Methotrexate-induced Severe Pancytopenia in a Patient with Rheumatoid
Arthritis: A Case Report and Review of Literature

Elham      Hosseini; Foroud      Shahbazi
doi:10.2174/1574886318666230516115737
Abstract

Toxicity associated with low doses of methotrexate (MTX) is low, but it may be fatal. Bone marrow suppression and mucositis are among the common side effects of low dose MTX toxicity. Different risk factors have been reported for toxicities associated with low doses of MTX, including accidental use of higher doses, renal dysfunction, hypoalbuminemia, and polypharmacy. In this paper, we present a female patient who had mistakenly used 7.5 mg of MTX daily instead of the same dose of MTX on Thursday and Friday. She was presented with mucositis and diarrhea to the emergency department. Moreover, we searched the databases Scopus and PubMed for available studies and case reports on toxicities associated with MTX dosing errors. The most frequently observed toxicities included gastrointestinal lesions, nausea, vomiting, skin lesions, and bone marrow suppression. Leucovorin, hydration, and urine alkalinization were among the most frequently used treatments. Finally, we summarize the data on the toxicities of low doses of MTX in different diseases.
Keywords: Methotrexate, pancytopenia, medication error, mucositis, rheumatoid arthritis, toxicity.
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[1]
Cronstein BN, Aune TM. Methotrexate and its mechanisms of action in inflammatory arthritis. Nat Rev Rheumatol  2020; 16(3): 145-54.
 [http://dx.doi.org/10.1038/s41584-020-0373-9] [PMID:  32066940]

[2]
Pivovarov K, Zipursky JS. Low-dose methotrexate toxicity. CMAJ  2019; 191(15): E423.
 [http://dx.doi.org/10.1503/cmaj.181054] [PMID:  30988043]

[3]
Romão VC, Lima A, Bernardes M, Canhão H, Fonseca JE. Three decades of low-dose methotrexate in rheumatoid arthritis: Can we predict toxicity? Immunol Res  2014; 60(2-3): 289-310.
 [http://dx.doi.org/10.1007/s12026-014-8564-6] [PMID:  25391609]

[4]
Solomon DH, Glynn RJ, Karlson EW, et al. Adverse effects of low-dose methotrexate. Ann Intern Med  2020; 172(6): 369-80.
 [http://dx.doi.org/10.7326/M19-3369] [PMID:  32066146]

[5]
Mustafa SH, Ahmad T, Balouch M, Iqbal F, Durrani T. Safety profile of methotrexate therapy in patients with rheumatoid arthritis. Cureus  2022; 14(7): e27047.
 [http://dx.doi.org/10.7759/cureus.27047] [PMID:  36000142]

[6]
Vanni KMM, Lyu H, Solomon DH. Cytopenias among patients with rheumatic diseases using methotrexate: A meta-analysis of randomized controlled clinical trials. Rheumatology  2020; 59(4): 709-17.
 [http://dx.doi.org/10.1093/rheumatology/kez343] [PMID:  31504937]

[7]
 Common terminology criteria for adverse events (CTCAE) v50.	US Department of Health and Human Services, National Institutes	of Health, National Cancer Institute 2017.

[8]
Lim AYN, Gaffney K, Scott DGI. Methotrexate-induced pancytopenia: Serious and under-reported? Our experience of 25 cases in 5 years. Rheumatology  2005; 44(8): 1051-5.
 [http://dx.doi.org/10.1093/rheumatology/keh685] [PMID:  15901903]

[9]
Kivity S, Zafrir Y, Loebstein R, Pauzner R, Mouallem M, Mayan H. Clinical characteristics and risk factors for low dose methotrexate toxicity: A cohort of 28 patients. Autoimmun Rev  2014; 13(11): 1109-13.
 [http://dx.doi.org/10.1016/j.autrev.2014.08.027] [PMID:  25172240]

[10]
Salliot C, van der Heijde D. Long-term safety of methotrexate monotherapy in patients with rheumatoid arthritis: A systematic literature research. Ann Rheum Dis  2009; 68(7): 1100-4.
 [http://dx.doi.org/10.1136/ard.2008.093690] [PMID:  19060002]

