrast (CTE) is the next best option to evaluate for bowel wall inflammation. [Minordi: 2021]
Capsule endoscopy, in which the patient swallows a camera pill that can image the entire GI tract, is available at some centers.
Genome-wide association studies (GWAS) can be used to confirm monogenic IBD genes, which can help differentiate other conditions causing IBD-like symptoms in infancy, such as severe combined immunodeficiency (SCID) and immunodysregulation polyendocrinopathy enteropathy X-linked syndrome (IPEX). The large majority of GWAS-associated loci involve non-coding variation, many of which modulate levels of gene expression. [McGovern: 2015] Meta-analyses of (genome-wide) association studies of adolescent and adult-onset IBD identified 163 IBD-associated genetic loci encompassing about 300 potential candidate genes. However, it is very important to consider that these 163 loci individually contribute only a small percentage of the expected heritability in IBD. This suggests that IBD, including Crohn’s disease and ulcerative colitis, can be regarded as a classical polygenic disorder. [Uhlig: 2014]
More discrete laboratory workups (i.e., ANCA and ASCA antibody panels) are used only in select cases to distinguish between ulcerative colitis and Crohn’s disease. They lack sufficient accuracy to belong in the routine diagnostic workup, are quite expensive, and should only be ordered by specialists. [Wong: 2008]

Clinical Classification

Classification of IBD is divided into remission, mild, moderate, and severe disease. For both Crohn’s disease and UC, pediatric activity index scores are calculated using patient’s growth, symptoms, most recent labs: PUCAI, pediatric ulcerative colitis activity index; PCDAI, pediatric Crohn disease activity index.
PUCAI scores are interpreted as follows:

0 to 9 – Remission
10 to 34 – Mild disease
35 to 64 – Moderate disease
65 to 85 – Severe disease

PCDAI scores are interpreted as follows:

0 to 10 -- inactive disease
11 to 30 --mild disease activity
>30 -- moderate to severe disease activity.

A decrease in PCDAI of ≥12.5 points reflects a clinical response (improvement from moderate/severe to mild/inactive disease).

Differential Diagnosis

Acute symptoms: Infection is the primary alternative diagnosis, particularly when symptoms present acutely in an otherwise healthy child who has no growth disturbance. Since IBD and acute infection cannot be distinguished by clinical criteria alone, stool studies should be performed to rule out infection prior to initiation of immunosuppressive medications or further (and more expensive) workups.

Alternative considerations: Bacteria (Clostridium difficile, Salmonella, Shigella, Campylobacter, Yersinia, Aeromonas, Enterohemorrhagic E. coli, and Aeromonas) and protozoa (including Entamoeba histolytica, Blastocystis hominis, Cryptosporidium, and Giardia species), which can present similarly to IBD

Abdominal pain: Recurrent or chronic abdominal pain is common in school-age children; non-organic causes predominate and include the spectrum of functional abdominal pain disorders. IBD almost never presents as pain without diarrhea or growth failure. The child with gassy abdominal pains and bloating, or with primarily periumbilical pain, who has no diarrhea, no fecal urgency, and normal growth is unlikely to have IBD. A normal CBC, CRP, ESR, CMP, and low to normal fecal calprotectin for an otherwise well child with chronic abdominal pain nearly always excludes IBD.

Alternative considerations: Irritable bowel syndrome, constipation, H. pylori infection, abdominal migraine, and celiac sprue

Rectal bleeding: Chronic constipation is a likely source of mild intermittent rectal bleeding. Hematochezia or melena can arise from intestinal polyps or a Meckel diverticulum; this is usually painless bleeding. Henoch-Schonlein purpura and hemolytic uremic syndrome can cause cramping, abdominal pain, and blood in the stool. Most often, though, it is acute in onset and has other features atypical of IBD. Intestinal lymphoma in its earlier stages may mimic IBD.
Growth failure: Although unusual, the first presentation of IBD may be growth failure alone. The differential diagnosis for a child presenting primarily with poor growth is quite broad.

Alternative considerations: Celiac disease, thyroid dysfunction, cystic fibrosis, giardia infection, anorexia or other eating disorders, adrenal insufficiency, chronic kidney disease, and malignancy can manifest in this way.

