Stopping Methotrexate Research Articles

P015 Nodular skin rash associated with relapsing polychondritis, a challenging diagnostic journey to VEXAS syndrome

Abstract Background/Aims VEXAS syndrome, first described in 2020, is a haemato-inflammatory disease caused by a mutation in the gene-UBA1.This syndrome can coexist with or without Myelodysplastic syndrome. What makes this case interesting is its long and challenging diagnostic journey and the involvement of different clinical specialties such as dermatology, ophthalmology, rheumatology, respiratory, haematology, and stroke teams. Ultimately, two years after the initial presentation, this appeared to be the first case of VEXAS with confirmed genetic mutation in the region. VEXAS being a relatively new entity, treating clinician/s were not aware of the possibility initially. Therefore, spreading awareness regarding the clinical picture of VEXAS is prudent. This case report highlights rheumatological and dermatological manifestations of the disease to aid in the timely diagnosis and management of future cases. Methods We report a 74-year-old previously healthy male presented in 2021 with a rash on his legs, arms, and torso since October 2019. It was progressive, painful, palpable, erythematous, non-pruritic, intermittent rash, cleared with hyperpigmentation. He also had oligoarticular arthritis, constitutional symptoms, recurrent episodes of polychondritis, uveitis, bibasal lung fibrosis, and an ESR and CRP above 100. He also had lymphadenopathy above the diaphragm, but the biopsy only showed necrotic material, and the bone marrow biopsy did not show any features of haematological malignancy. After excluding infections, he was started on high-dose oral prednisolone for relapsing polychondritis. The skin and inflammatory markers improved immediately following high doses of steroids. However, whenever steroids were weaned down, even with the help of Methotrexate, his skin was flaring. He also had unprovoked DVT and, while on anticoagulation, developed occipital infarction. He had extensive skin involvement when he had to stop Methotrexate following a chest infection. Results The skin biopsy was inconclusive. There was no significant cytopenia but persistent macrocytosis even after stopping Methotrexate. As a result, he underwent a repeat bone marrow biopsy, which showed Vacuoles and gene UBA1 mutation in 2023. Conclusion The heterogeneity and complexity of the disease are due to multi-organ involvement, including skin, joints, eyes, lungs, blood vessels, and cartilage, simultaneously or cumulatively. Skin involvement in VEXAS can also be vast, ranging from neutrophilic dermatosis, erythema nodosum-like lesions, leukocytoclastic, or urticarial vasculitis. Cutaneous manifestations develop in the majority with VEXAS syndrome and can be the first presenting symptom in this new rare syndrome. Disclosure M. Gunawardena: None. L. Yalakki: None. R. Moitra: None. E.L. Williams: None. H. Wong: None. D. D'Cruz: None.

Methotrexate toxicity encountered in dermatology department: A retrospective study at tertiary care center in western India

Methotrexate (MTX) is considered a relatively safe drug when prescribed at dose ranging from 7.5mg-30mg per week. Severe acute toxicity is rare and present with mucositis, cutaneous ulceration and pancytopenia. Most cases occur as the result of inadvertent overdosing due to erroneously taking the drug daily. A retrospective study of 10 cases of acute methotrexate toxicity in patients attending the dermatology OPD at P. D. U govt. medical College and hospital, Rajkot during a period of 1 year was done. Out10 patients, 7 had both oral and cutaneous involvement, 4 had genital mucosal involvement while 2 cases had only oral ulcerations. Organ -specific toxicities includes pancytopenia in all cases, as well as hepatoxicity, renal toxicity, and GI toxicity in 3 patients. Additionally, cutaneous toxicity was observed in 6 cases. “Of the 10 patients, 2 recovered after stopping methotrexate with supportive care. The remaining 8 received injectable folinic acid, resulting in recovery for 6 patients, but 2 patients unfortunately died during treatment. Although MTX appears to be a safe and effective medication when used at low-dose, acute MTX toxicity can be a life threating emergency when comorbidities are not addressed. Sensitization amongst doctors, general practitioners and resident doctors is of paramount importance to identify possible MTX toxicity in earlies phases and in a way ensure earliest management.

