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Methotrexate is a versatile antineoplastic and immunosuppressive agent. We report a case of a young adult on the Cancer and Leukaemia Group B 10403 treatment protocol for B-cell acute lymphoblastic leukaemia. She has previously completed the induction and consolidation phases with good tolerance then started on Capizzi methotrexate during the interim maintenance phase. Few days after receiving one intermediate dose of methotrexate, she developed severe multiorgan toxicities including pancytopaenia and several dermatologic toxicities. The patient underwent extensive diagnostic workup, with all results negative, pointing eventually towards severe methotrexate toxicity. This case highlights the broad spectrum of toxicities that can occur even with low doses of methotrexate. Capizzi methotrexate therapy implies no leucovorin therapy, hence putting patients at risk for multiorgan toxicity. Our experience reinforces the importance of close monitoring for patients receiving methotrexate, regardless of dose, and the prompt administration of high-dose leucovorin once toxicity suspected.

Methotrexate (MTX) is the most widely used drug in cancer chemotherapy and is considered to be the first-line drug for the treatment of a number of rheumatic and non-rheumatic disorders. The pulmonary toxicity, hepatotoxicity of MTX are two of its major side effects. Other toxicities such as endocrinological toxicity, GI toxicity, cutaneous toxicity, hematological toxicity, fatal malfunction or loss, and malignancy can also occur, but at a significantly lower rate of prevalence. This review aims to provide a comprehensive understanding of the molecular mechanisms of methotrexate toxic effects and Lastly, we discussed the management of this toxicity.

Methotrexate is used to treat autoimmune and oncologic diseases in children with Down syndrome. However, increased methotrexate-related toxicity is reported in this population. We evaluated differences in the concentrations and distribution of erythrocyte folates in children with Down syndrome as a potential basis for this enhanced toxicity.

Methotrexate is known as a folate antimetabolite. The side effects of methotrexate are not usually seen in low dosages. Here we present a patient with inflammatory colitis due to methotrexate use for psoriasis.A 29 year-old male who was diagnosed with psoriasis 1 year ago and started to use methotrexate for 2 weeks; applied to emergency with acute abdomen symptoms. According to the tests and examinations the patient was diagnosed with inflammatory colitis due to methotrexate toxicity. The patient was observed for abdominal pain without surgical interventions and had folic acid therapy combined with empiric antibiotherapy. Methotrexate side effects are usually seen as bone marrow suppression and mucosal tissue inflammation therefore some side effects can be missed in clinical examinations. As a result, we should consider that in patients applying to emergency with acute abdomen symptoms drugs can be the cause of this clinical presentation.

Methotrexate, a folate antimetabolite and one of the first few anti-neoplastic drugs, is now a commonly used drug in the treatment of many inflammatory disorders ranging from diseases like rheumatoid arthritis to psoriasis. The life-threatening toxicity of methotrexate in inflammatory diseases is not commonly encountered. Here we report a case of life-threatening multiorgan failure from methotrexate toxicity, which was given for skin lesions suspected to be psoriasis.

Methotrexate is one of the most widely used drugs in rheumatology due to its high efficacy-to-toxicity. However, patients treated with this drug are sometimes elderly, which increases toxicity risks, as well as mistakes in taking the medication. The case is presented of an 87 year-old patient, on multiple medications, with a history of cognitive impairment and low social support, who suffered acute methotrexate toxicity. A description is also presented on the characteristics of the toxicity cases due this drug admitted to this hospital in the last 7 years.

Overdosing is the major cause of acute methotrexate toxicity in psoriasis patients. There are no published data regarding the acute cumulative dose causing acute toxicity, duration to achieve acute cumulative toxic dose and various reasons for wrong dosing of methotrexate in Indian patients. We are presenting a series of seven cases of toxicity due to overdosing of methotrexate in psoriasis. The acute cumulative dose of methotrexate ranging from 35 mg to 150 mg, taken over 3-7 days was responsible for acute toxicity in the psoriasis cases. Lack of counselling regarding the disease course, drug dosing, schedule and awareness about possible outcome of high and daily dose were found to be the causes of overdosing and toxicity in our patients. All cases presented with ulceration, bleeding and pain in skin lesions and five cases had oral mucosal ulceration and genital mucosa was involved in two cases. All cases were given injectable folinic acid. Five cases recovered and two cases expired. Authors postulate counselling about the course of disease, regarding dosing schedule of methotrexate and consequences of methotrexate overdosing is mandatory for all patients of psoriasis in country like India where drug regulation is not strict to prevent methotrexate toxicity and its dreaded consequences.

