title: Fatal intra-alveolar hemorrhage after rituximab in a patient with non-Hodgkin lymphoma.
abstract: A 65-year-old male developed progressive dry cough and digital clubbing after starting rituximab-CHOP chemotherapy for non-Hodgkin lymphoma. A lung biopsy showed loose non-necrotic granulomas in a background of mild fibrosis and rare eosinophils, compatible with a drug-induced hypersensitivity pneumonia. Associated manifestations of this hypersensitivity reaction were a high eosinophil count, elevated serum levels of immunoglobulin E, and a skin rash consistent with pigmented purpuric dermatitis (Schamberg disease). Corticosteroids were marginally efficacious in treating this reaction. Few similar reactions have since been described, 2 of them ultimately fatal, but none was associated with pulmonary hemorrhage. A 2.5:1 ratio between the interstitial alveolar T4/T8 lymphocytes in our case is similar to the findings in methotrexate-induced pneumonitis and farmer lung disease. This report documents the serologic and immunohistologic findings associated with a pulmonary interstitial reaction to rituximab. A review of the pertinent literature is provided. The possible pathogenetic mechanisms, including the role of cytokines, cytotoxic T-lymphocytes and CD 20 positive T-cells in relation to the administration of rituximab are discussed.
authors.affiliation: Comprehensive Cancer Center, Our Lady of Mercy Medical Center, New York Medical College, Bronx, NY 10466, USA. mddoru@hotmail.com
authors.forename: Doru T
authors.initials: DT
authors.lastname: Alexandrescu
authors.forename: Janice P
authors.initials: JP
authors.lastname: Dutcher
authors.forename: Kevin
authors.initials: K
authors.lastname: O'Boyle
authors.forename: Mehmet
authors.initials: M
authors.lastname: Albulak
authors.forename: Stanley
authors.initials: S
authors.lastname: Oiseth
authors.forename: Peter H
authors.initials: PH
authors.lastname: Wiernik
mesh_terms: D000368:Aged; D000911:Antibodies, Monoclonal / Q000009:adverse effects*; D058846:Antibodies, Monoclonal, Murine-Derived; D000970:Antineoplastic Agents / Q000494:pharmacology; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage / Q000627:therapeutic use; D001706:Biopsy; D003520:Cyclophosphamide / Q000008:administration & dosage; D004317:Doxorubicin / Q000008:administration & dosage; D004804:Eosinophils / Q000166:cytology; D017809:Fatal Outcome; D006099:Granuloma / Q000139:chemically induced / Q000473:pathology; D006470:Hemorrhage / Q000139:chemically induced*; D006801:Humans; D007073:Immunoglobulin E / Q000097:blood; D007249:Inflammation; D008228:Lymphoma, Non-Hodgkin / Q000188:drug therapy* / Q000401:mortality; D008297:Male; D010859:Pigmentation Disorders / Q000188:drug therapy; D011239:Prednisolone / Q000008:administration & dosage; D011650:Pulmonary Alveoli; D000069283:Rituximab; D013997:Time Factors; D014057:Tomography, X-Ray Computed; D014750:Vincristine / Q000008:administration & dosage
chemical_list: D000911:Antibodies, Monoclonal; D058846:Antibodies, Monoclonal, Murine-Derived; D000970:Antineoplastic Agents; D007073:Immunoglobulin E; D000069283:Rituximab; D014750:Vincristine; D004317:Doxorubicin; D003520:Cyclophosphamide; D011239:Prednisolone