P384 A higher red blood cell methotrexate polyglutamate 3 concentration is associated with methotrexate drug-survival in patients with Crohn’s Disease: first results of a prospective cohort

Abstract Background Prediction and monitoring of drug response of methotrexate (MTX) in patients with Crohn’s disease (CD) is an unmet need. MTX-polyglutamates (MTX-PGs) in red blood cells (RBC) are potential markers for response in other immune-mediated inflammatory diseases. Our objectives were investigating the relation between MTX-PGs and efficacy and defining predictors of response in CD patients treated with MTX. Methods In a multicenter prospective cohort study, CD patients starting subcutaneous (s.c.) MTX without biologics were included and followed for 12 months or until MTX s.c. was discontinued or a concomitant step-up therapy was started. At baseline clinical and biochemical predictors were recorded. At 2, 3, 6 and 12 months after start of therapy or when dropping out, blood samples were collected and individual MTX-PGs (MTX-PG1 - MTX-PG5) were analyzed in RBC using a validated UHPLC-MS/MS method. The outcome was either MTX s.c. discontinuation or initiation concomitant step-up therapy, due to disease activity or toxicity. Predictors were analysed in an univariate Cox regression model and MTX-PGs in an extended Cox model, corrected for prednisone (at start) and budesonide. Results Eighty CD patients were included (age mean±SD 55±13y, 35% male). The median Harvey Bradshaw Index (HBI) was 4 (IQR 2-7). After 12 months 21 patients were still on MTX s.c. monotherapy, 21 patients stopped because of disease activity, 29 because of toxicity, 4 because of a combination of both and 5 patients were censored (4 ended study participation, 1 MTX was stopped on patient’s own initiative) [Figure 1]. A higher HBI at baseline was associated with an increased rate of MTX s.c. monotherapy discontinuation (HR 1.08, 95% CI 1.02-1.16). Predictors of discontinuation because of disease activity (cause specific hazards) were male sex (3.83, 1.62-9.05), baseline eGFR (1.06, 1.02-1.09), baseline HBI (1.12, 1.02-1.23) and baseline plasma folate (0.94, 0.88-0.99). Sex and plasma folate were not correlated with HBI. No cause specific hazards for stopping MTX because of toxicity were identified. MTX-PG3 was the most abundant MTX-PG subspecie with a median concentration of 51 nmol/L RBC (IQR 37-62) at month 3 and was associated with better MTX survival (HR 0.98, 95% CI 0.971-0.999). For every ten points increase in the MTX-PG3 concentration, the rate of MTX s.c. monotherapy discontinuation decreases with 14%. Conclusion Higher eGFR, higher HBI, lower plasma folate at baseline and male sex are predictors for MTX failure in the first year in CD patients. The last two parameters are likely predictors of MTX response specifically rather than prognostic disease factors. The measurement of MTX-PG3 in packed RBC holds potential as a tool for therapeutic drug monitoring in CD.

Possible association of methotrexate use with osteonecrosis of the jaw: Systematic review

The aim was to search systematically, evaluate, and then summarize scientific literature about possible methotrexate-associated osteonecrosis of the jaw (ONJ), its signs and symptoms, diagnosis, treatment, and prognosis in adults. After registration at PROSPERO this systematic review was conducted and reported according to the PRISMA checklist. The following databases were systematically searched: MEDLINE, EBSCO, The Cochrane Central Register of Controlled Trials (Central), SCIndex, Scopus, Google Scholar and Registry of clinical studies with human participants. In total 9 studies with 14 patients were included in the review. All cases of ONJ associated with methotrexate were described in patients suffering from Rheumatoid arthritis (RA), and only about 40% of them were taking other concomitant medication described to be associated with ONJ (bisphosphonates). Both sexes were equally affected, and the patients were rather old (over 60 years if age), already taking methotrexate for more than 12 years on average. Antibiotics were ineffective in the treatment of ONJ; after stopping methotrexate, all lesions healed after several months on average; however, half of the cases required covering of the exposed bone with mucosal flap. Recurrence of the methotrexate-associated ONJ was not observed for at least two years after the lesions were healed. Methotrexate-associated ONJ is serious clinical condition that may occur in patients with RA, but given the small number of cases we have found in the literature, direct involvement of methotrexate in the development of ONJ remains elusive.

