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CLINICAL PATHOLOGICAL CONFERENCE

Thanem, Khalil G. MD

Infectious Diseases in Clinical Practice: January 2001 - Volume 10 - Issue 1 - p 59-62
Special Articles
Free

This is a new feature of IDCP. The first presentation in this series is from Khalil G. Thanem, MD, a fellow in the Infectious Diseases Division at The Johns Hopkins University School of Medicine. The format is quite traditional except that we will disclose the opinion of the discussant and the opinion of the audience by vote from the options that are listed in the differential diagnosis from the discussant. Comments are welcome (reprinted from The Johns Hopkins University ID website, http://www.hopkins-id.edu, with permission).

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A 32-Year-Old Man with Chronic Diarrhea

History of present illness

A previously healthy 32-year-old man presented with a prolonged course of diarrhea. He had been in good health until 8 months before presentation when he developed watery diarrhea, occurring six to ten times per day, with frequent nocturnal episodes. He noted a 10-pound weight loss, occasional abdominal cramping, occasional blood in the stool, and improvement in symptoms with fasting. He denied fevers, chills, night sweats, nausea, vomiting, arthralgias, skin changes, or visual disturbances. He denied any sick contacts.

His primary physicians had sent samples of stool for routine bacterial cultures, ova and parasite examinations, and Clostridium difficile toxin assays—all of which were unrevealing. A flexible sigmoidoscopy with biopsies was performed and was reported as “normal.”

A 10-day empiric trial of Ciprofloxacin was not helpful. He was referred for further evaluation.

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Medical history

None

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Medications

None

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Social history

The patient lives in East Texas where he resides on a ranch (dogs, cats, horses, pigs, cattle). He is married and has a healthy 3-year-old son. He does not drink alcohol, smoke, or use illicit drugs. There is no history of recent travel outside of Texas.

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Family history

His mother has diabetes and his father has hypertension.

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Physical examination

A physical examination revealed the following: temperature 37.8°C; pulse 88; respiratory rate 12; blood pressure 120/55. Head, neck, skin, chest, and cardiovascular examinations were unremarkable. An abdominal examination revealed a soft, nondistended abdomen. The liver was 12 cm in total span and the spleen was not enlarged. Rectal examination revealed external hemorrhoids, normal sphincter tone, and brown stool that tested negative for occult blood. Neurologic examination was grossly intact.

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Laboratory results

TABLETABLE

Table. C

Table. C

Table

Table

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Radiographic studies

  • Chest radiograph, normal;
  • Upper GI series with small bowel follow-through, normal.
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Differential diagnosis

  • Inflammatory bowel disease
  • Bacterial overgrowth
  • Eosinophilic gastroenteritis
  • Spore-forming protozoa (Cryptosporidium, Microsporidia, Isospora, or Cyclospora)
  • Giardia lamblia
  • Strongyloidiasis
  • Entamoeba histolytica
  • Viral disease (CMA, HSV)
  • Mycobacterial diseases
  • Celiac sprue
  • Whipple’s disease
  • Fungal infection of the GI tract (histoplasmosis)
  • Malignancy (adenocarcinoma, lymphoma)
  • Brainerd’s diarrhea
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Discussion

This previously healthy 32-year-old man presents with an 8-month history of chronic diarrhea. Based on the information available, an osmotic or a secretory cause is likely.

Infectious causes of chronic diarrhea include Giardia lamblia, Cyclospora, Cryptosporidium, and amebiasis. Of note, agents of acute bacterial and viral diarrhea can produce a more chronic course (Salmonella spp., C. difficile, E. coli, etc.). An underlying immunodeficiency should be considered in any chronic infectious diarrhea, but particularly with agents such as microsporidia, Mycobacterium avium, and CMV, which rarely, if ever, cause gastrointestinal disease in normal hosts.

This patient has no history to suggest a congenital immunodeficiency and has no apparent risk factors for HIV. In the setting of multiple negative stool evaluations and a negative flexible sigmoidoscopy, bacterial, spore-forming protozoa as well as Giardia, herpes and CMV are less likely. Giardiasis may localize to the small bowel and be missed on routine ova and parasite stool examinations. Historically, difficult cases were diagnosed with the “string test,” or with EGD and small bowel biopsy. More recently, the stool Giardia antigen assay has improved the sensitivity of the diagnostic work-up for this pathogen.

