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Yersiniosis is an infectious disease caused by a bacterium of the genus Yersinia. In the United States, most human illness is caused by one species, Yersinia enterocolitica (Y. enterocolitica). Infection with Y. enterocolitica occurs most often in young children. more...

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Infection with Y. enterocolitica can cause a variety of symptoms depending on the age of the person infected. Common symptoms in children are fever, abdominal pain, and diarrhea, which is often bloody. Symptoms typically develop 4 to 7 days after exposure and may last 1 to 3 weeks or longer. In older children and adults, right-sided abdominal pain and fever may be the predominant symptoms, and may be confused with appendicitis. In a small proportion of cases, complications such as skin rash, joint pains, or the spread of bacteria to the bloodstream (bacteremia) can occur.


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Granulomatous colitis associated with botryomycosis of propionibacterium acnes
From Archives of Pathology & Laboratory Medicine, 11/1/01 by Wada, Ryuichi

* Propionibacterium acnes, an anaerobic, non-spore-forming, gram-positive bacillus, is a common inhabitant of the skin, and its virulence is considered to be low in humans. This report describes an unusual case of granulomatous colitis associated with P acnes infection in a 46-year-old woman. The affected cecum exhibited a tumor histologically characterized by massive transmural infiltrates of small lymphocytes and noncaseating epithelioid granulomas with multinucleated giant cells. Botryomycotic granules were also found in the muscular layer and paracolic connective tissues and consisted of gram-positive bacilli with filamentous growth. Polymerase chain reaction confirmed the presence of P acnes 16S ribosomal DNA in the surgical specimen of the colon. The patient developed a postoperative P acnes-induced peritonitis, which subsided with treatment with antibiotics and surgical drainage. The present case indicates that P acnes is one of the possible pathogens for granulomatous colitis.

(Arch Pathol Lab Med. 2001;125:1491-1493)

Propionibacterium aches is an anaerobic, non-spore-forming, gram-positive bacillus. This microorganism is a normal inhabitant in the skin, conjunctiva, respiratory tract, genitourinary tract, and gastrointestinal tract.1 It is generally considered that this organism has a low virulence to humans. Although severe opportunistic infections are infrequently encountered, patients with such infections usually develop acute purulent lesions in association with foreign bodies, previous surgical procedures, valvular diseases, diabetes mellitus, and previous steroid therapy. We herein report an unusual case of granulomatous colitis associated with botryomycosis of P aches. To the best of our knowledge, P aches infection in the colon has not been described in the literature.


A 46-year-old woman visited the Aomori Prefectural Hospital on May 16, 1997, with a complaint of lower abdominal pain. Her medical history was unremarkable. She had no history of steroid therapy or antibiotic therapy. The results of laboratory tests showed the presence of iron deficiency anemia. Her white blood cell count was 8.5 X 10^sup 9^/L, and her erythrocyte sedimentation rate was 103 mm/h. The tuberculin test result was negative. There was no evidence of diabetes mellitus or immune deficiency. There was no abnormal shadow in the lung field or swelling of hilar lymph nodes apparent on the chest x-ray films. Barium enema revealed a filling defect in the cecum (Figure 1, A), and colon endoscopy demonstrated a tumor mass with smooth surface at the appendical orifice of the cecum (Figure 1, B). There was no ulcer or cobblestone appearance, and other parts of the colon and ileum appeared normal. Biopsy specimens taken from the tumor showed a marked infiltration of lymphocytes in the lamina propria and submucosa of the colon.

The patient underwent an exploratory laparotomy under the suspicion of malignant tumor of the cecum or appendix. The wall of the cecum and ileum appeared to be fibrotic, and the paracolic lymph nodes were swollen. The omentum was adhered to the terminal ileum and cecum. Ileocecal resection was done, and the resected colon was subjected to histologic and microbiologic examinations. Microbiologic examinations on the specimens taken from the mucosal surface of the colon and cut surface of lymph nodes both revealed small amount of Bacteroides uniformis and Bacteroides vulgatus, whereas results of the examinations for Mycobacterium tuberculosis and Yersinia pseudotuberculosis were negative. After the operation, the patient was treated with cefmetazole at 2.0 g/d for 5 days.

Two weeks after the operation, the patient complained of abdominal pain and manifested severe signs of peritoneal irritation. Her white blood cell count increased to 10.1 x 10^sup 9^/L. She was treated with cefpodoxime at 600 mg/d and penicillin G at 1000 000 U/d for 3 days, but her symptoms persisted. She received peritoneal drainage, from which P acnes and Bacteroides fragilis were cultured. She was then treated with piperacillin, 4.0 g/d, for 6 days. Subsequent course was uneventful, and she was discharged.


