Identification of Mycobacterium cosmeticum sp. as a novel colitogenic infectious agent in a nonimmunocompromised patient.

We report here the first case of a nonimmunocompromised patient who developed a severe diffuse granulomatous colitis induced by a nontuberculous mycobacteriosis typed Mycobacterium cosmeticum that had never been identified to date as a colitogenic infectious agent. A 32-year-old Turkish patient was admitted complaining of dull abdominal pain, bloody diarrhea, and fever for 1 month. His personal and familial medical history was unremarkable. He emigrated to France 1 year previously, took no drugs, and had no toxic habits. No professional exposure in metals, including beryllium, was recorded. On admission, physical examination showed abdominal distension, tympanism, and tenderness in the right lower quadrant without abdominal mass and a substantial progressive loss of weight ( 4 kg in the last month). The liver, spleen, and superficial lymph nodes were not palpable. Skin examination failed to detect any lesions. Routine blood analysis showed an iron-deficiency anemia, whereas platelets and white blood cell counts as well as liver function tests were normal. Serum C-reactive protein was elevated (159 mg/L; normal <2 mg/L). Chest radiography and urinary analysis were unremarkable. Blood and stool culture including the use of selective culture media failed to detect any pathogenic bacteria or parasites and repeated tests by enzyme-linked immunosorbent assay (ELISA) for Clostridium difficile cytotoxins A and B were negative. The serologies for HIV, HTLV, HSV, CMV, EBV, and Yersinia, Campylobacter, Salmonella, and Shigella were negative. Abdominal computed tomography (CT) scan revealed a severe transmural segmental colitis located on the ascendant and transverse colon associated with centimetric mesenteric adenomegaly. The chest CT scan was normal. A rectosigmoidoscopy with biopsy revealed no macroscopic and histologic distal colonic lesions. The patient was empirically treated conservatively with intravenous antibiotics (ofloxacine 400 mg/ d and ceftriaxone 1 g/d) and parenteral nutritional support for 1 week without any evidence of clinical improvement. In contrast, the patient remained febrile and presented evident clinical signs of intestinal obstruction confirmed by a CT scan showing a more severe transmural ascendant and right transverse colitis associated with a small bowel distension. Therefore, the scheduled colonoscopy was canceled and the patient underwent an exploratory laparotomy and a segmental ascendant and right transverse colectomy with an ileotransverse anastomosis protected by a temporary loop ileostomy. Histologic analysis of the colon specimen confirmed a severe transmural colitis surprisingly associated with multiple nonnecrotizing epithelioid granulomas characterized by multinucleated Langhans giant cells located both into the colon lamina propria and mesenteric adenomegaly (Fig. 1). Histopathological colonic specimens revealed neither acid-alcohol-resistant bacilli on Ziehl-Neelsen staining nor intestinal parasites (Microsporidia, Cryptosporidia sp., Isospora belli). In addition, intestinal biopsy specimen cultures for mycobacteria, pathogenic bacteria species (Salmonella, Yersinia, Shigella, and Campylobacter) and yeast were negative. After surgery, the clinical outcome was progressively favorable. Cytomegalovirus (CMV) viral load assessed by polymerase chain reaction (PCR) and specific PCR detection for Tropheryma whipplei in colon were also negative. Serum immunoglobulin IgG, IgM, and IgA levels, LDH, b2-microglobulin, and angiotensin-converting enzyme were normal. Neither antinuclear antibodies (ANA) nor anti-Saccharomyces cerevisiae antibodies (ASCA) and perinuclear antineutrophil cytoplasmic antibodies (pANCA) were detectable in serum. A chronic granulomatous disease was excluded by a fluorescence activated-cell sorter (FACS) test using dihydrorhodamine 123. The patients did not manifest evidence of albinism or prolonged bleeding time and platelet dysfunction suggestive of Hermansky– Pudlak syndrome. Early morning urines samples and Mantoux Tb skin test did not demonstrate evidence of tuberculosis. Two months later and before closing the stoma, the patient was asymptomatic and an ileocolonoscopy revealed the presence of discontinuous reddish inflammatory lesions on the colonic mucosa with sometimes superficial erosions. Histopathological analysis of the multiple biopsy specimens performed on the left colon, sigmoid, and rectum showed similar previous microscopic findings, i.e., marked edema, diffuse inflammatory infiltrates, and extensive noncaseous epithelioid cell granulomas. In contrast, endoscopic and systematic histologic examination of the distal ileum was unremarkable. Interestingly, whereas Mycobacteria tuberculosis complex was undetectable, nontuberculous mycobacteria species were identified in colonic biopsies by a LightCycler real-time PCR-based method using our original species-specific probes (Patent WO/2007/034118) with a detection sensitivity of 5.10 CFU/mL. The following specific forward primers used were 50-ACCAACGATGGT GTGTCCAT-30 and reverse primers 50Copyright VC 2011 Crohn’s & Colitis Foundation of America, Inc. DOI 10.1002/ibd.21804 Published online 7 July 2011 inWiley Online Library (wileyonlinelibrary.com).