Methotrexate is a highly effective medication that is the mainstay of treatment for numerous complex dermatological and rheumatological disorders. However, its use requires close monitoring as it has serious side effects that could be fatal if not recognized promptly. Herein, we present an interesting case of methotrexate toxicity leading to a prolonged hospital stay with resultant increase in health care cost and patient dissatisfaction. It remains of pivotal importance for primary care physicians and hospitalists to be aware of its side effect profile. As such, early recognition of methotrexate toxicity can result in earlier initiation of goal-directed therapies, leading to improved outcomes and shorter hospital stay. Patient education and effective communication between health care providers and the patient are of utmost importance in ensuring patient safety.

High doses of methotrexate are an important chemotherapy agent in the treatment of many childhood cancers. Treatment with HDMTX can cause unwanted side effects and induce many types of toxicity (e.g. Renal toxicity, liver toxicity, neurotoxicity, Hematologic toxicity, Pulmonary toxicity, gastrointestinal toxicity and Cutaneomucous toxicity) so adding leucovorin rescue provides the advantage of safe administration. However, HDMTX therapy should only be initiated when plasma methotrexate monitoring is available to determine adequacy of drug removal and risk of serious toxicity. Monitoring is an effective tool in managing the toxicity profile and guiding the dose of leucovorin. Sufficient hydration, urine alklinization, monitoring of liver and kidney functions and avoiding drugs interaction promote safe administration.

Background: Acute lymphoblastic leukemia(ALL) is the most common type of hematologic malignancy in children. Based on COG protocol, one of the treatments for these children is methotrexate. Methotrexate has many complications in Pediatrics. Nowadays, the relationship between gene mutations and complications of each drug are discussed. This study aimed to evaluate the pharmacogenetics of methotrexate with emphasis on ABCB1 gene and its implications for the treatment of ALL children in Kurdistan province.Methods: Blood samples were obtained from children with ALL, and then DNA extraction and polymerase chain reaction (PCR) were performed with approximately 300μMol / μL of each direct primer in the final volume of 50µL. The PCR method was used to amplify the ABCB1 gene and the reaction products were identified by 0.5% agarose gel electrophoresis. The length of the PCR fragments was confirmed by observation by UV-Trans-illuminator. Moreover, blood and liver toxicity in all patients treated with methotrexate were measured by measuring leukocyte counts, platelets, neutrophil percentages, hemoglobin, alanine transaminase activity, and aspartate trans Aminase was evaluated.Results: 81 children with ALL, 45 males (55.5%) and 36 females with a mean age of 6.32 + 3.08 (y/o) were evaluated in this study. ABCB1 3435 C->T gene mutation frequency was 70.4% and the frequency of ABCB1 1199 G->A gene mutation was 4.9%.Frequency of gastrointestinal toxicity, leukopenia, anemia, thrombocytopenia, hepatotoxicity, neutropenia and renal toxicity were higher in patients with heterozygous and homozygous ABCB1 3435 C->T mutant polymorphisms than in patients with normal polymorphism, but the frequency of toxicity in patients with heterozygous and homozygous ABCB1 1199 G->A mutant polymorphisms were lower than patients with normal homozygous polymorphism, but these difference were not statistically significant.Conclusion: According to the results of our study, it can be concluded that methotrexate drug toxicity was higher in patients with ABCB1 3435 C->T gene mutation, but there was no significant correlation because of the low sample size. Furthermore it can be concluded that ABCB1 1199 G->A gene mutation may have a protective effect against the side effects of methotrexate, therefore it is recommended this hypothesis be tested in future studies.

