mercaptopurine and Lung-Diseases

Azathioprine and 6-mercaptopurine (6-MP) are effective in inflammatory bowel disease (IBD). However, between 10% and 29% of patients treated with these drugs are forced to stop therapy due to side effects. Pulmonary toxicity due to azathioprine/6-MP has been reported infrequently. We describe 3 patients who developed severe, noninfectious pulmonary toxicity within 1 month after the initiation of azathioprine or 6-MP for the treatment of IBD colitis (2 Crohn's disease and 1 ulcerative colitis). All patients presented with dyspnea, cough, and fever after initiation of azathioprine/6-MP. Evaluation for infectious etiologies, including bronchoscopy (3/3 patients) and open-lung biopsy (2/3 patients) was negative. Histopathologic examination of the lung biopsies revealed bronchiolitis obliterans organizing pneumonia in one, and usual interstitial pneumonitis in another patient. Cessation of purine analog therapy resulted in clinical improvement in all 3 cases. Azathioprine/6-MP-related pulmonary toxicity is a rare but serious side effect, and it is important for clinicians to have a high index of suspicion for this adverse reaction which occurs within 1 month after initiation of treatment for IBD.

Topics: Adult; Aged; Azathioprine; Crohn Disease; Female; Humans; Immunosuppressive Agents; Lung Diseases; Male; Mercaptopurine; Severity of Illness Index

Crohn's disease (CD) is a granulomatous systemic disorder of unknown etiology. Obvious pulmonary involvement is exceptional in patients with CD. We report a case of a 38-year-old man who suffered from CD for more than 14 years and was treated with oral steroids for more than 10 years. Surgical excision of parts of the ileum was performed for life-threatening ileal bleeding caused by CD. After acute tapering of oral steroids, pulmonary symptoms and radiologic abnormalities were noted. Lung biopsy through thoracoscopy was performed and revealed signs of chronic inflammation with multiple subepithelial noncaseating and epithelioid granulomas on pathologic examination. Intravenous steroids were required in the initial management of life-threatening pulmonary dysfunction after diagnostic thoracoscopy and led to marked improvement. Tuberculocidal therapy was performed until all microbiological cultures were negative. Oral steroid dosage had slowly been tapered over 1 month. He was discharged with clinical and radiologic improvements. After 36 months, the patient's condition is stable on continued treatment with prednisolone and mesalazine.

Topics: Adult; Angiography; Biopsy, Needle; Combined Modality Therapy; Crohn Disease; Drug Therapy, Combination; Follow-Up Studies; Granuloma; Humans; Ileum; Immunohistochemistry; Laparotomy; Lung Diseases; Male; Mercaptopurine; Prednisolone; Risk Assessment; Severity of Illness Index; Tomography, X-Ray Computed

Diffuse pulmonary diseases seen in patients receiving chemotherapy have a wide variety of etiologies including infection, involvement with the underlying disease, injury from radiation or diagnostic agents, and toxicity from chemotherapeutic drugs. In addition to concomitantly used therapeutic agents, previously administered cytotoxic drugs may enhance the toxicity of radiotherapy and vice versa. Together with the clinician, the radiologist may be able to assess the probability of drug-induced lung disease by correlating radiographic and clinical data. Useful clinical data include signs and symptoms related to the lungs, pulmonary function test results, dose and schedule of drug administration, and information concerning concomitant or previous drug or radiation therapy. Useful radiographic data include the distribution of densities seen on the chest radiograph, the presence or absence of thoracic adenopathy, and the presence or absence of pleural effusion. The diagnosis is difficult, and thus the incidence of clinical and subclinical drug-induced pneumonitis is not accurately known.

