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Volume 64, Issue 11 (10-2006)
Background: Rheumatoid arthritis (RA) is a chronic inflammatory condition. The condition can affected many tissues throught out the body, but the joints are usually most severely affected. The high incidence of RA, the conventional treatments and the experimental observation have shown by combination therapy, the disease symptoms of the patients reduce. To compare the efficacy and tolerability of single-agent Hydroxychloroquin (HCQ) with combination therapies composed of (HCQ) and Methotrexate (MTX) and (HCQ), (MTX) and Sulfasalazin (SSZ) in active rheumatoid arthritis patients with additive arthritis.
Methods: One hundred and twenty RA patients with active arthritis (male/female: 30/90) who were treated in rheumatology clinic between 2003 and 2005 were enrolled in this trial. Patients treated with (HCQ) alone(200 mg/day)were include in group (I), patients treated with combination of (HCQ) (200 mg/day)and (MTX) (7.5mg/week)in group (II),and patents treated with combination of (HCQ) (200mg/day),(MTX) (7.5mg/week)and (SSZ)(1 gr/day)in group (III), Forty patients (male/female:10/30) in group (I),(II) and (III)were eligible for statistical analysis at the end of study. Changes in variable were compared by the T-test.
Results: The combination of (MTX), (HCQ)and (SSZ) and the combination of (MTX) and (HCQ) were more effective regarding the clinical and laboratory parameters than (HCQ) alone (P<0.05). Moreover the combination of (MTX), (HCQ) and (SSZ) was more effective than the combination of (MTX) and (HCQ) (P<0.05). Combination therapies seem to be more effective and no more toxic than monotherapy in RA patients with additive arthritis.
Conclusion: Combination therapy with methotrexate, hydroxychloroquin and sulfasalazin is more effective than hydroxychloroquin alone or a combination of methotrexate and hydroxychloroquin in RA. We suggest starting combination therapy for the patients with early RA, when the diagnosis has been established.
Volume 65, Issue 8 (11-2007)
Background: The use of serial quantitative beta-human chorionic gonadotropin (β-HCG) with transvaginal ultrasound to enhance early diagnosis of ectopic pregnancy (EP) improves options for conservative treatment with methotrexate (MTX). The aim of this study was to evaluate the outcome of unruptured EP treated with a single dose of intramuscular MTX injection.
Methods: This clinical trial included 41 EP patients with specific inclusion criteria for medical treatment. For each patient, MTX (50 mg/ml) was administered intramuscularly and a repeat dose was given if the weekly decrease in the level of β-HCG was less than 15%. The therapy was considered successful if the level of β-HCG fell below 10 mIU/cc without surgical intervention.
Results: Overall, 78% of the patients were successfully treated, among whom 18.7% received second doses of MTX. Of the patients who were successfully treated, 60% presented with vaginal bleeding without pelvic pain however, of those patients in whom the treatment failed, 88% presented with pelvic pain together with vaginal bleeding. Furthermore, the presence of free peritoneal fluid on vaginal ultrasound was a significant predictor of treatment failure (p<0.005). There was no relation between the women's age, gravidity or parity, the size of the conceptus, gestational age, pretreatment serum β-HCG titer, endometrial thickness on vaginal ultrasound and the efficacy of treatment.
Conclusions: With a reasonably high success rate, we found systemic single-dose MTX treatment to be a safe, conservative therapy for EP. However, when free peritoneal fluid is noted upon transvaginal ultrasound or when the patient presents with pain, the threshold for surgical intervention may be lower.
