Acute respiratory distress syndrome due to pneumonitis following intrathecal methotrexate administration

Centre Henri Becquerel, Rouen, Haute-Normandie, France
Revue des Maladies Respiratoires (Impact Factor: 0.62). 05/2003; 20(2 Pt 1):273-7.
Source: PubMed


Methotrexate, given orally or systemically, is associated with pneumonitis in 7% of cases.
This case report describes acute respiratory distress syndrome, due to diffuse pneumonitis, in a patient with malignant non-Hodgkin's lymphoma being treated with combination chemotherapy which included doxorubicin, cyclophosphamide, bleomycin, vindesin and intrathecal methotrexate with G-CSF (filgrastine- Neupogen). The clinical course, the lack of an identifiable infectious agent and the complete response to corticosteroids suggested a drug-induced cause. After ruling out the other chemotherapy agents, methotrexate was considered to be the causal agent. The unusual feature of this case was that pneumonitis developed after intrathecal administration of methotrexate.
Methotrexate-associated respiratory complications can occur with whichever route the drug is administered.

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    ABSTRACT: Methotrexate-induced pneumonitis (MTX-P) is an unusual adverse drug reaction that typically manifests as an interstitial lung disease (ILD). Early diagnosis of this complication is desirable because discontinuation of MTX with or without steroid administration often results in a fast recovery. Conversely, a delay or a misdiagnosis may lead to death. Diagnostic workup is often problematic because underlying diseases leading to methotrexate administration, notably rheumatoid arthritis (RA), and opportunistic infections because of drug-induced immune impairment can also produce an ILD. In this clinical setting, bronchoalveolar lavage (BAL) plays a key role either in excluding infectious agents, especially in febrile presentations, or in looking for malignant cells. Unfortunately, BAL does not have specific features to allow clinicians to differentiate MTX-P from RA-associated ILD. Here, we present 2 definite cases of MTX-P in RA patients. BAL differential cell counts and alveolar CD4/CD8 values were found to be in agreement with those reported in the literature, but an increase in mast cells and the presence of foamy macrophages have never been reported among previously published cases. The presence of both mast cells and foamy macrophages could be helpful in differentiating MTX-P from many drug-unrelated ILDs, but does not assist in distinguishing MTX-P from Pneumocystis jiroveci pneumonia and RA-associated bronchiolitis obliterans organizing pneumonia.
    No preview · Article · Sep 2013 · Clinical Pulmonary Medicine
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    ABSTRACT: Background This study was designed to evaluate the effects of carvacrol (CRV) and pomegranate extract (PE) on methotrexate (MTX)-induced lung injury in rats. Material/Methods A total of 32 male rats were subdivided into 4 groups: control (group I), MTX treated (group II), MTX+CRV treated (group III), and MTX+PE treated (group IV). A single dose of 73 mg/kg CRV was administered intraperitoneally to rats in group III on Day 1 of the investigation. To group IV, a dose of 225 mg/kg of PE was administered via orogastric gavage once daily over 7 days. A single dose of 20 mg/kg of MTX was given intraperitoneally to groups II, III, and IV on Day 2. The total duration of experiment was 8 days. Malondialdehyde (MDA), total oxidant status (TOS), total antioxidant capacity (TAC), and oxidative stress index (OSI) were measured from rat lung tissues and cardiac blood samples. Results Serum and lung specimen analyses demonstrated that MDA, TOS, and OSI levels were significantly greater in group II relative to controls. Conversely, the TAC level was significantly reduced in group II when compared to the control group. Pre-administering either CRV or PE was associated with decreased MDA, TOS, and OSI levels and increased TAC levels compared to rats treated with MTX alone. Histopathological examination revealed that lung injury was less severe in group III and IV relative to group II. Conclusions MTX treatment results in rat lung oxidative damage that is partially counteracted by pretreatment with either CRV or PE.
    Full-text · Article · Oct 2014 · Medical science monitor: international medical journal of experimental and clinical research