[11]
Fragoulis GE, Paterson C, Gilmour A, et al. Neutropaenia in early rheumatoid arthritis: Frequency, predicting factors, natural history and outcome. RMD Open  2018; 4(2): e000739.
 [http://dx.doi.org/10.1136/rmdopen-2018-000739] [PMID:  30402267]

[12]
Nakafero G, Grainge MJ, Card T, et al. What is the incidence of methotrexate or leflunomide discontinuation related to cytopenia, liver enzyme elevation or kidney function decline? Rheumatology  2021; 60(12): 5785-94.
 [http://dx.doi.org/10.1093/rheumatology/keab254] [PMID:  33725120]

[13]
Mori S, Hidaka M, Kawakita T, et al. Factors associated with myelosuppression related to low-dose methotrexate therapy for inflammatory rheumatic diseases. PLoS One  2016; 11(4): e0154744.
 [http://dx.doi.org/10.1371/journal.pone.0154744] [PMID:  27128679]

[14]
Grove ML, Hassell AB, Hay EM, Shadforth MF. Adverse reactions to disease-modifying anti-rheumatic drugs in clinical practice. QJM  2001; 94(6): 309-19.
 [http://dx.doi.org/10.1093/qjmed/94.6.309] [PMID:  11391029]

[15]
Gutierrez-Ureña S, Molina JF, García CO, Cuéllar ML, Espinoza LR. Pancytopenia secondary to methotrexate therapy in rheumatoid arthritis. Arthritis Rheum  1996; 39(2): 272-6.
 [http://dx.doi.org/10.1002/art.1780390214] [PMID:  8849378]

[16]
Ajmani S, Preet Singh Y, Prasad S, et al. Methotrexate-induced pancytopenia: A case series of 46 patients. Int J Rheum Dis  2017; 20(7): 846-51.
 [http://dx.doi.org/10.1111/1756-185X.13004] [PMID:  28261918]

[17]
Cansu DÜ, Teke HÜ, Bodakçi E, Korkmaz C. How should we manage low-dose methotrexate-induced pancytopenia in patients with rheumatoid arthritis? Clin Rheumatol  2018; 37(12): 3419-25.
 [http://dx.doi.org/10.1007/s10067-018-4242-8] [PMID:  30056523]

[18]
Moore TJ, Walsh CS, Cohen MR. Reported medication errors associated with methotrexate. Am J Health Syst Pharm  2004; 61(13): 1380-4.
 [http://dx.doi.org/10.1093/ajhp/61.13.1380] [PMID:  15287234]

[19]
Vial T, Patat AM, Boels D, et al. Adverse consequences of low-dose methotrexate medication errors: data from French poison control and pharmacovigilance centers. Joint Bone Spine  2019; 86(3): 351-5.
 [http://dx.doi.org/10.1016/j.jbspin.2018.09.006] [PMID:  30243781]

[20]
Thompson JA, Love JS, Hendrickson RG. Methotrexate toxicity from unintentional dosing errors: Calls to a poison center and death descriptions. J Am Board Fam Med  2021; 34(6): 1246-8.
 [http://dx.doi.org/10.3122/jabfm.2021.06.210120] [PMID:  34772781]

[21]
Moisa A, Fritz P, Benz D, Wehner HD. Iatrogenically-related, fatal methotrexate intoxication: A series of four cases. Forensic Sci Int  2006; 156(2-3): 154-7.
 [http://dx.doi.org/10.1016/j.forsciint.2004.12.031] [PMID:  16343832]

[22]
Lee JS, Oh JS, Kim YG, Lee CK, Yoo B, Hong S. Methotrexate-related toxicity in patients with rheumatoid arthritis and renal dysfunction. Rheumatol Int  2020; 40(5): 765-70.
 [http://dx.doi.org/10.1007/s00296-020-04547-y] [PMID:  32170389]