Primary cutaneous methotrexate-associated B-cell lymphoproliferative disorders other than EBV-positive mucocutaneous ulcer: clinical, pathological, and immunophenotypic features

Methotrexate (MTX)-associated B-cell lymphoproliferative disorders (B-LPD) may first present in the skin. Epstein-Barr virus (EBV)-positive mucocutaneous ulcer (EBVMCU) is now a well known disease listed in the 2017 World Health Organization classification. However, primary cutaneous MTX-associated B-LPD (pcMTX B-LPD), other than EBVMCU, appear to be underestimated, and their distinctiveness remains unproven. This study aimed to document the clinicopathological characteristics of nine patients with pcMTX B-LPD that were not EBVMCU to extend our understanding of this peculiar disease. The cohort included three males and six females, with a median age of 74 years (range 54-83 years). All patients were treated with MTX for RA. Of nine patients, four presented with a solitary lesion, and five had multiple lesions. Histologically, five cases showed a polymorphic pattern, and four showed a monomorphic pattern. Immunohistochemically, four cases showed positive EBER staining, and one showed positive CD5 staining. In eight cases, once pcMTX B-LPD was diagnosed, methotrexate was immediately withdrawn. All eight of these patients experienced spontaneous regression and achieved complete remission (CR), without relapse. The patient with CD5 positivity received cytotoxic chemotherapy as the initial treatment. This patient achieved a CR after the initial treatment, but eventually experienced disease relapse resulting in death. We also revealed that pcMTX B-LPD and MTX-associated EBVMCU exhibited similar biological behaviours. We concluded that most pcMTX B-LPD cases could be cured by stopping MTX treatment. We also highlighted the fact that pcMTX B-LPD and MTX-EBVMCU had overlapping features. This finding suggested that pcMTX B-LPD and MTX-EBVMCU might share an underlying mechanism.

Méthotrexate : quel délai entre l’administration et une conception ?

In women of childbearing age, methotrexate is prescribed in many indications other than cancer, either chronically (psoriasis, rheumatoid arthritis, IBD, etc.) or occasionally (ectopic pregnancies). The time given to these patients to consider pregnancy is currently subject to great variability depending on the sources. Analysis of the available objective evidence suggests that it is not justified to unnecessarily lengthen this period, and that conceiving the menstrual cycle following stopping methotrexate is quite possible.

Primary Central Nervous System Methotrexate-associated Lymphoproliferative Disorder in a Patient with Rheumatoid Arthritis: Case Report and Review of Literature

Methotrexate (MTX) is an immunosuppressor that is widely used to treat autoimmune diseases, including rheumatoid arthritis (RA). However, it can have serious adverse effects including a lymphoma: MTX-associated lymphoproliferative disorder (MTX-LPD). Extranodal lesions are common in MTX-LPD patients. However, MTX-LPD in the central nervous system (CNS) is extremely rare with few reported cases. Here, we describe a case of primary CNS MTX-LPD in a patient with RA, with a review of the literature. A 68-year-old woman who had received MTX for her RA for more than 10 years was referred to our hospital. Head magnetic resonance imaging (MRI) showed multiple lesions with heterogeneous contrast enhancement scattered throughout both hemispheres. As immunosuppression caused by MTX was suspected, MTX was discontinued, based on a working diagnosis of MTX-LPD. We performed an open biopsy of her right temporal lesion. Histopathologic examination showed atypical CD20+ lymphoid cells, leading to a definitive diagnosis of diffuse large B-cell lymphoma (DLBCL). In situ hybridization of an Epstein-Barr virus-encoded small RNA (EBER) was positive. Sanger sequencing confirmed that both MYD88 L265 and CD79B Y196 mutations were absent. The LPD regressed after stopping MTX. Follow-up head MRI at 8 months after surgery showed no evidence of recurrence. Although primary CNS MTX-LPD is extremely rare, it should be included in the differential diagnosis when a patient receiving MTX develops CNS lesions. Diagnosis by biopsy and MTX discontinuation are required as soon as possible.