Histologic examinations of the cecum showed an extensive transmural infiltration of small lymphocytes and noncaseating epithelioid granulomas (Figure 2, A). The granulomas consisted of epithelioid cells and multinucleated giant cells (Figure 2, B). The granulomas were also found in the appendical mucosa and paracolic lymph nodes and often consisted of palisading epithelioid cells with central coagulative necrosis (Figure 2, C). There was no atypical gland or crypt abscess in the mucosa.

In the proprial muscular layer of the cecum, there were bacterial aggregates forming so-called botryomycotic granules associated with edema and small hemorrhage and surrounded by accumulated lymphocytes (Figure 3, A). The foci extended to the paracolic connective tissues. The granules were approximately 200 to 300 Vm in diameter. They were positively stained with Gram and Gomori methenamine-silver stain, showing rodlike structure with arborizing growth pattern, which was consistent with features of P aches (Figure 3, B).2 They were also positive for periodic acid-Schiff reaction but not for acid-fast staining. No other microorganisms were detected on the sections.


Propionibacterium aches 16S ribosomal DNA (rDNA) in the surgical sections was semiquantitated by polymerase chain reaction (PCR). Template DNA was extracted from the paraffin sections of the cecum that contained the botryomycotic granules of the current case, followed by the method described by Hykin et al.3 As control, paraffin sections of the cecum with colon cancer were used. Four hundred nanograms of extracted DNA was applied as template. The primers used for the assay were F: 5'AAGGCCCTGCTTTTGTGG-3' and R: 5'-TCC-ATCCGCAACCGCCGAA-3'.3 Fluorescent intensity of bands of PCR products electrophoresed in 3% agarose gel was measured by NIH Image (National Institutes of Health, Bethesda, Md), and copy numbers of the gene in the specimens were semiquantitated. A clear single band of 160 base pairs was amplified from the specimen of the current case and a faint band from control specimen (data not shown). Sequencing of these PCR products confirmed 98% homology to P aches 16S rRNA gene sequences registered in GenBank (AF076032, AF145256, and AF154832). The copy number of P aches 16S rDNA present in the surgical specimen of the current case was approximately 37-fold the levels in control specimen.


Propionibacterium aches infection usually manifests as an acute purulent lesion. This microorganism is known to stimulate an immune system and cause a granulomatous reaction. Propionibacterium aches has been identified as a causative agent for the granulomatous lesions in cases of meningitis,4 pneumonia 5 hepatitis,6 and soft tissue inflammation.7 To the best of our knowledge, the current case was the first case of P aches infection in the colon. The pathologic structure of the infected colon was characterized by a granulomatous inflammation associated with botryomycotic granules of P aches.

The ileocecal region is preferentially affected with granulomatous diseases, such as Crohn disease, tuberculosis, and other infectious diseases.8 The diagnosis of these diseases requires careful clinical, histologic, and microbiologic examinations. The infection of P aches in the present case was evident by the botryomycotic granules and amplification of 16S rDNA by PCR. Beeken and Kanich9 reported a change of the intestinal flora and overgrowth of P aches in Crohn disease. Propionibacterium aches is a normal inhabitant in the intestine, and this microorganism may overgrow in the colon under altered environmental conditions. There may be a critical question regarding whether this microorganism is a primary etiologic agent for the granulomatous lesions or an agent simply superimposed to the preexisting inflammatory bowel diseases. This issue is important in making a definitive diagnosis and deciding an appropriate therapy.

The clinicopathologic features of the current case were different from those found in the typical Crohn disease or other specific inflammatory bowel diseases. Our case lacked skip lesions, fissurings, and circumferential ulcers. Systemic signs, such as swellings of the hilar lymph nodes and immunologic abnormalities, were not present, In surgical specimens, Gaseous necrosis and necrotizing lymphadenitis characteristic of tuberculosis and yersiniosis were absent. The current case lacked any evidence for other underlying colon diseases or systemic diseases. In addition, results of microbiologic examinations were negative for microorganisms that cause granulomatous lesions such as M tuberculosis,10 Y pseudotuberculosis,11 Salmonella spp,12 or Campylobacter spp.13 Instead, we could identify P aches in the resected colon as the botryomycotic granules. It is therefore likely that P aches attributed to the granulomatous inflammation of the colon in our case. Although further cases and pathologic changes need to be analyzed in more detail, P aches should be considered as one of the causative microorganisms of granulomatous colitis.

