Methotrexate-associated lymphoproliferative disorder complicated by severe acute respiratory failure and ileal perforation:a case report

Suzuki, Eiji; Kanno, Takashi; Kimura, Satoru; Irie, Tetsumi; Odajima, Hajime; Migita, Kiyoshi

doi:10.5387/fms.2017-23

Cited by 6 publications

(5 citation statements)

References 19 publications

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“…Therefore, MTX prevents immune cell proliferation and suppresses the activation of the immune system, which is one of the main mechanisms of MTX to treat RA [ 2 ]. In addition to immunocytes, MTX also inhibits the proliferation of other cells, such as bone marrow cell, hepatocyte, pneumonocyte, nephrocyte, and gastrointestinal cells [ 6 , 7 , 27 ], leading to organic damage. Particularly, gastrointestinal toxicity is one of the most common side effects related to MTX, which results in malabsorption and diarrhea [ 28 , 29 ].…”

Section: Discussionmentioning

confidence: 99%

Mesenchymal Stem Cells Enhance Therapeutic Effect and Prevent Adverse Gastrointestinal Reaction of Methotrexate Treatment in Collagen-Induced Arthritis

Zhai

Dong

Zhang

et al. 2021

Stem Cells International

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Rheumatoid arthritis (RA) is a systemic autoimmune disease characterized by articular destruction and functional loss. Methotrexate (MTX) is effective in RA treatment. However, MTX induces several adverse events and 20%-30% of patients do not respond to MTX. Thus, it is urgent to enhance the therapeutic effects and reduce the side effects of MTX. Recent studies showed that mesenchymal stem cells (MSCs) were participants in anti-inflammation, immunoregulation, and tissue regeneration. However, whether the combined application of MSCs and MTX promotes the therapeutic effects and reduces the side effects of MTX has not been studied. In this study, we used bovine type II collagen to induce rheumatoid arthritis in mice (collagen-induced arthritis, CIA). Then, CIA mice were subjected to MTX or MSC treatment, or both. The therapeutic effect and adverse events of different treatments on RA were evaluated with micro-CT, HE staining, and immunohistochemistry in vivo. Apoptosis and proliferation of MODE-K cells were measured after treated with MTX or/and cocultured with UCs. To test M2 polarization, Raw264.7 macrophages were stimulated by MTX with different concentrations or cocultured with UCs. We found that the combined application of MSCs and MTX increased the therapeutic effects on RA, as evidenced by decreased arthritis score, inflammatory responses, and mortality. Moreover, in this combination remedy, MTX prefers to suppress inflammation by facilitating macrophage polarization to M2 type while UCs prefer to eliminate gastrointestinal side effects of MTX via mitigating the apoptosis of intestinal epithelial cells. Thus, a combination of MTX and UCs is a promising strategy for RA treatment.

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Section: Discussionmentioning

confidence: 99%

Mesenchymal Stem Cells Enhance Therapeutic Effect and Prevent Adverse Gastrointestinal Reaction of Methotrexate Treatment in Collagen-Induced Arthritis

Zhai

Dong

Zhang

et al. 2021

Stem Cells International

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“…9 A study by Harigai revealed a 58.7month mean duration from MTX initiation to LPD development, with a cumulative MTX dose of 1400 mg. 10 OIIA LPD often presents in extranodal regions such as the liver, stomach and duodenum, 1 and lungs. 11 However, there have been few reports of OIIA LPD cases, in which the skin is the primary lesion site, particularly with histopathological findings of cutaneous DLBCL. 12,13 In our patient, in situ hybridization was used to detect the positive expression of EBV.…”

Section: Discussionmentioning

confidence: 99%

Case report: Management of Epstein–Barr virus positive and methotrexate‐associated B‐cell lymphoma