Clinicopathological Analysis of “Other Iatrogenic Immunodeficiency-Associated Lymphoproliferative Disorders” Reveals a Favorable Outcome Independent of the Effectiveness of Methotrexate Discontinuation in Autoimmune Disease Patients

[Background] Patients treated with immunosuppressive drugs for autoimmune diseases may suffer "other iatrogenic immunodeficiency-associated lymphoproliferative disorders" (OIIA-LPD). Some OIIA-LPDs regress after drug withdrawal but others need cytotoxic chemotherapy. However, the factors associated with a response to drug cessation remain unknown. [Methods] We collected clinical data on OIIA-LPD diagnosed between 2009 and 2018 at the University of Tsukuba Hospital and Toranomon Hospital in Japan. Clinicopathological features were retrospectively analyzed. The probability of overall survival (OS) and progression-free survival (PFS) was calculated using the Kaplan-Meier method. OS was defined as the time between the date of diagnosis of OIIA-LPD and the date of death or last follow-up. PFS was defined as the time from the date of diagnosis of OIIA-LPD to the date of commencing chemotherapy or the date of death or last follow up. [Results] Fifty-four cases of OIIA-LPD were identified, of which 25 were diagnosed at the University of Tsukuba Hospital and 29 at Toranomon Hospital. The male to female ratio was 1:3.5 and the median age at diagnosis was 70 years (range, 35-85). Thirty-four patients (63%) had an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1. Most patients (n=50 [93%]) had rheumatoid arthritis (RA). The remaining 4 patients had systemic lupus erythematosus (SLE), myasthenia gravis (MG), polymyalgia rheumatica (PMR), and polymyositis (PM), respectively. Methotrexate (MTX), tacrolimus, and biological agents were used in 49, 17, and 16 cases, respectively. Histological diagnoses of OIIA-LPD type were diffuse large B-cell lymphoma (DLBCL) (n=24), composite lymphoma of DLBCL and follicular lymphoma (FL) (n=1), Hodgkin lymphoma (HL) (n=18), MALT lymphoma (n=2), peripheral T-cell lymphoma, not otherwise specified (PTCL-NOS) (n=2), angioimmunoblastic T-cell lymphoma (AITL) (n=1), B-cell lymphoma, unclassifiable, with features intermediate between DLBCL and classic HL (n=1), extranodal NK/T-cell lymphoma (ENKTL) (n=1), Burkitt lymphoma (n=1), and not specified (n=3). Epstein-Barr virus (EBV) was detected in 61% of cases tested (31/51) by in situ hybridization for EBER. At diagnosis of OIIA-LPD, 44 cases (81%) were under MTX treatment. MTX was discontinued in all of these, after which spontaneous regression was observed in 27 (61%). There was no clinical response in 5 patients (11%) within 2 months of MTX cessation, and 12 patients (27%) received chemotherapy without confirming whether stopping MTX would have been sufficient intervention. In 27 cases with spontaneous regression after cessation of MTX, 18 achieved complete remission without chemotherapy, but 9 needed chemotherapy due to re-initiation of LPD. Regarding the histological diagnosis, spontaneous regression was observed in OIIA-LPD patients with DLBCL in 12 of 24 cases (50%) and those with HL in 8 of 18 (44%). After achieving spontaneous regression, patients with DLBCL (10/12 cases, 83%) did not require any form of chemotherapy more often than those with HL (4/8 cases, 50%). Neither EBV positivity nor histology were associated with spontaneous regression. With a median follow-up of 26.1 months (range, 1-120.7), 2-year OS and PFS was 91.9% and 30.1%, respectively. The 2-year PFS of DLBCL and HL was 33.1% and 17.5%, respectively (p=0.533). Only four patients died due to the progression of OIIA-LPD. [Conclusion] Fifty-four cases of OIIA-LPD were retrospectively analyzed. Spontaneous regression after MTX discontinuation was observed in approximately 60% of these patients. No factors associated with response to drug cessation were associated with histological features or EBV positivity, but patients with DLBCL remained in complete remission more frequently than those with HL. Despite the fact that 2-year PFS is low, our retrospective analyses revealed favorable OS of OIIA-LPD because chemotherapy resulted in a good response regardless of whether MTX discontinuation was effective. Disclosures No relevant conflicts of interest to declare.