Introduction Methotrexate intoxication following high-dose methotrexate-induced acute kidney injury is a life-threatening complication. Glucarpidase can quickly reduce extracellular methotrexate to safe levels, but the effectiveness and safety of its use in different episodes of nephrotoxicity remain an unknown area. Case Report A 30-year-old male diagnosed with acute lymphoblastic T-cell lymphoma received methotrexate 5 g/m2 intravenous (IV) as part of the first consolidation cycle. On Consolidation 3, he restarted methotrexate at a dose of 3 g/m2 IV showing slow methotrexate elimination, associated myelosuppression, and hepatic toxicity. Glucarpidase was administered (total dose of 2000 International Units (IU)). No adverse events were observed, and his renal function returned to normal. One hundred and six days later, he was diagnosed with leptomeningeal and cerebellar relapse and treatment with methotrexate 3,5 g/m2 IV day 1 and cytosine arabinoside (Ara-C) 2 g/m2 IV twice per day days 1, 3, and 5 was started. At 36 h from methotrexate infusion, serum creatinine increased up to 1.89 mg/dL and methotrexate concentration was 100 µmol/L. Management and Outcome: Ara-C was suspended, and a second administration of glucarpidase (2000 IU) was dispensed. No adverse events were noticed, methotrexate levels decreased and renal function progressively improved, recovering completely three weeks later. Discussion The effectiveness and safety of the use of glucarpidase in different episodes of nephrotoxicity remain an unknown area, and the rate and consequences of antiglucarpidase antibody formation remain poorly understood. This case report is, to our knowledge, the first case of a second administration of glucarpidase in a different cycle of high-dose methotrexate in an adult patient.

Introduction: Methotrexate (MTX), a classic antifolate, is one of the most widely used and well-studied anticancer agents. High-dose methotrexate (HD-MTX) with folinic acid (leucovorin) rescue is one of the standard therapies for osteosarcoma. High-dose methotrexate (HDMTX) can exert significant toxicity and requires complex pharmacokinetic monitoring and leucovorin rescue. The side effect profile of MTX varies markedly according to the dose. Regimens containing MTX are classified as high, intermediate, or low-dose. High-dose methotrexate (HD-MTX; 12 g/m2) is a part of the golden standard therapy for pediatric osteosarcoma (OS). Risk factors associated with MTX toxicity in children with OS are not well defined. Case Presentation: We report here a case of pediatric osteosarcoma with nephrotoxicity associated with delayed MTX excretion who was successfully managed using supportive measures that encouraged us to re-challenge with a full dose of MTX then we reduced the dose to 50% to attain the final critical decision about continuation or changing the regimen of treatment for the patient. Our patient developed moderate renal complications during therapy that improved with supportive care, so we challenged with more cycles of a high dose MTX, but the patient developed serious renal complications. A reduced dose of MTX with 50% was given successfully without any renal impairment. Conclusion: Methotrexate toxicity that might not occur during the initial courses of high-dose MTX is not a predictive of the tolerability of further courses and re-challenging with HDMTX is risky, but reduced dose methotrexate is a good option rather than changing the regimen, with good tolerability and rapid clearance of HDMTX. HDMTX-induced renal impairment occurs in a low percentage of patients with osteosarcoma and can be managed successfully by maximum supportive care. MTX clearance can be affected by gender and age.

Methotrexate (MTX) has long been a critically important chemotherapeutic agent for the treatment of nonmalignant and malignant conditions. At the high-doses typically used for hematologic malignancies, the wide therapeutic index of MTX has made it one of the clearest examples of the advantages of therapeutic drug monitoring aimed at maintaining a drug’s efficacy while reducing the risk of severe toxicities. Here we present a case of high-dose MTX-related multiorgan toxicity that demonstrates critical factors regarding the appropriate administration of MTX, prevention of excessive toxicities, and rescue from toxicities with the use of glucarpidase. Moreover, we review standard assays for therapeutic drug monitoring of MTX and its metabolites and show that liquid chromatography mass spectrometry (LC–MS/MS) for MTX measurements has extremely high sensitivity and specificity, making it an ideal candidate to monitor MTX levels in certain situations.

We propose and implement a pharmacokinetic model to estimate optimal dosages of methotrexate as a function of the patient's characteristics. This approach tries to improve the standard protocol that is based on either fixed doses or a function of single covariates, which are generally sub-optimal for most patients. Specifically, we focus on high-dose methotrexate administration and apply two pharmacokinetic models from the literature to assess the dose-response as a function of the individual degree of renal function, due to its importance in methotrexate elimination. We estimate model-informed optimal doses according to different targets, and the risk of methotrexate toxicity. We perform a Monte Carlo analysis to estimate the uncertainty associated with both suggested doses and the toxicity threshold. Results show how pharmacokinetic models can support clinical drug administration by identifying room for improvement in current drug dosing and guiding the design of improved personalized clinical treatments.

Interstitial lung disease (ILD) can arise in a variety of connective tissue diseases (CTDs) and various treatment interventions are being explored. In 2020, advances in the treatment of CTD-associated ILD have included the re-evaluation of methotrexate-induced lung injury and emerging insights on anti-IL-6 therapy and anti-fibrotic therapy in this condition.

