mercaptopurine and Diarrhea

Crohn's disease is rare in South African black people and primary sclerosing cholangitis (PSC) is also rare in black patients with IBD, from South Africa. The presence of HLA-B27 is generally associated with seronegative spondylo-arthropathies and correlates with the occurrence of ankylosing spondylitis, recurrent mouth ulcers and uveitis, in patients with IBD. We describe two women with the combination of Crohn's disease, PSC and HLA-B27 from our cohort of the last 5 years of three black patients with Crohn's disease. Crohn's disease, PSC and HLA-B27 respectively, occur rarely in black South Africans and their concurrent presence in two black women suggests a pathogenetic link of HLA-B27 between Crohn's disease and PSC in this population. Female gender might be an additional determinant in this setting.

Topics: Adult; Alkaline Phosphatase; Azathioprine; Back Pain; Black People; Cholagogues and Choleretics; Cholangiopancreatography, Magnetic Resonance; Cholangitis, Sclerosing; Colonoscopy; Crohn Disease; Diarrhea; Female; gamma-Glutamyltransferase; Genetic Predisposition to Disease; HLA-B27 Antigen; Humans; Immunosuppressive Agents; Mercaptopurine; Methotrexate; Severity of Illness Index; South Africa; Treatment Outcome; Ursodeoxycholic Acid

Cryptosporidium species is considered to be an important cause of significant morbidity in immunocompromised individuals. A prospective case-control study of sporadic diarrhea due to Cryptosporidium infection was conducted on children with acute lymphoblastic leukemia (ALL).. Forty children with ALL on maintenance chemotherapy according to the Berlin-Frankfurt-Munster (BFM-90) protocol and 45 sex- and age-matched controls were studied. The ALL group included 25 patients with acute diarrhea and 15 without diarrhea, and the control group included 30 children with acute diarrhea and 15 without. Collected stool specimens were examined using modified Ziehl-Neelsen (MZN) and modified trichrome stains. Serum Cryptosporidium Parvum immunoglobulin G (IgG) antibodies were detected by enzyme-linked immunosorbent assay.. Cryptosporidium oocysts, pathogenic Gram-negative organisms, Giardia lamblia, and Entamoeba histolytica were identified in the stool samples (fecal specimens) of six (24%), eight (32%), four (16%), and two (8%), respectively, of the 25 patients with ALL and actute diarrhea and in one (3%), two (6.5%), six (20%), and five (16.5%), respectively, of the 30 control patients with diarrhea. Serum IgG antibodies were positive in four of the six ALL patients and in one of the control group patients with Cryptosporidium diarrhea who tested positive for oocysts in the stool. Diarrhea duration and severity were greater in ALL patients with stool-positive Cryptosporidium oocysts than in those with non-Cryptosporidium-positive diarrhea (p < 0.000).. Cryptosporidium infection should be considered in children with ALL presenting with prolonged or severe watery diarrhea during chemotherapy, especially those treated with methotrexate and 6-mercaptopurine. Since Cryptosporidium is not routinely tested for in stool examination, a MZN stain is recommended.

Topics: Adolescent; Case-Control Studies; Child; Child, Preschool; Cryptosporidiosis; Cryptosporidium parvum; Diarrhea; Egypt; Entamoeba histolytica; Feces; Female; Gastroenteritis; Giardia lamblia; Gram-Negative Bacteria; Humans; Immunocompromised Host; Immunosuppressive Agents; Infant; Maintenance Chemotherapy; Male; Mercaptopurine; Methotrexate; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Prospective Studies

Azathioprine and its active metabolite 6-mercaptopurine are of increasing importance in the treatment of chronic inflammatory bowel disease. Most of the toxicity and the side effects of the medications are well known. However, it is relatively unknown that azathioprine toxicity itself can produce devastating diarrhea in patients with inflammatory bowel disease. This leads to great difficulties in differential diagnosis. We describe 2 patients with severe intestinal toxicity. This was life-threatening in 1 patient after reintroducing the drug. We therefore believe that any rechallenge with azathioprine should be only undertaken in a controlled hospital environment when a reaction to azathioprine is suspected. In addition, we found that this devastating intestinal toxicity did not reoccur after rechallenge with its active metabolite 6-mercaptopurine. Azathioprine and 6-mercaptopurine therefore cannot be used interchangeably.

Topics: Adult; Azathioprine; Colitis, Ulcerative; Crohn Disease; Diarrhea; Female; Humans; Immunosuppressive Agents; Male; Mercaptopurine; Middle Aged