Medical Conditions Causing Inflammatory Bowel Disease

IBD that becomes symptomatic or is diagnosed before 6 years of age is termed "very early-onset IBD" (VEO-IBD). Compared with children whose IBD develops later in life, those with VEO-IBD, and particularly those with onset before 2 years of age (sometimes termed "infantile IBD") are more likely to have single gene defects that alter immune function or disturb epithelial barrier function, and they often have a more severe disease course. The disorders include defects in interleukin-10 (IL-10) signaling and can be seen in additional immunodysregulation conditions, such as atypical severe combined immunodeficiency, common variable immunodeficiency, chronic granulomatous disease and other neutrophil defects, Wiskott-Aldrich syndrome, agammaglobulinemia, hyperimmunoglobulin M syndrome, familial hemophagocytic lymphohistiocytosis, and IPEX (immune dysregulation, polyendocrinopathy, enteropathy, X-linked) or other autoimmune enteropathy. [Uhlig: 2014]
Case reports describe apparent ulcerative colitis presenting in infants with genetic mutations of familial Mediterranean fever. [Sari: 2008] Presenting symptoms include bloody diarrhea, failure to thrive, anemia, and leukocytosis. These reports and epidemiologic studies in populations of adults suggest that the genes responsible for familial Mediterranean fever may have a disease-modifying effect on IBD. [Cattan: 2000]

Comorbid & Secondary Conditions

One of the most common extraintestinal manifestations with IBD is musculoskeletal conditions, particularly juvenile arthritis or polyarticular arthritis. These can occur in up to 40-50% of patients with IBD and can often signal an intestinal flare or poor medication response; they sometimes occur as a separate condition even in the presence of intestinal remission. [Malik: 2021] [Levine: 2011] Sacroileitis is present in up to 25% of patients with IBD, particularly those with HLA-B27 positivity.
Hepatobiliary disease can occur in up to 50% of patients with IBD. The most common of these is primary sclerosing cholangitis and conditions that cause liver inflammation and biliary tract fibrosis and scarring. Studies have shown this occurs in >10% of pediatric patients with ulcerative colitis. [Deneau: 2013]
Patients with IBD, particularly UC, can develop primary sclerosing cholangitis (PSC) and are at risk for developing cirrhosis and end-stage liver disease. PSC children have high rates of autoimmune hepatitis. Patients with PSC have higher rates of liver and colon cancer. [Deneau: 2017] For liver cancer, screening with annual CA 19-9 at age 18 and US is recommended.
Other less common secondary conditions (<15%) include cutaneous, ocular as well as vascular inflammatory conditions. Practitioners should have a low threshold for monitoring and screening for any systemic condition in patients with IBD.
Patients on anti-TNF alpha biologics (infliximab, adalimumab) can also have medication-induced autoimmune conditions or complications such as vasculitis, peripheral neuropathy, psoriasis, and temporary joint pains. Many patients have to discontinue medication use due to these conditions, even if their intestines are in remission.

History & Examination

A full history should include detailed questioning about the onset of symptoms, recent travel, food intolerances, medication (including antibiotics and non-steroidal anti-inflammatory drugs), and history of appendectomy. Particular attention should be paid to well-proven risk factors, including smoking, family history, and recent infectious gastroenteritis.
Diagnosis usually occurs between the ages of 10–20 years (less likely below age 10; rarely occurs below age 5). These symptoms should particularly prompt consideration of IBD:

Daily diarrhea
Nighttime stooling
Fecal urgency or tenesmus
Persistent bloody stools
Poor weight gain or linear growth failure
Right lower quadrant tenderness on exam
Perianal skin tags, fistulae
Rapid weight loss with diarrhea

Current & Past Medical History

Current and past history:

Fecal urgency, especially if child wakes from sleep to have an urgent bowel movement
Blood or mucus in stools (after constipation has been excluded)
Growth disturbance
Pubertal delay
Fevers, anorexia, malaise, fatigue (signs of systemic inflammation)
Recurrent oral or genital ulcerations (extraintestinal manifestations)
Arthritis, especially oligoarticular, large joint, and primarily early-morning (extraintestinal manifestations)
Rashes (pyoderma gangrenosum or erythema nodosum)
Eye inflammation (anterior uveitis)

Ask about any side effects of medications. Risk factors for developing IBD may include a history of too many antibiotic prescriptions in youth, whether a patient was delivered via cesarean or vaginal method, chemicals and additives to foods, and the types of bacteria inside the gut.

Family History

Ask about family history; affected relatives increase the likelihood of IBD.

Pregnancy/Perinatal History

The risks of IBD to pregnancy are significant and manifold, including miscarriage, delivery of a small-for-gestational-age infant, premature delivery, poor maternal weight gain, and complications of labor and delivery (e.g., preeclampsia, placental abruption, increased probability of cesarean delivery). [Mahadevan: 2019]
Ideally, a pregnant patient with IBD is monitored by both a gastroenterologist specializing in IBD and an MFM specialist with assistance from nutritionists, lactation counselors, and colorectal surgeons, as needed.

