Cryptosporidiosis of the biliary tract mimicking pancreatic cancer in an AIDS patient

Diarrhea caused by Cryptosporidium sp is frequent in patients with AIDS, but involvement of other organs of the digestive tract is uncommon. We report a case of Cryptosporidium-associated obstruction of the biliary tract mimicking cancer of the head of the pancreas in a 43-year-old woman with AIDS. Key-words: Cryptosporidiosis. AIDS. Biliary tract. Pancreatitis.

Cryptosporidiosis is one of the most common human enteric infections, mainly among children 2 14 , which has been recognized after onset of the AIDS pandemic 11 13 .The etiologic agent is Cryptosporidium sp, which was described in mice by Tyzzer in 1907 20 .The first case of human cryptosporidiosis was reported only in 1976 in an immunocompetent patient with acute enterocolitis 17 .
The occurrence of asymptomatic intestinal infections caused by Cryptosporidium sp has been documented; these infections are rare in normal individuals but frequent in AIDS patients 11 .Disease manifestations include self-limited acute, chronic and fulminating forms.Spreading of Cryptosporidium sp leads to hepatobiliary and respiratory infection, affecting the nasal and sinus mucosa 5 9 .Pitlik et al 18 reported the first case of gallbladder infection in an AIDS patient.There have been other reports of this complication of intestinal cryptosporidiosis in immunocompromised patients 13 17 .
Despite being a frequent cause of morbidity, cryptosporidiosis is rarely the sole cause of death, even among AIDS patients.However, cryptosporidiosis may be the disease defining AIDS 21 , in these patients.
According to the AIDS Epidemiological Bulletin 4 , cryptosporidiosis is diagnosed in 2.8% of patients aged 13 or older and in 2.7% of individuals aged less than 13 years old.Prospective studies carried out in Brazil on patients with AIDS reported a prevalence of 12 to 20% 6 8 .However, cryptosporidiosis of the biliary tract has not been described to date.
The objective of the present study was to present the case of a patient with AIDS and biliary tract cryptosporidiosis mimicking malignant neoplasia of the head of pancreas.

CASE REPORT
A 43-year-old white female patient was admitted to the Surgical Gastroenterology Ward with a three-month history of anorexia, weakness and a weight loss of 15kg.Forty days after the onset of symptoms, the patient presented jaundice, fecal acholia and choluria.One month later, she started to show lower limb edema (LLII), diarrhea (3-4 times/day) and abdominal pain, without any respiratory symptoms.Physical

-Axial contrast-enhenced CT image at the level of the pelvis demonstration thick walled colon and rectum (!). Figure 2 -Axial contrast-enhenced CT image demonstrates common bile duct, pancreatic canal and intrahepatic biliary dilatation (!). Figure 5 -Cryptosporidiosis in suppurative colangitis -Dot-like organisms on the surface epithelium (arrows) (HE 400x).
Souza LR et al examination revealed regular to poor general condition, 40kg of weight, skin and mucosal jaundice, whitish lesions on the palate, LLII edema, a tense abdomen with pain upon palpation in the right hypochondrium and epigastrium, and discrete hepatomegaly.Ultrasonography showed hepatomegaly with a discrete and diffuse increase in the echogenicity of the parenchyma, an enlarged head of pancreas, and dilatation of the intrahepatic bile ducts and of the common bile duct.Computed tomography (CT) of the abdomen, using oral contrast dye followed or not by intravenous injection of contrast dye, demonstrated hepatomegaly, dilatation of the intrahepatic bile ducts, common bile duct and pancreatic duct, an increased head of pancreas, discrete enlargement of the left suprarenal gland, and thickening of the rectal and sigmoid walls (Figures 1 to 4).These results suggested neoplasia of the head of pancreas and the patient was submitted to gastroduodenopancreatectomy.During surgery, a lymph node was removed from the head region of the pancreas and histological examination of a frozen biopsy revealed, rare granulomas surrounded by fibrotic scar tissue with Paracoccidioides brasiliensis yeasts.The patient was then transferred to the Tropical Disease Ward.Since she was a woman outside the expected age range for the juvenile form of paracoccidioidomycosis (PCM), with poor epidemiologic history for this mycosis, and with intense impairment of general and nutritional status, and the presence of a history favoring the possibility of HIV infection, the patient was submitted to anti-HIV antibody detection by ELISA, with a positive result.However, no anti-P.brasiliensis antibody was detected.Histological examination of the surgical specimen revealed suppurative cholangitis associated with Cryptosporidium sp infection (Figure 5).Cryptosporidia were observed in the head of pancreas near the surface of the pancreatic duct epithelium close to the papilla.Enzymatic necrosis of the pancreatic parenchyma was absent.Although the patient did not have any respiratory complaints, a simple chest X-ray revealed discrete and diffuse linear and micronodular interstitial infiltration.The CD4 + T cell count showed 35 cells/mm 3 .Antiretroviral treatment with stavudine, lamivudine and indinavir was initiated.The patient received intravenous clarithromycin (1g/day) and fluconazole for the treatment of cryptosporidiosis and oral candidiasis, respectively.The patient showed clinical improvement after two months and was discharged from the hospital.She did not return for outpatient follow-up and died at home two months later.

