Fatal intra-alveolar hemorrhage after rituximab in a patient with non-Hodgkin lymphoma

Leuk Lymphoma. 2004 Nov;45(11):2321-5. doi: 10.1080/10428190410001697359.

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.

Publication types

  • Case Reports

MeSH terms

  • Aged
  • Antibodies, Monoclonal / adverse effects*
  • Antibodies, Monoclonal, Murine-Derived
  • Antineoplastic Agents / pharmacology
  • Antineoplastic Combined Chemotherapy Protocols / administration & dosage
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use
  • Biopsy
  • Cyclophosphamide / administration & dosage
  • Doxorubicin / administration & dosage
  • Eosinophils / cytology
  • Fatal Outcome
  • Granuloma / chemically induced
  • Granuloma / pathology
  • Hemorrhage / chemically induced*
  • Humans
  • Immunoglobulin E / blood
  • Inflammation
  • Lymphoma, Non-Hodgkin / drug therapy*
  • Lymphoma, Non-Hodgkin / mortality
  • Male
  • Pigmentation Disorders / drug therapy
  • Prednisolone / administration & dosage
  • Pulmonary Alveoli
  • Rituximab
  • Time Factors
  • Tomography, X-Ray Computed
  • Vincristine / administration & dosage

Substances

  • Antibodies, Monoclonal
  • Antibodies, Monoclonal, Murine-Derived
  • Antineoplastic Agents
  • Immunoglobulin E
  • Rituximab
  • Vincristine
  • Doxorubicin
  • Cyclophosphamide
  • Prednisolone

Supplementary concepts

  • VAP-cyclo protocol