Leukopenia due to Parvovirus B19 in a Crohn's Disease Patient Using Azathioprine

Thiopurines such as azathioprine (AZA) and 6-mercaptopurine are frequently used for the treatment of inflammatory bowel diseases. Patients with low or absent thiopurine S-methyltransferase (TPMT) activity, resulting in high 6-thioguanine nucleotide levels, have an increased risk of developing leukopenia. Alternatively, certain viral infections could induce leukopenia. We present the case of an adult Crohn’s disease patient with a parvovirusB19 infection and leukopenia during long-term AZA therapy. The uncomplicated long-term use of adequately-dosed AZA and stable non-toxic metabolite levels could not acknowledge TPMT deficiency as a primary cause of the leukopenia. ParvovirusB19 was assumed to induce the leukopenia by restraining myeloid proliferation. In addition, AZA probably potentiated susceptibility to this viral infection and may have inhibited adequate immunological defense. Leukopenia during thiopurine therapy not explained by TPMT deficiency could be induced by parvovirusB19 infection and compels temporal but not permanent cessation of thiopurine therapy.

[1]  J. Gisbert,et al.  Thiopurine-Induced Myelotoxicity in Patients With Inflammatory Bowel Disease: A Review , 2008, The American Journal of Gastroenterology.

[2]  A. V. van Kuilenburg,et al.  Paradoxical elevated thiopurine S-methyltransferase activity after pancytopenia during azathioprine therapy: potential influence of red blood cell age. , 2008, Therapeutic drug monitoring.

[3]  S. Sahasranaman,et al.  Clinical pharmacology and pharmacogenetics of thiopurines , 2008, European Journal of Clinical Pharmacology.

[4]  Michael V. Bland,et al.  Trinucleotide repeat variants in the promoter of the thiopurine S-methyltransferase gene of patients exhibiting ultra-high enzyme activity , 2008, Pharmacogenetics and genomics.

[5]  Michael D. Green,et al.  Infectious Complications of Immunosuppressive Medications in Organ Transplant Recipients , 2007, The Pediatric infectious disease journal.

[6]  D. Hommes,et al.  Pancytopenia due to high 6-methylmercaptopurine levels in a 6-mercaptopurine treated patient with Crohn's disease. , 2007, Digestive and liver disease : official journal of the Italian Society of Gastroenterology and the Italian Association for the Study of the Liver.

[7]  A. Timmer,et al.  Azathioprine and 6-mercaptopurine for maintenance of remission in ulcerative colitis. , 2007, The Cochrane database of systematic reviews.

[8]  M. Rapoport,et al.  Successful treatment of prolonged agranulocytosis caused by acute parvovirus B19 infection with intravenous immunoglobulins. , 2006, European journal of internal medicine.

[9]  P. Söderkvist,et al.  Pharmacogenetics during standardised initiation of thiopurine treatment in inflammatory bowel disease , 2006, Gut.

[10]  H. Rudich,et al.  Agranulocytosis associated with parvovirus B19 infection in otherwise healthy patients. , 2004, European journal of internal medicine.

[11]  K. Schmiegelow,et al.  Serologic Study on Parvovirus B19 Infection in Childhood Acute Lymphoblastic Leukemia During Chemotherapy: Clinical and Hematologic Implications , 2002, Journal of pediatric hematology/oncology.

[12]  S. Modrow,et al.  Chronic autoimmune thrombopenia/neutropenia in a boy with persistent parvovirus B19 infection. , 2001, Journal of clinical virology : the official publication of the Pan American Society for Clinical Virology.

[13]  B. Bonaz,et al.  Genotypic analysis of thiopurine S-methyltransferase in patients with Crohn's disease and severe myelosuppression during azathioprine therapy. , 2000, Gastroenterology.

[14]  S. Targan,et al.  Pharmacogenomics and metabolite measurement for 6-mercaptopurine therapy in inflammatory bowel disease. , 2000, Gastroenterology.

[15]  G. Barlow,et al.  Parvovirus B19 causing leucopenia and neutropenia in a healthy adult. , 2000, The Journal of infection.

[16]  G. Fick,et al.  Azathioprine for maintaining remission of Crohn's disease. , 1998, The Cochrane database of systematic reviews.

[17]  B. Korelitz,et al.  Significance of WBC differential when leukopenia is induced by 6-MP for IBD. , 1997, Gastroenterology.

[18]  N. Young,et al.  Parvovirus B19 infection and hematopoiesis. , 1995, Blood reviews.

[19]  W. Watson,et al.  Viral-associated haemophagocytosis with parvovirus-B19-related pancytopenia , 1992, The Lancet.

[20]  N. Young,et al.  PERSISTENT B19 PARVOVIRUS INFECTION AS A CAUSE OF SEVERE CHRONIC ANAEMIA IN CHILDREN WITH ACUTE LYMPHOCYTIC LEUKAEMIA , 1988, The Lancet.

[21]  M. Söderlund-Venermo,et al.  [Human parvoviruses]. , 1987, Annales de pediatrie.

[22]  B. Cant,et al.  PARVOVIRUS-LIKE PARTICLES IN HUMAN SERA , 1975, The Lancet.