DISCUSSION
The present case demonstrates the difficulty in obtaining the diagnosis of pancreatic and bile duct diseases.The clinical signs and symptoms of the patient suggested neoplasia of the head of the pancreas.Although, this disease is more frequent in male patients (1.5:1) over 60 years of age, the present case was a 43-year-old woman.
The diagnosis of PCM was suggested, but this disease is much more frequent in men (10.7:1) and an age range below 30 years old is expected for the acute or subacute form 15 .The absence of rural working, abdominal and superficial adenomegaly, splenomegaly, and the histopathological findings of granulomas with latent yeast forms did not point to subacute PCM diagnosis.In addition, the confirmation of the diagnosis of pancreatic and biliary tract cryptosporidiosis, which is a disease defining AIDS, indicated the need for the determination of anti-HIV antibodies that confirmed this diagnosis.
Biliary cryptosporidiosis has been observed in 15% of the AIDS patients 13 .Such a localization favors the occurrence of relapses, with the biliary tract serving as a reservoir of this agent 11 .These patients commonly present chronic disease, manifesting with diarrhea, weight loss and malabsorption of nutrients, water-soluble vitamins, D-xylose and fat 11 17 .In the present study, the patient did not present chronic diarrhea as usually reported 11 16 , but showed biliary tract involvement and intense weight loss.
Biliary involvement by Cryptosporidium seems to be related to a more advanced stage of the disease and a low CD4 + T lymphocyte count, especially when it falls below 50 cells/mm 3 , with a higher risk of death due to cryptosporidiosis 21 .Our patient had a CD4 + T lymphocyte count of 35 cells/mm 3 , a twomonth hospital stay and died two months after discharge.
Clinical manifestations of cryptosporidiosis can be misdiagnosed, and in AIDS patients it can mimic sclerosing cholangitis, cholecystitis and pancreatitis 16 .In AIDS patients, stone-free cholecystitis and thickening of the gallbladder are mainly caused by Cryptosporidium sp and cytomegalovirus 1 .
Imaging findings are nonspecific.Hashmey et al 12 performed 38 diagnostic imaging studies on 20 cryptosporidiosis patients.Ultrasonography detected thickening of the gallbladder wall in five out of 10 patients, biliary sludge in two, dilatation of the bile duct in two, and calculi in one.Computed tomography scan revealed dilatation of the bile ducts in 3 out of 4 patients.Endoscopicretrograde cholangiopancreatography (ERCP) detected Cryptosporidium sp oocysts in material obtained by brushing and/or biopsy of the bile ducts in three patients.Narrowing of Vater's ampulla and alternating narrowing and dilatation of the intrahepatic bile ducts could also be observed by this method.These authors considered Cryptosporidium sp to be the primary cause of cholecystitis in AIDS patients.
In our case, abdominal CT scan and ultrasonography showed alterations suggestive of sclerosing cholangitis, such as dilatation of both common and intrahepatic bile ducts.Enlargement of the head of the pancreas was also observed, suggesting neoplasia.
Autopsy studies 10 have shown the presence of Cryptosporidium sp inside the pancreatic duct, with evidence of periductal inflammation.In the present case, histological examination demonstrated Cryptosporidium sp near the surface of the pancreatic duct epithelium close to the papilla, in addition to lymphoplasmocytic inflammation, a fact that might explain the enlargement of the head of the pancreas as detected by ultrasonography, CT scan and during surgery.Goodwin 10 reported the occurrence of pancreatic disease with periductal inflammation and interstitial edema in five cases, generally observed in the head region of the pancreas, without histopathological evidence of pancreatitis.Our patient did not present enzymatic necrosis of the pancreatic parenchyma, which is fundamental for the diagnosis of pancreatitis.
In the present study, a chest plain film showed mild and diffuse linear and micronodular interstitial infiltration of the lungs.Although some authors 3 7 have suggested pulmonary involvement by Cryptosporidium sp, more frequent etiologies such as Pneumocystis carinii cannot be excluded.
Diagnostic confirmation of extraintestinal cryptosporidiosis is difficult.Vakil et al. 21established the diagnosis in 9 (38%) patients with biliary symptoms by demonstrating Cryptosporidium sp in the biliary tract through the analysis of biliary brushings obtained by endoscopy and histological examination of gallbladder material obtained by biopsy.In our study, the diagnosis of cryptosporidiosis was confirmed by histological examination of the surgical specimen.
Treatment of cryptosporidiosis is difficult, and variable degrees of efficacy were observed with macrolides, paromomycin and sulfonamides 11 19 21 .Our patient showed an excellent response to clarithromycin maintained for 38 days.
Sphincterotomy has been reported to provide a rapid result and substantial relief of pain in the right hypochondrium in most AIDS patients with biliary cryptosporidiosis 1 .Endoscopic papillotomy and cholecystectomy have also been used with favorable results 21 .In the present study, the probably overly extensive surgery, led to the removal of the distal obstacle of the common bile duct, with a similar effect to that obtained with papillotomy and sphincterotomy.
Our experience with the case presented herein leads us to consider the extraintestinal cryptosporidiosis in AIDS patients with biliary tract involvement.

Figure
Figure 4 -Axial contrast-enhenced CT image at the level of the pelvis demonstration thick walled colon and rectum (!).