Methotrexate (MTX) is widely used in the treatment of some forms of cancer but having severe side effects. The present work aimed to investigate the protective role of propolis treatment against alterations induced by MTX on the hepatic and renal tissues. Rabbits were exposed to MTX (0.25 mg/kg), with or without propolis (50 mg/kg) while hepatic and renal biopsies were examined for histological and histochemical abnormalities. Methotrexate induced hydropic degeneration, pyknosis, sinusoidal dilatation and bile duct hyperplasia in the liver together with renal tubular degeneration, glomerular shrinkage and hyaline droplet precipitation. While propolis partially ameliorated some of the morphometric and biochemical alterations, none of the hepatic alterations induced by MTX was protected by propolis treatment. Nevertheless glomerular shrinkage and renal tubule degeneration were partially protected in animals received both MTX plus propolis. It is concluded that propolis treatment has little or no ameliorative effect in protecting the hepatic and renal tissues from MTX toxicity.

We developed a bedside algorithm for individually adjusting the high-dose methotrexate (HDMTX) dose (5 g/m) given to patients with acute lymphoblastic leukemia at high risk for methotrexate toxicity. Data were reviewed for 8 patients receiving 21 cycles of HDMTX as per our algorithm. Eleven cycles began with 5 g/m, 10 cycles began with a preinfusion 20% to 25% dose reduction. Neither mean MTX AUC (2320.5±179.1 vs. 2080.4±161.7 μmol×h/L), mean Cpss (64.3±7.9 vs. 60.8±6.1 μM), nor toxicities were statistically different between groups. Our algorithm allowed the safe administration of HDMTX to patients at risk of MTX toxicities and obviated the need for preinfusion dose reduction.

Pulmonary involvement in Henoch‐Schonlein purpura (HSP) although rare is an important treatable cause of hospital admission in patients. Its diagnosis is difficult due to the vague symptoms and non-specific radiographic findings. We present one such case of a known case of HSP presenting with pulmonary involvement and treated successfully with steroids and immunosuppressant medications after ruling out all other causes. This particular case could also have an additional component of methotrexate induced lung involvement. Overall it is an interesting case with some much needed learning points.

Methotrexate is a chemotherapy originally used in oncology that is also applied in several nononcologic diseases, such as rheumatoid arthritis, because it has an anti-inflammatory effect in low doses. A 68-year-old leucoderm man attended our service with complaint of oral sores for 1 month. As a personal background he had rheumatoid arthritis, diabetes, hypertension, and hypothyroidism. The patient said the ulcers began to appear after the dose of methotrexate had been changed. Clinical history and anamnesis as well as a conversation with his physician led to the conclusion that a possible methotrexate toxicity was related to the oral ulcers despite the use of the medication in low doses (25 mg weekly). Extensive sore of the oral mucosa, especially in the labial lips region, was observed with a yellowish membrane. This case report aims to demonstrate that the toxic effects of methotrexate are seen even in low doses.

Methotrexate continues to be one of the most widely used systemic immunosuppressive agents in chronic plaque psoriasis. In addition to the important well characterized adverse effects such as hepatotoxicity and myelosuppression, methotrexate may induce a number of mucocutaneous adverse events including methotrexate induced mucocutaneous ulcerations. We present a case of methotrexate induced severe cutaneous ulcerations in patient with chronic plaque psoriasis. 45 year old male known case of chronic plaque psoriasis on methotrexate therapy manifested as methotrexate toxicity leading to acute kidney injury with painful ulcerated plaques with active bleeding over previously psoriatic plaques over extremities and trunk with mucosal ulcerations responding effectively to leucovorin therapy. Dermatologists need to be alert to the possibility of cutaneous adverse events associated with methotrexate therapy especially ulcerations of psoriatic plaques.

Aim Methotrexate (MTX) is the first-line disease-modifying antirheumatic drug in rheumatoid arthritis (RA). However, this anchor may cause some side effects that may range from nausea to mortality. The clinical features of MTX toxicity are under-researched. In this study, we aimed to find out the potential predisposing factors and outcomes of the MTX toxicity (n = 31). Methods The data were collected from 31 patients whose ages ranged from 25 to 81 years, who were suffering from immune-mediated inflammatory diseases and major MTX-related toxicity. Results Out of 31 patients, six (19.4%) used MTX every day, and 13 (41.9%) patients had renal insufficiency who were admitted to the hospital because of mucositis (90.3%) and fever (71%). While using MTX, 27 patients (87.1%) were discharged after the treatment and four patients (12.9%) died. Conclusions Although MTX has high efficacy for the toxicity ratio, wrong use and dosage of MTX may be harmful to patients. Thus, patients should be informed about the proper use of MTX.

