Case Report

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A 33-year-old white homosexual man with AIDS and Kaposi sarcoma was seen because of diarrhea of 3 months duration and 11 kg weight loss. He claimed 10 to 40 bowel movements per day, which were often malodorous, awakened him from sleep, and were associated with cramping but not tenesmus. The volume, consistency, and frequency varied. Diarrheal volume roughly correlated with the volume of food consumed and was worsened by fatty foods and dairy products. Nonspecific antidiarrheal medications brought partial relief of symptoms. He had no fever, and a physical examination was unremarkable. Stool examinations for enteric bacteria and parasites were negative on three occasions. The patient was severely immunosuppressed, with a CD4 lymphocyte count of 5/mm³ (normal range, 532 to 1571 mm³). D-Xylose absorption was subnormal, with serum concentrations of 0.84 and 0.62 mmol/L 1 and 2 hours after the test dose (normal range, 1.3 to 3.3 mmol/L), and urinary xylose excretion of 0.056 (normal, >0.20). Upper endoscopic biopsy specimens showed mild villus atrophy, moderate crypt hyperplasia, and inflammatory changes. No organisms were seen in small-bowel biopsy specimens, touch preparations, or jejunal lavage specimens examined by either light or transmission electron microscopy.

Colonic biopsy specimens revealed nonspecific inflammation with mild to moderate degrees of epithelial injury. Dense focal collections of coccobacilli were seen adhering to the surface of superficial enterocytes, but not those in the crypts in ileal and colonic biopsy samples (Figure 1). The bacteria were deeply basophilic on hematoxylin and eosin staining. The lesion was spotty. The epithelium was disorganized with cells that varied in shape from cuboidal to flat as well as hyperchromatic nuclei. The cytoplasm was vesiculated and contained lipid vacuoles and prominent lysosomes. Intraepithelial lymphocytes and neutrophils were present.

View larger version (112K): [in this window] [in a new window]   Figure 1. Attaching and effacing lesion. Top. Light microscopic view of bacteria adherent to the superficial epithelium in the cecum (hematoxylin and eosin; original magnification, x 160). Bottom. Three bacteria are intimately associated with the luminal plasma membrane of an ileal epithelial cell. Note the absence of microvilli, the plaque-like attachments, and the concentration of cytoplasmic filaments (original magnification, x 17 000).

On transmission electron microscopic examination, bacteria were intercalated into the enterocyte brush border, which showed variable microvillus atrophy and loss (Figure 1). Many of the bacteria formed plaque-like attachment sites. Degeneration, in the form of organelle swelling and increased numbers of secondary lysosomes, cell lysis, and sloughing, was seen.

The patient was treated with ciprofloxacin, 500 mg twice a day, for 4 weeks. The diarrhea stopped almost immediately, and the patient gained 3.6 kg during the first 2 weeks. Diarrhea recurred near the end of the month of therapy, then slowly improved while the patient was not receiving therapy. Stool samples did not show Clostridium difficile toxin. The patient has no diarrhea and his weight is stable 10 months after treatment.

Discussion

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The morphologic features in this case are strikingly similar to those seen in infants who have a protracted enteropathy, with malabsorption and inability to tolerate oral feedings [6]. The condition, initially reported in 1980, described a novel interaction of bacteria with the intestine, adherence, and the production of disease without invasion or toxin production [7]. The bacteria infect the duodenum, jejunum, ileum, and colon. The adherence factor, which connotes virulence, is plasmid associated, implying that it may be found in many different serotypes of enteric bacteria [8]. The exact mechanism of enterocyte injury is not known.

Gastroenteritis due to enterocyte adherent bacteria is common and is self-limited in immunocompetent persons. Its protracted nature in certain infants and in patients with AIDS is probably related to deficiencies in either T- or B-lymphocyte function [9]. The incidence of this infection in AIDS is unknown. A retrospective review has disclosed six other cases with identical light and electron microscopic features. Ongoing studies will determine if the organisms producing the attaching and effacing ultrastructural lesion are the same as those that cause disease in infants. The lack of the pretreatment stool isolate and post-treatment histologic studies precludes us from reaching firm conclusions about the results of therapy in this case.

Further studies will be required to demonstrate definitively the incidence and role of adherent bacteria in producing intestinal injury and diarrhea in patients with AIDS, as well as its response to antibiotic treatment.