Developmental & Educational Progress

Monitor school progress, which may reflect symptom control—those who miss more than a little school due to exacerbations may have difficulty keeping up. Behavior problems may reflect depression or problems with peers (perhaps due to symptom manifestations at school). Many patients report experiencing “brain fog” or fatigue prior to diagnosis, as they have a high-calorie demand to keep up with ongoing intestinal inflammation. Therefore, an unexpected decrease in grades or poor school performance may be a sign of new-onset IBD.

Maturationalprogress

Delayed pubertal development and/or primary amenorrhea can result from chronic inflammation.

Social & Family Functioning

Ask about support from family members. Establishing care with a behavioral health specialist is encouraged as a chronic illness diagnosis can lead to adjustment disorder, anxiety, depressive episode, or evolve into long-term depression for some patients.

Physical Exam

General

Monitor for fecal urgency, nighttime stooling, abnormal stools (loose consistently / bloody), fevers, malaise, fatigue, oral or genital ulcers, symptoms of arthritis, and rashes.

Vital Signs

Monitor BP in children on steroids.

Growth Parameters

Monitor height, weight, and weight for height or BMI: Low weight for age, with or without low height for age, or a low weight for height may reflect growth failure caused by IBD. Chart height, weight, and weight for height or BMI every 6 months. Watch for excessive weight gain in children taking steroids. Delayed pubertal development may reflect nutritional deficiency or chronic inflammation.

Skin

Check for deep ulcerative lesions (pyoderma gangrenosum) or erythema and subcutaneous nodularity, often most prominent on the pretibial area (erythema nodosum). Also, check for striae if taking steroids.

HEENT/Oral

Check mouth/oropharynx for ulcerations, suggesting Crohn's disease; cracked lips; beefy macroglossia, suggesting vitamin/mineral deficiency associated with malnutrition; and tooth enamel erosion, suggesting self-induced vomiting that might be seen in anorexia nervosa or another condition. Pale conjunctivae may reflect anemia.
Ocular manifestations can include episcleritis (inflammation of the blood-rich episclera), scleritis, uveitis, and conjunctivitis. Patients should see an ophthalmologist annually for an eye examination.

Chest

Subclinical disturbances in lung function are common in IBD patients. Clinically significant disease is extremely rare. Pulmonary granulomas are often seen as incidental findings with chest imaging. Some granulomas can cause chronic cough in IBD patients. Chronic bronchitis, subglottic stenosis, bronchiectasis, and bronchiolitis have all been reported in association with IBD. [Levine: 2011]

Heart

New systolic murmurs may reflect anemia.

Abdomen

Expect a normal exam with mild disease. RLQ tenderness can be a specific feature of Crohn’s disease with proximal colon or terminal ileum involvement. LLQ pain is a more likely feature of ulcerative colitis due to rectosigmoid inflammation, often associated with constipation. Isolated epigastric pain in Crohn’s disease is rare. RUQ pain is also unlikely in IBD and may be suggestive of gallbladder disease or functional dyspepsia. Peritoneal signs can be suggestive of severe disease and complication, such as perforation.
Anal skin tags (especially off the sagittal plane), fissures, fistulae, ulcers, or generalized inflammation suggests Crohn’s disease. Visual inspection of the anus is frequently skipped, but it is critical to perform; 1:4 patients with Crohn’s disease has rectal involvement that may be isolated or an initial manifestation of more diffuse disease. Abdominal tenderness may reflect active disease.

Extremities/Musculoskeletal

Musculoskeletal pain can occur in more than 50% of IBD patients and is considered the most common extraintestinal manifestation. [Levine: 2011] [Malik: 2021] Associated findings include clubbing (suggesting chronic inflammation), arthritis (oligoarticular, large joint, non-erosive), brittle nails or spoon nails (suggesting vitamin/mineral deficiency associated with malnutrition), and finger ulcerations (suggesting self-induced vomiting, which may be seen in individuals with anorexia nervosa). Miscellaneous manifestations are osteoporosis, aseptic necrosis, polymyositis, and periostitis.

Neurologic Exam

IBD with neurologic and neuromuscular involvement is rare and often controversial. Thrombotic complications are common in IBD patients, but cerebral vascular involvement is rare. Peripheral neuropathy (PN) is one of the most frequently reported neurological complications in IBD patients. Drug-induced neuropathy has been ascribed to several medications commonly used to treat IBD, including cyclosporine A, metronidazole, sulfasalazine, Infliximab, and adalimumab.

