Asymptomatic Inflammatory Bowel Disease Presenting With Mucocutaneous Findings
Sheila S. Galbraith et al.
Abbreviations: IBD, inflammatory bowel disease • 6-MP, 6-mercaptopurine • ESR, erythrocyte sedimentation rate
Inflammatory bowel disease (IBD) is a group of gastrointestinal disorders characterized by relapsing and remitting signs and symptoms. Intestinal manifestations such as abdominal pain, diarrhea, fever, weight loss, and extraintestinal manifestations including mucocutaneous lesions, iritis, and arthritis may be associated with IBD. Mucocutaneous lesions are relatively common during the course of IBD. Less commonly, however, they can be a presenting finding, thereby alerting the clinician to the diagnosis of IBD before the onset of gastrointestinal symptoms. We describe 9 children from 2 medical institutions in whom mucocutaneous lesions preceded abdominal manifestations and led to an early diagnosis of IBD.
Patient 1
A 6-year-old white boy presented with a 5-month history of intermittent upper-lip swelling associated with eczematous skin changes and gingival edema (Fig 1). Over the subsequent 3 years, he developed worsening of the upper-lip swelling as well as angular cheilitis and lower-lip involvement (Fig 2). He denied any systemic symptoms including facial paralysis, abdominal pain, and diarrhea. A biopsy specimen from the oral mucosa showed a hyperplastic mucosa with spongiosis and a dense lymphocytic infiltrate with small granulomas in the submucosa. Patch tests, complete blood count, tuberculosis skin tests, chest radiograph, and pulmonary function tests were within normal limits.
A repeat biopsy was planned because of lack of improvement with several therapies including topical steroids, antihistamines, amoxicillin-clavulanate, and minocycline for presumed Melkersson-Rosenthal syndrome. On returning to the clinic for biopsy, his mother mentioned a perianal pustule that had been present for some time. Given this new information, the oral biopsy was not performed; he instead was referred to a gastroenterologist. The patient was found to have microcytic anemia (hemoglobin: 11.1 g/dL; mean corpuscular volume: 75 fL) and hypoalbuminemia (3.3 g/dL) at that time. Esophagogastroduodenoscopy was unremarkable; however, patchy erythema, erosions, and pseudopolyps were seen during colonoscopy. Biopsies from the colon showed gastritis, terminal ileum granulomas, and granulomatous colitis, confirming the diagnosis of Crohn's disease.
The perianal lesion proved to be a fistula, and 6-mercaptopurine (6-MP) was started. Metronidazole was added intermittently to treat the fistula further. There was mild improvement of the granulomatous cheilitis; however, the fistula remained patent. Infliximab was started, with complete resolution of the oral lesions, closure of the fistula, and normalization of laboratory abnormalities after 3 infusions. He is in clinical and biochemical remission without intestinal or extraintestinal manifestations while maintained on scheduled 8- to 10-week-interval infliximab therapy.
Patient 2
An 8-year-old white boy had a 2-year history of recurrent oral ulcerations with hyperplastic ridges in the inferior gingival sulcus bilaterally (Fig 3). He denied any gastrointestinal symptoms. A previous oral biopsy was reviewed and showed a small granuloma in the submucosa. He also had a history of perianal skin tags and fissures. Gastrointestinal evaluation revealed esophagitis, gastritis, and multiple aphthous ulcers in the sigmoid colon. Biopsy specimens showed esophagitis with granulomas and granulomatous colitis consistent with Crohn's disease. Work-up subsequently revealed hypoalbuminemia (3.2 g/dL) and an elevated erythrocyte sedimentation rate (ESR) (32 mm/hour). Monotherapy with 6-MP resulted in resolution of his oral ulcers.
Patient 3
A 12-year-old obese white boy (body mass index: 97th percentile) presented with a 6-month history of an erythematous plaque on his right lower extremity that more recently had become warm to the touch, tender, and ulcerated with indurated violaceous borders (Fig 4). The patient denied any trauma to the area. Two biopsies performed elsewhere were consistent with folliculitis, and the patient had been treated with Augmentin and topical antibiotics with no improvement. Repeat biopsy showed suppurative folliculitis which, along with the typical clinical presentation, was consistent with pyoderma gangrenosum. Fungal culture and acid-fast bacillus stains were negative. His ESR was slightly elevated (14 mm/hour). The patient denied any gastrointestinal complaints, but upper and lower endoscopy showed multiple ulcerations in the gastric antrum and ileum. Biopsy specimens showed gastritis, ileitis, and crypt destruction with giant-cell reaction in the colon consistent with Crohn's disease. He initially received intralesional corticosteroids for the pyoderma gangrenosum; however, after the diagnosis of Crohn's disease was made, infliximab and methotrexate were initiated, which led to almost complete resolution of the pyoderma gangrenosum.
In our series of children with silent IBD, mucocutaneous lesions appeared before gastrointestinal signs as the manifestation of Crohn's disease (8 of 9) or ulcerative colitis (1 of 9). (Table 1 provides a summary of these cases.) Of the 9 patients, 8 were male, and the mean age was 8 years. Although patients with IBD tend not to be overweight, 2 of our patients were obese (patients 3 and 8). Six children presented with oral manifestations, 1 had genital lesions, and 2 had pyoderma gangrenosum. All patients were asked about gastrointestinal symptoms, fever, weight loss, and joint pain at presentation and denied any such symptoms. The majority of our patients (7 of 9) had perianal lesions at presentation; however, several of the perianal lesions were not discovered on initial evaluation but only became apparent during subsequent examinations. The time to diagnosis of IBD after development of the mucocutaneous findings ranged from 1 month to 42 months. In general, patients with oral and perianal lesions experienced a longer time until diagnosis compared with patients with lesions that presented elsewhere. One patient (patient 8) was diagnosed with Crohn's disease on repeat endoscopy after the initial endoscopy that was performed 1.5 years prior was normal. In all patients followed after instituting therapy, the mucocutaneous lesions responded to therapy for their IBD.