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

Abstract

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.

Epstein-Barr Virus Positive B-Cell Lymphoproliferative Disorder of the Gastrointestinal Tract

“…In the English language literature, 30 cases of giEBVMCU have been reported (Table 1) [18][19][20][21][22][23][24]58,60,[63][64][65][66][67][68][69][70][71][72]. The most common clinical setting is iatrogenic immunosuppression in the context of inflammatory bowel disease, followed by post-organ transplant, immune-related colitis (irColitis), rheumatoid arthritis (RA), and treated-lymphoma (Table 2).…”

EBV-Driven Lymphoproliferative Disorders and Lymphomas of the Gastrointestinal Tract: A Spectrum of Entities with a Common Denominator (Part 1)

“…The occurrence of EBVMCU in GIT is rather uncommon, with just about 30 cases reported so far [ 13 , 17 , 18 , 19 , 20 , 21 , 22 , 23 , 24 , 27 , 28 , 29 , 30 , 31 , 32 , 33 , 34 , 35 , 36 , 37 , 38 ].…”

“…EBVMCU develops in the context of iatrogenic IS (56-66%), in advanced age favored by immunosenescence (27% to 40% of cases) or in primary immunodeficiency (2% to 4% of cases) [14]. It has been reported in patients on immunosuppressive treatments such as methotrexate (MTX), cyclosporin A (CYA), Tacrolimus (Tac), prednisolone (PSL), azathioprine (AZA) or TNF-alpha inhibitors for autoimmune conditions or for solid organ/bone marrow transplantation [1,[13][14][15][16][17][18][19][20][21][22][23][24][25][26][27][28][29][31][32][33][34][35][36][37][38]. EBVMCU is also reported after another lymphoma or tumor treatment [30].…”

“…The occurrence of EBVMCU in GIT is rather uncommon, with just about 30 cases reported so far [13,[17][18][19][20][21][22][23][24][27][28][29][30][31][32][33][34][35][36][37][38].…”

“…The review consists of three parts. In this first part, EBVMCU [ 8 , 13 , 14 , 15 , 16 , 17 , 18 , 19 , 20 , 21 , 22 , 23 , 24 , 25 , 26 , 27 , 28 , 29 , 30 , 31 , 32 , 33 , 34 , 35 , 36 , 37 , 38 ], EBV-positive diffuse large B-cell lymphoma not otherwise specified (EBV-positive DLBCL, NOS) [ 8 , 39 , 40 , 41 , 42 , 43 , 44 , 45 , 46 , 47 , 48 , 49 , 50 , 51 , 52 , 53 , 54 , 55 ] and classic Hodgkin lymphoma (cHL) [ 8 ] are discussed.…”