Testing

Endoscopic evaluation
Intestinal biopsies or tissue samples are the gold standard for diagnosing inflammatory bowel conditions. With clinical and laboratory suspicion per below, typically patients should undergo upper endoscopy (esophagogastroduodenoscopy) and colonoscopy as soon as possible. Histology of the tissue is then analyzed by a pathologist. Findings of granulomas in the tissue, which are a chronic remodeling of the intestinal tissue, are indicative of Crohn disease. Patients with Crohn disease often have areas of normal colonic appearance with “skip” areas of inflamed tissue, whereas ulcerative colitis often has pancolitis—meaning contiguous inflammation from rectum to cecum. During endoscopy, severity of colitis can be characterized using the Mayo scores for visual grading of mucosa. Mayo 0-1 describes mild appearance to colonic surface, with a Mayo 3 score describing the most severe mucosal breakdown.

Laboratory Testing

Exclusion of infectious etiology is the first step in the workup for any patient with prolonged diarrhea. GI PCR film array including Clostridium difficile toxin assay, routine stool culture, and a microscopic examination for ova and parasites are generally sufficient in covering the most common organisms with presentations similar to IBD. More cultures may be indicated if there is supportive history.
In children with IBD, hemoglobin and ESR and CRP are the most likely routine blood tests to be abnormal. Elevated white count, and high or low platelets, can be seen. Serum albumin (half-life is about 3 weeks) may be low as a result of prolonged protein-losing enteropathy. A subset of patients with mild to moderate IBD will have normal labs.
Fecal calprotectin has adequate sensitivity and specificity to identify those patients most likely to have organic bowel disease and can help differentiate IBD from functional disease, such as irritable bowel syndrome (IBS). [Walsham: 2016] Recent studies show this test may have less sensitivity in Crohn’s disease than in UC. [Quail: 2009]
Current serologies such as the Prometheus IBD-7 panel lack the sensitivity and specificity to make them useful to distinguish between IBD and other disorders. Antibody panels such as ANCA/ASCA are expensive, lack sufficient positive and negative predictive value, and are not recommended.

Imaging

Imaging of the small bowel may identify lesions suggestive of Crohn's disease. The best radiographic studies are magnetic resonance enterography or CT enterography, which requires NJ tube placement for contrast infusion directly into the small bowel. Magnetic resonance enterography (MRE) is an MRI of the small bowel. It is preferred over CT enterography because there is no radiation exposure to the pediatric patient, and MRE provides real-time visualization of peristalsis, which helps evaluate for possible strictures. Capsule endoscopy, in which the patient swallows a camera pill that can image the GI tract not able to be directly visualized via endoscopy, is available at some centers.

Genetic Testing

Next-generation DNA-sequencing technologies are available to diagnose monogenic causes of IBD. Routine genetic screening is not recommended for all IBD patients. Genetic testing should be considered depending on age of IBD-onset (infantile IBD, very early-onset IBD, pediatric or young adult IBD), and further criteria, such as family history, relevant comorbidities, and extraintestinal manifestations. Genetic testing is also recommended in advance of hematopoietic stem cell transplantation. [Uhlig: 2021]

Other Testing

Antibody testing has limited utility for discriminating between ulcerative colitis and Crohn's disease, and practice guidelines for children and adults are equivocal regarding its use. [Bousvaros: 2007] The most common antibody tests are perinuclear antineutrophil cytoplasmic antibodies (P-ANCA) and anti-saccharomyces cerevisiae antibodies (ASCA). When combined into panels, the antibody tests have reasonably high sensitivities for detecting IBD (>90 percent in populations with symptoms), but their ability to distinguish between ulcerative colitis and Crohn’s disease is not well validated. Thus, antibody testing for IBD does not generally contribute useful information to management decisions.
The anti-OmpC antibody has been identified as a potential serologic marker of IBD. In a study of 198 children, anti-OmpC was detected in 25 percent of patients with Crohn's disease, 11 percent of patients with UC, and 5 percent of controls. Because anti-OmpC was positive in nine children with IBD who were not detected by ASCA (IgA and IgG) or P-ANCA, the addition of anti-OmpC to these antibody assays increased the sensitivity from 63 to 70 percent but decreased the specificity from 97 to 94 percent. [Zholudev: 2004]
Antibodies to the bacterial flagellin CBir1 are found in approximately 50 percent of individuals with Crohn’s disease and have been associated with small bowel, internal-penetrating, and fibrostenosing patterns. [Papadakis: 2007]

Specialty Collaborations & Other Services

Pediatric Gastroenterology (see RI providers [18])

Refer to confirm the diagnosis and to assist with management.

Dieticians and Nutritionists (see RI providers [3])

Periodic visits may help with surveillance and prevention of nutritional deficiencies.