Topics: Adult; Aged; Antibiotics, Antineoplastic; Antineoplastic Agents; Bleomycin; Busulfan; Carmustine; Cyclophosphamide; Female; Humans; Lomustine; Lung Diseases; Lung Neoplasms; Male; Mercaptopurine; Methotrexate; Middle Aged; Pulmonary Fibrosis; Radiography

Topics: Abnormalities, Drug-Induced; Adolescent; Adult; Antineoplastic Agents; Busulfan; Carcinogens; Central Nervous System Diseases; Chemical and Drug Induced Liver Injury; Child; Female; Heart Diseases; Humans; Lung Diseases; Male; Menstruation Disturbances; Mercaptopurine; Methotrexate; Neoplasms; Neoplasms, Radiation-Induced; Pregnancy; Radiotherapy; Urinary Bladder Diseases

Cytotoxic drugs, which are widely used as immunosuppressive and antiinflammatory agents in patients with neoplastic conditions, and cancer chemotherapy preparations, are of long-range concern due to the problem of cumulative organ toxicity which is not manifested until damage is extensive. These considerations have arisen because of their widespread use in recent years. Those involved in hepatic toxicity are the antimetabolites methotrexate and 6-mercaptopurine. Bisulfin, bleomycin, and methotrexate have been linked to pulmonary toxicity. Daunomycin and adriamycin, used as anticarcinogens, are examined for their cardiac toxicity. Cyclophosphamide and streptozotocin affect the urinary tract. These drugs have specific toxic effects on fertility in both males, through its disruption of the testicular function, and in females, for ovarian disruptions. Antifolics, 6-mercaptopurine, azathioprine, and alkylating agents, used for therapy in pregnant women, particularly in the first 4 months, are linked to the appearance of fetal abnormalities. The process of carcinogenesis is examined for clues to possible chemotherapy-related 2nd tumors, which appear during the course of treatment.

Topics: Alkylating Agents; Antineoplastic Agents; Azathioprine; Bleomycin; Busulfan; Carcinogens; Chemical and Drug Induced Liver Injury; Daunorubicin; Doxorubicin; Female; Fetus; Folic Acid Antagonists; Follow-Up Studies; Humans; Immunosuppression Therapy; Immunosuppressive Agents; Infertility, Female; Infertility, Male; Liver; Lung Diseases; Male; Mercaptopurine; Methotrexate; Myocarditis; Neoplasms; Ovary; Pregnancy; Procarbazine; Streptozocin; Testis; Urologic Diseases

Topics: Adolescent; Adult; Antilymphocyte Serum; Azathioprine; Dactinomycin; Female; Histocompatibility Testing; Humans; Hydrocortisone; Immunosuppressive Agents; Lung Diseases; Lung Transplantation; Male; Mediastinum; Mercaptopurine; Methods; Middle Aged; Pneumonia; Postoperative Complications; Prednisolone; Respiration; Respiratory Insufficiency; Thymus Gland; Time Factors; Tissue Donors; Transplantation Immunology; Transplantation, Homologous

There are challenges for diagnosis and treatment of idiopathic pulmonary hemosiderosis (IPH). This clinical trial was to review the diagnosis and evaluate the efficacy of maintenance therapy with dose-adjusted 6-mercaptopurine (6MP) in IPH children. Fifteen children were enrolled. Prednisone was administered at 2 mg/kg/day for 4 weeks in acute phase of the disease followed by taper. 6MP was also started at 60 mg/m(2)/day simultaneously and continued for 3 years in outpatient. The delay in diagnosis of IPH is common and probably due to a lack of classical triad of IPH in most children. All the patients exhibited response to the initial treatment. Only one of eight patients with relative leukopenia on 6MP maintenance recurred while 5 of 7 others recurred (P < 0.05) during median 4.5-year follow-up. Of the latter five patients who recurred, 4 remained recurrence-free after adjusting the dose of 6MP upwards to keep relative leucopenia. It suggests that children with IPH could achieve steroid-free long term remission on 6MP maintenance therapy, and relative leukopenia on 6MP might be a simple maker of predicting clinical response in most IPH children.

