Orofacial Granulomatosis and Crohn’s Disease: A Case Series

Background: Inflammatory bowel disease (IBD), specifically Crohn’s disease (CD), is a systemic condition that manifests not only in the gastrointestinal (GI) tract, but also in extraintestinal organs in many patients. A rare syndrome that may occur in association with CD is orofacial granulomatosis (OFG), which is composed of granulomatous cheilitis (GC) and Melkersson-Rosenthal syndrome. OFG is found in less than 1% of patients with CD and is characterized by inflammation and swelling of the lip(s) with surrounding tissue swelling. OFG can have a chronic, disfiguring course that is exceedingly difficult to manage and can significantly impact the quality of life in affected patients. Given the paucity of data available regarding this rare syndrome, we aimed to retrospectively review our institutional experience to better describe the clinical features, presentation, and outcomes of OFG in patients with CD. Methods: Using a bioinformatics tool to mine the electronic medical record at a tertiary referral center, 297 patients with ICD codes for “orofacial granulomatosis” and “Crohn’s disease” were identified. Relevant demographic and clinical data were abstracted. Results: Five patients met inclusion criteria (40% female) with a median age of 15- and 14-years at the time of CD and OFG diagnoses, respectively. A majority (80%) had ileocolonic distribution of CD. Two (40%) patients had upper GI involvement and one (20%) had perianal involvement. Non-stricturing/penetrating (80%) was the most common CD phenotype. OFG was diagnosed in one patient (20%) prior to CD, two (40%) concurrently with CD, and two (40%) after CD diagnosis. At the time of OFG diagnosis, CD was active in two (40%) and quiescent in two (40%) patients. OFG was confirmed histologically with the presence of granulomas on oral biopsies for all patients. The most common presenting symptom associated with OFG was lip swelling (80%). Previous treatments for luminal CD included no medications (20%), 5-aminosalicylate only (20%), oral corticosteroids (20%), anti-tumor necrosis factor (anti-TNF) +/- immunomodulator (60%), and ustekinumab (20%). Only one patient had prior surgical resection for CD. The most common treatment strategies for OFG included intralesional corticosteroids (4 patients), oral corticosteroids (3 patients), and anti-TNF agents, specifically infliximab (3 patients). Although intralesional corticosteroid administration was followed by partial response in 3 patients, recurrences were common after initial injection. One patient had no response to topical corticosteroids, oral corticosteroids, antihistamines, or oral antibiotics, but partial response to intralesional corticosteroids and infliximab. None of the patients had complete response to any therapies directed at OFG. Conclusions: OFG is a rare syndrome that may occur in association with CD. OFG associated with CD may occur before, concurrently with, or after the diagnosis of CD and most often occurs in younger patients. Ileocolonic distribution of CD is a common association, in addition to the presence of upper GI involvement and perianal disease. Response may be achieved with a variety of immunosuppressive therapies, including biologic agents approved for treatment of CD. However, treatment of OFG remains challenging and patients should be counseled that OFG may be characterized by partial responses and periodic worsening and may require long-term therapy.