Pediatric Ophthalmology (see RI providers [8])

Refer for annual eye examinations to evaluate for ocular extraintestinal manifestations.

Developmental - Behavioral Pediatrics (see RI providers [12])

Periodic visits help with developing coping skills dealing with the seriousness of diagnosis, potential for lifelong flares, and adherence to medications. It is recommended that adolescents with IBD ages 12 and older be screened for depression annually. [Mackner: 2020]

Pediatric Dentistry (see RI providers [41])

Refer patients to a pediatric dentist or dentistry group who is comfortable taking care of children for dental checkups every 6 months as bone mineral density is often low in patients with IBD.

Treatment & Management

Pearls & Alerts for Treatment & Management

Test for tuberculosis before use of biologic agents

Children should be tested for tuberculosis prior to receiving biologic agents (Infliximab and adalimumab monoclonal antibodies), and they should be monitored for opportunistic infections.

Live virus vaccinations

Patients with IBD on immunosuppressive medications are considered to have secondary immunodeficiency due to treatments that can include human immune mediators like interleukins and colony-stimulating factors, immune modulators, and medicines like tumor necrosis factor-alpha inhibitors and anti-B cell agents. The CDC recommends that non-live and live vaccines be administered 2 or more weeks before initiating such therapies. Live vaccines should be withheld 3 months following such therapies, and both non-live and live vaccines should be withheld at least 6 months following therapy with anti-B cell agents. Risks and benefits should always be discussed with families of patients on immunosuppression therapy prior to administration of live vaccines, especially in the context of possible travel outside the United States.

Pneumonia vaccination

Children with IBD should be immunized with 2 doses of pneumococcal polysaccharide vaccine (PPSV23) in addition to pneumococcal conjugate vaccine (PCV13). [Centers: 2022]

COVID-19 vaccination

The COVID vaccinations are safe and effective for patients with IBD, and patients should follow CDC guidelines on immunization booster schedule for immunosuppressed individuals, as their antibody response to vaccines may be altered by their medications.

Surgical emergencies

Complications of IBD, such as perforation, obstructive strictures, and toxic megacolon, are surgical emergencies.

How should common problems be managed differently in children with Inflammatory Bowel Disease ?

Growth or Weight Gain

Growth failure (subnormal gains in height or weight, or weight loss) and/or delayed puberty are common, especially in those with Crohn's disease. Nonetheless, a substantial number of children are overweight when they present with IBD because overweight and obesity are common in most populations.
Malabsorption is common in IBD, making it difficult to absorb necessary nutrients in the small intestine, such as proteins, fats, sugars, vitamins, and minerals. It can be caused by inflammation in the intestines. The degree of malabsorption depends on how much of the small intestine is affected. Malabsorption and nutrient deficiencies are often more significant if larger sections of the small intestine are inflamed or have been surgically removed. If a significant portion of the ileum or the terminal ileum / ileo-cecal valve is inflamed or removed, the absorption of fat-soluble vitamins A, D, E, K, and B12 will likely be affected. [Crohn’s: 2021]
Therefore, some patients may require both enteral nutrition via a nasogastric (NG) or nasojejunal (NJ) tube and parenteral nutrition at onset of diagnosis or during flares.
Common supplements recommended for IBD patients are a multivitamin that contains calcium, folic acid, iron, zinc, B12, fat-soluble vitamins A, D, E, K.
Patients with ulcerative colitis may have less significant nutrient deficiencies, though severe diarrhea and blood loss can cause weight loss.
A known risk for reduced height in IBD patients includes exposure to 3 months or greater of corticosteroids before puberty. [Wyllie: 2006]
It is encouraged that families have the support of a registered dietician to help with growth and weight gain.

Development (Cognitive, Motor, Language, Social-Emotional)

Studies on development outcomes of patients with IBD are limited. One study compared a Danish population of children exposed to IBD in utero to an unexposed population. At 18 months, exposed children were significantly less likely to "use word-like sounds," but there was no difference between the use of "sentences of 2 words." At 6 and 18 months, there were no other obvious differences in language and motor development. At 7 years, cognitive scores (emotional, conduct, hyperactivity, peer and social scores) and motor development (gross/fine motor skills and general coordination) were similar between the 2 groups. [Friedman: 2020]

Viral Infections

Most cases of viral respiratory and gastrointestinal infections pass normally in children with IBD, even in patients on immunosuppressive medications. Yet, care must be taken with chickenpox or zoster rash exposures in patients on biologic medications: some patients require prophylactic antiviral medicines. Care must also be taken with EBV (mono) infections, which can evolve into serious systemic inflammatory responses in the spectrum of hemophagocytic lymphohistiocytosis.
Gastroenterology should be contacted immediately for exposure to a virus, and patients on immunosuppression should be treated with antivirals for documented positive tests of influenza viruses.

