Oral effects of low-dose methotrexate treatment

Kalantzis, Athanasios; Marshman, Zoe; Falconer, Denis; Morgan, Peter; Odell, Edward

doi:10.1016/j.tripleo.2004.08.020

Cited by 95 publications

(63 citation statements)

References 67 publications

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“…The oral lesions seem to be dose-dependent, and a possible early sign of drug toxicity. Stomatitis has been referred in approximately 14%, and treatment discontinue in 3% of the patients, thus oral clinicians may be encountered with a MTX-induced lesion more often than previously thought (3). The risk of MTX-induced ulcers appears to be increased in patients with pre-existing folate deficiency.…”

Section: Discussionmentioning

confidence: 99%

“…Elevated drug levels in the saliva acting topically are considered to promote the oral lesions development. Measurement of the excreted MTX concentration in the saliva has been proposed useful in predicting oral ulceration (3,4). …”

Section: Discussionmentioning

confidence: 99%

“…MTX toxicity is generally dose-dependent and rapidly dividing tissues, such as the bone marrow and the gastrointestinal tract are most commonly affected. Oral ulcerative stomatitis may be seen in about 14% of patients demonstrating a wide histopathologic spectrum that ranges from non-specific ulceration to lichenoid reactions to EBV (+/-) lymphoproliferative disorders (LPDs) (2,3). …”

Section: Introductionmentioning

confidence: 99%

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Atypical methotrexate ulcerative stomatitis with features of lymphoproliferative like disorder: Report of a rare ciprofloxacin-induced case and review of the literature

Katsoulas¹,

Chrysomali²,

Piperi³

et al. 2016

J Clin Exp Dent

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Methotrexate (MTX) is an established immunomodulating agent used in low doses (LDMTX) to treat several autoimmune diseases. Ulcerative stomatitis (US) may be observed as a long-term LDMTX adverse effect showing a wide histopathologic spectrum. A 73-year old female presented with painful oral ulcers of 5 days duration. The patient had been under treatment for rheumatoid arthritis with LDMTX, while one week before presentation she was prescribed ciprofloxacin for a urinary infection. Histopathologic examination of a lingual ulcer revealed a polymorphous lymphohistiocytic proliferation with scattered binucleated atypical lymphocytes. Immunohistochemically, most cells were of T-cell lineage while the EBER test was negative and a diagnosis of MTX-induced reactive ulceration was rendered. MTX cessation resulted in complete resolution of the ulcers with no recurrences reported so far. The clinical and histopathologic features of MTX-induced oral ulcers are not always diagnostic and a detailed history and an extensive clinicopathologic investigation may be needed to exclude a lymphoproliferative disorder. Key words:Atypical oral ulcers, ciprofloxacin, lymphoproliferative disorders, methotrexate.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Atypical methotrexate ulcerative stomatitis with features of lymphoproliferative like disorder: Report of a rare ciprofloxacin-induced case and review of the literature

Katsoulas¹,

Chrysomali²,

Piperi³

et al. 2016

J Clin Exp Dent

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“…As described by Katalanzis et al, the variety of oral lesions ranges from nonhealing ulcers to destructive lymphomalike lesions [32]. Other authors presented cases of progressing necrotizing ulcerative gingivitis involving lips and oral mucosa, chronic ulcer of the hard palate and MTX therapy-related impairment of the oral mucosa in general [33].…”

Section: Discussionmentioning

confidence: 99%

In vitro inhibition of HUVECs by low dose methotrexate – insights into oral adverse events