Bacterial overgrowth is usually associated with small bowel abnormalities such as achlorhydria, blind loop syndromes, impaired motility, surgery, strictures, diverticula, or radiation. Sometimes, an episode of acute infectious diarrhea may lead to the establishment of bacterial overgrowth.

Inflammatory bowel disease (especially Crohn’s disease with its classic skip lesions that may be missed on flexible sigmoidoscopy) and malignancy were considered in the evaluation of this patient and could certainly be consistent with his disease course.

Eosinophilic gastroenteritis may involve any portion of the GI tract, and may cause nausea and vomiting, in addition to diarrhea. This syndrome, however, is associated with peripheral eosinophilia in more than 75% of cases.

Whipple’s disease, a rare disorder caused by the bacterium Tropheryma whippelii that usually presents with diarrhea, abdominal pain, arthralgias, weight loss, and impaired absorption, must also be considered in this case. Lymphadenopathy, increased skin pigmentation, heart failure, and central nervous manifestations may also occur. The diagnosis is made by the histologic finding of macrophages laden with PAS-positive cytoplasmic granules as well as dilated lymphatics in jejunal biopsy specimens and blunting of the intestinal mucosa.

Brainerd diarrhea is a term applied to outbreaks of chronic diarrhea of unknown etiology characterized by an acute onset and duration of weeks to months without response to antimicrobial therapy. This syndrome has been associated with ingestion of raw milk as well as “contaminated” water sources, but the pathogenic agent remains cryptic.

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Discussant’s vote

Neoplasm

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Audience’s vote

Neoplasm versus HIV-associated infection

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Diagnostic procedure

An HIV antibody test was negative. A colonoscopy was performed which revealed normal-appearing colonic mucosa. Multiple biopsies of the rectum, sigmoid, descending, transverse, and ascending colon were obtained. Histology revealed normal architecture with a densely packed false brush border (Figs. 1 and 2) on all specimens. A Warthin-Starry stain (Fig. 3) confirmed the diagnosis of Intestinal Spirochetosis.

FIGURE 1.

FIGURE 1.

FIGURE 2.

FIGURE 2.

FIGURE 3.

FIGURE 3.

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Clinical course

As no other etiology for his diarrhea was found, the patient was treated with a 4-week course of metronidazole. By the third week, his symptoms had completely resolved. A follow-up flexible sigmoidoscopy with biopsies revealed the disappearance of the false brush border.

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Comment

The term ‘intestinal spirochetosis’ was coined in 1967 by Harland et al. [1] who described an infection of the large bowel wherein spirochetes were found to be attached by one end to the colonic epithelium forming a dense “false brush border.” Although the prevalence of spirochetes on rectal biopsy of hospitalized patients was noted to range from 1.9% to 6.9% in one study [2], the majority of patients with this finding are asymptomatic. Hence, there has been considerable controversy over the pathologic significance of this colonization. In some patients, diarrhea has been reported and in others, rectal bleeding.

The characterization of the spirochetes has also spawned controversy. Two potential pathogens have been described on the basis of differential growth patterns on media and molecular typing techniques:Serpulina pilosicoli and Brachyspira aalborgi [3,4]. It is unclear whether one, both, or neither are responsible for the clinical manifestations seen in intestinal spirochetosis.

Successful treatment with neomycin and metronidazole has been reported. In other patients, observation without antimicrobial therapy led to complete resolution of symptoms [5].

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References

1. Harland WA, FD Lee. Intestinal spirochaetosis. Br Med J 1967;2:718–9.
2. Lee FD, Krazewski A, Gordon J, et al. Intestinal spirochetosis. Gut 1981; 22:1035–41.
3. Mikosza AS, et al. PCR amplification from fixed tissue indicates frequent involvement of Brachyspira aalborgi in human intestinal spirochetosis. J Clin Microbiol 1999; 37:2093–8.
4. Trivett-Moore NL, et al. Isolation of Serpulina pilosicoli from rectal biopsy specimens showing evidence of intestinal spirochetosis. J Clin Microbiol 1998; 36:261–5.
5. Lo TCN, et al. Intestinal Spirochaetosis. Postgrad Med J 1994; 70:134–7.
© 2001 Lippincott Williams & Wilkins, Inc.