A Surprising Granulomatous Cheilitis

Abstract

Question: A 17-year-old Algerian girl who had lived in France for 2 years was referred to our dermatologic unit for a painful infiltrated crusty cheilitis. She was under anti–tumor necrosis factor-α (anti-TNF-α) therapy for active Crohn disease (CD). CD was diagnosed in 2011 on rectal bleeding, weight loss and ileal ulcerations at colonoscopy. She was previously treated with 5-ASA and azathioprine without efficacy. Adalimumab was introduced in May 2015 after a pretherapeutic evaluation that included negative interferon-gamma release assay (IGRA). Dose of adalimumab was majored to 40 mg per week in December 2015 because her CD remained active. Four months later, labial lesions appeared, with edema and vesicles, and progressed to a painful infiltrated and crusty cheilitis. Antibiotics and valaciclovir treatments were unsuccessful. Oral examination revealed a unilateral cobblestone aspect with pustules on the lip mucosa without affecting the rest of oral cavity (Figure A, B). A centimetric right cervical adenopathy was noticed. She did not have any other complaints, and the rest of physical findings were normal. Laboratory results from blood chemistry, complete blood cell count, liver, and kidney analysis were within reference range. C-reactive protein was elevated (117 mg/L). Infectious workup (human immunodeficiency virus and syphilitic serology, leishmania, and herpes polymerase chain reaction) was negative. Standard chest radiography was normal. Magnetic resonance enterography revealed an asymptomatic terminal ileitis with an enhancement of the submucosa. Labial biopsies showed an epithelioid and giant cell granuloma without caseous necrosis (Figure C); Ziehl-Neelsen, Grocott and periodic acid–Schiff stains were negative for acid-fast bacilli and fungi, respectively. No viral inclusion body was seen. What is the diagnosis? Look on page 1240 for the answer and see the Gastroenterology website (www.gastrojournal.org) for more information on submitting your favorite image to Clinical Challenges and images in GI. Initially, we suspected cutaneous metastatic Crohn’s disease. Indeed, she had severe CD resistant to a classical dose of adalimumab, and histology revealed a noncaseous granulomatous skin lesion. Negative special stains for bacteria, fungi, and parasites failed to show any microbiologic organism. New lip biopsies were performed for tuberculosis (TB) cultures, IGRA was repeated, and her treatment was intensified with infliximab and azathioprine. Two weeks later, Mycobacterium tuberculosis culture was positive on the tissue specimen. IGRA, negative before anti-TNF-α therapy, was positive. A computed tomography scan revealed nodular and micronodular opacities in superior lobes, associated with ground glass opacities. M tuberculosis was secondary found in sputum cultures. The new retained diagnosis was a TB cutis orificialis or orificial TB,1Kakisi O.K. Kechagia A.S. Kakisis I.K. et al.Tuberculosis of the oral cavity: a systematic review.Eur J Oral Sci. 2010; 118: 103-109Crossref PubMed Scopus (69) Google Scholar secondary to autoinoculation from an active pulmonary TB under anti-TNF-α therapy for a CD. After 3 weeks of anti-TB therapy and infliximab discontinuation, the lesions started to heal and showed complete resolution at the end of 6 months of treatment. Because the distinction between intestinal TB and CD is a significant source of error, colonoscopy was repeated and confirmed ileitis (Figure D). Biopsies showed a focally active ileitis with granuloma and rare giant cells without caseous necrosis. Ziehl-Neelsen staining and culture were negative after 3 months. These findings were consistent with the initial diagnosis of CD. The main cause of diagnosis error is the absence on caseous necrosis and the lack of sensibility of Ziehl stain on histologic analyses.2Wei J.-P. Wu X.-Y. Gao S.-Y. et al.Misdiagnosis and mistherapy of Crohn’s disease as intestinal tuberculosis: case report and literature review.Medicine (Baltimore). 2016; 95: e2436Crossref PubMed Scopus (11) Google Scholar TB in a context of anti-TNF-α therapy is difficult to diagnose with few symptoms, extrapulmonary presentations, and a potentially severity with a rapid evolution. This observation suggests a repeated screening for TB during the follow-up of these patients, all the more if other risk factors are associated, namely, concomitant immunosuppressant use, a history of latent or active TB, birth or travel in endemic region of TB, and/or exposure to a person with TB.3Shim T.S. Diagnosis and treatment of latent tuberculosis infection in patients with inflammatory bowel diseases due to initiation of anti-tumor necrosis factor therapy.Intest Res. 2014; 12: 12-19Crossref PubMed Google Scholar