Pediatric ulcerative colitis patients suffer from digestive, cutaneous, ocular and articular symptoms. The disease is more severe in the pediatric population than the adult one. Initial symptoms are usually abdominal pain, diarrhea and rectal bleeding. Based on their complaints, patients can be divided into four groups: pancolitis, extended colitis, left sided colitis and isolated proctitis [1]. Unfortunately, no matter what initial presentation suggests, extension is a general rule, with 60% of patients suffering from extensive colitis at some point during disease evolution. Furthermore, symptoms suggest extensive disease from the beginning in 60 to 80% of pediatric patients, twice more frequent than adults [2].

Mild forms of the illness cause diarrhea and hematochezia. However, these findings do not have systemic repercussions like weight loss and are not accompanied by fever. Constipation may also be an early symptom [3]. Moderate disease consists of abdominal pain and cramps, urgency to defecate and bloody diarrhea. The patient may be anemic and febrile and have supplementary complaints like lack of appetite and weight loss. Severe cases are more rare, accounting for 10% of cases and are characterized by more than 6 bloody stools per day, vomiting, fatigability and all other complaints encountered in moderate disease individuals. The biochemical and hematological panels reveal anemia, hypoalbuminemia and leukocytosis. The physician should keep in mind that these individuals may suffer complications of the disease at any time, such as toxic megacolon, intestinal perforation and severe blood loss. The Pediatric Ulcerative Colitis Activity Index is a valid tool doctors can use while trying to assess the need for therapy escalation in fulminant colitis [4]. Ulcerative colitis generally has a more aggressive course in children than adults, with a shorter duration of the disease before surgery is needed [5]. Colectomy rates have been reported to vary between 10% [6] and 40% [7].

Extraintestinal manifestations may predominate in certain children, but may also be noticed during clinical examination in cases presenting for digestive system related complaints. They consist of growth failure, articular phenomenon and cutaneous manifestations. The child's skin may be pale, as an expression of chronic blood loss. Dehydration expresses itself as decreased turgor. Examination may also reveal jaundice, spider angiomata and caput medusae, in cases where hepatic disease (associated sclerosing cholangitis or autoimmune hepatitis) is present. Pyoderma gangrenosum and erythema nodosum are rarely seen. Sexual development is sometimes delayed.

Periodical ophthalmological examination is a must in pediatric ulcerative colitis. Visual inspection may reveal scleral icterus or erythematous eye. The child may complain about ocular pain, indicative of episcleritis or about visual impairment, suggestive for cataract.

Pain may be also be present in joints area, but arthritis per se is less frequent. The arthralgia commonly involves the knees and elbows, ankles and wrists, but smaller articulations are not always spared. 1% of cases develop ankylosing spondylitis.

The general appearance of the patient depends on the duration and severity of the disease. He or she may be malnourished, may experience muscle wasting, may have a cushingoid facies as a result of long term steroid treatment or may appear toxic in acute episodes. Fever leads to tachycardia, as does dehydration. Tachypnea may represent a compensatory mechanism for acidosis.

Abdominal palpation may reveal tenderness or frank pain, accompanied by guarding and rebound tenderness, suggestive for severe illness or perforation. Auscultation can find normal, hypoactive or hyperactive abdominal sounds. If an abnormal mass in palpated, the physician must think about intestinal obstruction, more prevalent in prolonged evolution cases or about magacolon. The spleen may be enlarged and anal region inspection may diagnose hemorrhoids, fissures or erythema.

• Weight Loss

  Two other items were scored lower: lack of appetite (1.1) and weight loss (0.6). [ncbi.nlm.nih.gov]

  However, eating a healthy amount of calories, vitamins and protein is important to avoid malnutrition and weight loss. Children with ulcerative colitis frequently lose weight and growth may slow down before they are diagnosed. [rileychildrens.org]

  Symptoms may include: anemia due to blood loss diarrhea, which may have some blood in it fatigue malnutrition, because the colon doesn’t absorb nutrients as well rectal bleeding stomach pain unexplained weight loss Sometimes, a child’s ulcerative colitis [healthline.com]

  Signs and symptoms include bloody stools, abdominal pain, ulcers in the colon, diarrhea, and weight loss. Without treatment, symptoms can worsen over time. [nyulangone.org]

• Anemia

  Laboratory investigations revealed elevated erythrocyte sedimentation rate (82%), anemia (75%), thrombocytosis (72%), and hypoalbuminemia (33%). [ncbi.nlm.nih.gov]

