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References 1. Troeltzsch M, von Blohn G, Kriegelstein S, Woodlock T, Gassling V, Berndt R, Troeltzsch M . 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:e28-e33. 2. Lee JH, Hong KS, Seo KJ, Lee D, Sung SH . A Case of Cutaneous Side Effect of Methotrexate Mimicking Behçet’s Disease. Ann Dermatol , 2011; 23(3):412-414. 3. Kalantzis A, Marshman Z, Falconer TD, Morgan RP, Odell WE . Oral effects of low-dose methotrexate

References 1. Kamps WA, van der Pal-de Bruin KM, Veerman AJ, Fiocco M, Bierings M, Pieters R. Long-term results of Dutch Childhood Oncology Group studies for children with acute lymphoblastic leukemia from 1984 to 2004. Leukemia. 2010;24(2):309-19 DOI: 10.1038/ leu.2009.258 2. Kampen KR. The discovery and early understanding of leukemia. Leuk Res. 2012;36(1):6-13. DOI: 10.1016/j. leukres.2011.09.028 3. Mantadakis E, Cole PD, Kamen BA. High-dose methotrexate in acute lymphoblastic leukemia: where is the evidence for its continued use? Pharmacotherapy. 2005

References 1. Aschhoff B.: Retrospective study of Ukrain treatment in 203 patients with advanced-stage tumors. Drugs Exp Clin Res 2000, 26 , 249-252. 2. Bangert C.A., Costner M.I.: Methotrexate in dermatology. Dermatol Ther 2007, 20 , 216-228. 3. Blower P., de Wit R., Goodin S., Aapro M.: Drug - drug interactions on oncology: Why are they important and can they be minimized? Crit Rev Oncol Hematol 2005, 55 , 117-142. 4. Chatham W.W., Morgan S.L., Alarcón G.S.: Renal failure: a risk factor for methotrexate toxicity. Arthritis Rheum 2000, 43 , 1185-1186. 5

. Toxicology and Industrial Health 25: 329-335. Bauerova K, Paulovičova E, Mihalova D, Drafi F, Ktrosova M, Mascia C, Biasi F, Rovensky J, Kucharska J, Gvozdjakova A, Ponint S. (2010). Combined methotrexate and coenzyme Q10 therapy in adjuvant-induced arthritis evaluated using parameters of infl ammation and oxidative stress. Acta Biochim Pol 57: 347-354. Bauerova K, Ponist S, Nosal R, Stancikova M, Rovensky J. (2011). Modern pharmacological approaches to therapies: substances tested in animal models of rheumatoid arthritis, in Rheumatoid arthritis - Treatment 1 th


Introduction: Liver represents the main place of drug metabolisation. Drugs and toxic substances reach the level of liver after absorption at gastro-intestinal level. Drug hepatotoxicity represents an important chapter of iatrogenic pathology, because the hepatic lesions induced by drugs include extremely diverse clinical, biological and histological expressions that can take the aspect of any form of acute or chronic hepatobiliary disease. Hepatic lesions induced by drugs (LHIM) represent a histological and/or biochemical alteration caused and attributed to the consumption of a drug. Hepatic elastography (Fibroscan) represents a noninvasive method of quantification of hepatic fibrosis.

Material and method: We carried out a retrospective study and longitudinally prospective study that included a set of patients under treatment with Methotrexate, amounting to 76, divided into 2 subsets: a subset consisting of patients with hepatitis to Methotrexate, subset 1, of 23 patients, a subset of patients under treatment with Methotrexate but with normal hepatic samples, subset b, of 53 patients.

Results: We carried out fibroscan at all the patients treated with Methotrexate, obtaining a medium score of fibrosis of 6.23 for the subset a with hepatitis at Methotrexate and of 5.33 for the subset b with normal hepatic samples. We made a correlation between the cumulated dose of Methotrexate and the change of hepatic samples.

Conclusions: There is a significant correlation between hepatic fibrosis induced by Methotrexate and the cumulated dose of Methotrexate. The possibility of utilization of fibroscan which is a completely painless method, reproducible, for the monitoring of the treatment with Methotrexate both at patients with changed values of the hepatic tests as weir as those with normal values must be considered.

