aDepartment of Infectious Diseases, Sacré-Coeur Hospital
bDepartment of Infectious Diseases, Notre-Dame Hospital
cDepartment of Medicine, Verdun Hospital, University of Montreal, Montreal, Quebec, Canada.
Correspondence to Valéry Lavergne, MD, MSc, Department of Infectious Diseases, Sacré-Coeur Hospital, University of Montreal, 5400 Boulevard Gouin Ouest, Montreal, QC H4J 1C5, Canada. Tel: +1 514 338 2222 x7221; fax: +1 514 338 3307; e-mail: firstname.lastname@example.org
Received 7 June, 2011
Accepted 21 June, 2011
Immune reconstitution inflammatory syndrome (IRIS) is a frequent complication of HIV-infected patients following initiation of antiretroviral therapy (ART). Although a wide variety of opportunistic pathogens are associated with IRIS, parasites have rarely been reported . We report the first case of IRIS following cryptosporidial cholangitis.
A 30-year-old man presented to our emergency room with a long-standing history of severe diarrhea, 25-kg weight loss, as well as epigastric and abdominal pain. He was returning from Turkey where he had drunk contaminated water.
Investigation confirmed the presence of Cryptosporidium oocysts in stool; other usual and opportunistic pathogens were absent. HIV-1 serology was positive, CD4 cell count was 120 × 106 cells/l and viral load was 395 160 copies/ml (5.6 log). Renal and hepatic enzymes were normal.
An abdominal computed tomography scan showed a 12-mm dilatation of the distal common bile duct. Endoscopic retrograde cholangiopancreatography (ERCP) revealed diffuse mucosal inflammation with fine diffuse nodularities of the duodenum, the common and hepatic bile ducts. Biopsies confirmed the presence of Cryptosporidium oocysts. Sphincterotomy was performed and ART was started with zidovudine, lamivudine and efavirenz. The working diagnosis was HIV-associated cryptosporidial cholangitis.
A week later, the patient developed right upper quadrant pain associated with mild cytolysis and cholestasis without associated pancreatitis (Fig. 1). Abdominal studies showed unchanged aspect of the bile ducts and duodenum. This episode was felt to be related to the previous sphincterotomy. Enzymes and symptoms progressively resolved.
Eight weeks after ART initiation, the patient was readmitted with isolated right upper quadrant and epigastric pain with marked elevation of liver enzymes (Fig. 1). Stools samples failed to show Cryptosporidium. The CD4 cell count had markedly increased to 310 × 106 cells/l and viral load decreased to 315 copies/ml (2.5 log). This episode spontaneously resolved during the next 2 months.
HIV-associated cholangiopathy is manifested by biliary obstruction due to infection-related strictures [2,3], which historically affected 25% of AIDS patients prior to the advent of ART [4,5]. This entity is usually diagnosed on the basis of clinical features, elevated alkaline phosphatase levels, classic imagery on ERCP  and pathogen identification on tissue biopsy (duodenum, ampulla, bile duct or liver). In its acute phase, identification of organisms (Cryptosporidium, Microsporidium, cytomegalovirus or Cyclospora cayetanensis) can be made in approximately 75% of cases [3,6,7] with Cryptosporidium being the most prevalent [6,8].
Disease severity and evolution of biliary cryptosporidiosis in HIV patients largely depends on the immune status of the host. A vulnerable immunity may not efficiently clear a large parasitic burden. For this reason, judicious prescription of ART, instead of antiparasitic therapy, is the preferred initial treatment in cryptosporidiosis. Occasionally, endoscopic sphincterotomy becomes necessary to decompress the biliary system, although the disease can nevertheless progress and become chronic [7,9].
A recent meta-analysis reported a 16.1% incidence of IRIS in HIV-patients starting ART . The following diagnostic criteria for IRIS are generally accepted: HIV patient responding to ART (rapid decrease in plasma viral load by more than 1 log10 or rapid increase in CD4 cell count); atypical inflammatory reaction unexpected in the course of the opportunistic infection; exclusion of others causes that could explain the clinical presentation [11–13].
