Colon Biopsy in a Patient With Diarrhea--Possible Etiologic Agent.
At colonoscopy, the mucosa appeared normal. Random biopsies from the colon were taken and submitted for histopathologic examination.
The colonic biopsies were composed of 4 small pieces of gray-tan tissue, each measuring 0.2 cm. The mucosa appeared architecturally normal, and there was minimal inflammation (Figure, a). The surface epithelium, however, was coated by a fuzzy blue, hematoxyphilic layer, as illustrated in the inset in the Figure, part a. This layer was composed of numerous slender organisms, as demonstrated by Warthin-Starry stain (Figure, b).
What is your diagnosis?
Pathologic Diagnosis: Intestinal Spirochetosis
Spirochetes have been described in the intestines of patients presenting with diarrhea. In several case reports, the abdominal symptoms of diarrhea and the presence of spirochetes have been eliminated from patients following treatment with agents such as metronidazole. The term intestinal spirochetosis (IS) was coined in 1967 to describe this condition. However, as a variety of other intestinal bacteria are also very susceptible to this agent, it is impossible to make a dogmatic statement regarding the pathogenicity of these spirochetes. Rodgers et al showed blunting and destruction of the cellular microvilli in cases of IS. They suggested that these cell surface changes, together with the presence of intracellular bacteria in the cells of the rectum, are the cause of the persistent diarrhea often associated with this condition. Ming and Goldman speculated that initial colonization by IS, like Helicobacter pylori, may produce mild symptoms followed by transition to an asymptomatic carrier state.
Spirochetes in humans and other species presumably result from fecal-oral contamination, but largely appear to be nonpathogenic. Spirochetes are part of the normal flora of pigs, although Treponema hyodysenteriae causes swine diarrhea. The colonization rate in human colon is variable and is influenced by many factors, including immune function, sexual practices, diet, sanitation, and community structure. The colonization rate of spirochetes in Europe is 2.5% to 9%; in the North of England, 1.5%; in Scotland, 6.9%[1,4]; in Washington, DC, 1.9%[1,4]; in Southern India, 64%; and in natives of West Africa, 100%. After World War I, the prevalence was 30% in Chicago, which was at least 10 times as high as that seen from 1975 to 1984. The prevalence in the homosexual population in the United States appears to be in the range of 28% to 36%.
There is no distinct symptom complex associated with IS. Diarrhea is the most common symptom, although in most patients with diarrhea, spirochetosis is an incidental finding. Invasive disease in human spirochetosis, although rare, has been described in 5 patients with advanced infection with the human immunodeficiency virus, 4 patients with symptomatic colitis,[5,6] and 1 patient with hepatitis. Dissemination to other organs is extremely rare.
There are no distinct gross or endoscopic findings. Ulcerative and pustular lesions have been described in 2 patients with invasive gastrointestinal spirochetosis. The lesions, when present, are usually found incidentally in biopsy specimens.
By light microscopy, 2 variants are described. The first is a fuzzy blue, 3- to 7-[micro]m-thick, hematoxyphilic line on the luminal border of the large intestine, which may be confused with glycocalyx and distinct larger organisms. The inflammatory response is usually minimal or absent. A local immune response in the form of an increase in immunoglobulin E-producing plasma cells has been described in one study. The organism is usually seen throughout the large bowel, but sometimes can be focal.
Spirochetes can be easily demonstrated using silver stains, such as Warthin-Starry or Churukian-Schenk stains. They also stain, although less intensely, with Giemsa, periodic acid-Schiff, and Alcian blue at pH 2.5. Immunohistochemistry using polyclonal spirochete antibodies may facilitate the histologic diagnosis, but generally is not very helpful. Electron microscopy and molecular studies can also be used not only to identify the spirochetes, but also to help determine the species of the spirochete. The 2 best-characterized human species are Brachyspira aalborgi and Serpulina pilosicoli.
Spirochetes are difficult to grow on culture media owing to their fastidious nature. They grow poorly or not at all in the absence of serum supplements. Due to this limitation, there are no published data characterizing the organisms. Jones et al isolated spirochetes from 11 homosexual males who had diarrhea using Trypticase soy agar supplemented with 5% horse or human blood and studied them biochemically. This study suggested that the human colon may harbor unique strains of cultivable spirochetes and that several different biotypes can be discerned.
Our patient underwent a complete workup, including testing for human immunodeficiency virus and syphilis, as well as stool studies for Cryptosporidium, ova and parasites, Clostridium difficile toxin, and culture, all of which were negative. In view of a mildly elevated transaminase level (aspartate aminotransferase, 67 mg/dL), a viral hepatitis workup was initiated, which was also negative (hepatitis A, B, and C). The patient was started on oral metronidazole with resolution of his symptoms in 3 to 4 days.
[1.] Abrams GD. Infectious disorders of the intestines. In: Ming SC, Goldman H, eds. Pathology of the Gastrointestinal Tract. 2nd ed. Baltimore, Md: Williams & Wilkins; 1998:664.
[2.] Trivett-Moore NL, Gilbert GL, Law CL, Trott DJ, Hampson DJ. Isolation of Serpulina pilosicoli from rectal biopsy specimens showing evidence of intestinal spirochetosis. J Clin Microbiol. 1998;36:261-265.
[3.] Rodgers FG, Rodgers C, Shelton AP, Hawkey CJ. Proposed pathogenic mechanism for the diarrhea associated with human intestinal spirochetes. Am J Clin Pathol. 1986;86:679-682.
[4.] Nielsen RH, Orholm M, Pedersen JO, Hovind-Hougen K, Teglbjaerg PS, Thaysen EH. Colorectal spirochetosis: clinical significance of the infestation. Gastroenterology. 1983;85:62-67.
[5.] Guccion JG, Benator DA, Zeller J, Termanini B, Saini N. Intestinal spirochetosis and acquired immunodeficiency syndrome: ultrastructural studies of two cases. Ultrastruct Pathol. 1995;19:15-22.
[6.] Kostman JR, Patel M, Catalano E. Invasive colitis and hepatitis due to previously uncharacterized spirochetes in patients with advanced human immunodeficiency virus infection. Clin Infect Dis. 1995;21:1159-1165.
[7.] Gebbers J-O, Ferguson DJP, Mason C, Kelly P, Jewell DP. Spirochetosis of the human rectum associated with an intraepithelial mast cell and plasma cell response. Gut. 1987;28:588-593.
[8.] De Brito T, Sandoval MP, Silva AG, Saad RC, Colaiacovo W. Intestinal spirochetosis: first cases reported in Brazil and the use of immunohistochemistry as an aid in histopathological diagnosis. Rev Inst Med Trop Sao Paulo. 1996;38:45-52.
[9.] Lee JI, McLaren AJ, Lymbery AJ, Hampson DJ. Human intestinal spirochetes are distinct from Serpulina hyodysenteriae. J Clin Microbiol. 1993;31:16-21.
[10.] Jones MJ, Miller JN, George WL. Microbiological and biochemical characterization of spirochetes isolated from the feces of homosexual males. J Clin Microbiol. 1986;24:1071-1074.
Accepted for publication September 18, 2000.
From the Departments of Surgical Pathology (Drs Shah and Badve) and Infectious Disease (Dr Stosor), Northwestern University Medical School, Chicago, Ill.
Reprints not available from the author.
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|Author:||Shah, Rajshri N.; Stosor, Valentina; Badve, Sunil|
|Publication:||Archives of Pathology & Laboratory Medicine|
|Date:||May 1, 2001|
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