[23]
Cairns R, Brown JA, Lynch AM, Robinson J, Wylie C, Buckley NA. A decade of Australian methotrexate dosing errors. Med J Aust  2016; 204(10): 384.
 [http://dx.doi.org/10.5694/mja15.01242] [PMID:  27256650]

[24]
Shea B, Swinden MV, Ghogomu ET, et al. Folic acid and folinic acid for reducing side effects in patients receiving methotrexate for rheumatoid arthritis. J Rheumatol  2014; 41(6): 1049-60.
 [http://dx.doi.org/10.3899/jrheum.130738] [PMID:  24737913]

[25]
Prey S, Paul C. Effect of folic or folinic acid supplementation on methotrexate-associated safety and efficacy in inflammatory disease: a systematic review. Br J Dermatol  2009; 160(3): 622-8.
 [http://dx.doi.org/10.1111/j.1365-2133.2008.08876.x] [PMID:  18945303]

[26]
Kalb RE, Strober B, Weinstein G, Lebwohl M. Methotrexate and psoriasis: 2009 National Psoriasis Foundation Consensus Conference. J Am Acad Dermatol  2009; 60(5): 824-37.
 [http://dx.doi.org/10.1016/j.jaad.2008.11.906] [PMID:  19389524]

[27]
Hall JJ, Bolina M, Chatterley T, Jamali F. Interaction between low-dose methotrexate and nonsteroidal anti-inflammatory drugs, penicillins, and proton pump inhibitors. Ann Pharmacother  2017; 51(2): 163-78.
 [http://dx.doi.org/10.1177/1060028016672035] [PMID:  27701081]

[28]
Narumi K, Sato Y, Kobayashi M, et al. Effects of proton pump inhibitors and famotidine on elimination of plasma methotrexate: Evaluation of drug-drug interactions mediated by organic anion transporter 3. Biopharm Drug Dispos  2017; 38(9): 501-8.
 [http://dx.doi.org/10.1002/bdd.2091] [PMID:  28801980]

[29]
Wang X, Song Y, Wang J, et al. Effect of proton pump inhibitors on high-dose methotrexate elimination: A systematic review and meta-analysis. Int J Clin Pharm  2020; 42(1): 23-30.
 [http://dx.doi.org/10.1007/s11096-019-00958-5] [PMID:  31916121]

[30]
Suzuki K, Doki K, Homma M, et al. Co-administration of proton pump inhibitors delays elimination of plasma methotrexate in high-dose methotrexate therapy. Br J Clin Pharmacol  2009; 67(1): 44-9.
 [http://dx.doi.org/10.1111/j.1365-2125.2008.03303.x] [PMID:  19076159]

[31]
Boerrigter E, Crul M. A non-interventional retrospective cohort study of the interaction between methotrexate and proton pump inhibitors or aspirin. Ann Pharm Fr  2017; 75(5): 344-8.
 [http://dx.doi.org/10.1016/j.pharma.2017.06.002] [PMID:  28705331]

[32]
Ranchon F, Vantard N, Henin E, et al. Delayed methotrexate elimination: Incidence, interaction with antacid drugs, and clinical consequences? Hematol Oncol  2018; 36(2): 399-406.
 [http://dx.doi.org/10.1002/hon.2479] [PMID:  28983943]

[33]
Reeves DJ, Moore ES, Bascom D, Rensing B. Retrospective evaluation of methotrexate elimination when co-administered with proton pump inhibitors. Br J Clin Pharmacol  2014; 78(3): 565-71.
 [http://dx.doi.org/10.1111/bcp.12384] [PMID:  24646036]

[34]
Vakily M, Amer F, Kukulka MJ, Andhivarothai N. Coadministration of lansoprazole and naproxen does not affect the pharmacokinetic profile of methotrexate in adult patients with rheumatoid arthritis. J Clin Pharmacol  2005; 45(10): 1179-86.
 [http://dx.doi.org/10.1177/0091270005280100] [PMID:  16172183]

