To the Editor:

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, β2-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 5.103 CFU/mL. The following specific forward primers used were 5′-ACCAACGATGGT GTGTCCAT-3′ and reverse primers 5′-CTTGTCGAACCGCATACCCT-3′.1 The amplified 16sRNA gene from Mycobacteria sp. in colonic biopsy specimens were then sequenced allowing identification of a M. cosmeticum sp. Hence, the patient was orally treated with antibiotics (clarithromycin 500 mg plus ofloxacin 500 mg twice daily) for 3 months. After treatment the patient was asymptomatic and no endoscopic and histologic recurrence was recorded. Further search for mycobacteria by PCR analysis from colonic biopsies remained negative. Closure of the stoma was finally performed and 4 years later the patient remained free of recurrence.

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Figure 1. Representative picture of the multiple nonnecrotizing inflammatory granulomas with multinucleated giant cells (arrows) in the colon of a patient with a severe colitis induced by Mycobacterium cosmeticum sp. [Color figure can be viewed in the online issue, which is available at]

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Few observations have described the occurrence of a nontuberculous mycobacteriosis in the gut occurring in an immunocompetent patient. The type strain M. cosmeticum sp. (ATCC BAA878T) is a rapidly growing, nontuberculous pathogenic mycobacteria species first isolated in 2004 from a culture of a sink drain in a nail salon and from a granulomatous skin lesion in a female patient undergoing mesotherapy in Venezuela.2 Several other cases of skin and soft tissue infection involving M. cosmeticum sp. and following mesotherapy were reported.3 The pathogenic potential of M. cosmeticum sp. has also been illustrated by three additional cases in which this mycobacterium subspecies was responsible for a pulmonary disease and for a catheter-associated bacteremia.4 In these cases, identification of M. cosmeticum sp. was confirmed by both high-performance liquid chromatography mycolate analyses and by PCR restriction (partial sequences of the rpoB, 16SrRNA, and hsp65 genes previously demonstrated as distinct from those of all recognized mycobacterium species). To the best of our knowledge, the present case represents the first one reporting M. cosmeticum sp. as a colitogenic agent. Because many of the nontuberculous mycobacteria are ubiquitous, distinguishing between colonization and active infection often remains difficult. However, in our case its degree of imputability in the granulomatous colitis is based on 1) its identification by specific PCR (confirmed by sequencing) from several colon biopsy specimens; 2) the absence of other etiology leading to a symptomatic granulomatous colitis despite extensive clinical and laboratory investigations; 3) the beneficial impact of long-standing antibiotics known to have a consistent efficacy against atypical mycobacteria; and finally 4) the absence of further recurrence of the infectious disease despite a several-year follow-up. However, the means of contamination in our report remains unknown since the patient was never undergoing mesotherapy or beauty care. In addition, infection by M. cosmeticum sp. occurred in a nonimmunocompromised patient as assessed by a normal count of circulating T-lymphocyte subsets, a normal concentration of serum immunoglobulins, the absence of phagocyte dysfunction, or immunosuppressive treatment.

In conclusion, M. cosmeticum sp. is a new colitogenic agent capable to mimic Crohn's disease or intestinal tuberculosis and able to be pathogenic. The means of contamination remains unknown and exposure through the food chain may not be excluded. This case emphasizes the critical contribution of specific PCR for the detection and the identification of the subspecies of nontuberculous mycobacteria from histopathologic tissue specimens and stress the need to search for emerging pathogens responsible for intestinal granulomatous inflammation.


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  • 1
    Telenti A, Marchesi F, Balz M, et al. Rapid identification of Mycobacteria to the species level by polymerase chain reaction and restriction enzyme analysis. J Clin Microbiol. 1993; 31: 175178.
  • 2
    Cooksey RC, de Waard JH, Yakrus MA, et al. Mycobacterium cosmeticum sp. nov., a novel rapidly growing species isolated from a cosmetic infection and from a nail salon. Int J Syst Evol Microbiol. 2004; 54: 23852391.
  • 3
    Beer K, Waibel J. Disfiguring scarring following mesotherapy-associated Mycobacterium cosmeticum infection. J Drugs Dermatol. 2009; 8: 391393.
  • 4
    Cooksey RC, de Waard JH, Yakrus MA, et al. Mycobacterium cosmeticum, Ohio and Venezuela. Emerg Infect Dis. 2007; 13: 12671269.

Gilles Boschetti MD* ¶, Eddy Cotte MD†, Driffa Moussata MD*, Marion Chauvenet MD*, Franck Breysse PhD‡, Monique Chomarat PhD‡, Sylvie Isaac MD§, Françoise Berger MD§, Dominique Kaiserlian PhD¶, Stéphane Nancey MD* ¶, Bernard Flourie MD* ¶, * Hospices Civils de Lyon, Service d'Hépato-Gastroentérologie, Centre Hospitalier Lyon-Sud, Lyon-Sud, France, † Service de Chirurgie Générale, Centre Hospitalier Lyon-Sud, Lyon-Sud, France, ‡ Laboratoire de Microbiologie, Centre Hospitalier Lyon-Sud, Lyon-Sud, France, § Laboratoire d'Anatomie Pathologique, Centre Hospitalier Lyon-Sud, Lyon-Sud, France, ¶ INSERM, U851, 21 Avenue Tony Garnier, Lyon, 69007, France.