2063 A Stellar Case of Stelara in the Treatment of Lymphocytic Colitis

INTRODUCTION: Lymphocytic colitis is a chronic inflammatory disease manifesting with chronic, watery, non-bloody diarrhea. Patients have a normal appearing colon with biopsies showing histological changes. Medications are believed to be typical culprits, however data on causality is lacking. Treatment is focused on symptom management, however in refractory cases budesonide has been shown to provide both clinical and histological remission. There is limited data to guide practitioners for patients who fail to have improvement on budesonide. We present a case of a female who failed budesonide and was treated with ustekinumab for her lymphocytic colitis. CASE DESCRIPTION/METHODS: A 54-year-old woman with a history of indeterminate colitis presented with diarrhea, severe fatigue, and abdominal pain in January 2019. She was presumably diagnosed with ulcerative colitis (UC) in 2000 but without evidence of endoscopic or histologic findings. Her diagnosis was subsequently changed to Crohn’s disease (CD) in 2008 based on serologic markers alone again without evidence of endoscopic inflammation. Previous colonoscopy in 2015 showed endoscopically normal mucosa with biopsies suggestive of lymphocytic colitis (Figure 1). Due to her symptoms, she was started on ustekinumab. At that time, ustekinumab levels were found to be 9.9 (Inform Tx). At presentation, she was on ustekinumab q8 weeks, budesonide, and methotrexate. She was started on azathioprine while continuing budesonide and stopping methotrexate. After 3 months (March, 2019), her symptoms persisted, so her ustekinumab level was checked and was found to be low at 2.2. Therefore, she received a booster 90 mg SQ dose of ustekinumab. Budesonide was discontinued. Colonoscopy in May 2019 revealed endoscopic and histologic remission of the lymphocytic colitis. DISCUSSION: First line treatment options for lymphocytic colitis include avoidance of culprit medications and symptomatic treatment. In patients with persistent symptoms, budesonide has been effective in inducing clinical and histological remission in 6 weeks. In cases refractory to budesonide, there is very limited data on alternative treatment options. Although immunomodulators and biologics have been used for CD and UC, their utility in microscopic colitis remains unknown. Case reports have described varying success using agents such as azathioprine, infliximab, adalimumab, and mercaptopurine. We present a case of lymphocytic colitis successfully treated with a combination of ustekinumab and azathioprine.

R08 Real-life use of MRP8/14 serum level measurement in clinical practice as a predictor of outcome after stopping methotrexate in patients with juvenile idiopathic arthritis

R08 Real-life use of MRP8/14 serum level measurement in clinical practice as a predictor of outcome after stopping methotrexate in patients with juvenile idiopathic arthritis

Low-Dose Methotrexate Prevents Primary and Secondary Humoral Immune Responses and Induces Immune Tolerance to a Recombinant Immunotoxin.