Acute methotrexate overdose rarely causes systemic toxicity due to saturable absorption and rapid renal elimination. We present a case of methotrexate toxicity following acute overdose.A 56-year-old female presented soon after an overdose of 1250 mg of methotrexate, zopiclone and tramadol. The methotrexate was initially under-reported (500 mg) and folinic acid was not provided. Despite normal renal function, the patient developed toxicity. She represented 5 days following the overdose with mucositis, bone marrow suppression and prolonged febrile neutropenia. Treatment included folinic acid, broad-spectrum antibiotics, filgrastim, red cell and platelet transfusion. Her bone marrow began to recover 12 days following the overdose. She was discharged home on Day 17.Severe toxicity following an acute ingestion of a large amount of methotrexate is rarely reported. The development of toxicity was unexpected in this case given methotrexate's pharmacokinetics and the patient's normal renal function. The serum methotrexate concentrations were below the treatment threshold of the folinic acid rescue therapy nomogram suggesting that the nomogram should not be relied on in acute ingestions. Large acute oral methotrexate poisoning can result in systemic toxicity and folinic acid therapy should be provided in ingestions1000 mg.

Methotrexate (MTX) is an antimetabolite which competitively inhibits dihydrofolic acid reductase; inhibits purine and thymidylic acid synthesis, which in turn interferes with DNA synthesis, repair, and cellular replication. MTX is a good treatment option for neoplastic, rheumatic and dermatological diseases. However, rarely, may cause side effects, such as agranulocytosis and bone marrow suppression, mucosal tissue inflammation and necrotic changes, liver cell necrosis and hepatic cirrhosis, pulmonary fibrosis, and severe renal dysfunction. Herein, we report a 67-year-old female patient with a history of psoriasis for 15 years and MTX 15 mg/sc/week use for 8 years who was admitted due to the complaints of pancytopenia, mucositis and ulcers on psoriatic plaques despite low-dose MTX use. We present this case to remind that MTX toxicity might occur with low-dose MTX usage and to draw attention to various factors that facilitate the low-dose MTX toxicity, such as age, renal insufficiency, low albumin levels, infections, proton pump inhibitors and non-steroidal anti-inflammatory drugs.

Methotrexate is one of the most used drugs in the treatment of psoriasis with indication of systemic therapy. Cutaneous and mucous side effects are described by pharmacological characteristics of the drug itself or due to overdose. We report the case of a patient with ulcerations in oral mucosa and psoriatic plaques after incorrect use of Methotrexate. Prescribed in a weekly dose, it was used continuously for 10 days and without simultaneous intake of folic acid. It is important to ensure correct comprehension of the prescription.

Objectifs - Le but de cette étude est de déterminer l’impact du polymorphisme gammaglutamyl hydrolase (GGH) c.452C> T (rs 11545078 dbSNP Id) GIT) chez les patients atteints de polyarthrite rhumatoïde (PR) sur l’apparition des réactions indésirables au combinaméthotrexate (MTX) et sur la toxicité gastro-intestinale (TGI). Matériels et méthodes - Soixante et un patients atteints de PR ont été inclus dans cette étude. Le génotypage a été effectué par la réaction en chaîne par polymérase polymorphisme de longueur de fragment de restriction (PCR-RFLP). Les données ont été analysées par test ?2.Résultats - Nos résultats suggèrent que les distributions de fréquences des allèles et génotypes de ce polymorphisme sont similaires entre les deux groupes avec et sans toxicité. Cependant, il existe une distribution significative des génotypes GGH 452TT (p = 0,03) et GGH 452CT + 452TT (p = 0,02) entre les groupes avec ou sans TGI. La même corrélation à été retrouvez pour l’allèle GGH 452T (p = 0,008) Conclusion - Nous avons montré pour la première fois dans la population de l’Ouest Algérien que le polymorphisme GGH c.452C> T influence l’apparition de la toxicité intestinale gastro-intestinale du MTX.

