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• W2004755725 abstract "INTRODUCTION Oral manifestations of inflammatory bowel disease (IBD) are relatively common, and their incidence in IBD has been cited to range from 6% to 20% (1). Oral manifestations of Crohn disease (CD) and ulcerative colitis (UC) may be either asymptomatic or painful and tender. Severe oral manifestations characterized by pain cause anorexia, malnutrition and growth failure (2), significantly affecting the quality of life in patients with IBD. 5-Aminosalicylic acid (5-ASA) is effective for the treatment of mild and moderately active UC and CD. It is also used to control remissions because of minimal adverse effects. Recently, it has been reported that combination treatment of orally and topically administered 5-ASA was effective to treat UC (2,3). In a study using topical administration of 5-ASA, the topical concentration of 5-ASA was significantly higher than that used in an orally administered 5-ASA group. The topical concentration of 5-ASA is a good marker for estimation of its efficacy in the treatment of UC (4). For oral ulcerations, topical 5-ASA suspension and cream have been reported to be effective in patients with Behçet disease and in healthy people (5,6). However, no report describes topical treatment using 5-ASA spray for refractory oral ulcerations in patients with IBD. In the present report, we describe effective topical treatment with 5-ASA ointment and spray for refractory oral and pharyngeal ulcerations in a pediatric patient with CD. CASE REPORT A 12-year-old girl presented to our hospital with a 1-year history of recurrent oral ulcerations. Recurrent oral ulcerations affected her labial mucosa, lips, tongue, and soft plate. Because of pain, she was unable to take food by mouth, and her body weight was reduced. In addition, an irregular perianal ulceration caused severe anal pain, and her quality of life was significantly affected. A previous biopsy specimen from her buccal mucosa revealed hyperplastic mucosa and a dense lymphocytic infiltrate without granulomas. Fungal culture was negative. Topical agents previously prescribed failed to produce any clinical benefits, and included lidocaine mouth rinse and 1% triamcinolone acetonide in carboxymethylcellulose paste. Systemic prednisolone (10 mg/day for 4 weeks) had caused transient improvement in both oral and perianal ulcerations. On clinical examination, irregular ulcerations were present on the soft plate, lower lip and bilateral buccal mucosa (Fig. 1A). In addition, bilateral buccal mucosal ulcerations were very deep and adjacent to the commissure of the mouth. Upper and lower lips were diffusely swollen. Laboratory studies showed elevations of the C-reactive protein level at 3.1 mg/dL and erythrocyte sedimentation rate at 44 mm/h. Tuberculosis skin tests and chest radiographic findings were normal. There was no evidence of Behçet disease or immunodeficiency syndrome. Upper endoscopic examination revealed an irregular longitudinal ulceration in the esophagogastric junction with no symptoms. Lower endoscopic examination revealed a similar ulceration in the perianal area, and discontinuous colitis. Histological specimens showed moderate inflammation without granuloma formation, but findings were consistent with CD. Initially, the patient received oral administration of 5-ASA (80 mg/kg per day), and an elemental diet therapy (210 kJ/kg per day). These therapies controlled her symptoms, and her esophageal and perianal ulcerations seemed to heal. The patient gained 10 kg within 2 months after the start of treatment. However, oral ulcerations had not improved yet. Therefore, we started topical treatment with 5% 5-ASA ointment (5 mg/g TID in ointment base) to treat oral ulcerations. Two months later, there was progressive healing of oral ulcerations (Fig. 1B), and the patient could eat much easier and started gaining more weight. Four months later, the patient was unable to take food once again because of ulcerations on the posterior pharyngeal wall (Fig. 2A). Because of prior treatment, it was impossible to directly apply the topical medication to the posterior pharyngeal wall, so we needed to modify the method of administration. We decided to use topical treatment using 5% 5-ASA spray (5 mg/mL TID in oral liquid medicine of sodium alginate). Another 2 months later, there was progressive healing of the pharyngeal ulceration (Fig. 2B), and the patient found eating much easier, and started to gain additional weight once again. During oral and topical treatments with 5-ASA, no adverse effects were observed. We