Methotrexate-Related Lymphoproliferative Disorder in Patients With Osteonecrosis of the Jaw: A 3-Case Report and Literature Review

Furudate, Ken; Satake, Anna; Narita, N; Kobayashi, Wataru

doi:10.1016/j.joms.2017.05.027

Cited by 15 publications

(8 citation statements)

References 16 publications

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“…Although extranodal lesions have been reported in 40% of MTX-LPD cases, cases of the oral region are relatively rare. After performing a comprehensive English literature search, it was noted that 26 cases of MTX-LPD in the oral region have been reported, and 13 of them were accompanied by ONJ (Table 1) [4][5][6][10][11][12][13][14][15][16][17][18][19][20][21][22][23][24]. The average age was 70.9 years, and the male-to-female ratio was 1: 2.7, which Clinical findings in patients with bone exposure were similar to those of MRONJ, but at least 5 patients had not taken antiresorptive agents [4][5][6].…”

Section: Discussionmentioning

confidence: 99%

“…After performing a comprehensive English literature search, it was noted that 26 cases of MTX-LPD in the oral region have been reported, and 13 of them were accompanied by ONJ (Table 1) [4][5][6][10][11][12][13][14][15][16][17][18][19][20][21][22][23][24]. The average age was 70.9 years, and the male-to-female ratio was 1: 2.7, which Clinical findings in patients with bone exposure were similar to those of MRONJ, but at least 5 patients had not taken antiresorptive agents [4][5][6]. Although the mechanism of jaw osteonecrosis in MTX-LPD has not been clarified, it is considered that free radicals of MTX disrupt the mucosal barrier, and immunosuppression reduces the ability to protect against bacterial infection [25,26].…”

Section: Discussionmentioning

confidence: 99%

“…Medication-related osteonecrosis of the jaw (MRONJ), which is associated with bisphosphonates, anti-receptor activator of nuclear factor κB ligand (anti-RANKL) (denosumab), and antiangiogenic medications, has been widely recognized [3]. Recently, it has been reported that several cases of MTX-LPD in the gingiva accompany osteonecrosis of the jaw (ONJ) without antiresorptive and antiangiogenic medications [4][5][6]. Besides, to our knowledge, half of the MTX-LPD cases show regression by MTX withdrawal [2,7], and no case that caused massive bleeding because of progression of the lesion has been reported in the oral region.…”

Section: Introductionmentioning

confidence: 99%

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Massive hemorrhage and osteonecrosis of the jaw in the patient with methotrexate-associated lymphoproliferative disorder: Report of a case and review of literature

Yasui¹,

Nagamine²,

Yajima³

et al. 2021

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Introduction: Methotrexate-associated lymphoproliferative disorder (MTX-LPD) is one of the adverse effects of methotrexate (MTX). We report a case of MTX-LPD that caused osteonecrosis and massive bleeding without regression following MTX withdrawal.Case Report: A 61-year-old woman was referred to our hospital because of delayed socket healing after dental extraction. She had been diagnosed with rheumatoid arthritis (RA) and received MTX treatment for six years. At the first visit, a 15 mm × 15 mm bone exposure and swelling of the surrounding gingiva in the right upper molar region were observed. We performed an incisional biopsy of the necrotic bone and surrounding mucosal tissue. The histopathological diagnosis was diffuse large B-cell lymphoma (DLBCL). Therefore, we referred the patient to the Department of Hematology in our hospital. She was diagnosed with MTX-LPD based on the history of MTX therapy for RA, and MTX was discontinued immediately. However, the lesion progressed and caused bleeding that required blood transfusion and

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Massive hemorrhage and osteonecrosis of the jaw in the patient with methotrexate-associated lymphoproliferative disorder: Report of a case and review of literature

Yasui¹,

Nagamine²,

Yajima³

et al. 2021

Int J Case Rep Images

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“…Thus, in many cases described in the literature, in addition to MTX, patients had also been treated previously or concomitantly with bisphosphonates and/or corticoids (70). On the other hand, in some cases, the presence of necrotic bone could be secondary to a Methotrexate-related chronic lymphoproliferative disorder and it would therefore be arguable whether it should be considered as MRONJ, in the absence of a detailed histopathological study of the lesion (71). However, authors such as Henien et al (72), have recently described cases of MRONJ in patients treated for RA with low oral doses of MTX over long periods of time, in the absence of a lymphoproliferative disorder and with no administration of other antiresorptive or antiangiogenic medications.…”