[35]
Karim A, Tolbert DS, Hunt TL, Hubbard RC, Harper KM, Geis GS. Celecoxib, a specific COX-2 inhibitor, has no significant effect on methotrexate pharmacokinetics in patients with rheumatoid arthritis. J Rheumatol  1999; 26(12): 2539-43.
 [PMID:  10606360]

[36]
Pflugbeil S, Böckl K, Pongratz R, Leitner M, Graninger W, Ortner A. Drug interactions in the treatment of rheumatoid arthritis and psoriatic arthritis. Rheumatol Int  2020; 40(4): 511-21.
 [http://dx.doi.org/10.1007/s00296-020-04526-3] [PMID:  32052146]

[37]
Kwon OC, Lee JS, Kim YG, Lee CK, Yoo B, Hong S. Safety of the concomitant use of methotrexate and a prophylactic dose of trimethoprim-sulfamethoxazole. Clin Rheumatol  2018; 37(12): 3215-20.
 [http://dx.doi.org/10.1007/s10067-018-4005-6] [PMID:  29383453]

[38]
Watts CS, Sciasci JN, Pauley JL, et al. Prophylactic trimethoprim-sulfamethoxazole does not affect pharmacokinetics or pharmacodynamics of methotrexate. J Pediatr Hematol Oncol  2016; 38(6): 449-52.
 [http://dx.doi.org/10.1097/MPH.0000000000000606] [PMID:  27322715]

[39]
Sosin M, Handa S. Lesson of the week: Low dose methotrexate and bone marrow suppression. BMJ  2003; 326(7383): 266-7.
 [http://dx.doi.org/10.1136/bmj.326.7383.266] [PMID:  12560282]

[40]
Cudmore J, Seftel M, Sisler J, Zarychanski R. Methotrexate and trimethoprim-sulfamethoxazole: Toxicity from this combination continues to occur. Can Fam Physician  2014; 60(1): 53-6.
 [PMID:  24452563]

[41]
Hamid M, Lashari B, Ahsan I, Micaily I, Sarwar U, Crocetti J. A deadly prescription: Combination of methotrexate and trimethoprim-sulfamethoxazole. J Community Hosp Intern Med Perspect  2018; 8(3): 149-51.
 [http://dx.doi.org/10.1080/20009666.2018.1466598] [PMID:  29915656]

[42]
Carretero G, Puig L, Dehesa L, et al. Guidelines on the use of methotrexate in psoriasis. Actas DermoSifiliogrEnglish Edition  2010; 101(7): 600-13.
 [http://dx.doi.org/10.1016/S1578-2190(10)70682-X] [PMID:  28709542]

[43]
Bourré-Tessier J, Haraoui B. Methotrexate drug interactions in the treatment of rheumatoid arthritis: A systematic review. J Rheumatol  2010; 37(7): 1416-21.
 [http://dx.doi.org/10.3899/jrheum.090153] [PMID:  20436072]

[44]
Colebatch AN, Marks JL. van der HEIJDE DM, Edwards CJ. Safety of nonsteroidal antiinflammatory drugs and/or paracetamol in people receiving methotrexate for inflammatory arthritis: A Cochrane systematic review. J Rheumatol Suppl  2012; 90(0): 62-73.
 [http://dx.doi.org/10.3899/jrheum.120345] [PMID:  22942332]

[45]
Angelis-Stoforidis P, Vajda FJ, Christophidis N. Methotrexate polyglutamate levels in circulating erythrocytes and polymorphs correlate with clinical efficacy in rheumatoid arthritis. Clin Exp Rheumatol  1999; 17(3): 313-20.
 [PMID:  10410264]

[46]
Dervieux T, Greenstein N, Kremer J. Pharmacogenomic and metabolic biomarkers in the folate pathway and their association with methotrexate effects during dosage escalation in rheumatoid arthritis. Arthritis Rheum  2006; 54(10): 3095-103.
 [http://dx.doi.org/10.1002/art.22129] [PMID:  17009228]

