1 Chair of Nephrology Department of Internal Medicine University of Torino2 Divisione Malattie Infettive C Ospedale Amedeo di Savoia Torino Italy
Correspondence and offprint requests to: Giorgina Barbara Piccoli, MD, Chair of Nephrology of the University of Torino, Corso Bramante 8688, 10126 Torino, Italy. Email: gbpiccoli{at}yahoo.it, giorgina.piccoli{at}unito.it
Keywords: cryptosporidiosis; diarrhoea; immunodepression; kidney transplantation; pancreas transplantation
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Case |
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The intermittent abdominal pain and diarrhoea initially lasted for 2 dayswith up to 10 liquid stools per day and flatulence. The problem remitted for 3 days and reappeared the night before she was first seen by us.
Her clinical history included the (pre-emptive) pancreaskidney graft 1 year earlier. She had had no prior infectious complications or acute rejection.
Her serum creatinine ranged from 1.2 to 1.4 mg/dl. She had neither proteinuria nor urinary tract infection; and her creatinine clearance was 75 ml/min.
Her immunosuppressive regimen comprised tacrolimus (present levels 810 ng/ml), mycophenolate mofetil (1250 mg/day) and steroids (prednisone, 5 mg/day). Long-term prophylaxis with sulfamethoxazole/trimethoprim and nystatin (400 mg/800 mg and 300 mg, respectively) had been stopped 2 weeks after her return to Italy. During her stay in Cuba, she had no fever, diarrhoea or any other problems, except for a short, self-limited episode of acute cystitis. We started treating her with oral lactic acid-producing organisms and a combination of neomycin (25 000 UI/day) and bacitracin (2500 UI/day).
The patient's symptoms gradually remitted over 2 days, to reappear 3 days later. Stool samples were gathered for cultures for Escherichia coli, Entamoeba histolytica, Giardia lamblia, Campylobacter, Salmonella, Shigella, rotavirus, Yersinia enterocolitica and for miscroscopic inspection for parasites. All these tests were negative. During the patient's acute diarrhoeal phases, her serum levels of tacrolimus increased remarkably (up to 27.9 ng/ml) as did her serum creatinine levels (to 1.8 mg/dl). For better control of the symptoms and to perform further tests, she was hospitalized in the transplantation ward. The results of her renal scintigraphy, abdominal ultrasounds and Doppler ultrasound were normal. No specific deviations from normal were found in her blood tests; stool, blood and urine cultures again tested negative. Since the only consistent change was the marked increase in her serum tacrolimus, concomitant with the diarrhoeal episodes, she was discharged with the diagnosis of tacrolimus-induced diarrhoea.
Despite an initial improvement, however, her symptoms recurred 1 week later.
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Questions |
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What additional tests would you suggest doing?
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Answer to the quiz on the preceding page |
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Following the advice of an infectious disease specialist, we carried out additional stool cultures (for Isospora and Cryptosporidium). In one of the three stool specimens, we found acid-fast oocysts of C. parvum, and started treatment with high doses of rifaximin (600 mg thrice daily). The patient's symptoms resolved within 1 week. Mycophenolate was reduced to 1 g/day. More than 1 year after that episode, the patient has been free from recurrences.
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Discussion |
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Usually when faced with such cases (diarrhoea associated with a history of international travel), the first inclination of physicians is to supspect pathogens that are rare in temperate climates; and as a result expensive tests are often performed in search of often difficult to find pathogens.
The diagnosis of a tacrolimus side effect occurring in our patient was very appealing, although the temporal sequence was not satisfactory, because her diarrhoea had appeared before the increase in her blood levels of tacrolimus.
Interestingly, the elusive microorganism that indeed was found in this patient is ubiquitousand the risk of infection with it is increased for immunocompromised patients, in any climate [1].
The coccidian protozoan C. parvum is an intestinal parasite of domestic and wild animals. It causes an infection that is more prevalent in poorly developed countries. The prevalence of C. parvum infection in Europe is 12%; in North America, it is 0.65%; and in Asia, Africa and Central and South Americas, 520%. The parasite is transmitted primarily by the fecaloral route. Outbreaks have been traced to municipal water, and person-to-person and animal-to-person transmissions have also been described.
Infection with C. parvum is a frequent cause of traveller's diarrhoea [6]. Healthy carriers of oocysts may play a role in its transmission. Diarrhoea is its main symptom, which can range in severity from mild to cholera-like diarrhoea. Abdominal cramps, nausea, vomiting and anorexia usually accompany the diarrhoea. Fever is uncommon. The severity of the infection depends on the immune status of the patient [7]; the more severe cases are observed in patients with CD4+ lymphocyte counts of <50 cells/mm3. Cryptosporidiosis may involve the gallbladder, bile ducts, pancreatic ducts, bronchi and lungs. The results of conventional stool cultures are commonly negative in infected cases. The diagnosis depends on the identification of the parasite in faeces, in tissue specimens or in bodily fluids, using the ZiehlNeelsen or Giemsa stains or fluorescent auraminerhodamine, Sheather's sucrase flotation and indirect immunofluorescence [8,9].
The only factor that increases the risk of infection appears to be the use of common restroomssomething that is difficult to avoid in the course of such work as teaching dance [13].
Even though the techniques for detecting the parasite in patients (or in their environments) have progressed during recent years, cryptosporidiosis remains a serious problem in immunocompromised persons, because the organism is difficult to remove from the environment, is easy to acquire and is almost impossible to treat properly [1,4,5].
This case is interesting because it underlines the importance of suspecting infection by this ubiquitous microorganism in any immunocompromised patient who develops recurrent diarrhoea (in temperate climates, or elsewhere) in the absence of other clear aetiological factors.
Conflict of interest statement. None declared.
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