Despite improvements in the prognosis of acute myelogenous leukemia in patients with Down syndrome, the prognosis of acute lymphocytic leukemia (DS-ALL) in these patients is still poorer than that of ALL in the general population. We compared treatment results between 4 patients with DS-ALL and 16 non-Down syndrome patients with ALL (NDS-ALL). Four patients with DS-ALL treated with TCCSG protocols achieved complete remission by the end of the induction phase. During the high-dose methotrexate (HD-MTX) phase, the dosage of MTX was reduced from 3 to 2 g/m2 after the syndrome of inappropriate ADH secretion developed in the first patient. All DS-ALL patients had severe mucositis and a longer period of anorexia than NDS-ALL patients, even after dose reductions, resulting in a longer HD-MTX phase in DS-ALL patients than in NDS-ALL patients. The mean dosages of 6-MP and MTX during the maintenance phase were significantly lower in DS-ALL patients than in NDS-ALL patients (6-MP 22.1 ± 9.9 mg/m2 and MTX 16.1 ± 4.5 mg/m2 vs. 6-MP 43.5 ± 23.1 mg/m2 and MTX 25.2 ± 8.8 mg/m2, respectively). All DS-ALL patients have been in complete remission for a median of 10 years 0 month (range: 8 years 10 months-14 years 1 month) as of January 1, 2017. DS-ALL patients may receive the same treatment protocol as that for NDS-ALL patients with adequate care and few modifications, and this strategy may result in the expansion of treatment protocols suitable for DS-ALL patients in the future.

An 87-year-old female presented to the emergency department with fever and a rash, out of concern for possible Steven’s Johnson syndrome. Ultimately, it was discovered she had a medication error involving methotrexate, and the rash was felt to be due to methotrexate toxicity, rather than true Steven’s Johnson syndrome. The case discusses both Steven’s Johnson toxicity as well as methotrexate toxicity.

Methotrexate is a mainstay treatment for autoimmune and inflammatory conditions in the field of Dermatology. However, in some patients, its use is associated with significant side effects and toxicity. Folate supplementation with either folic acid or folinic acid often mitigates side effects and reduces the incidence of systemic toxicity related to methotrexate. Although the value of methotrexate is clear, debate remains about folate supplementation. There is little agreement about the proper dosing or frequency of folate supplementation as many believe that daily folate supplementation can reduce methotrexate efficacy. Although daily use of folic acid does not appear to affect methotrexate efficacy, dosing of folinic acid close to methotrexate administration may hinder methotrexate efficacy. Therefore, folic acid should be used daily with methotrexate to ameliorate side effects, whereas folinic acid should only be used for methotrexate toxicity.

The prescription of Methotrexate is well-recognized for various neoplastic diseases. For Rheumatoid arthritis, it is prescribed once a week, low-dose regimen for the treatment of psoriasis and rheumatoid arthritis. Apart from providing therapeutic benefit, it is not devoid of side effects like oral ulceration which may be due to over dosage regarding its once-weekly regime. This case report describes a patient with inherent Methotrexate toxicity that developed oral mucositis due to Methotrexate being given for rheumatoid arthritis.

We describe two cases of low dose methotrexate (MTX) toxicity in patients with psoriasis. Patient was a 49-year-old male, known case of chronic plaque psoriasis from 10 years on and off. He was advised to take MTX 2.5 mg 2 days a week but patient took 2.5 mg twice daily (BD) for 6 continuous days following which he developed ulceration over psoriatic plaques and bone marrow suppression. MTX is safe and effective if adhered to standard treatment guidelines but inadverent use may lead to it’s toxicity.

Rationale:Consensus guidelines on the management of methotrexate-induced nephrotoxicity using glucarpidase (Voraxaze) may be relatively unfamiliar to the nephrology community.Presenting concerns of the patient:A 61-year-old man with intravascular large B-cell lymphoma was admitted for cycle #1 of high-dose methotrexate (HDMTX) following 2 cycles of R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone) chemotherapy. On admission, he was clinically euvolemic and had a creatinine clearance of 98 mL/min. He received standard HDMTX toxicity prophylaxis with volume expansion, urinary alkalinization, and leucovorin rescue.Diagnoses:Despite prophylactic efforts, he developed a severe acute kidney injury, creatinine 63 to 226 µmol/L (2.56 mg/dL), following HDMTX, impaired methotrexate clearance, and neurotoxicity manifested by status epilepticus.Interventions:He was given glucarpidase to convert extracellular methotrexate into its inactive metabolites, glutamate and DAMPA (4-deoxy-4-amino- N10-methylpteroic acid) at 52 hours post-HDMTX. Cross-reactivity between commercial methotrexate immunoassays with DAMPA led to falsely elevated methotrexate concentrations for much longer than expected based on the current guideline (5 days instead of Outcomes:The patient remained nonoliguric and did not develop acute indications for dialysis. Serum creatinine peaked at 608 µmol/L (6.88 mg/dL) 6 days after HDMTX. He ultimately had a full renal and neurologic recovery.Lessons learned:Glucarpidase is an effective option for nonrenal elimination of methotrexate-induced nephrotoxicity. Timing of methotrexate concentration monitoring to assess for toxicity, how to access the drug, and the need for ongoing monitoring by mass spectrometry beyond the guideline recommendation are highlighted for centers where HDMTX therapy may be used.

