Case report
An otherwise healthy 18-year-old female was referred for gingival overgrowth and desquamative gingivitis to the Department of Oral and Maxillofacial Diseases Head and Neck Center, Helsinki University Hospital, Helsinki, Finland.
The patient did not have any systemic diseases, medications, or gastrointestinal symptoms; neither did she smoke or use alcohol regularly. She had an allergy to cats, dogs, and horses. There was no family history of IBD or other autoimmune diseases.
Histopathological examination of a biopsy from gingival overgrowth in the right incisal-premolar region of the maxilla revealed normal surface epithelium with a slight decrease in cell cohesion. Under the epithelium, among the inflammatory cells, granuloma structures with histiocytic and multinucleated giant cells were seen (August 2017) (Figure 1). Having found this granulomatous inflammation, the pathologist raised the possibility of Crohn’s disease. Consequently, the patient was referred for gastro- and colonoscopy with biopsies, which all turned out normal. Liver and kidney laboratory tests, including celiac antibodies and CRP, were normal. Microcytic anemia was considered to be associated with menstruation and was treated with iron supplementation. Sarcoidosis was ruled out by an ear, nose, and throat specialist.
The first appointment at the Department of Oral and Maxillofacial Diseases Head and Neck Center, Helsinki University Hospital was one year after initial examinations (August 2018). The patient still had no gastrointestinal symptoms at that time. According to the patient, the only symptom was bleeding gums when brushing her teeth. The patient brushed her teeth twice a day with fluorine toothpaste, but interdental cleaning was not performed regularly. Non-foaming, sodium lauryl sulfate free toothpaste and interdental cleaning with a silicone brush were recommended. Eating and drinking habits were recorded in more detail. The patient consumed cola drinks three times per week; accordingly, she was asked to stop drinking cola drinks with benzoate compounds.
Extra- and intraoral clinical examination with panoramic tomography was performed. Extraoral findings were normal; facial skin and lips were healthy. Intraorally, the interproximal gums were swollen, with some periodontal pseudopockets 4 mm deep. The bleeding on probing (BOP) index was 18%, measured from six sites per tooth. There were no infection foci, no alveolar bone loss, no caries, and no periapical lesions in panoramic tomography. Professional anti-infective treatment was performed, and oral self-care instructions were given. After five months, oral self-care was improved and the BOP index dropped under 10%; however, swollen gums in interproximal areas were still seen in the upper jaw. A biopsy was taken in March 2019 from the marginal gingiva in the maxillary canine region, revealing chronic inflammation.
Clinical examination with new laboratory tests were carried out after six months (October 2019). Clinically, the lower lip was slightly swollen, angular cheilitis with cracks in the corners of the mouth was seen (Figure 2A), and gingiva in right upper maxilla was swollen (Figure 2B). Other oral mucosal lesions (OMLs) included small tissue tags in the sulcus in the lower jaw (Figure 2C) and in the base of the mouth. In laboratory tests, complete blood count, antinuclear antibody (ANCA), and angiotensin-converting enzyme (ACE) turned out to be normal, but fecal calprotectin, which reflects inflammation in the colon and is a useful marker for IBD, was slightly elevated – 115 μg/g (reference < 100 μg/g). The patient had a gastroenterology consultation, but since no intestinal symptoms were found, and calprotectin was only slightly elevated, no further examinations were made at that point. Oral mucosal monitoring was recommended in our department.
A new biopsy was taken in November 2019 from the buccal sulcular fold and revealed chronic inflammation. Since the gums still bled easily, some extra laboratory tests (S-Ferrit, P-TfR, S-B12-TC2, fS-Folaat, P-D 25) were made. Ferritin (S-Ferrit) 11 μg/l (15–125 μg/l), and vitamin D 23 nmol/l (> 50 nmol/l) were under the reference values. Ferritin and vitamin D supplementation were recommended. Still, no other symptoms except bleeding on brushing were noticed by the patient. Laboratory values were controlled, and both ferritin and vitamin D values were corrected.
The patient was closely followed up in our clinic, and supportive periodontal therapy was arranged on regular basis.
Almost four years after oral granulomatous inflammation was first diagnosed, the patient complained of abdominal pain for the first time (February 2021). Beginning autumn 2020, she suffered from diarrhea twice a week. The gums were swollen and the mouth was sore, she had cracked lips and angular cheilitis. Intraoral examination revealed swollen marginal hyperplastic strawberry-like gingivitis and slightly folded mucosa in the sulcus areas of the maxilla (Figure 2D-E). The gingiva bled easily on probing. A biopsy was taken from the swollen, inflamed area of the left premolar area of the maxilla. Histopathologically, granulomatous inflammation was diagnosed. Fecal calprotectin was elevated – 186 µg/l. fS-ACE, P-Ferrit, S-D-25, and ANCA were within the reference limits. See Table 1 for details for main oral and systemic symptoms, manifestations, and pathology, laboratory and end­­­oscopy findings.
A colonoscopy performed in April 2021 showed segmental mild inflammation in the colon and rectum. Mucosal biopsies confirmed a diagnosis of Crohn’s disease. Gastroscopy was normal. Magnetic resonance imaging (MRI) revealed an uncomplicated and asymptomatic perianal fistula. The patient was started on standard intravenous infliximab. A repeated colonoscopy in March 2022 showed moderate pancolitis, and the patient was shown to be a non-responder to infliximab therapy. In addition, oral lesions (sore mouth, lips and corners of the mouth cracking easily, swollen gingiva/folded mucosa) persisted (Figure 2F-I). She was switched to subcutaneous ustekinumab in May 2022.
At the time of the diagnosis of Crohn’s disease, alkaline phosphatase (ALP) was elevated – 425 U/L (reference 35–105 U/L) – and alanine aminotransferase (ALT) was 214 U/L (reference < 35 U/L). A liver biopsy showed findings consistent with primary sclerosing cholangitis (PSC). An endoscopic retrograde cholangiography (ERC) in November 2021 showed slight biliary narrowing of the common hepatic duct and choledochus, in line with mild PSC.