Abstract
The treatment of ulcerative colitis is based on systemic corticosteroids, immunomodulators such as cyclosporine and azathioprine and TNF-α antagonists. Patients undergoing such immunosuppressive treatment are more susceptible for infectious pathogens. Here, we report the case of a patient with a 13-year history of ulcerative colitis, treated initially with systemic corticosteroids in combination with immunomodulators, and subsequently with infliximab. The patient presented with severe watery diarrhoea, abdominal cramps, weight loss and low-grade fever. Stool examinations for cytomegalovirus, bacteria and parasites were negative. Following detection of numerous oocytes of Isospora belli (IB) in direct smear preparations of the diarrhoeic stool samples, the patient was successfully treated with trimethoprim-sulfamethoxazole (co-trimoxazole).
Background
Parasites and other infections are a significant problem for immunocompromised patients and represent a serious and underestimated source of complications especially in patients with inflammatory bowel disease (IBD) because of the similarity of their symptoms.
Case presentation
A 61-year-old man was diagnosed with ulcerative colitis 13 years ago. Ten years after diagnosis, he was successfully treated with cyclosporine (4 mg/kg body weight (BW) as induction therapy)/azathioprine (2.5 mg/kg BW as maintenance therapy) because of chronically active steroid-dependent disease. He became unresponsive to this therapy 2 years later, leading to initiation of infliximab (5 mg/kg BW). One year later, despite being in stable remission on azathioprine and infliximab, the patient developed weight loss and watery diarrhoea. Cytomegalovirus (CMV)-colitis was diagnosed histologically, and he was successfully treated with ganciclovir (5 mg/kg BW) over 3 weeks. Six months later, after returning from a vacation in India, he was admitted to our centre with abdominal cramps, severe debilitating watery diarrhoea (8–10 bowel movements per day), marked weight loss and low-grade fever.
Investigations
CMV testing was negative. The results of conventional stool examinations for bacteria (incl Clostridium difficile) and parasites were also negative. Further parasite examination by means of an ethyl alcohol/formaldehyde concentration technique revealed suspicious oocyst-like features. Using acid-fast stain on a fresh smear, these features were shown to be Isospora belli oocysts. No other intestinal parasites were detected at that time.
Treatment
Initial treatment with metronidazole and ciprofloxacine effected no improvement of his condition. After detection of I belli oocysts, the patient was treated with 160 mg trimethoprim and 800 mg sulfamethoxazole administrated as a double-strength (DS) tablet twice daily (TMP-SMX-DS) for 14 days.
Outcome and follow-up
The patient responded clinically as well as microbiologically. Treatment success was measured by cessation of diarrhoea at day 3 and negative stool examinations at day 7. The patient remained disease-free for at least 9 months.
Discussion
Isospora belli (IB), an opportunistic protozoon, is one of the most commonly recognised causes of diarrhoea in patients with AIDS. It has also been reported in other immunosuppressive diseases, such as lymphoblastic leukaemia, adult T-cell leukaemia and Hodgkin's disease. IB infection has also been described in patients taking immunosuppressive drugs following transplantation.1 2 Here, we describe for the first time, a case of immunosuppression-related IB infection in a patient with ulcerative colitis undergoing treatment with azathioprine in combination with infliximab. IB belongs to the coccidia subclass of the family Eimeria, is only known to infect humans and is transmitted mainly by ingestion of infective oocysts in faecally contaminated food or water.3 Infected individuals may be asymptomatic carriers, or may suffer from gastrointestinal disease ranging from mild to severe malabsorption syndrome characterised by loose, foul-smelling stools.
IB infection is diagnosed by examination of stool and/or duodenal biopsy specimens. However, diagnosis of IB infection is difficult, especially if the concentrated sediment is from polyvinyl alcohol-preserved stool, as the oocysts of the organism are difficult to differentiate from some other faecal matter. Acid-fast and/or iodine staining are used for detection of I belli oocysts. Fluorescence-microscopic analysis is also effective for Isospora detection, staining with the fluorescent dyes auramine and rhodamine.4 It should be noted that stool preparations must be examined with great care to avoid misinterpretation of oocysts among faecal compounds revealed by iodine staining. In oocysts of I belli, the inner germinal mass (sporoblast) stains an intense red (figure 1).
Figure 1.
Isospora belli oocysts in stool smear preparation: Iodine staining (×400).
In summary, isosporiasis should be suspected along with viral infection in immunocompromised patients with ulcerative colitis suffering from chronic persistent diarrhoea, abdominal cramps and weight loss. However, symptoms are non-specific and stool samples must be investigated meticulously for possible existence of oocytes, especially for I belli oocysts. Also, TMP-SMX (co-trimoxazole) is the drug of choice in patients suffering from isosporiasis.5
Learning points.
Isosporiasis should be suspected along with viral infection in immunocompromised patients with inflammatory bowel disease suffering from chronic persistent diarrhoea, abdominal cramps and weight loss.
If Isospora belli is suspected, acid-fast and/or iodine staining should be used for detection.
TMP-SMX (co-trimoxazole) is the drug of choice in patients suffering from isosporiasis.
Footnotes
Contributors: JS analysed and interpreted the data, drafted the article, revised the manuscript critically for important intellectual content and approved the final version to be published. ET carried out the microbiological and parasitological diagnostics, revised the manuscript critically for important intellectual content and approved the final version to be published. FH provided clinical data, revised the manuscript critically for important intellectual content and approved the final version to be published.
Competing interests: None.
Patient consent: Obtained.
Provenance and peer review: Not commissioned; externally peer reviewed.
References
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