Bacterial Infections

Patients on immunosuppression who develop a chronic cough should be worked up for tuberculosis, histoplasmosis, coccidiomycosis, and blastomycosis, depending on exposure history.

Over the Counter Medications

There is mixed evidence that non-steroidal anti-inflammatory medicines (NSAIDs) like ibuprofen (Advil, Motrin) should be avoided in people with IBD since they may cause disease flares or worsen bleeding symptoms.
Patients with IBD also have an increased incidence of inflammatory bowel syndrome (IBS) symptoms. Many of these patients can treat their dyspepsia or IBS with peppermint oil or ginger extract capsules, stool softeners, and probiotic supplements, for example.

Prescription Medications

Some IBD patients can develop IBS like symptoms, including abdominal pain and nausea, and may benefit from the prescribed medications below:

Hyoscyamine (Levsin)—0.125 – 0.25mg up to 4 times per day as needed for abdominal pain symptoms
Cyproheptadine—for morning nausea and appetite stimulation. Can cause or worsen constipation as a side effect

Common Complaints

Gastrointestinal symptoms—Loose stools or bloody diarrhea, abdominal pain, or cramping
Systemic symptoms—Fatigue is common at presentation and during flares of disease
Extraintestinal manifestations—Oral ulcerations (aphthous stomatitis), swollen digits (clubbing), rash (erythema nodosum or pyoderma gangrenosum), eye pain due to eye inflammation (uveitis), yellowing eyes or skin (jaundice), joint pain in one or multiple joints (arthritis)

Systems

Gastro-Intestinal & Bowel Function

Therapy goals are to induce and then maintain disease remission. The aim is to decrease inflammation (and thus decrease frequency of stooling, pain, and hematochezia), restore adequate nutrition, and avoid need for long-term corticosteroids. This is done with a combination of nutritional regimens, therapies (amino salicylates, antibiotics, and probiotics), and immuno-suppression using corticosteroids, azathioprine, or biologic agents. Various formulations of medication target different locations of inflammation in the bowel; delayed-release capsules deliver topical steroid to the distal small bowel, and enemas or suppositories are for rectal inflammation. Attempt to wean from steroids or immuno-suppressives when disease severity permits.
Specific Therapies

Biologic agents: Several monoclonal antibody medicines are directed against tumor necrosis factor-alpha and are used in moderate and severe disease that is refractory to other medications. These agents are associated with an increased risk for lymphoproliferative disorders and opportunistic infections. All patients need screening for tuberculosis prior to initiation of therapy. Biologic agents are currently the most effective medicines for top-down therapy for all types of IBD; the trend in treating IBD is to get patients who are not in remission with other therapies onto biologic medicines as soon as possible.
Aminosalicylates: Sulfasalazine and mesalamine are not systemically absorbed and, when taken orally or rectally, provide topical anti-inflammatory effects at the site of diseased bowel. They can induce remission in mild-moderate UC. Sulfa products may cause dose-dependent adverse reactions, but non-sulfa alternatives are much more expensive. Sulfasalazine is the only 5-ASA product that is available as a suspension.
Antibiotics: Ciprofloxacin and/or metronidazole are effective primarily in Crohn’s disease, especially with perianal involvement. In addition to eliminating some bacteria to which the intestinal immune system is inappropriately responding, they may have anti-inflammatory and antioxidant properties.
Corticosteroids provide potent and quick systemic anti-inflammatory effects. They can induce remission or treat flares in moderate or severe IBD, though at the cost of various sequelae of long-term use (Cushing syndrome, hypertension, osteopenia, growth failure). Steroids are not a long-term solution for IBD. Patients “stuck” on daily doses of steroids or who require more than one prolonged taper of steroids should be stepped up to a stronger class of immunosuppression.
Probiotics: Specific combinations of multiple intraluminal bacterial strains that assist the intestinal microbiome may be effective in helping to induce remission in those with UC, but they are not effective monotherapy. They are available online without a prescription but typically expensive ($150-$300 monthly, depending on dose).
Thiopurine antagonists: These immunosuppressants are useful in combination with steroids to induce remission and then as monotherapy after steroid taper. Patients are followed for bone marrow suppression and hepatotoxicity. Idiosyncratic pancreatitis can occur.
New agents: The introduction of anti-TNFs to the therapeutic landscape of IBD has resulted in improved patient outcomes on multiple fronts. However, a significant proportion of patients will have nonresponse, loss of response, or intolerance to this class of drugs, and there is a need for safe and effective alternatives for disease management. Mesenchymal stem cell therapy, JAK/STAT inhibitors are therapies being explored.