  Tests for ulcerative colitis in children can include: blood tests to check for high white blood cells levels indicating immune system problems, and low red blood cell levels indicating anemia stool samples to look for bacteria, parasites, and presence [medicalnewstoday.com]

  Diagnostic testing to confirm a diagnosis may include: Blood test: To check for anemia, infection, or high white blood cell count. Stool sample: To check for blood, inflammation, or infection in the colon or rectum. [childrensgimd.com]

  Symptoms may include: anemia due to blood loss diarrhea, which may have some blood in it fatigue malnutrition, because the colon doesn’t absorb nutrients as well rectal bleeding stomach pain unexplained weight loss Sometimes, a child’s ulcerative colitis [healthline.com]

• Fever

  Liver injury—jaundice (yellow skin and eyes), dark brown urine, right-sided abdominal pain, fever, or severe tiredness. Blood disorders—fever that doesn’t go away, bruising, bleeding or severe paleness. [remicade.com]

  Adverse reactions were observed in 8 patients (33%) (liver enzyme elevation n = 1, fever n = 3, nausea n = 3), requiring discontinuation of MTX in 2 patients (8%) (1 because of intractable nausea and 1 because of recurrent fever). [journals.lww.com]

  • Reactivation of HBV—feeling unwell, poor appetite, tiredness, fever, skin rash and/or joint pain. • Liver injury—jaundice (yellow skin and eyes), dark brown urine, right-sided abdominal pain, fever, or severe tiredness. • Blood disorders—fever that [jnj.com]

  […] that lasts more than 2 or 3 days or a fever higher than 100.4°F (38°C) without an explanation Nausea and vomiting that lasts more than a day vomit has a bit of yellow/green color Skin sores or lesions that do not heal Joint pain that keeps your child [mountsinai.org]

• Anorexia

  While most children present with typical symptoms of abdominal pain and rectal bleeding, it is important for clinicians to recognize atypical symptoms such as growth failure and anorexia [4]. [pedsurglibrary.com]

  Due to the malnutrition, the patients sometimes diagnosed as anorexia nervosa [9]. However, compared to Crohn’s disease, UC had shorter interval between onset of symptoms and signs and the diagnosis. [clinmedjournals.org]

  However, the sulfapyridine moiety has several dose-limiting side effects, including headaches, nausea, anorexia, and reversible oligospermia, that can be seen in approximately one-third of patients.10 Newer formulations, including mesalamine, olsalazine [ncbi.nlm.nih.gov]

• Cushingoid

  He or she may be malnourished, may experience muscle wasting, may have a cushingoid facies as a result of long term steroid treatment or may appear toxic in acute episodes. Fever leads to tachycardia, as does dehydration. [symptoma.com]

• Diarrhea

  Though diarrhea is a typical symptom of ulcerative colitis in kids, don’t panic if your child has a bout here and there. Usually UC is characterized by frequent and urgent diarrhea. [everydayhealth.com]

  Based on how severe their ulcerative colitis is and how they respond to treatment, they may need to take one or more of these medicines: Anti-diarrhea drugs can help when she has bad diarrhea. You can buy loperamide (Imodium) without a prescription. [mountsinai.org]

  This inflammation causes diarrhea or frequent emptying of the colon. Your child may also have stomach pain and diarrhea. Treatment may include avoiding foods that cause symptoms, taking medicine, and having surgery. [urmc.rochester.edu]

  Children with ulcerative colitis occasionally have symptoms severe enough to require hospitalization to correct malnutrition and to stop diarrhea and loss of blood, fluids, and mineral salts. [childrensnational.org]

• Abdominal Pain

  The pediatric Colazal trial defined clinical response using the Modified Sutherland UC Activity Index, which excluded abdominal pain and functional assessment. [ncbi.nlm.nih.gov]

  While most children present with typical symptoms of abdominal pain and rectal bleeding, it is important for clinicians to recognize atypical symptoms such as growth failure and anorexia [4]. [pedsurglibrary.com]

  She complained of diffuse abdominal pain for 6 months prior to admission. [karger.com]

• Rectal Bleeding

  The following items were identified by the children, in decreasing order of weights: abdominal pain (importance × frequency weight 3.9), rectal bleeding (3.6), stool frequency (3.0), stool consistency (3.0), general well-being/fatigue (2.9), urgency [ncbi.nlm.nih.gov]