[47]
Stamp LK, O’Donnell JL, Chapman PT, et al. Methotrexate polyglutamate concentrations are not associated with disease control in rheumatoid arthritis patients receiving long-term methotrexate therapy. Arthritis Rheum  2010; 62(2): 359-68.
 [http://dx.doi.org/10.1002/art.27201] [PMID:  20112376]

[48]
Mohamed HJ, Sorich MJ, Kowalski SM, et al. The role and utility of measuring red blood cell methotrexate polyglutamate concentrations in inflammatory arthropathies-a systematic review. Eur J Clin Pharmacol  2015; 71(4): 411-23.
 [http://dx.doi.org/10.1007/s00228-015-1819-x] [PMID:  25687918]

[49]
Ahmadzadeh A, Zamani N, Hassanian-Moghaddam H, Hadeiy SK, Parhizgar P. Acute versus chronic methotrexate poisoning; A cross-sectional study. BMC Pharmacol Toxicol  2019; 20(1): 39.
 [http://dx.doi.org/10.1186/s40360-019-0316-8] [PMID:  31269977]

[50]
Kitchlu A, Shirali AC. High-flux hemodialysis versus glucarpidase for methotrexate-associated acute kidney injury: What’s best? J Onco Nephrol  2019; 3(1): 11-8.
 [http://dx.doi.org/10.1177/2399369319827305]

[51]
Conway R, Low C, Coughlan RJ, O’Donnell MJ, Carey JJ. Methotrexate	use and risk of lung disease in psoriasis, psoriatic arthritis,	and inflammatory bowel disease: Systematic literature review and	meta-analysis of randomised controlled trials. BMJ  2015; 350(mar13 17): h1269.
 [http://dx.doi.org/ 10.1136/bmj.h1269] [PMID:  25770113]

[52]
Raghavendra S, Khurrana T, Malhotra AK. Yet another case of acute methotrexate toxicity due to accidental overdose. J Assoc Physicians India  2020; 68(1): 69.
 [PMID:  31979693]

[53]
Jariwala P, Kumar V, Kothari K, Thakkar S, Umrigar DD. Acute methotrexate toxicity: A fatal condition in two cases of psoriasis. Case Rep Dermatol Med  2014; 2014: 1-3.
 [http://dx.doi.org/10.1155/2014/946716] [PMID:  25276442]

[54]
Asghar M, Shoaib H, Kang W, Tariq I, Chatterjee T. Methotrexate toxicity: A simple solution to a complex problem. Cureus  2021; 13(4): e14364.
 [http://dx.doi.org/10.7759/cureus.14364] [PMID:  33972915]

[55]
Bidaki R, Kian M, Owliaey H, Babaei Zarch M, Feysal M. Accidental chronic poisoning with methotrexate; report of two cases. Emergency   2017; 5(1): e67.
 [PMID:  28894782]

[56]
Kumar RR, Makar N, Singh V, Goyal S, Chhabra R. A iatrogenic accidental overdose of methotrexate. J Clin Rheumatol  2021; 27(6): e248.
 [http://dx.doi.org/10.1097/RHU.0000000000001753] [PMID:  34054071]

[57]
Arnet I, Bernhardt V, Hersberger KE. Methotrexate intoxication: The Pharmaceutical Care process reveals a critical error. J Clin Pharm Ther  2012; 37(2): 242-4.
 [http://dx.doi.org/10.1111/j.1365-2710.2011.01263.x] [PMID:  21463347]

[58]
Singh A, Handa AC. Medication error: A case report of misadventure with methotrexate. JNMA J Nepal Med Assoc  2018; 56(211): 711-5.
 [http://dx.doi.org/10.31729/jnma.3538] [PMID:  30381772]

[59]
Srinivasa BM, Padmini S, Kumar P, et al. A case report on methotrexate overdose induced pancytopenia and mucocutaneous ulcerations. Indian J Phar Pract  2020; 13(4): 359-61.
 [http://dx.doi.org/10.5530/ijopp.13.4.61]