IRIS can follow any type of opportunistic infection, but has rarely been described with parasites [10,14]. To the author's knowledge, Plasencia et al. reported the only case of an IRIS related to a cryptosporidial infection in an HIV patient with recurring ileitis.
Our patient initially presented with a classic case of cryptosporidial cholangitis, confirmed by the presence of Cryptosporidium oocyst on histopathology. The following clinical presentation, 8 weeks after the initial diagnosis, was likely caused by IRIS, as it fits the accepted criteria mentioned earlier: first, the patient had a clear immunologic/virologic response to ART, as confirmed by the quick improvement in CD4 cell count and viral load; second, cryptosporidiosis had resolved completely during that period and was not expected to recur in a HIV patient with markedly improved immunity; third, the timing of the recurrence correlated precisely with the immune reconstitution; and finally, there was no sign of Cryptosporidium or other pathogens on stool sampling. The diagnosis of IRIS is often difficult to pose and was unfortunately delayed in our patient. Had it been suspected earlier, anti-inflammatory drugs or corticosteroids could have been considered.
In conclusion, to the authors’ knowledge, this is the first case of IRIS-mediated cholangitis following cryptosporidial infection. Although rare, clinicians should be aware of this possibility following initiation of ART after a documented parasitic infection.
Conflicts of interest
There are no conflicts of interest.
1. Lawn SD. Immune reconstitution disease associated with parasitic infections following initiation of antiretroviral therapy
. Curr Opin Infect Dis
2. Chen XM, LaRusso NF. Cryptosporidiosis and the pathogenesis of AIDS-cholangiopathy
. Semin Liver Dis
3. Ducreux M, Buffet C, Lamy P, Beaugerie L, Fritsch J, Choury A, et al. Diagnosis and prognosis of AIDS-related cholangitis
4. Chen XM, Keithly JS, Paya CV, LaRusso NF. Cryptosporidiosis
. N Engl J Med
5. Vakil NB, Schwartz SM, Buggy BP, Brummitt CF, Kherellah M, Letzer DM, et al. Biliary cryptosporidiosis in HIV-infected people after the waterborne outbreak of cryptosporidiosis in Milwaukee
. N Engl J Med
6. Bouche H, Housset C, Dumont JL, Carnot F, Menu Y, Aveline B, et al. AIDS-related cholangitis: diagnostic features and course in 15 patients
. J Hepatol
7. Forbes A, Blanshard C, Gazzard B. Natural history of AIDS related sclerosing cholangitis: a study of 20 cases
8. Benhamou Y, Caumes E, Gerosa Y, Cadranel JF, Dohin E, Katlama C, et al. AIDS-related cholangiopathy. Critical analysis of a prospective series of 26 patients
. Dig Dis Sci
9. Cello JP, Chan MF. Long-term follow-up of endoscopic retrograde cholangiopancreatography sphincterotomy for patients with acquired immune deficiency syndrome papillary stenosis
. Am J Med
10. Muller M, Wandel S, Colebunders R, Attia S, Furrer H, Egger M. IeDEA Southern and Central AfricaImmune reconstitution inflammatory syndrome in patients starting antiretroviral therapy for HIV infection: a systematic review and meta-analysis
. Lancet Infect Dis
11. Murdoch DM, Venter WD, Van Rie A, Feldman C. Immune reconstitution inflammatory syndrome (IRIS): review of common infectious manifestations and treatment options
. AIDS Res Ther
12. Shelburne SA, Visnegarwala F, Darcourt J, Graviss EA, Giordano TP, White AC Jr, et al. Incidence and risk factors for immune reconstitution inflammatory syndrome during highly active antiretroviral therapy
13. Tsang CS, Samaranayake LP. Immune reconstitution inflammatory syndrome after highly active antiretroviral therapy: a review
. Oral Dis
14. French MA. HIV/AIDS: immune reconstitution inflammatory syndrome: a reappraisal
. Clin Infect Dis
15. Plasencia LD, Socas Mdel M, Valls RA, Fernandez EM, Higuera AC, Gutierrez AB. Terminal ileitis as a manifestation of immune reconstitution syndrome following HAART