Specialty Collaborations & Other Services

Pediatric Gastroenterology (see RI providers [18])

Timing of visits will depend on disease severity and may be needed every 1–2 months while starting therapy, decreasing to every 6–12 months for children in remission.

Surgery

As a last resort, surgery to remove diseased portions of the bowel is an option. There are few randomized, controlled trials of medical or surgical therapies in the pediatric population, and much of what is done in children is extrapolated from the adult literature. Removal of the entire colon can control symptoms of ulcerative colitis and is indicated in refractory disease or disease with complications like uncontrolled hemorrhage. However, it leaves the patient with an ileostomy (with consequent care and lifestyle changes) or an internal ileal pouch with anal anastomosis (that still often requires the patient to stool 5–7 times a day, or more). Many patients eventually elect to have surgery as the risk of colon cancer increases the longer the disease has been present. Surgery is not curative for Crohn’s disease since any portion of the GI tract can be involved. Which children will need surgery is not well understood. Previous studies have shown that approximately half of Crohn’s disease patients will require a surgical procedure at some point for complications like abscess, fistula, or occasionally for intractable symptoms originating from a specific bowel segment, but a recent study suggests the risk is about 20%. [Schaefer: 2010] Early and aggressive use of biologic agents may be altering the natural history of IBD, allowing more patients to go without surgeries.

Specialty Collaborations & Other Services

Pediatric General Surgery (see RI providers [4])

Referral may be necessary if there is an insufficient response to medical therapy.

Nutrition/Growth/Bone

Nutritional support helps prevent and correct malnutrition, promote growth and development, including pubertal development, and prevent osteoporosis, which is especially important in children who are frequently on steroids. Although nutritional deficits are often observed in children with IBD, those with Crohn’s disease are at greater risk for nutritional deficiencies. [El-Matary: 2010] Osteoporosis,iron deficiency anemia, and vitamin D, folic acid, vitamin B12, and micronutrient deficiency are common problems. Bone mineral density is often low. Because children with IBD may be underweight or overweight, it is important that weight alone is not the primary factor used to determine nutritional adequacy. [Wiskin: 2010] [Conklin: 2010]

Specialty Collaborations & Other Services

Dieticians and Nutritionists (see RI providers [3])

Routine visits may help prevent nutritional deficiencies in at-risk children.

Mental Health/Behavior

Children and adolescents with IBD may experience anxiety and depression due to chronic symptoms. The medical home clinician should monitor mental health during well-child and acute-care visits. Noncompliance with chronic medications may be a problem for adolescents with IBD and should be considered a potential explanation for renewed symptoms. [Schurman: 2010] Cognitive therapy, relaxation techniques, and adequate support in school, especially when there are frequent absences, can be helpful. [Szigethy: 2010]

Specialty Collaborations & Other Services

Developmental - Behavioral Pediatrics (see RI providers [12])

Counseling or other behavioral health interventions such as mindfulness training and biofeedback can help children and teens deal more effectively with the issues of living with a chronic disease.

Complementary & Alternative Medicine

Exclusive enteral nutrition (EEN) has been shown to be more effective than corticosteroids in achieving mucosal healing in children with Crohn´s disease without the adverse effects of these drugs. [Moriczi: 2020]
Some therapies are useful to help manage symptoms, but at this stage in the knowledge of the complex immune system defects in IBD, they have no role in the main management of the disease. Complementary and alternative therapies targeted at general well-being, stress relief, anxiety reduction, and pain control might benefit any patient with chronic illness. There is no contraindication to trying breathing exercises, biofeedback, acupuncture, or aromatherapy. Peppermint oil supplements may help nausea. As with all conditions, it is best to ask about complementary therapy attempts, especially prior to their initiation. To learn more about what alternative therapies patients may be trying, see Integrative Medicine for CYSHCN.

Ask the Specialist

Can NSAIDs be used in IBD patients?

Regular (≥ 5 times/monthly) NSAID and acetaminophen use were associated with active Crohn's disease, but not UC. Less frequent NSAID use was not associated with active Crohn’s disease or UC. These findings indicate that regular NSAID use may increase Crohn’s disease activity or that NSAID use may be a marker of a less robust remission, thus reflecting subclinical disease activity.

Which vaccinations are contraindicated in IBD patients?

Live virus vaccines cannot be given during or within 8 weeks of starting immunosuppression with Humira (adalimumab) or Remicade (infliximab). These include nasal spray forms of the influenza vaccine, varicella, and MMR. Other vaccines on the standard immunization schedule can be safely administered at any time.