[60]
Widemann BC, Adamson PC. Understanding and managing methotrexate nephrotoxicity. Oncologist  2006; 11(6): 694-703.
 [http://dx.doi.org/10.1634/theoncologist.11-6-694] [PMID:  16794248]

[61]
Widemann BC, Schwartz S, Jayaprakash N, et al. Efficacy of glucarpidase (carboxypeptidase g2) in patients with acute kidney injury after high-dose methotrexate therapy. Pharmacotherapy  2014; 34(5): 427-39.
 [http://dx.doi.org/10.1002/phar.1360] [PMID:  24132809]

[62]
Proudfoot AT, Krenzelok EP, Vale JA. Position paper on urine alkalinization. J Toxicol Clin Toxicol  2004; 42(1): 1-26.
 [http://dx.doi.org/10.1081/CLT-120028740] [PMID:  15083932]

[63]
Bleyer WA. The clinical pharmacology of methotrexate.new applications of an old drug. Cancer  1978; 41(1): 36-51.
 [http://dx.doi.org/10.1002/1097-0142(197801)41:1<36:AID-CNCR2820410108>3.0.CO;2-I] [PMID:  342086]

[64]
Buchen S, Ngampolo D, Melton RG, et al. Carboxypeptidase G2 rescue in patients with methotrexate intoxication and renal failure. Br J Cancer  2005; 92(3): 480-7.
 [http://dx.doi.org/10.1038/sj.bjc.6602337] [PMID:  15668713]

[65]
Perazella MA, Moeckel GW. Nephrotoxicity from chemotherapeutic agents: Clinical manifestations, pathobiology, and prevention/therapy. Semin Nephrol  2010; 30(6): 570-81.
 [http://dx.doi.org/10.1016/j.semnephrol.2010.09.005] [PMID:  21146122]

[66]
Relling MV, Fairclough D, Ayers D, et al. Patient characteristics associated with high-risk methotrexate concentrations and toxicity. J Clin Oncol  1994; 12(8): 1667-72.
 [http://dx.doi.org/10.1200/JCO.1994.12.8.1667] [PMID:  8040679]

[67]
Shamash J, Earl H, Souhami R. Acetazolamide for alkalinisation of urine in patients receiving high-dose methotrexate. Cancer Chemother Pharmacol  1991; 28(2): 150-1.
 [http://dx.doi.org/10.1007/BF00689708] [PMID:  2060085]

[68]
Ackland SP, Schilsky RL. High-dose methotrexate: A critical reappraisal. J Clin Oncol  1987; 5(12): 2017-31.
 [http://dx.doi.org/10.1200/JCO.1987.5.12.2017] [PMID:  3316519]

[69]
Fabre I, Fabre G, Goldman ID. Polyglutamylation, an important element in methotrexate cytotoxicity and selectivity in tumor versus murine granulocytic progenitor cells in vitro. Cancer Res  1984; 44(8): 3190-5.
 [PMID:  6204743]

[70]
Bookstaver PB, Norris L, Rudisill C, DeWitt T, Aziz S, Fant J. Multiple toxic effects of low-dose methotrexate in a patient treated for psoriasis. Am J Health Syst Pharm  2008; 65(22): 2117-21.
 [http://dx.doi.org/10.2146/ajhp070676] [PMID:  18997139]

[71]
Pathirana D, Ormerod AD, Saiag P, et al. European S3-guidelines on the systemic treatment of psoriasis vulgaris. J Eur Acad Dermatol Venereol  2009; 23(S2): 1-70.
 [http://dx.doi.org/10.1111/j.1468-3083.2009.03389.x] [PMID:  19712190]

[72]
Ouellette S, Shah R, Razi S, Ashforth G, Wassef C. Fatal low‐dose methotrexate toxicity: A case report and literature review. Dermatol Ther  2022; 35(12): e15945.
 [http://dx.doi.org/10.1111/dth.15945] [PMID:  36259229]

