A clinicopathologic analysis of AIDS-related... : AIDS

ARTICLES

Lumadue, Jeanne A.1,5; Manabe, Yukari C.2; Moore, Richard D.3; Belitsos, Peter C.4; Sears, Cynthia L.2,4; Clark, Douglas P.1,6

1Department of Pathology, The Johns Hopkins University School of Medicine, Baltimore, Maryland, USA

2Divisions of Infectious Diseases, The Johns Hopkins University School of Medicine, Baltimore, Maryland, USA

3Divisions of General Internal Medicine, The Johns Hopkins University School of Medicine, Baltimore, Maryland, USA

4Divisions of Gastroenterology, Department of Medicine, The Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.

5Present address: Children's National Medical Center, Washington, DC, USA.

6Requests for reprints to: Dr Douglas Clark, Department of Pathology, The Johns Hopkins School of Medicine, Room 406, Pathology Building, 600 N. Wolfe Street, Baltimore, MD 21287, USA.

Sponsorship: This work was funded in part by NIH grant R29 A141345; D.P.C. is the recipient of a Merck Clinician Scientist Award.

Date of receipt: 6 May 1998; revised: 3 September 1998; accepted: 11 September 1998.

Abstract

Objective:

To characterize the histology of AIDS-associated cryptosporidiosis and identify features that explain the clinical variability.

Design:

A retrospective analysis of HIV-positive individuals with cryptosporidiosis who underwent endoscopy at the Johns Hopkins Hospital between 1985 and 1996.

Methods:

The histologic features (intensity of Cryptosporidium infection, inflammation, mucosal damage, copathogens) of gastrointestinal biopsies from 37 HIV-positive individuals with cryptosporidiosis were systematically graded. These histologic features were correlated with the severity of the diarrheal illness obtained from a patient chart review.

Results:

Histologic features associated with Cryptosporidium infection include a neutrophilic infiltrate in the stomach, villus blunting in the duodenum, cryptitis and epithelial apoptosis in the colon, and reactive epithelial changes in the stomach and duodenum. The nature and intensity of the inflammatory response varied widely; however, duodenal biopsies from a subset of patients (37%) revealed marked acute inflammation that was associated with concomitant cytomegalovirus infection. Although duodenal infection was common (93% of individuals), infection of other sites was variable (gastric cryptosporidiosis in 40% and colonic cryptosporidiosis in 74%). Widespread infection of the intestinal tract, which included both the large and small intestine, was associated with the most severe diarrheal illness.

Conclusions:

Cryptosporidium infection produces histologic evidence of gastrointestinal mucosal injury. The inflammatory response to the infection is variable, and may be modified by copathogens such as cytomegalovirus. The clinical manifestations are influenced, in part, by the anatomic distribution of the infection, with extensive infections involving both small and large intestines producing the most severe illness.