References Walker RW, Allen JC, Rosen G, Caparros B. Transient cerebral dysfunction secondary to high-dose methotrexate. J Clin Oncol 1986; 4: 1845-50. García-Tena J, López-Andreu JA, Ferrís J, Menor F, Mulas F, Millet E, et al. Intrathecal chemotherapy-related myeloencephalopathy in a young child with acute lymphoblastic leukemia. Pediatr Hematol Oncol 1995; 12: 377-85. Oka M, Terae S, Kobayashi R, Sawamura Y, Kudoh K, Tha KK, et al. MRI in methotrexate-related leukoencephalopathy: Disseminated necrotising leukoencephalopathy in comparison with mild

reduced folate carrier ( RFC ), located in a 40719 bp region at chromosome 21q22.3, is coding for solute folate carrier ( RFC1 ), a major transporter of folates and antifolates into the cell. The antifolate methotrexate (MTX) is a cytotoxic drug which is used in current treatment regimens for childhood acute lymphoblastic leukaemia (ALL) 2 , and non-Hodgkin malignant lymphoma (NHML). 3 , 4 The most frequently studied SLC19A1 polymorphism is rs1051266 in the second exon of the SLC19A1 , which results in amino acid substitution of arginine for histidine (H27R) 5 in


Methotrexate (MTX) is a cytostatic agent used in oncology. Because of its immunosuppressive properties, MTX is also used in autoimmune disorders. Low-dose MTX regimens in the treatment of rheumatoid arthritis and severe psoriasis are considered to be safe. However, pharmacovigilance centers warn of serious and even fatal incidents due to errors in oral MTX administration. The aim of this case series presentation was to identify the specific factors related to the development of adverse drug reactions (ADRs) induced by MTX. A prospective pharmacovigilance study was conducted at the Clinic of Dermatology, University Hospital, Stara Zagora. We report 3 cases of patients with psoriasis vulgaris in which severe haematological abnormalities associated with previous administration of MTX were detected during hospitalization. A 73-year old female with malaise, vomiting and oral ulcers who had taken approximately 120 mg MTX was found to have pancytopenia. A 59-year old male hospitalized for psoriatic erythroderma who had erroneously taken 10 mg MTX daily instead of weekly for 8 days, was diagnosed with bicytopenia and toxic hepatitis. An 88-year old male with psoriatic arthritis presented with aphthous stomatitis, erosive crusted lesions, ecchymoses and aplastic anemia 2 weeks after treatment with 12.5 mg MTX once weekly plus i.m. Movalis®, followed by Diclophenac Duo®. The main predisposing factors for the development of these ADRs were patient-related dosage errors and concomitant administration of NSAIDs. Safe use of oral MTX requires clear dosing instructions and strict patient compliance. Potential drug interactions of MTX with other drugs should also be considered.

-286; DOI: 10.1016/0378-5173(90)90119-O. D. Giron, C. Goldbronn, M. Mutz, S. Pfeffer, P. Piechon and P. Schwab, Solid state characterizations of pharmaceutical hydrates, J. Therm. Anal. 68 (2002) 453-465. B. K. Saha, A. Nangia and M. Jaskolski, Crystal engineering with hydrogen bonds and halogen bonds, Cryst. Eng. Comm. 7 (2005) 355-358; DOI: 10.1039/b501693b. Martindale, The Complete Drug Reference , 34 th ed., Pharmaceutical Press, London 2005, p. 553. H. K. Chan and I. Gonda, Methotrexate: Existence of different types of solid, Int. J. Pharm. 68 (1991) 179

References 1. Bangert CA, Costner MI. Methotrexate in dermatology. Dermatol Ther 2007;20(4): 216-28. 2. Milojević M. Citotoksična sredstva. U: Karadaglić Đ.Dermatologija. Beograd: Vojnoizdavački zavod; 2000. str. 2251-6. 3. Barker J, Horn EJ, Lebwohl M, Warren RB,Nast A, Rosenberg W, et al. Assessment and management of methotrexate hepatotoxicity in psoriasis patients: report from a consensus conference to evaluate current practice and identify key questions toward optimizing methotrexate use in the clinic. J Eur Acad Dermatol Venereol 2011;25(7):758-64. 4