Successful Treatment of Oral Crohn's Disease by Ustekinumab.

Oral lesions, such as cheilitis or ulcerative lesions in the oral cavity, have been reported in a subset of patients with Crohn’s disease (CD) and may even precede gastrointestinal involvement.[1] Little has been published regarding therapy of oral CD, but recent case-reports describe a beneficial effect of anti-TNF-alpha antagonists.[2] Ustekinumab, an antibody targeting the p40 subunit of interleukin-12 and interleukin-23, has demonstrated efficacy in CD.[3] However, up to date ustekinumab has not been described as treatment of Crohn’s cheilitis. Here we report a case of successful treatment with ustekinumab for a severe refractory oral manifestation of CD.

A 57-year-old female was diagnosed with perforating ileal CD after an ileocecal resection. Six months later, she presented with minor abdominal symptoms but particularly painful lips, mouth, and throat, leading to severe dysphagia. First, she was treated with consecutive topical and then systemic steroids without any response. Subsequently, she responded to infliximab but lost response despite adequate trough concentrations and had a primary nonresponse to vedolizumab. She further deteriorated with progressive dysphagia and a trismus caused by cheilitis and tonsillitis. Laboratory results displayed elevated inflammatory markers (C-reactive protein [CRP]: 18 mg/L, fecal calprotectin: 761 ug/g). Imminent malnutrition required placement of a percutaneous endoscopic gastrostomy (PEG) tube. Biopsy was performed on a cheilous ulcer to investigate the association with CD. Histology showed active and chronic inflammation and granuloma formation compatible with an oral manifestation of CD (Fig. 1). Finally, therapy was switched to ustekinumab, according to the licensed dose for CD. Thereafter, her symptoms and inflammatory parameters gradually improved up to complete remission of both oral and intestinal CD allowing removal of the PEG tube. She is in sustained remission up to the writing of this article (follow-up 15 months).

FIGURE 1.

Biopsy of cheilous ulcer showing nonspecific active and chronic inflammation with granuloma formation

Oral CD remains a clinical challenge with the lack of controlled clinical studies. It has been hypothesized that oral CD may represent a distinct phenotype[4] and genotype.[5] This may support the role of biological therapies targeting other immunological cascades than the conventional drugs that are used for intestinal CD. In this case, we report a beneficial effect of targeting the IL-12/23 pathway with ustekinumab for the treatment of cheilitis and tonsillitis as oral manifestations of CD. Currently several drugs selectively targeting a part of the same immunological pathway, such as anti-IL-12/23p40 (briakinumab) and anti-IL-23p19 (risankizumab, brazikumab) antibodies, are studied for CD. Future studies may also investigate the therapeutic potential of these drugs for oral manifestations of CD.