Topics: Adolescent; Anemia; Antimetabolites; Child; Child, Preschool; Dose-Response Relationship, Drug; Female; Hemosiderosis; Humans; Lung Diseases; Male; Mercaptopurine

Topics: Adult; Azathioprine; Child; Child, Preschool; Clinical Trials as Topic; Female; Humans; Leukemia; Leukemia, Lymphoid; Leukemia, Myeloid, Acute; Lung Diseases; Male; Mercaptopurine; Radiography, Thoracic; Vincristine

Diffuse alveolar hemorrhage is an uncommon and often fatal condition in children that is characterized by distinct histopathological etiologies. Herein, we discuss the case of an 11-year-old girl who presented with acute worsening of hypoxia and left-sided chest pain. The patient had lung biopsy-proven idiopathic pulmonary capillaritis and was being treated with prednisolone every alternate day, azathioprine, and hydroxychloroquine. A contrast-computed tomography (CT) scan of the chest showed an acute left lower-lobe pulmonary embolism. Negative results were obtained on a test for thrombophilia. In children, pulmonary embolism with anti-neutrophil cytoplasmic antibody-negative idiopathic pulmonary capillaritis is a rare clinical condition. The exact cause of thrombus formation in this case is unknown; however, obesity, immobility, and chronic systemic corticosteroid therapy probably played a role.

Topics: Acute Disease; Antibodies, Antineutrophil Cytoplasmic; Capillaries; Chest Pain; Child; Female; Hemorrhage; Heparin, Low-Molecular-Weight; Humans; Hydroxychloroquine; Hypoxia; Lung; Lung Diseases; Mercaptopurine; Prednisolone; Pulmonary Alveoli; Pulmonary Embolism; Treatment Outcome; Vasculitis

Topics: Adult; Anus Diseases; Axilla; Combined Modality Therapy; Drug Therapy, Combination; Histiocytosis, Langerhans-Cell; Humans; Lung Diseases; Male; Mercaptopurine; Organ Specificity; Perineum; Prednisolone; Vinblastine

Topics: Biopsy; Bone Diseases; Cyclosporine; Femur; Glucocorticoids; Histiocytosis, Langerhans-Cell; Humans; Immunosuppressive Agents; Infant; Lung Diseases; Male; Mercaptopurine; Methotrexate; Methylprednisolone; Prednisone; Radiography; Skin; Skin Diseases, Papulosquamous

Juvenile xanthogranuloma (JXG), one of the most common forms of Langerhans-dendritic cell proliferation in young children, usually presents as spontaneously regressing cutaneous lesions. JXG with systemic (extracutaneous) involvement is a rare histiocytic disorder in which significant morbidity and death may occur. The systemic type, especially combined with multiple central nervous system lesions in young children, has a very poor prognosis. The patient described here presented with disseminated disease including lungs, liver, kidneys, ribs, scalp, and central nervous system. The patient was treated with multiagent chemotherapy based on the Langerhans cell histiocytosis II treatment protocol. The regimen used included an additional intrathecal therapy with methotrexate and prednisolone to control central nervous system lesions. The patient was treated for 28 months and has been in remission for almost 5 years.

Topics: Central Nervous System Diseases; Combined Modality Therapy; Craniotomy; Drug Therapy, Combination; Female; Follow-Up Studies; Humans; Infant; Injections, Spinal; Liver Diseases; Lung Diseases; Mercaptopurine; Methotrexate; Paresis; Prednisolone; Skin Diseases; Vinblastine; Xanthogranuloma, Juvenile

Topics: Age Factors; Bone Diseases; Child, Preschool; Drug Therapy, Combination; Female; Histiocytosis, Langerhans-Cell; Humans; Infant; Langerhans Cells; Lung Diseases; Male; Mercaptopurine; Prednisone; Prognosis; Radiotherapy Dosage; Vinblastine

Topics: Adult; Antineoplastic Combined Chemotherapy Protocols; Cyclophosphamide; Drug Therapy, Combination; Humans; Lung Diseases; Lymphoma; Male; Mercaptopurine; Nocardia Infections; Prednisolone; Sulfamethoxazole; Trimethoprim; Vincristine

Topics: Child; Child, Preschool; Female; Hemosiderosis; Humans; Lung Diseases; Mercaptopurine; Prednisone