measured whole blood concentrations of 5-ASA, and found that there was no difference in concentration between before and after topical 5-ASA administration. The patient is still treated with a combination of oral and topical 5-ASA to control remission, and ulcerations have not recurred for 6 months.FIG. 1: Oral ulcerations before and after topical treatment with 5% 5-ASA ointment. A, Deep ulcerations in the soft plate, buccal mucosa and lower lip before the treatment. B, Oral ulcerations progressively healed with scarring after 5% 5-ASA ointment treatment.FIG. 2: Pharyngoscopic findings before and after topical treatment with 5% 5-ASA spray. A, Deep ulceration in the posterior pharyngeal wall before treatment. B, Progressive healing of the pharyngeal ulceration after 5% 5-ASA spray treatment.DISCUSSION Crohn disease affects children and adolescents with an increasing incidence (7). The burden of illness imposed on young patients is considerable, particularly when the disease is accompanied by growth failure, which is a specific complication for the pediatric population. Currently, available therapeutic agents for CD include aminosalicylate formulations, antibiotics, nonsystemic and systemic glucocorticoids, immunomodulators and monoclonal antibodies that target tumor necrosis factor -α (8). Although all these agents have been used to successfully treat CD, it is important to recognize their potential adverse effects to comprehend and correctly make use of the benefits/risk ratio for each therapeutic class of drugs. Oral 5-ASA is effective for CD with ileal and colonic involvements, and because of minimal adverse effects, it is also used to control remission. The mechanism of action of 5-ASA is still unknown, but it is likely caused by a combination of anti-inflammatory properties (9). Recently, Greenfield et al. (10) described that mucosal tissue concentration of 5-ASA might be an important determinant of therapeutic response, as anti-inflammatory effects of 5-ASA were thought to be dose related. However, by only increasing the oral dose, no therapeutic effects were seen in the treatment of UC (11). Safdi et al. (4) described that topical concentration of 5-ASA should be significantly high, and combination treatment of oral and topical 5-ASA produced earlier and more complete relief of symptoms in UC (12). In addition, Ranzi et al. (5) and Collier et al. (6) reported that 5-ASA suspension and cream were effective treatments of oral ulcerations in patients with Behçet disease and healthy people. Consequently, it was quite likely that combination treatment with oral and topical 5-ASA would be useful for treatment of refractory lesions in patients with CD. Our patient was unable to take food by mouth because of pain caused by oral and pharyngeal ulcerations and, therefore, her body weight was reduced. Oral administration of 5-ASA and elemental diet therapy controlled some symptoms, particularly, esophageal and anorectal ulcerations clearly improved. However, oral and pharyngeal ulcerations were intractable, and we suggested that additional treatment was required. A maximal dose of oral 5-ASA (80–100 mg/kg per day) was already administered. Further increasing the oral dose would not produce additional therapeutic effects in our patient. Therefore, combination treatment with oral and topical 5-ASA was started to help elevate the topical concentration and anti-inflammatory effects. The method of topical 5-ASA administration was modified to directly apply treatment to the site of ulcerations, and the oral liquid medicine of sodium alginate was used for the sticky liquid base of the 5-ASA spray to allow maintenance of 5-ASA in the posterior pharyngeal wall. After these treatments, ulcerations healed progressively. The patient was able to eat much easier and started to gain weight. There were no adverse effects with topical 5-ASA administration, and no difference in whole blood concentrations of 5-ASA was found between before and after topical 5-ASA administration. In conclusion, our experimental results suggest that refractory ulcerations in a patient with CD could be successfully treated with topical 5-ASA administration. Therefore, we recommend to use topical 5-ASA treatment as an effective method in the treatment of refractory lesions in patients with IBD." @default.
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• W2004755725 title "Successful Treatment With Topical 5-Aminosalicylic Acid Ointment and Spray of Refractory Oral and Pharyngeal Ulcerations in a Child With Crohn Disease" @default.
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