Recombinant immunotoxins (RITs) are chimeric proteins being developed for cancer treatment. They are composed of an Ab fragment that targets a cancer Ag and a cytotoxic portion of Pseudomonas exotoxin A. They are effective for patients with hematologic malignancies with defective immunity, but their efficacy against solid tumors is limited by anti-drug Ab (ADA) responses in immune-competent patients. Pre-existing Abs or immune memory owing to previous toxin exposure represent additional hurdles because they induce rapid and strong ADA responses. Here, we evaluated the efficacy of methotrexate (MTX) to prevent ADA formation against the mesothelin-targeting RIT LMB-100 in naive mice and in mice with pre-existing Abs. We found that low-dose MTX combined with LMB-100 completely suppressed the formation of ADAs in a dose- and frequency-dependent manner. Suppression of the immune response restored blood levels of LMB-100 and prevented its neutralization. Furthermore, combination of MTX with LMB-100 did not compromise the immune response against a second Ag given after stopping MTX, indicating specific immune tolerance. Adoptive transfer of splenocytes suppressed Ab responses to LMB-100 in recipient mice, indicating a durable immune tolerance. We conclude that combination of MTX and LMB-100 is effective at preventing immune responses in a durable, Ag-specific manner. We propose combining low-dose MTX in immune-competent cancer patients receiving RIT therapy to prevent immunogenicity. This approach could be applied to other immunogenic therapeutic agents and to proteins for which there is pre-existing immunity.

Unexpected Twists and Turns in a Patient With Acute Hepatitis, Rash and Chronic Methotrexate Use

A 63 year-old man with a history of rheumatoid arthritis and hypertension was referred for abnormal liver tests including AST 68, ALT 122, alkaline phosphatase 161 units/L. The patient complained of generalized fatigue and three weeks of throat pain. Rheumatoid arthritis had been managed with methotrexate for several years with a cumulative dose >2.5g. Sulfasalazine was his only other medication and he denied taking supplements. He noted a remote history of substance abuse including alcohol, tobacco and amphetamines. Liver tests at his visit were AST 80, ALT 130, alkaline phosphatase 511 unit/L. Further testing revealed +ANA (1:80), + anti-mitochondrial antibody (0.1U), elevated IgG (1943 mg/dL) and +anti smooth muscle antibody (1:40). Testing for hepatitis A, B and C was negative. Liver biopsy performed one week after his visit revealed a predominantly lobular hepatitis with lymphocytic infiltrate and patchy portal inflammation. Differential diagnosis based on pathology favored drug reaction vs less likely autoimmune hepatitis. Following the biopsy, methotrexate was suspected to be the etiology of hepatitis and was discontinued. The patient was simultaneously being evaluated for a two month history of a maculopapular, erythematous rash which started at the anterior chest and spread over the back and extremities. Skin biopsy showed numerous Treponema pallidum spirochetes, consistent with secondary syphilis. RPR was positive at 1:128; HIV testing was negative. On further questioning, the patient disclosed that he had engaged in unprotected anal intercourse with a man shortly before the onset of the rash. Immunohistochemical staining of the liver biopsy sample revealed spirochetes consistent with syphilitic hepatitis. The patient received a single dose of penicillin-G 2.4 million units. Liver tests had begun trending down the week prior to treatment (after stopping methotrexate) and had completely normalized 8 weeks post penicillin treatment. Syphilitic hepatitis is an uncommon complication of secondary syphilis, however recognition is particularly relevant given the rising rates of primary and secondary syphilis reported in the US. A high index of suspicion and thorough sexual history are necessary for the diagnosis as liver biopsy may be non-specific. Staining for spirochetes must be considered before the diagnosis can be made with histology. Methotrexate-induced liver injury and underlying autoimmune illness further complicated the diagnosis in this case.Figure: Portal inflammation.Figure: Liver tissue with spirochetes.