Topics: Allopurinol; Anaphylaxis; Anemia; Antibiotics, Antineoplastic; Bicarbonates; Blood Transfusion; Child; Child, Preschool; Cystitis; Disseminated Intravascular Coagulation; Erythrocytes; Female; Furosemide; Heart Arrest; Heparin; Humans; Hydrogen-Ion Concentration; Kidney; Leukemia; Lung Diseases; Male; Mercaptopurine; Mutation; Neoplasms; Phospholipids; Renal Dialysis; Thrombocytopenia; Uric Acid

Cytotoxic drugs, principally bleomycin, methotrexate and busulfan, have been associated with pulmonary toxicity. Cytotoxic drug-induced lung disease may be difficult to establish with certainty because other causes of pulmonary disease are frequently present. We discuss the clinical, roentgenographic and histologic effects of the administration of bleomycin, methotrexate, busulfan and other cytotoxic agents on the lungs and suggest that these agents may also cause pulmonary malignancies. We note the importance of careful patient monitoring and withdrawal of a demonstrated offending agent.

Topics: Antibiotics, Antineoplastic; Azathioprine; Bleomycin; Busulfan; Cyclophosphamide; Dose-Response Relationship, Drug; Humans; Lung Diseases; Lung Neoplasms; Mercaptopurine; Methotrexate; Radiography

Thirteen patients with Wegener's granulomatosis have been treated with cytotoxic agents. Only one died from the disease whereas two died of infectious complications of therapy and one of heart disease. Seven of the nine survivors are well without medication; one is alive with renal insufficiency and one is in the 5th year of treatment. Cholorambucil was least toxic and should be tried first. Cyclophosphamide was more effective than cholorambucil or azathioprine but, because of side effects, should rarely be used initially. Differentiation of Wegener's granulomatosis from lymphomatiod granumatosis, which it resembles clinically, roentgenologically and pathologically, is important since the latter disease responds differently to cytoxic drug therapy.

Topics: Azathioprine; Cyclophosphamide; Drug Evaluation; Granuloma; Granulomatosis with Polyangiitis; Hodgkin Disease; Humans; Lung Diseases; Mercaptopurine; Prednisone; Prognosis; Remission, Spontaneous

Topics: Adult; Biopsy; Diagnosis, Differential; Glucocorticoids; Hemoptysis; Hemosiderosis; Humans; Lung Diseases; Lupus Erythematosus, Systemic; Male; Mercaptopurine

Topics: Azathioprine; Child, Preschool; Cyclophosphamide; Hemosiderosis; Humans; Immunosuppressive Agents; Lung Diseases; Male; Mercaptopurine

Topics: Adult; Aged; Antineoplastic Agents; Azathioprine; Chlorambucil; Female; Granulomatosis with Polyangiitis; Humans; Lung Diseases; Male; Mercaptopurine; Middle Aged; Prednisone; Radiography

Topics: Hemosiderosis; Humans; Lung Diseases; Male; Mercaptopurine

A 15-year-old boy ingested a mouthful of paraquat and developed severe respiratory distress. Treatment included the transplantation of one lung, but subsequently changes developed in the graft which are thought to have been due to paraquat, and the patient died two weeks after the operationThe dangers of keeping poisonous substances in incorrectly labelled bottles has once again been demonstrated, while the pattern of paraquat poisoning, especially the development of proliferative alveolitis and terminal bronchiolitis, is confirmed.Immediate forced diuresis followed by haemodialysis is necessary to remove paraquat, thereby perhaps avoiding initiation of the changes in the lungs. The technical feasibility of human lung transplantation has again been demonstrated. It has also been shown that infection does not necessarily pose an insuperable problem, at any rate if, as in the case described, there was no preoperative pulmonary infection in either recipient or donor.

Topics: Adolescent; Azathioprine; Diuresis; Herbicides; Humans; Hydrocortisone; Lung; Lung Diseases; Lung Transplantation; Male; Mercaptopurine; Postoperative Care; Prednisone; Pyridines; Quaternary Ammonium Compounds; Renal Dialysis