{'fraction_non_alphanumeric': 0.0243283266342289, 'fraction_numerical': 0.007404273323460969, 'mean_word_length': 5.229249011857707, 'pattern_counts': {'":': 0, '<': 0, '<?xml version=': 0, '>': 0, 'https://': 0, 'lorem ipsum': 0, 'www.': 0, 'xml': 0}, 'pii_count': 0, 'substrings_counts': 0, 'word_list_counts': {'cursed_substrings.json': 0, 'profanity_word_list.json': 0, 'sexual_word_list.json': 0, 'zh_pornsignals.json': 0}}
Adalimumab as therapy for fistulizing orofacial Crohn's disease.

To the Editor: We report the case of 24-year-old man with a background of oral and colonic Crohn’s disease (CD) who presented with a discharging orofacial fistula. The patient was diagnosed with CD at age 16 years, manifest by a 3year intermittent history of mouth ulcers that were responsive to prednisone therapy. Assessment by a gastroenterologist revealed endoscopic evidence of scattered ulceration at the splenic flexure and a small perianal abscess. The perianal abscess resolved with several weeks of oral metronidazole and mesalamine therapy was commenced. His CD remained quiescent for a subsequent 3-year period; however, persistent mouth ulceration and diarrhea prompted reattendance at this stage. Colonoscopy showed a patchy mild pancolitis and azathioprine was commenced in addition to continued mesalamine. 6-Mercaptopurine (6-MP) was substituted for azathioprine within 2 weeks (due to nausea and vomiting) and was tolerated. The patient’s diarrhea resolved over the next 3 months, but he remained symptomatic from persistent oral ulceration requiring further courses of steroids. Infliximab therapy (5 mg/kg induction and maintenance) was commenced and symptom resolution was finally achieved with combined use of infliximab and 6-MP. Over the next 9 months he remained symptom-free. The patient’s infliximab therapy was interrupted during a subsequent 18month period of travel in Australia. On his return the patient presented to the gastroenterology clinic, taking no medication, with a 3-week history of swelling and fluid discharge originating from his left cheek. On examination there was evidence of a discharging orofacial fistula (Fig. 1a). Infliximab was resumed (in conjunction with oral metronidazole); however, after 3 infusions there was no improvement. It was decided, therefore, to switch to adalimumab, starting with an initial subcutaneous injection of 160 mg, an 80-mg dose 2 weeks later, and a maintenance dose of 40 mg every 2 weeks. 6-MP was recommenced but discontinued within 1 week by the patient. After 3 injections of adalimumab, swelling at the fistula site was much less prominent and discharge from the fistula ceased. On review 6 months later, a small facial skin tag was the only visible external remnant of fistula (Fig. 1b). Adalimumab therapy was well tolerated, although brief pain at the fistula site (with associated nausea and vomiting) was reported following his 8th injection. No other adverse events were noted. The patient remains well and is symptom-free, both from the point of view of oral and colonic disease, following 12 months of adalimumab therapy. CD is a pan-enteric disorder and oral manifestations are well described. CD in the oral cavity usually takes the form of aphthous ulceration of the mucosal surface. Aphthae and mucosal tags are frequently seen if the oral cavity is carefully evaluated in patients with newly diagnosed CD. Deep tissue inflammation occurs uncommonly and may lead to labial, lingual, and facial swelling and fistula formation can result. CD sometimes presents only with orofacial manifestations and these lesions may predate the presence of intestinal disease. Indeed, classification of granulomatous orofacial disease is complex (particularly in the absence of inflammation elsewhere) and there is considerable overlap (especially with follow-up over time) between orofacial CD, Melkersson Rosenthal syndrome (MRS), cheilitis granulomatosa, and the other orofacial granulomatoses. Effective treatment strategies that are specific for orofacial CD have not been defined. Therapy usually involves use of agents with proven efficacy in enteric CD, including topical and systemic corticosteroids and immunomodulatory agents. Biologic agents that target TNF-a have more recently been established as effective therapies and are now the treatment of choice for fistulizing CD. Infliximab, the chimeric monoclonal antibody to TNF-a, is the longest established anti-TNF agent in the treatment of CD. Case reports have suggested that infliximab is an effective therapy in orofacial CD and orofacial fistula healing and closure is described. We report the case of a patient with an orofacial fistula related to CD whose disease had previously proven responsive to infliximab. Loss of response to infliximab was observed on retreatment (following an interruption in therapy); however, sustained fistula healing was achieved with a switch to regular subcutaneous adalimumab. This case illustrates once again that anti-TNF therapy is effective for fistulizing orofacial CD and that loss of treatment response can be reestablished by switching to an alternative anti-TNF agent.