Identification of P aches in clinical specimens by bacteriologic culture has been difficult. The isolation of P aches requires long incubation under anaerobic condition. This bacterium is occasionally considered as a contaminant in clinical specimens. Once the surgical specimens are exposed to an aerobic condition or fixed in formalin for routine pathologic examinations, it becomes unfeasible to isolate this microorganism by culture. On histologic examination, P aches looks like a highly pleomorphic gram-positive rod, and it may show a beaded appearance and branching.2 Gram, PAS, and Gomori methenamine-silver stainings could reveal the characteristic appearances of this bacterium, and plastic embedding may also be useful for the detailed observation of this microorganism.14 Because of the applicability of formalin-fixed paraffin-embedded materials to PCR analysis, we can now have a sensitive diagnostic option for P aches infection to differentiate from other common granulomatous diseases of the colon.


1. Brook I. Anaerobic gram-positive nonsporulating bacilli. In: Mardell G, Douglas RG, Bennett JE, eds. Principles and Practice of Infectious Disease. New York, NY: Churchill Livingston; 1995:2206-2208.

2. Schaal KP, Schofield GM, Pulverer G. Taxonomy and clinical significance of Actinomycetaceae and Propionibacteriaceae. Infection. 1980;8(suppl 2):57225130.

3. Hykin PG, Tonal K, McIntyre G, Matheson MM, Towler HM, Lightman SL. The diagnosis of delayed post-operative endophthalmitis by polymerase chain reaction of bacterial DNA in vitreous samples. J Med Microbiol. 1994;40:408415.

4. French RS, Ziter FA, Spruance SL, Smith CB. Chronic meningitis caused by Propionibacterium acnes: a potentially important clinical entity. Neurology. 1974; 24:624-628.

5. Claeys G, Verschraegen G, De Potter C, Cuvelier C, Pauwels R. Bronchopneumonia caused by Propionibacterium acnes. Eur] Clin Microbiol Infect Dis. 1994; 13:747-749.

6. Ullmann Aj, Helm reich-Becker I, Maeurer MJ, et al. Hepatic granuloma due to Propionibacterium acnes in a patient with acute myelogenous leukemia. Clin Infect Dis. 2000;30:219-220.

7. Esteban J, Cuenca-Estrella M, Ramos JM, Soriano F. Granulomatous infection due to Propionibacterium acnes mimicking malignant disease. Fur J Clin Microbiol Infect Dis. 1994; 13:1084.

8. Lavy A, Militianu D, Eidelman S. Diseases of the intestine mimickingCrohn's disease. J Clin GastroenteroL 1992;15:17-23.

9. Beeken WL, Kanich RE. Microbial flora of the upper small bowel in Crohn's disease. Gastroenterology. 1973;65:390-397.

10. Ehsannulah M, Isaacs A, Filipe MI, Gazzard BG. Tuberculosis presenting as inflammatory bowel disease: report of two cases. Dis Colon Rectum. 1984; 27:134-136.

11. Macfarlane PI, Miller V. Yersinia enterocolitica mimicking Crohn's disease. J Pediatr Gastroenterol Nutr. 1986;5:671.

12. Vender RJ, Marignani P. Salmonella colitis presenting as a segmental colitis ' resembling Crohn's disease. Dig Dis Sci 1983;28:848-851.

13. Green ES, Parker NE, Gellert AR, Beck ER. Campylobacter infection mimicking Crohn's disease in an immunodeficient patient. BMJ. 1984;289:159-160. 14. Schwartz DA, Finkelstein SD. Propionibacterium acnes cerebral botryo

mycosis: the role of plastic embedding in the diagnosis of grain-producing infections. Am] Clin Pathol. 1986;86:682-685.

Ryuichi Wada, MD, PhD; Chizuko Kawamura, MT; Shigeaki Inoue, MD, PhD; Kunitomo Watanabe, MD, PhD; Mitsuomi Kaimori, MD, PhD; Soroku Yagihashi, MD, PhD

Accepted for publication May 31, 2001.

From the Department of Pathology, Hirosaki University School of Medicine, Hirosaki, Japan (Drs Wada and Yagihashi); Departments of Clinical Pathology (Ms Kawamura and Dr Kaimori) and Surgery (Dr Inoue), Aomori Prefectural Central Hospital, Aomori, Japan; and Institute of Anaerobic Bacteriology, Gifu University School of Medicine, Gifu, Japan (Dr Watanabe).

Reprints: Ryuichi Wada, MD, PhD, Department of Pathology, Hirosaki University School of Medicine, 5 Zaifu-cho, Hirosaki 036-8562, Japan (e-mail:

Copyright College of American Pathologists Nov 2001
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