Wang,

Chan

2024

Int J of Rheum Dis

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INTRODUC TI ONMethotrexate (MTX), a folic acid antagonist, is effective against various autoimmune diseases, including rheumatoid arthritis (RA). 1 However, though MTX benefits patients with RA, it may cause lymphoproliferative disease (LPD) in such patients. 2 Ellman et al. reported the first case of MTX-induced lymphoma in a patient with RA in 1991. 3 Subsequently, the World Health Organization (WHO) has added MTXinduced LPD to its existing categories of LPD, classifying it as "other iatrogenic immunodeficiency-associated LPD" (OIIA LPD). 2 In patients with OIIA LPD, 40%-50% of primary lesions exhibit an extranodal pattern at different anatomical sites. 1 Diffuse large Bcell lymphoma (DLBCL) is the most common histopathological type. 1 In a previous study, following cessation of MTX treatment, spontaneous regression of OIIA LPD was observed in approximately 60% of patients with RA. 4 Nevertheless, another study reported that chemotherapy and targeted therapies, particularly regimens involving rituximab, are effective against OIIA LPD. 5Herein, we describe a patient with RA and MTX-induced DLBCL who was initially controlled with R-miniCHOP and MTX discontinuation. However, the patient later relapsed upon MTX readministration and was subsequently managed via R-CVOP chemotherapy.

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“…Extranodal lesions have been found in the digestive tracts of 4.1% of affected patients, and 1.4% had small intestinal lesions [ 15 ]. Small-intestine perforations due to MTX-LPD can occur but are extremely rare, with 7 cases reported in the Japanese literature and a single case reported in the English literature [ 4 , 16 ] (Table 2 ). All cases were diagnosed as DLBCL, and association with EBV was observed in 5 cases.…”

Section: Discussionmentioning

confidence: 99%

Cessation of methotrexate and a small intestinal resection provide a good clinical course for a patient with a jejunum perforation induced by a methotrexate-associated lymphoproliferative disorder: a case report

et al. 2021

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Background Methotrexate (MTX) is a frequently used drug in the treatment of rheumatoid arthritis (RA), but occurrences of lymphoproliferative disorders (LPD) have been reported in patients undergoing an MTX regimen. Almost half of the patients with methotrexate-associated lymphoproliferative disorders (MTX-LPD) have extranodal lesions; moreover, although extremely rare, digestive tract perforations resulting from the extranodal lesions of MTX-LPD have also been reported. Case presentation We describe the case of an 81-year-old woman with RA who had been prescribed MTX at 6 mg per week for the past 11 years. She was admitted to our hospital with occasional abdominal pain and was first diagnosed with enteritis. Her abdominal pain did not improve, and a computed tomography scan showed abdominal effusion and free air in the abdominal cavity. She was diagnosed with a digestive tract perforation and underwent emergency surgery. The perforation site was identified in the jejunum, and she underwent small intestinal resection around the perforated region. The pathological findings showed an ulcer in the jejunum and infiltration of large atypical lymphocytes around the perforated region. An immunohistochemical examination revealed the expression of a cluster of differentiation 20 and latent membrane protein 1. Considering the patient’s history of RA treated with MTX, she was diagnosed as having Epstein–Barr virus (EBV)-related MTX-LPD with a histological diagnosis of EBVMCU. MTX was discontinued after the surgery, and her soluble interleukin-2 receptor (sIL-2R) levels had returned to normal 1 year later. She has had a good course for the 2 years since surgery and remains asymptomatic with no recurrence of MTX-LPD, as confirmed by the sIL-2R levels. Conclusion We experienced a rare case of the jejunum perforation induced by MTX-LPD. Since only a few cases have been reported of a patient with small intestinal perforation induced by MTX-LPD, further research is necessary to evaluate the clinicopathological features of MTX-LPD. The patient had disease remission after surgery and by discontinuing MTX treatment; our case did not require chemotherapy. EBV-positive patients, especially those with a pathological presentation of EBVMCU, could have a higher likelihood of remission, which could have been a factor in the present case.

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Methotrexate-associated lymphoproliferative disorder complicated by severe acute respiratory failure and ileal perforation:a case report

Cited by 6 publications

References 19 publications

Mesenchymal Stem Cells Enhance Therapeutic Effect and Prevent Adverse Gastrointestinal Reaction of Methotrexate Treatment in Collagen-Induced Arthritis

Mesenchymal Stem Cells Enhance Therapeutic Effect and Prevent Adverse Gastrointestinal Reaction of Methotrexate Treatment in Collagen-Induced Arthritis

Case report: Management of Epstein–Barr virus positive and methotrexate‐associated B‐cell lymphoma

Cessation of methotrexate and a small intestinal resection provide a good clinical course for a patient with a jejunum perforation induced by a methotrexate-associated lymphoproliferative disorder: a case report

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