Attitudes and Approaches for Withdrawing Drugs for Children with Clinically Inactive Nonsystemic JIA: A Survey of the Childhood Arthritis and Rheumatology Research Alliance.

To assess the attitudes and strategies of pediatric rheumatology clinicians toward withdrawing medications for children with clinically inactive juvenile idiopathic arthritis (JIA). Members of the Childhood Arthritis and Rheumatology Research Alliance (CARRA) completed an anonymous electronic survey on decision making and approaches for withdrawing medications for inactive nonsystemic JIA. Data were analyzed using descriptive statistics. Of 388 clinicians in CARRA, 124 completed surveys (32%), predominantly attending pediatric rheumatologists. The most highly ranked factors in decision making for withdrawing medications were the duration of clinical inactivity, drug toxicity, duration of prior activity, patient/family preferences, joint damage, and JIA category. Diagnoses of rheumatoid factor-positive polyarthritis and persistent oligoarthritis made respondents less likely and more likely, respectively, to withdraw JIA medications. Three-quarters of respondents waited for 6-12 months of inactive disease before stopping methotrexate (MTX) or biologics, but preferences varied. There was also considerable variability in the strategies used to reduce, taper, or stop medications for clinically inactive JIA; most commonly, clinicians reported slow medication tapers lasting at least 2 months. For children receiving combination MTX-biologic therapy, 63% of respondents preferred stopping MTX first. Most clinicians reported using imaging only seldom or sometimes to guide decision making, but most were also reluctant to withdraw medications in the presence of asymptomatic imaging abnormalities suggestive of subclinical inflammation. Considerable variability exists among pediatric rheumatology clinicians regarding when and how to withdraw medications for children with clinically inactive JIA. More research is needed to identify the most effective approaches to withdraw medications and predictors of outcomes.

下顎歯肉に発生した顎骨壊死を伴うメトトレキサート関連リンパ増殖性疾患の1例

Methotrexate is widely used as an anchor drug for rheumatoid arthritis. However, there are several reports of methotrexate-associated lympho-proliferative disorders, although most of them describe cases which occurred in maxillary gingiva with additional drugs like bisphosphonate. In particular, in almost all cases osteonecrosis of the jaw occurred in maxillary bone. We report a case of methotrexate-associated lympho-proliferative disorder with jaw necrosis in the mandibular gingiva.A 71-year-old woman who had been treated for 10 years with methotrexate and steroids for rheumatoid arthritis was found to have pain and ulcer after tooth extraction of the lower cuspid. We suspected this lesion was due to incomplete healing after extraction or tumor, so we performed a biopsy for suspected tumor. The pathological diagnosis was methotrexate-associated lympho-proliferative disorder. After methotrexate therapy was stopped, the local pain disappeared. On day 64 after stopping methotrexate, the tooth with bone necrosis was removed under local anesthesia. After operation, the wound was covered with mucosal epithelium, and there has been no recurrence to date.

Gynecomastia in a Rheumatoid Arthritis Patient; a Rare Side Effect of Methotrexate Therapy

We are reporting a case of a 51-year-old male patient with 3-year history of Rheumatoid Arthritis who developed gynecomastia 2 - 3 months after starting Methotrexate (MTX) therapy, without folate supplementation. Two months after stopping MTX therapy and initiating folate supplementation, gynecomastia started resolving. Very few cases of gynecomastia due to MTX therapy have been reported worldwide, although it is a rare yet a significant occurrence and should always be considered in male patients with Rheumatoid Arthritis.