[73]
Mitsuboshi S. Risk of haematological events and preventive effect of folic acid in methotrexate users with chronic kidney disease and rheumatoid arthritis: Analysis of the Japanese Adverse Drug Event Report database. Br J Clin Pharmacol  2021; 87(5): 2286-9.
 [http://dx.doi.org/10.1111/bcp.14641] [PMID:  33179261]

[74]
Mhaskar R, Clark OAC, Lyman G, Engel Ayer Botrel T, Morganti Paladini L, Djulbegovic B. Colony-stimulating factors for chemotherapy-induced febrile neutropenia. Cochrane Libr  2014; 2022(1): CD003039.
 [http://dx.doi.org/10.1002/14651858.CD003039.pub2] [PMID:  25356786]

[75]
Smith TJ, Bohlke K, Lyman GH, et al. Recommendations for the use of WBC growth factors: American society of clinical oncology clinical practice guideline update. J Clin Oncol  2015; 33(28): 3199-212.
 [http://dx.doi.org/10.1200/JCO.2015.62.3488] [PMID:  26169616]

[76]
Al-Samkari H, Geredeli C, Arslan C, et al. Two randomized controlled trials of romiplostim for chemotherapy-induced thrombocytopenia in patients with solid tumors. Blood  2022; 140(S1): 11250-2.
 [http://dx.doi.org/10.1182/blood-2022-155931]

[77]
Kondo H, Date Y. Benefit of simultaneous rhG-CSF and methylprednisolone ‘pulse’ therapy for methotrexate-induced bone marrow failure in rheumatoid arthritis. Int J Hematol  1997; 65(2): 159-63.
 [http://dx.doi.org/10.1016/S0925-5710(96)00549-X] [PMID:  9071820]

[78]
Warren RB, Weatherhead SC, Smith CH, et al. British Association of Dermatologists’ guidelines for the safe and effective prescribing of methotrexate for skin disease 2016. Br J Dermatol  2016; 175(1): 23-44.
 [http://dx.doi.org/10.1111/bjd.14816] [PMID:  27484275]

[79]
Knoll K, Anzengruber F, Cozzio A, French LE, Murer C, Navarini AA. Mucocutaneous ulcerations and pancytopenia due to methotrexate overdose. Case Rep Dermatol  2016; 8(3): 287-93.
 [http://dx.doi.org/10.1159/000446692] [PMID:  27920680]

[80]
Troeltzsch M, von Blohn G, Kriegelstein S, et al. Oral mucositis in patients receiving low-dose methotrexate therapy for rheumatoid arthritis: Report of 2 cases and literature review. Oral Surg Oral Med Oral Pathol Oral Radiol  2013; 115(5): e28-33.
 [http://dx.doi.org/10.1016/j.oooo.2012.12.008] [PMID:  23601229]

[81]
Yélamos O, Català A, Vilarrasa E, Roé E, Puig L. Acute severe methotrexate toxicity in patients with psoriasis: A case series and discussion. Dermatology  2014; 229(4): 306-9.
 [http://dx.doi.org/10.1159/000366501] [PMID:  25401478]

[82]
Uce Ozkol H, Toptas T, Calka O, Akdeniz N. The efficiency of granulocyte colony-stimulating factor in hemorrhagic mucositis and febrile neutropenia resulted from methotrexate toxicity. Cutan Ocul Toxicol  2015; 34(2): 173-5.
 [http://dx.doi.org/10.3109/15569527.2014.918139] [PMID:  24964172]

[83]
Çaliskan E, Tunca M, Açikgöz G, Arca E, Akar A. Accidental high-dose methotrexate toxicity due to an electronic prescribing error. Indian J Dermatol Venereol Leprol  2014; 80(3): 268-9.
 [http://dx.doi.org/10.4103/0378-6323.132264] [PMID:  24823414]
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DOI https://dx.doi.org/10.2174/1574886318666230516115737	Print ISSN 1574-8863
Publisher Name Bentham Science Publisher	Online ISSN 2212-3911
Current Drug Safety

Methotrexate-induced Severe Pancytopenia in a Patient with Rheumatoid Arthritis: A Case Report and Review of Literature

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