Annussek¹,

Szuwart²,

Kleinheinz³

et al. 2014

Head Face Med

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BackgroundWith socio-economic changes, dentists and maxillofacial surgeons are more and more faced with medically compromised patients. Especially, the admission of antirheumatic drugs has increased remarkably. So dentists and maxillofacial surgeons should be aware of related adverse reactions that affect the craniofacial region. To identify possible cellular effects of disease modifying antirheumatic drugs (DMARDs) we investigated the influence of methotrexate (MTX) on human umbilical vein endothelial cells (HUVECs).MethodsHUVECs were incubated with various concentrations of MTX, corresponding to serum concentrations found in rheumatoid arthritis (RA) patients. The effect of MTX on cell proliferation, differentiation as well as mitochondrial activity was measured by use of immunostaining, cell counting and 3-(4, 5-dimethylthiazol-2-yl)- 2, 5-diphenyltetrazolium bromide (MTT) assay.ResultsAll samples incubated with MTX (1-1000 nM) showed significantly decreased cell viability when compared to controls. Cells were less proliferating, but did not lose their ability to synthesize endothelial proteins. A slight dose dependency of inhibiting effects was demonstrated. The observed differences between control and sample groups were rising with longer duration.ConclusionBecause of the crucial role of endothelial cells and their precursor cells in wound healing, a negative influence of MTX on oral health has to be supposed, correlating to clinical observations of adverse reactions in the oral cavity, such as ulcerative or erosive lesions.

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“…Mucocutaneous toxicities of LDM may occur commonly and include stomatitis, oral ulceration, alopecia, and rashes 47,48 . The risk of lymphoproliferative disorders is increased among RA patients compared to the general population, primarily in the setting of high disease activity and some have ascribed this risk to LDM, although other RA-specific factors may also contribute 13,49–52 .…”

Section: Introductionmentioning

confidence: 99%

Investigating methotrexate toxicity within a randomized double-blinded, placebo-controlled trial: Rationale and design of the Cardiovascular Inflammation Reduction Trial-Adverse Events (CIRT-AE) Study

Barbhaiya

Karlson

Ritter

et al. 2017

Seminars in Arthritis and Rheumatism

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Background The role of low dose methotrexate (LDM) in potential serious toxicities remains unclear despite its common use. Prior observational studies investigating LDM toxicity compared LDM to other active drugs. Prior placebo-controlled clinical trials of LDM in inflammatory conditions were not large enough to investigate toxicity. The Cardiovascular Inflammation Reduction Trial (CIRT) is an ongoing NIH-funded, randomized, double-blind, placebo controlled trial of LDM in the secondary prevention of cardiovascular disease. We describe here the rationale and design of the CIRT-Adverse Events (CIRT-AE) ancillary study which aims to investigate adverse events within CIRT. Design CIRT will randomize up to 7,000 participants with cardiovascular disease and no systemic rheumatic disease to either LDM (target dose 15–20 mg/week) or placebo for an average follow-up period of 3–5 years; subjects in both treatment arms receive folic acid 1 mg daily for six days each week. The primary endpoints of CIRT include recurrent vascular events, incident diabetes, and all-cause mortality, and the ancillary CIRT-AE study has been designed to adjudicate other clinically important adverse events including hepatic, gastrointestinal, respiratory, hematologic, infectious, mucocutaneous, oncologic, renal, neurologic, and musculoskeletal outcomes. Methotrexate polyglutamate levels and genome-wide single nucleotide polymorphisms will be examined for association with adverse events. Summary CIRT-AE will comprehensively evaluate potential LDM toxicities among subjects with cardiovascular disease within the context of a large, ongoing, double-blind, placebo-controlled trial. This information may lead to a personalized approach to monitoring LDM in clinical practice.

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Oral effects of low-dose methotrexate treatment

Cited by 95 publications

References 67 publications

Atypical methotrexate ulcerative stomatitis with features of lymphoproliferative like disorder: Report of a rare ciprofloxacin-induced case and review of the literature

Atypical methotrexate ulcerative stomatitis with features of lymphoproliferative like disorder: Report of a rare ciprofloxacin-induced case and review of the literature

In vitro inhibition of HUVECs by low dose methotrexate – insights into oral adverse events

Investigating methotrexate toxicity within a randomized double-blinded, placebo-controlled trial: Rationale and design of the Cardiovascular Inflammation Reduction Trial-Adverse Events (CIRT-AE) Study

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