The efficiency and toxicity of treatment regimens for nonintensive cytoreduction in 57 outpatients with refractory acute leukemia (mean age 56 years, 51 AML, six ALL/AUL) were retrospectively studied. Seventeen patients received one treatment regimen, 19 patients two treatment regimens, and 21 patients three or more treatment regimens. The treatment regimens analyzed were 6-thioguanine p.o. (daily) (T), 6-thioguanine p.o. (4-7 days/week) + cytarabine s.c./i.v. (once a week) (T+C), 6-mercaptopurine p.o. (daily) (MP), 6-mercaptopurine p.o. (daily) + methotrexate p.o./i.v. (once a week) (MP+MTX), etoposide p.o. (daily) (E), and mitoxantrone i.v. (M). The median leukocyte count was higher for M (73 x 10(9)/l) than for the other treatment regimens (T: 27 x 10(9)/l, T+ C: 37 x 10(9)/l, MP: 24 x 10(9)/l, MP + MTX: 30 x 10(9)/l, E: 31 x 10(9)/l). A cytoreduction >50% in the peripheral blood was achieved by T in 11/19, by T+C in 7/11, by MP in 5/8, by MP+MTX in 3/6, by E in 3/4, and by M in 16/22 patients. The period of cytoreduction was regarded as the duration of response - T: median 53 days, range 5-98; T+C: median 61 days, range 14-226; MP: median 37 days, range 4-192; MP + MTX: median 58 days, range 36-59; E: median 121 days, range 26-159; M: median 39 days, range 8-78. T and T + C were well tolerated by all but three patients (stomatitis, diarrhea, WHO grade 2). MP was accompanied by a rise of transaminases (WHO 1-3) in 5/6 patients. E led to stomatitis (WHO 1,2) in 4/5 and M to nausea/vomiting (WHO 1,2) in 5/22 and to stomatitis (WHO 2) in 4/22 cases. The mean survival time after start of palliative cytoreduction was 16 weeks (2-65). In summary, 6-thioguanine +/- cytarabine was best tolerated with effective but in oral monotherapy - often protracted cytoreduction in 60% of patients. Mitoxantrone showed tolerable side effects and potent cytoreduction in 73% of patients even after ineffective palliative pretreatment. Palliative cytoreductive therapy does not reduce the quality of life and can prevent complications of significant leukocytosis in refractory acute leukemia.

Topics: Acute Disease; Administration, Oral; Adult; Aged; Aged, 80 and over; Antineoplastic Combined Chemotherapy Protocols; Cytarabine; Diarrhea; Female; Humans; Injections, Intravenous; Injections, Subcutaneous; Leukemia; Leukocyte Count; Male; Mercaptopurine; Methotrexate; Middle Aged; Nausea; Palliative Care; Retrospective Studies; Stomatitis; Thioguanine

Hypersensitivity mimicking gastroenteritis is a rare complication of azathioprine therapy for which the mechanism is unknown. We report a case of devastating diarrhoea and vomiting due to azathioprine treatment in which hypersensitivity to the imidazole moiety of azathioprine was demonstrated. This has important therapeutic implications: in this situation, 6-mercaptopurine, which is the portion of azathioprine responsible for the cytotoxic therapeutic effect, can be administered without recurrence of side-effects.

Topics: Adult; Azathioprine; Diagnosis, Differential; Diarrhea; Ear Diseases; Gastroenteritis; Humans; Keratitis; Male; Mercaptopurine; Syndrome; Vestibular Diseases

Large dosage of 5-fluorouracil given by slow intravenous infusion has proved to be very effective in the treatment of gestational trophoblastic neoplasms. From 1965 through 1975, 5-fluorouracil was used as a single chemotherapeutic agent in 173 cases of invasive mole and 139 cases of choriocarcinoma. Complete remission was achieved in 84.9% of cases of invasive mole and in 59.3% of cases of choriocarcinoma when 5-fluorouracil was used as the initial treatment. Seven recurrences with three deaths occurred during follow-up in 216 patients who had achieved complete remission, providing a recurrence rate of 3.2% and recurrence death rate of 1.4%. All of the survivors were followed up for more than 5 years and 85.6% for more than 10 years. Toxicity of 5-fluorouracil was milder and less frequent than that of 6-mercaptopurine or methotrexate. The toxic reaction specific to 5-fluorouracil was diarrhea, which can result in pseudomembranous colitis if improperly treated. One of the two toxic deaths was due to this complication.

Topics: Choriocarcinoma; Diarrhea; Female; Fluorouracil; Follow-Up Studies; Humans; Hydatidiform Mole, Invasive; Mercaptopurine; Methotrexate; Neoplasm Recurrence, Local; Pregnancy; Uterine Neoplasms

Topics: Adrenocorticotropic Hormone; Atropine; Azathioprine; Colitis, Ulcerative; Crohn Disease; Diarrhea; Diet; Glucocorticoids; Humans; Immunosuppressive Agents; Mercaptopurine; Nutrition Disorders; Pain; Prednisolone; Prednisone; Sulfasalazine

Topics: Animals; Antineoplastic Agents; Blood Platelets; Bone Marrow; Bone Marrow Cells; Deoxyribonucleosides; Diarrhea; Dogs; Dose-Response Relationship, Drug; Drug Evaluation, Preclinical; Erythrocyte Count; Feeding and Eating Disorders; Female; Haplorhini; Hematocrit; Humans; Injections, Intravenous; Leukocyte Count; Leukopenia; Lymphocytes; Macaca; Male; Mercaptopurine; Neutrophils; Thrombocytopenia; Time Factors; Vomiting

Topics: Adolescent; Anemia, Aplastic; Antineoplastic Agents; Central Nervous System; Child; Child, Preschool; Cyclophosphamide; Daunorubicin; Diarrhea; Drug Combinations; Female; Follow-Up Studies; Humans; Leukemia, Lymphoid; Male; Mercaptopurine; Methotrexate; Nausea; Pneumonia, Pneumocystis; Prednisone; Radiotherapy; Recurrence; Remission, Spontaneous; Stomatitis, Aphthous; Vincristine; Vomiting