Methotrexate is the most common disease-modifying antirheumatic drug used in the treatment of rheumatoid arthritis. The side effects which are known to occur include pancytopenia, hepatic dysfunction, pulmonary toxicity, and acute renal failure. This is a case report of a patient who presented with florid manifestations of methotrexate toxicity which happened due to mistaken overdosing of methotrexate which had been prescribed to her for rheumatoid arthritis.

Psoriasis is a common, chronic, disfiguring, inflammatory, and proliferative condition of the skin. It manifests with varying degrees of severity and can be treated with various immune modulators. This is a case report of a 57-year-old male patient of psoriasis on long-term oral methotrexate, who developed methotrexate toxicity when given an injection of methotrexate for unstable psoriasis. After recovery, the patient was started on cyclosporine 100 mg twice a day. After a week, he developed thrombocytosis, which reverted a week after cyclosporine was stopped. The patient is currently being managed with acitretin. The aim of this case report is to emphasize the various unpredictable adverse reactions encountered during treatment of psoriasis, especially when a combination or sequential treatment is used. There is a need for caution, as late sequelae of long-term administration of the systemic agents used in the treatment of psoriasis are still unknown.

Severe methotrexate toxicity due to medical treatment of an ectopic pregnancy is presented. The feasibility of low-dose use and success of methotrexate makes it the first drug in the medical treatment of ectopic pregnancies. Besides its advantages, it should be used with caution and severe toxicity should be kept in mind.

OZET: Psoriazis eritemli, skuamli ve endure plaklarla karakterize, en sik sacli deri ve ekstansor yuzeyleri tutan kronik bir dermatozdur. Metotreksat psoriazis tedavisinde yaygin kullanilan sentetik bir folik asit analogudur. Kanda nadiren toksik duzeylere ulasarak siddetli yan etkilere sebep olur. Bu durumda akut donemde psoriatik plaklarda ulserasyon ve nekrozla karakterize cilt bulgulari ortaya cikar. Cogu olguda sebep, ilacin yanlislikla haftalik rejim yerine daha kisa surelerde veya bir defada cok miktarda alinmasidir. Eslik eden ileri yas ve renal yetmezlik gibi nedenler de toksisiteye katkida bulunur. Metotreksat toksisitesini erken donemde tanimak ve hemen tedaviye baslamak acisindan kutanoz bulgular oldukca onemlidir. Burada klinigimize basvuran bir olgudan hareketle akut metotreksat toksisitesine yaklasim ele alinacaktir.. ANAHTAR KELIMELER: kutanoz ulser, metotreksat, psoriazis ACUTE METHOTREXATE TOXICITY PRESENTING WITH CUTANEOUS ULCERATIONS ABSTRACT: Psoriasis is a chronic dermatosis characterized by erythematosus, scaly and indurated plaques which are most often located on scalp and extensor surfaces. Methotrexate is a synthetic folic asid analogue which is commonly used for the treatment of psoriasis. It rarely reaches toxic levels in the blood and causes severe adverse effects. In this situation, skin findings characterized by ulcerations and necrosis on psoriatic plaques emerge at the acute stage. In the most of the cases, the reason is misuse of the drug which is taking medicine at short intervals or too much during a treatment session instead of weekly regimen. Additional causes such as renal failure and older age contribute toxicity. Cutaneous findings are quite important to recognize methotrexate toxicity at the early stages and to start the treatment immediately. Herein, the approach to acute methotrexate toxicity will be discussed with reference to a case who is referred to our clinic. KEYWORDS: cutaneous ulceration, methotrexate, psoriasis