How do I manage a fever in an immunosuppressed patient?

Subacute fevers associated with symptoms of a viral upper respiratory infection, gastroenteritis, or a general viral syndrome are generally benign and do not need extensive workup. Fevers lasting longer than 5-7 days, especially those associated with chronic cough, bone pain, or chickenpox, and especially in patients on biologic agents, should be evaluated semi-urgently by the patient's gastroenterologist to exclude opportunistic infection or malignancy.

Resources for Clinicians

On the Web

Inflammatory Bowel Disease (OMIM)
Extensive review of literature that provides technical information on genetic disorders; Online Mendelian Inheritance in Man site, hosted by Johns Hopkins University.

Helpful Articles

PubMed search for inflammatory bowel diseases in children, last 2 years.

Leung Y, Heyman MB, Mahadevan U.
Transitioning the adolescent inflammatory bowel disease patient: guidelines for the adult and pediatric gastroenterologist.
Inflamm Bowel Dis. 2011;17(10):2169-73. PubMed abstract / Full Text

Fell JM.
Update of the management of inflammatory bowel disease.
Arch Dis Child. 2012;97(1):78-83. PubMed abstract / Full Text

Hommel KA, Greenley RN, Maddux MH, Gray WN, Mackner LM.
Self-management in pediatric inflammatory bowel disease: A clinical report of the North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition.
J Pediatr Gastroenterol Nutr. 2013;57(2):250-7. PubMed abstract / Full Text

Clinical Tools

Letters of Medical Necessity

Appeal Letters (CCFA)
Templates for requesting school accommodations and appealing denials of funding for medications and procedures; Crohn's & Colitis Foundation of America.

Patient Education & Instructions

Parents' Guide to Inflammatory Bowel Disease (CCFA)
Provides information about diagnosis and treatment, helpful tips for lifestyle changes, and resources for emotional support; Crohn's and Colitis Foundation of America.

Resources for Patients & Families

Inflammatory Bowel Disease (FAQ)

Information on the Web

A Guide for Teachers to Inflammatory Bowel Disease (CCFA)
Information for school personnel about the diagnosis, sports participation, and planning for potential school absences; Crohn's and Colitis Foundation of America.

Ulcerative Colitis (MedlinePlus)
Diagnosis and management information; sponsored by the U.S. National Library of Medicine.

Crohn's Disease (MedlinePlus)
Diagnosis and management information; sponsored by the U.S. National Library of Medicine.

Inflammatory Bowel Disease (KidsHealth.com)
Family-focused information about IBD; from the Nemours Foundation.

Caring for your Child with IBD (Johns Hopkins Health Book)
A 304-page resource for the family living with IBD; by the North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition.

Just Like Me! Teens with IBD (CCFA)
Information for teens with IBD including an ask-the-expert section, a chat room, and "Hot Topics" related to dating, family, friends, and school; Crohn's & Colitis Foundation of America.

National & Local Support

Crohn's & Colitis Foundation of America (CCFA)
Credible disease information with an extensive “kids and teens” section, information about summer camps, and lists of support groups at the local level.

Studies/Registries

Inflammatory Bowel Disease (clincialtrials.gov)
A listing of registries and clinical trials for children with inflammatory bowel disease; National Institutes of Health.

Services for Patients & Families in Rhode Island (RI)

Service Categories	RI	NW		NM	NV
Developmental - Behavioral Pediatrics	12	1	2	3	9
Dieticians and Nutritionists	3	1	1	4	6
Pediatric Dentistry	41	2	6	25	50
Pediatric Gastroenterology	18		2	5	2
Pediatric General Surgery	4		4	5	2
Pediatric Ophthalmology	8	1	6	6	4

For services not listed above, browse our Services categories or search our database.

* number of provider listings may vary by how states categorize services, whether providers are listed by organization or individual, how services are organized in the state, and other factors; Nationwide (NW) providers are generally limited to web-based services, provider locator services, and organizations that serve children from across the nation.

Authors & Reviewers

Initial publication: January 2011; last update/revision: April 2022

Current Authors and Reviewers:

Authors:	Adam Cardullo, MD, MS
	Anna Ermarth, MD, MS
Reviewer:	Catherine Sampert, DO

Authoring history

2021: update: Anna Ermarth, MD, MS^A; Adam Cardullo, MD, MS^A

2015: update: Mark Deneau, MD^A

2011: first version: Mark Deneau, MD^A

^AAuthor; ^CAContributing Author; ^SASenior Author; ^RReviewer

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