  While most children present with typical symptoms of abdominal pain and rectal bleeding, it is important for clinicians to recognize atypical symptoms such as growth failure and anorexia [4]. [pedsurglibrary.com]

  This inflammation is what causes the major symptoms of UC, which are stomach pain or cramping, rectal bleeding, and diarrhea. [diseaseinfosearch.org]

  Other common symptoms include: abdominal pain fatigue weight loss loss of appetite rectal bleeding loss of body fluids and nutrients anemia caused by severe bleeding Some patients may also experience: skin lesions joint pain eye inflammation liver disorders [childrenshospital.org]

• Abdominal Cramps

  Affected children present with diarrhea, bloody stools, abdominal cramps, as well as extraintestinal manifestations, such as arthritis, signs of hepatobiliary disease and ocular disorders. [symptoma.com]

  These may include abdominal cramping, constipation, and diarrhea. Unlike with inflammatory bowel disease, IBS does not lead to inflammation that damages the gastrointestinal tract. [nyulangone.org]

  Symptoms of ulcerative colitis include: Frequent diarrhea, often with pus or blood Abdominal cramping and pain Urgent need to have a bowel movement Rectal pain and bleeding Fever Unexplained fatigue Loss of appetite Weight loss Anemia or low iron level [childrensgimd.com]

  Abdominal cramps and diarrhea may be helped by medications that reduce inflammation in the colon. More serious cases may require steroid drugs, antibiotics, or drugs that affect the body's immune system. Hospitalization. [childrensnational.org]

• Failure to Thrive

  Symptoms of ulcerative colitis can vary and may include: Abdominal pain or cramping Blood in the stool Constant feeling of needing to empty the bowels Diarrhea Fatigue Fever Joint pains Poor appetite Vomiting Weight loss Failure to thrive Delayed puberty [rileychildrens.org]

  In addition, children may present with jaundice and other cutaneous abnormalities, dehydration, weight loss and failure to thrive. [symptoma.com]

  Symptoms can include irritability, failure to thrive, lack of appetite and vomiting. Investigation can reveal high blood levels of sodium. [pituitary.org.uk]

• Scleral Icterus

  Visual inspection may reveal scleral icterus or erythematous eye. The child may complain about ocular pain, indicative of episcleritis or about visual impairment, suggestive for cataract. [symptoma.com]

Workup in ulcerative colitis patients should include hematological and biochemical tests, as well as imaging methods. A complete cell blood count will often highlight the presence of chronic hemorrhagic anemia, with microcytic and hypochromic red blood cells. Other cases may present with normocytic anemia. Fulminant disease is accompanied by severe drop in hemoglobin and hematocrit levels. Inflammation markers, such as the erythrocyte sedimentation rate and C-reactive protein are found to be increased during active disease episodes. Liver function tests may be modified and serum albumin may be low, because of the malabsorbtive process or because of the liver dysfunction.

Serological inflammatory markers are not specific for ulcerative colitis, but increased levels offer additional information. Anti-neutrophil cytoplasmic antibodies are more frequently found positive in ulcerative colitis children (60-80%) than Crohn disease cases (40%) [8] but do not correlate to disease activity [9]. Anti-Saccharomyces cerevisiae antibodies have been proposed as an useful test, but have subsequently been demonstrated to be present in only 12% of cases. Perinuclear anti-neutrophil cytoplasmic antibodies are more specific for ulcerative colitis and their presence suggests severe disease that will soon require surgical intervention.

Fecal calprotectin level is increased in all inflammatory conditions of the bowel. Increased levels (above 100 mg/g) predict clinical relapse. Stool samples should also be examined via cultures, to rule out an infectious cause for the symptoms. Clostridium difficile toxins A and B should also be ruled out.

The definite diagnosis cannot be established without a full colonoscopy. Inflammation is visible from the rectum and extends upwards in a contiguous manner. In 5% of cases, the rectum can be spared [10]. The normal vascular markings disappear and the mucosa appears friable, granular and erythematous. When possible, efforts to visualize the terminal ileum should be made. Biopsies should be obtained from more than one level. The antomopathological examination will reveal the presence of polymorphonuclear leukocytes in the base of the crypts, cryptitis and crypt abscesses. The lamina propria is invaded by eosinophils, mast cells and lymphocytes. When present, noncaseating granulomas are considered highly specific. However, imaging should not be limited to the lower gastrointestinal tract, in order to correctly determine the extent of the disease. Superior segments should be investigated via upper endoscopy, supine and upright abdominal radiography, upper gastrointestinal series, barium enema or video capsule. This latter method has superior sensitivity compared to barium radiography when it comes to diagnosing small bowel lesions [11]. The barium enema is useful when it comes to diagnosing strictures or polyps (as an alternate source of bleeding), especially in cases where colonoscopy cannot be performed. An abdominal obstruction series does not diagnose ulcerative colitis, but it can show the presence of complications, such as toxic megacolon or obstruction leading to dilated intestinal loops. Nuclear imaging and magnetic resonance imaging are good methods to search for intestinal wall inflammation, while computer tomography scanning should be chosen to evaluate obstruction and intestinal wall thickening.