Tolerability and Adherence Problems in Patients on a Stable Dose of Methotrexate: Results of a Multicentre Survey

Methotrexate is commonly used in patients with inflammatory arthritis. The aim of the present study was to ascertain the prevalence of side effects that patients on methotrexate were tolerating and to establish their adherence to the medication. A questionnaire was developed for completion by the healthcare professional with the patient, and piloted in one centre. The questionnaire was then used in six other centres, with the addition of a question about the attractiveness of stopping methotrexate treatment. Efficacy and toxicities were scored for severity on a 10-cm visual analogue scale (VAS). Adherence to the drug was also explored. The prevalence of 'any side effect' ranged from 57% to 86%. The most frequent side effects were fatigue (53%); nausea (38%); mouth ulcers (23%) and hair loss (23%). Efficacy averaged 6.5 cm on the VAS. Results from the combined survey revealed that toxicity averaged 5.9 cm for fatigue, 4.8 cm for nausea, 4.4 for mouth ulcers, 3.9 cm for hair loss and 5.7 cm for 'other' side effects. 13.5% of patients revealed that they had forgotten to take the drug for an average of two weeks, and 25% for an average of 2.5 weeks in the previous year. Participants were more likely to reveal this to a nurse than a doctor. Patients put up with a considerable number of side effects in order to benefit from methotrexate therapy. Adherence to this drug merits further study. Copyright © 2015 John Wiley & Sons, Ltd.

Tapering and discontinuation of methotrexate in patients with RA treated with TNF inhibitors: data from the DREAM registry

ObjectivesTo study the number of patients that taper or discontinue concomitant methotrexate (MTX) in daily practice in patients with rheumatoid arthritis (RA) treated with tumour necrosis factor inhibitor (TNFi) and...

Eosinophilic fasciitis: clinical characteristics and response to methotrexate

To describe our experience with 16 patients with eosinophilic fasciitis (EF) treated in our clinic over 14years. We retrospectively reviewed the charts of all patients with biopsy-proven EF. We collected data regarding demographics, clinical presentations, possible triggers, labs, imaging, treatment and response to therapy on follow-up. Eight women and eight men with a mean age of 52years were included in the study. Three patients related the onset to prior strenuous exercise and one was exposed to vibratory machinery. Fourteen patients had a gradual onset and presented with induration of the skin. Two other patients presented with acute-onset and significant edema and weight gain. All patients required immunosuppressive therapy. Methotrexate (MTX) was used in all of our patients. The rate of complete remission was ~60%. Although the recurrence rate after stopping MTX was 70%, these patients responded well to re-treatment with MTX. We believe that MTX represents an effective treatment option for EF. The rarity of this disease would make a double-blind controlled trial study difficult to perform.

Reasons for stopping methotrexate treatment in patients with juvenile idiopathic arthritis

We included 98 patients (median age 15.4 ± 7.5 years) who had a definitive diagnosis of JIA and used MTX. Seventy-six (78%) patients were females. The JIA subtype most frequently observed was polyarticular. Routes of administration of MTX observed were subcutaneous (55%) and oral (13%), but many patients throughout the treatment used both adminis tration (32%) in order to improve adherence to treatment. After a mean follow-up time of 5 years, 51 (52%) of these patients discontinued treatment and 47 (48%) of them were still on treatment, but only 35 (74%) were adherent. Sixty-eight (69%) JIA patients reported the presence of sporadic episodes of adverse reactions during treatment. Episodes of adverse reactions related to MTX was mainly gastric intolerance (abdominal discomfort, nausea and vomiting). There were three cases of elevated transaminase levels and one case of neutropenia. The reasons for JIA patients discontinue treatment with MTX was presence of side effects (35%), interruption on their own decision (27%), treatment abandonment (12%) and other reasons such as pregnancy, chickenpox and lack of medication in the public hospitals (12%), improvement of the disease (8%), and inefficacy (6%). All patients who discontinued MTX on their own decision had additionally the presence of side effects. Conclusion

OP0150 Long-Term Persistence with Oral Methotrexate in Patients with Early Inflammatory Arthritis

BackgroundPersistence with methotrexate (MTX) therapy is longer compared to other conventional synthetic disease-modifying antirheumatic drugs (csDMARDs) in patients with rheumatoid arthritis (RA). The majority of patients with RA stop MTX...