Section: Active Ingredientmentioning

confidence: 99%

Review and update on drugs related to the development of osteonecrosis of the jaw

Eguia¹,

Bagán-Debón²,

Cardona³

2020

Med Oral

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Background: Medication-related osteonecrosis of the jaw (MRONJ) is a rare, but serious adverse effect of certain drugs, of which bisphosphonates are the most widely known. This pathology is also associated with other medications such as the biologic antiresorptive agent, denosumab and some antiangiogenics such as sunitinib, bevacizumab or aflibercept. Very recently, new medications have also been associated with osteonecrosis of the jaw (ONJ). The objectives were to update the list of medications associated with ONJ, to analyze the fundamental aspects of this list and to describe the level of evidence available. Material and Methods: A narrative bibliographic review was made, using the PubMed-MedLine, DOAJ and SCI-ELO databases. Additional information was obtained through the online Medication Information Centre of the Spanish Agency of Medicines and Medical Devices (AEMPS-CIMA), the websites of the US Food & Drugs Administration (Drugs@FDA) and the European Medicines Agency (EMA). Results: The latest drugs identified as potential facilitators of this pathology include a number of anti-VEGF based antiangiogenic drugs and anti-TKI and different types of immunomodulators. Neither the level of evidence in this association nor the risk are equal for all these drugs. On the other hand, over the coming years, new drugs will be marketed with similar action mechanisms to those that are recognized as having this adverse effect. Conclusions: No effective therapy is currently known for the treatment of ONJ. Therefore, in order to prevent new cases of MRONJ, it is essential for all oral healthcare professionals to be fully up-to-date with the etiopathogenic aspects of this pathology and to be aware of those drugs considered to be a risk.

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“…Daroontum et al . reported a patient with MTX-EBVMCU who developed EBV+ P-LPD and EBV+DLBCL within 3 years 95 . Similar to MTX-P-LPD, chemotherapy for aggressive MTX-EBVMCU is decided according to the pathological features of M-LPD such as DLBCL and CHL.…”

Section: Clinical Management Of Mtx-lpdmentioning

confidence: 99%

Clinical management for other iatrogenic immunodeficiency-associated lymphoproliferative disorders

Tokuhira¹,

Tamaru²,

Kizaki³

2019

JCEH

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Other iatrogenic immunodeficiency-associated lymphoproliferative disorders (OIIA-LPD), a category of immunodeficiency-associated LPD according to the World Health Organization classification, is associated with immunosuppressive drugs (ISDs). Several factors, including autoimmune disease (AID) activity, Epstein-Barr virus (EBV) infection, ISD usage, and aging, influence the development of OIIA-LPD, resulting in complicated clinical courses and outcomes. Most OIIA-LPD develops in patients with rheumatoid arthritis using methotrexate (MTX-LPD). The management of MTX-LPD is based on the clinical course, i.e., with/without regression, with/without relapse/regrowth event (RRE), LPD subtype, and ISDs for AIDs after LPD development. There are three clinical courses after ISD withdrawal: regressive LPD without relapse/regrowth (R-G), regressive LPD with RRE (R/R-G), and persistent LPD (P-G). The majority of EBV+ diffuse large B-cell lymphomas are classified in R-G, whereas classic Hodgkin lymphoma is generally classified in R/R-G. Polymorphic LPD (P-LPD) in MTX-LPD develops with heterogeneous pathological features similar to monomorphic LPD. Chemotherapy for MTX-LPD is selected according to that for de novo LPD, although the strategy for aggressive P-LPD and non-specific LPD is not well established. The absolute lymphocyte count in the peripheral blood has been suggested as a candidate marker for MTX-LPD development and RRE. Several clinical issues, including correct diagnosis among overlapping clinicopathological features in MTX-LPD and clinical management of LPD by ISDs other than MTX, require further investigation.

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Methotrexate-Related Lymphoproliferative Disorder in Patients With Osteonecrosis of the Jaw: A 3-Case Report and Literature Review

Cited by 15 publications

References 16 publications

Massive hemorrhage and osteonecrosis of the jaw in the patient with methotrexate-associated lymphoproliferative disorder: Report of a case and review of literature

Massive hemorrhage and osteonecrosis of the jaw in the patient with methotrexate-associated lymphoproliferative disorder: Report of a case and review of literature

Review and update on drugs related to the development of osteonecrosis of the jaw

Clinical management for other iatrogenic immunodeficiency-associated lymphoproliferative disorders

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