mercaptopurine and Opportunistic-Infections

The use of thiopurines is well established in the management of inflammatory bowel disease. A wealth of data and experience, amassed over several decades, supporting their efficacy has recently been challenged by trials that failed to show a benefit in Crohn's disease when used early in the disease course, although other trials continue to support their role both as monotherapy and in combination with anti-TNF. Recent reports of previously unrecognized toxicity have also emerged. Fortunately, the absolute incidence of serious toxicity remains low, and an improved understanding of how best to minimize risk and the recognition of groups of patients at higher risk of toxicity from thiopurines means that they remain a relatively safe therapy in the majority of patients. In this paper, we review the literature evaluating the role of thiopurines in inflammatory bowel disease as well as their toxicity. We conclude that education regarding the spectrum of thiopurine side effects and optimal monitoring during therapy may help with optimizing safety and efficacy of these important medications.

Topics: Azathioprine; Chemical and Drug Induced Liver Injury; Colitis, Ulcerative; Crohn Disease; Humans; Immunosuppressive Agents; Mercaptopurine; Nausea; Neoplasms; Neutropenia; Opportunistic Infections; Pancreatitis

Topics: Adrenal Cortex Hormones; Azathioprine; Crohn Disease; Cyclosporins; Humans; Immunosuppressive Agents; Mercaptopurine; Methotrexate; Multicenter Studies as Topic; Opportunistic Infections

Topics: Adolescent; Antineoplastic Combined Chemotherapy Protocols; Asparaginase; Bacterial Infections; Child, Preschool; Cyclophosphamide; Cytarabine; Daunorubicin; Encephalitis, Herpes Simplex; Fatal Outcome; Female; Hematopoietic Stem Cell Transplantation; Herpes Simplex; Humans; Induction Chemotherapy; Infant; Male; Mercaptopurine; Methotrexate; Opportunistic Infections; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Prednisone; Simplexvirus; Stomatitis, Herpetic; Vincristine; Virus Activation

Topics: Aged, 80 and over; Antibodies, Monoclonal; Crohn Disease; Humans; Immunosuppression Therapy; Immunosuppressive Agents; Infliximab; Male; Mercaptopurine; Nocardia Infections; Opportunistic Infections; Pneumonia, Bacterial

Allopurinol has been presented as a safe and effective adjunct to thiopurine therapy in inflammatory bowel disease (IBD). We aimed to determine the rate of infectious complications and clinical successes with a combination of thiopurine/allopurinol in IBD, and to identify which variables predict 6-thioguanine, 6-methylmercaptopurine, and white blood cell levels. Additionally we aimed to identify which variables predict complications.. A retrospective database search identified patients with inflammatory bowel disease on both thiopurines and allopurinol. Regression modeling was used to identify which variables predicted metabolite levels, white blood cell levels, and complications.. Twenty-seven subjects were found, with 20 treated intentionally and 7 inadvertently after a concurrent gout diagnosis. Thirteen of 20 patients had a major clinical improvement and 7 of 16 stopped steroids. Five infectious complications occurred. These included 2 cases of shingles, and one each of PCP, EBV, and viral meningitis. Significant predictors of metabolite levels included the dose of thiopurine and allopurinol, age, and BMI. Low white blood cell count levels were associated with increased doses, high BMI, and older age. Despite having only 5 events, there was a difference in absolute lymphocyte count between patients with and without infection (median 200 per mm³ vs 850 per mm³ respectively, p=0.0503).. Adjunctive allopurinol therapy in shunting patients produced major clinical improvement in 48% of patients. However, a surprising number of opportunistic infections have occurred. Low absolute lymphocyte count may be a previously unrecognized indicator of risk of opportunistic infections.

Topics: Adult; Allopurinol; Azathioprine; Colitis, Ulcerative; Crohn Disease; Drug Therapy, Combination; Female; Humans; Immunosuppressive Agents; Inflammatory Bowel Diseases; Male; Mercaptopurine; Middle Aged; Opportunistic Infections; Retrospective Studies; Young Adult

A 68-yr-old man with steroid refractory distal ulcerative colitis was treated with low-dose 6-mercaptopurine, and corticosteroids were successfully discontinued. He later presented with dyspnea and fever, was diagnosed with Pneumocystis carinii pneumonia by bronchoalveolar lavage, and died despite aggressive therapy. Serological tests for HIV were negative, and his white blood cell count was normal. This is the first report of P. carinii pneumonia complicating therapy of inflammatory bowel disease with 6-mercaptopurine. Although the mechanism is not entirely clear, 6-mercaptopurine appears to decrease cell-mediated immunity. Opportunistic infections such as P. carinii pneumonia should be added to the list of potential bronchopulmonary complications of antimetabolite immunosuppressive therapy of inflammatory bowel disease.

Topics: Aged; Aminosalicylic Acids; Anti-Inflammatory Agents; Anti-Inflammatory Agents, Non-Steroidal; Antimetabolites; Betamethasone; Bronchoalveolar Lavage Fluid; Colitis, Ulcerative; Fatal Outcome; Glucocorticoids; HIV Seronegativity; Humans; Immunity, Cellular; Immunosuppressive Agents; Male; Mercaptopurine; Mesalamine; Opportunistic Infections; Pneumonia, Pneumocystis; Prednisolone; Sulfasalazine

Mucormycosis is a rare fungal infection that has been described mainly in oncologic and diabetic patients. We here report the cases of two leukaemic patients in whom pulmonary mucormycosis was diagnosed. Prompt diagnosis, therapy with amphotericin B and surgery when possible, are the cornerstones in the treatment of this fungal infection. Although infrequent, this infection must be suspected in oncohaematological patients with lung infiltrates.

Topics: Adult; Aged; Amphotericin B; Antineoplastic Combined Chemotherapy Protocols; Cytarabine; Fatal Outcome; Granulocyte Colony-Stimulating Factor; Humans; Immunologic Factors; Itraconazole; Leukemia, Promyelocytic, Acute; Lung Diseases, Fungal; Male; Mercaptopurine; Methotrexate; Mitoxantrone; Mucormycosis; Neutropenia; Opportunistic Infections; Precursor Cell Lymphoblastic Leukemia-Lymphoma

We describe an unusual case of disseminated subcutaneous abscesses caused by Nocardia asteroides in a 17-year-old female with AML undergoing allogeneic BMT. She was receiving immunosuppressive therapy with CYA and a corticosteroid for acute GVHD, and maintenance therapy with ganciclovir for interstitial pneumonia (IP) caused by CMV, but was not neutropenic. The subcutaneous abscesses spread from the primary infection on her right anterior leg to both thighs, the left buttock, both upper arms, the left forearm and right shoulder, indicating hematogenous dissemination. Nocardia asteroides was identified from biopsy material in culture. The patient was successfully treated with a combination of trimethoprim/sulfamethoxazole (TMP/SMX) and minocycline, given for 3 months. The possibility of nocardiosis should be considered in the differential diagnosis of such patients.

Topics: Abscess; Adolescent; Antineoplastic Combined Chemotherapy Protocols; Bone Marrow Purging; Bone Marrow Transplantation; Combined Modality Therapy; Cytarabine; Daunorubicin; Female; Humans; Immunocompromised Host; Incidence; Leukemia, Myeloid, Acute; Mercaptopurine; Neutropenia; Nocardia asteroides; Nocardia Infections; Opportunistic Infections; Prednisolone; Remission Induction; Skin Diseases, Infectious