The first-line therapy in children with mild-to-moderate colitis is oral aminosalicylates, which can be combined with topical aminosalicylates to increase remission rate, if tolerated. Aminosalicylates are used in induction and maintenance treatment of UC. The aminosalicylates of choice are mesalazine and sulfasalazine. Their effectiveness is quite similar, but sulfasalazine is considered superior to mesalazine in patients with associated arthropathy, although dose-dependent adverse events (headaches, nausea, and fatigue) are more frequent. Oral mesalazine dosage for pediatric population is 60–80 mg/kg/day in one or two daily doses with a maximal dose of 4, 8 g/daily. Rectal mesalazine is dosed 25 mg/kg up to 1 g once daily. Sulfasalazine is dosed 40–70 mg/kg/day in one or two daily doses up to 4 g/day. To minimize side effects, sulfasalazine may be started at a dose of 10–20 mg/kg/day with a gradual dose increase over a 2-week period. In addition, sulfasalazine impairs folic acid absorption, so its supplementation is recommended to prevent anemia. Maintenance dose of mesalazine is the same as used for induction therapy. Because of their safety profile, they could be continued indefinitely. Dosage may be reduced after a long period of complete remission. Serious side effects are uncommon, and they usually resolve when the medication is stopped. Acute intolerance to aminosalicylates may mimic a flare of colitis, and it precludes any further usage of that drug. Patient’s response to medication may be evaluated 2 weeks after onset of therapy. If no response is seen then, rectal therapy (if not started already) or oral steroids should be offered.

Left-sided colitis and proctitis are usually managed with topical mesalazine or topical steroids. Mesalazine is available as enema and suppositories. They can be used for induction and maintenance remission. Suppositories are useful for proctitis, while left-sided colitis is treated with enemas, as long as they can reach the left colon. Corticosteroids enema or suppositories are useful for induction therapy, but prolonged treatment may cause systemic side effects. Often, oral aminosalicylates are added to the topical therapy in patients with moderate left-sided colitis.

Oral steroids are useful in inducing remission in pediatric patient with moderate colitis and systemic symptoms. Because of their well-known side effects (e.g., weight gain, fluid retention, growth retardation, mood disorders, osteopenia, aseptic necrosis, glaucoma, cataracts), corticosteroids should be tapered shortly after remission is achieved. Standard corticosteroids therapy involves oral prednisone or prednisolone, which are dosed 1 mg/kg up to 60 mg/day once daily. Beclomethasone dipropionate is an alternative steroid that may be used orally or rectally in mild-to-moderate colitis, with fewer systemic steroids side effects.

Severe acute colitis is a potentially life-threatening condition, defined by PUCAI greater than 65. It requires hospitalization for further evaluation and management. Assessment of vital sign and key blood test evaluation are essential. Stool samples should be collected for culture and Clostridium difficile toxin detection. Severe UC first-line therapy is intravenous corticosteroids. Methylprednisolone is dosed 1–1.5 mg/kg/day up to 60 mg/day in one or two doses daily. In addition, supportive treatment may be required: fluid rehydration, correction of electrolytes imbalance, blood transfusion, and albumin infusion. PUCAI score should be evaluated daily. A score of greater than 45 on day 3 of admission is predictive of lack of response to corticosteroids. A score of greater than 70 on day 5 guided the start of rescue therapy. There is no agreement about intravenous corticosteroid therapy duration; 7–14 days of therapy are usually enough to obtain a good clinical response. Recently, a consensus statement for managing acute severe ulcerative colitis in children from ECCO, ESPGHAN, and the Porto IBD Group of ESPGHAN has been published. Key points of this document are the following:

A second-line medical therapy is usually preferred than surgery in children. However, colectomy may be required in several circumstances, such as patients with severe colitis unresponsive to medical therapy, patients with complications (toxic megacolon and/or perforation), and if precancerous lesions are identified. Colectomy could be discouraged in children younger than 5 years old, in whom it could be difficult to distinguish between UC and CD.

The most common medical rescue therapy in steroid-refractory acute severe UC is calcineurin inhibitors (cyclosporine, tacrolimus) and biological agents (infliximab, adalimumab). Several studies reported a high rate of short-term success, though there is a low rate of long-term success of calcineurin inhibitors. Because of its long-term renal toxicity, cyclosporine should only be administered as a “bridge” to thiopurine treatment (azathioprine), which is typically effective after 3–4 months. Although not structurally related to cyclosporine, tacrolimus has a similar mechanism of action and efficacy, though there is a more tolerable side effect profile. Calcineurin inhibitors may also be used as a steroid-sparing “bridge” to surgery. There aren’t any comparative prospective trials between cyclosporine and infliximab in children. Infliximab is a monoclonal antibody to tumor necrosis factor-alpha. The recommended dose is 5 mg/kg at 0.2 and 6 weeks, followed by maintenance therapy every 8 weeks. Unlike cyclosporine, infliximab can be continued as long-term maintenance therapy. Infliximab seems to be more effective in obtaining mucosal healing than immunomodulators. Combination therapy with infliximab and azathioprine should be discouraged because of the potential risk or lymphoma, even if combination therapy has reported a good response in many adult studies.

Adalimumab is a fully human monoclonal antibody to tumor necrosis factor-alpha. Extrapolating from the adult literature and pediatric case series, adalimumab should be started at 100 mg/m² up to 160 mg, followed by 50 mg/m² up to 80 mg after 2 weeks and then 25 mg/m² up to 40 mg every other week; dose individualization may be needed. It is generally used in children who either fail to tolerate or become intolerant to infliximab. Adalimumab is an effective and safe treatment that should be considered as the rescue treatment before colectomy in children [1, 4–7].

The gold standard technique is ileal pouch-anal anastomosis (IPAA) firstly described in 1978 by Parks and Nicholls [8]. It consists of colectomy and rectal mucosectomy with an endorectal ileoanal pull-through, creation of a distal reservoir and ileorectal anastomosis (Fig. 23.2). If urgent surgery is required, the treatment of choice is to perform a colectomy and ileostomy leaving a rectal stump.