The superior digestive endoscopy can diagnose focal, diffuse or erosive gastritis [12], while gastric ulcers, esophagitis and erosive duodenitis are considered to be rare in ulcerative colitis [13].

Symptoms that are similar to those of ulcerative colitis can occur in infants, as well, but in this age group the physician should first think about allergic colitis or immunodeficiency. Therefore, they should undergo an allergic evaluation [14] and classical and more rare immunodeficiencies should be ruled out [15].

• Albumin Increased

  Hemoglobin and albumin increased from 10 ± 1.9 to 11.2 ± 1.4 (P = 0.035) and 3.6 ± 0.6 to 4 ± 0.4 (P = 0.063), respectively. [academic.oup.com]

• Normocytic Anemia

  A complete cell blood count will often highlight the presence of chronic hemorrhagic anemia, with microcytic and hypochromic red blood cells. Other cases may present with normocytic anemia. [symptoma.com]

The pediatric patient suffering from ulcerative colitis needs immediate therapy aiming to induce and maintain clinical and laboratory remission [16]. Long term goals are to prevent bowel neoplasms, to increase life quality and to prevent normal growth impairment [17]. The first step is represented by medical therapy, using several therapeutic classes: corticosteroids, 5-aminosalicylates (5-ASA), antibiotics, probiotics, thiopurine immunomodulators, calcineurin inhibitors and anti-tumor necrosis factor (TNF)- α agents. An accelerated step-up approach is considered optimal [18].

Mild disease requires oral and rectal 5-ASA administration, effective in 70-80% of cases. Treatment can be performed on an outpatient basis [19]. Probiotics represent important adjuvant agents, but administration of 5-ASA should be continued indefinitely. Moderate to severe disease patients need more aggressive treatment, consisting of corticosteroid administration. In corticosteroid dependent cases, 6-mercaptopurine or azathioprine administration is recommended. However, immunomodulatory agents are not useful in acute exacerbations of the illness. Treatment for fulminant disease include immunosuppressive agents (cyclosporine), T-lymphocyte function inhibitors (tacrolimus) [20] and monoclonal antibodies against tumor necrosis factor (infliximab) [21].

Proctocolectomy with ileal pouch-anal anastomosis is considered to be curative [22] and preventive of colorectal cancer, that occurs in 8% of patients in 10 to 25 years. However, in children it is only indicated in fulminant cases where medical therapy proves ineffective or when dysplasia or malignancy is detected. Surgery can be performed laparoscopically.

Pediatric ulcerative colitis patients should avoid ingesting seeds, nuts and uncooked vegetables. Fulminant disease entails complete oral food elimination until the disease becomes stable.

If no complications arise, the disease may have a mild course. However, as the disease progresses, acute exacerbations become more frequent and cause severe distress. Toxic megacolon rarely occurs, but when it does, it represents an emergency, as it can lead to massive hemorrhage and gram-negative sepsis. In this case, patients are febrile and complain about abdominal pain and distension. Severe pain accompanied by guarding may signify colonic perforation. Risk factors are represented by pancolitis, Clostridium difficile infection, recent use of antidiarrheal agents, colonoscopy or barium enema.

Colonic malignancy represents a delayed complication, especially found in pancolitis cases. 40% of children who develop ulcerative colitis before the age of 14 will have colorectal cancer by the time they turn 35, therefore periodic screening by colonoscopy and biopsy is mandatory. Even if no dysplasia is encountered in biopsy specimens, some authors recommend prophylactic colectomy during adulthood for former pediatric ulcerative colitis patients.

Hepatobilliary tract disease can precede or accompany intestinal manifestations or can occur after surgical resection. It may consist of cholelithiasis, primary sclerosing cholangitis, chronic active hepatitis, amyloidosis, hepatic steatosis, granulomatous hepatitis or pericolangitis.

The disease in accompanied by a hypercoagulable state resulting from an increase in procoagulant factors levels and platelets number and a decrease of anticoagulant levels. This can result in pulmonary embolism, or peripheral in situ thrombosis.

Up to one quarter of adolescent suffer from arthritis that usually involves large joints in an asymmetrical and transient manner. Other, less frequent complications include anterior uveitis, episcleritis and pyoderma gangrenosum, a chronic cutaneous ulceration.

The etiology of pediatric ulcerative colitis is thought to be represented by a genetically determined defective down-regulation of the inflammatory intraluminal processes or by primary defects in epithelial cell functionality. Triggers may be represented by aerobic bacteria. The disease becomes chronic when, despite the intestine's increased healing ability, exposure to harmful intraluminal components is continuous.

Ulcerative colitis incidence has two peaks: one between the ages of 15 and 30 and one between 60 and 80. 30% of cases occur in patients younger than 20 years old and young children, below the age of 5 become more frequently affected. In general 2 out of 100.000 children acquire this disease, initially located in the colon, but that can progress to the whole intestine.

The pathophysiology of pediatric ulcerative colitis can be resumed as follows: enteric pathogens or their toxins induce nonspecific intestinal mucosa inflammation, leading to its increased permeability and therefore absorption of these products. In genetically susceptible hosts, the inflammatory response is not down-regulated, as opposed to the normal organism. This leads to the activation and amplification of the immune cascade. The intestinal mucosa becomes chronically inflamed, with subsequent destruction and fibrosis.

Modern medicine des not yet possess effective prevention methods for pediatric ulcerative colitis, but certain lifestyle changes have been demonstrated to prevent symptom escalation in many patients. The amount of ingested fibers should be increased, whereas other types of food, including dairy products, raw fruits, beans, spices, popcorn, cabbage, beans and stimulants such as alcohol, chocolate, coffee and soda should be reduced to a minimum. Patients should not ingest large quantities of food at once, but rather divide intake into small and frequent portions. Affected children should be advised to maintain adequate hydration by ingesting appropriate amounts of water, thus keeping the stools soft.

Vitamin deficiencies are probable in pediatric ulcerative colitis because of the intestinal malabsorbtion, but can be prevented by multivitamin administration, when needed. Daily stress should be reduced to a minimum, since it has been proven to have a noxious effect on the entire digestive system. Mild exercise is considered beneficial.

Pediatric ulcerative colitis is a polymorphic intestinal disease occurring in the genetically susceptible host. The illness is caused by inflammation, beginning in the rectum and extending upwards in a continuous manner. Symptoms depend on the extent of the inflammatory process, that may affect the entire large intestine. Patients are divided into four categories, depending on their complaints: isolated proctits, left-sided colitis, extended colitis, and pancolitis [23]. Affected children present with diarrhea, bloody stools, abdominal cramps, as well as extraintestinal manifestations, such as arthritis, signs of hepatobiliary disease and ocular disorders. In addition, children may present with jaundice and other cutaneous abnormalities, dehydration, weight loss and failure to thrive.

Workup should include standard hematological, biochemical and coagulation panels, as well as specific tests, such as calprotectin, standard inflammation markers, anti-neutrophil cytoplasmic antibodies and anti-Saccharomyces cerevisiae antibodies. Stool sample analysis should include cultures and clostridium difficile toxins evaluation. The definite diagnosis is achieved via colonoscopy and antomopathological examination of the biopsy specimen. Upper digestive endoscopy should also be performed due to the variable extent of the inflammation.

Treatment should include anti-inflammatory agents, like 5-aminosalicylates and corticosteroids, but also other therapeutic classes, if needed, such as thiopurine immunomodulators, calcineurin inhibitors and anti-tumor necrosis factor (TNF)- α agents, as well as antibiotics and probiotics.

Pediatric ulcerative colitis is a disease that affects the large intestine to a variable degree. Mild forms are located in the rectum, whereas severe cases are characterized by inflammation that extends to the whole colon. This leads to abdominal cramps, diarrhea and bloody stools, but also extraintestinal complaints related to articular and ocular involvement. The diagnosis can b established via colonoscopy and examination of the biopsy piece. However, since the whole digestive tract may be involved, an upper endoscopy is also sometimes needed.

Medical treatment alleviates symptoms in most cases and consists of anti-inflammatory agents administration. However, in severe forms, surgical excision of the affected segment is needed. Since digestive malignancies are often associated with this disease, active periodical screening is imperative.

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