Volume 72, Issue 4 (7-2014)
Background: The use of Methotrexate (MTX) is a good and common practice for the treatment of women who were diagnosed early with ectopic pregnancy (EP). The aim of this study is to determine the predictors of treatment failure with a single dose of MTX injection. Methods: In this quasi-experimental research, we studied 70 women with ectopic preg-nancies who were treated with MTX, according to a single dose protocol from 2010 to 2013. EP was diagnosed whenever an intrauterine gestational sac was not identified by transvaginal ultrasonography (TVUS), accompanied by an abnormal rise or plateau in human chorionic gonadotropin (beta-hCG) concentration. Briefly, women with ectopic pregnancies were considered candidates for MTX treatment if they were hemodynami-cally stable did not desire surgical therapy, agreed to weekly follow-up and did not have hepatic, hematologic, or renal disease. A Patient was considered a treatment suc-cess (group 1) if her beta-hCG levels decreased ≤10 m IU/ml after the first dose of MTX. Treatment failure (group 2) was defined as the need for a second or a third dose of MTX or surgery. The following risk factors were compared between the two groups: serum beta-hCG on the days 1 and 4, a ≥ 15% decrease in serum beta-hCG between the days 1-4 of the treatment, age, parity, gravidity, the size of the ectopic mass and the endometrial thickness. Results: The success rate of MTX treatment was 77.1%. There were no significant dif-ferences between the two groups in regard to the age, parity, gravidity, the size of ec-topic mass and the endometrial thickness in vaginal sonography, but the mean serum beta-hCG concentration on days 1 and 4 was lower in the success group than the failure group. We also observed a ≥ 15% decrease in serum beta-hCG in 80.9% of the women from the success group and in 38.5% of the cases whose treatment had failed. The presence of fetal heart activity was seen in only one patient and this patient’s treatment failed. Two patients had previous history of ectopic pregnancy and the treatment of both ended in failure. Conclusion: Among women with ectopic pregnancies who were candidates for MTX treatment, a high serum beta-hCG concentration on the days 1-4 and also a ≤ 15% fall in serum beta-hCG between the days 1-4 treatment, are the most important factors associated with the failure of the treatment with a single dose MTX protocol. It is better to use these factors for making decisions about the initiation of the treatment or the continuation of it.
Volume 72, Issue 10 (1-2015)
Background: Cervix is a rare and dangerous site for ectopic pregnancy. When the placenta is implanted lower than internal cervical os, it is called “cervical pregnancy”. Known risk factors for cervical pregnancy are previous cesarean section, cigarette smoking, premature transfer of fertilized ovum before having suitable endometrium and pelvic inflammatory disease. In the past, hysterectomy was the usual treatment. Nowadays, with the newer diagnostic and therapeutic managements, cases of cervical pregnancy treated by fertility sparing methods have been reported. Conservative treatments include using methotrexate and KCl, hyperosmolar glucose, and prostaglandins. Also, surgical methods with fertility sparing have been reported. The purpose of this study is introducing two cases of cervical pregnancies treated by fertility sparing. Case presentation: The first patient had six weeks pregnancy with live fetus and detectable fetal heart beat. There was six weeks menstrual retard and βhCG titer was 10.000 UI/ml. Two doses of methotrexate were prescribed and pregnancy terminated successfully. The other patient had eight weeks pregnancy with fetal heart beat. There was eight weeks retardation and βhCG titer was 70379 UI/ml with no gestational sac in sonography in both patients. After prescribing two doses of methotrexate and doing curettage three days after the last dose of methotrexate, pregnancy terminated. The known risk factors for our patients were history of endometrial curettage in one and history of cesarean section in both of them. Conclusion: Conservative method may be considered for the treatment of cervical pregnancy in patients who desire to preserve their fertility. The treatment is associated with high success rates. Methotrexate (MTX) is the most common medicine for resolving ectopic cervical pregnancy, other medications such as KCl, hyperosmolar glucose, RU486 and prostaglandins have also been used with different success rate. Methotrexate may be administered systemic (intramuscular or intravenous) or local (intra-amniotic transfusion or intrauterine).
Volume 73, Issue 7 (10-2015)
Background: Standard treatment of Gestational Trophoblastic Disease (GTD) is chemotherapy. Single-agent chemotherapy regime including Methotrexate (MTX) or Actinomycin. Single-agent is widely used in treatment of persistent trophoblastic disease. We reported an uncommon toxicity of low-dose single-agent methotrexate in a patient. Case Presentation: A 20-year-old woman, primary gravid after two months missed period and spotting with diagnosis of incomplete abortion with uterine size equivalent of ten weeks pregnancy (8-10 cm) underwent evacuation curettage. In serial follow-up, based on rise of beta-hCG titer and absence of metastatic disease, it was categorized as low-risk persistent trophoblastic disease. She was referred to gynecology oncology center of Ghaem Hospital, Mashhad University of Medical Sciences in May 2014. Because of rise of beta-hCG titer, after complete metastatic work-up and lack of disease in other sites, persistent disease was diagnosed and candidate for chemotherapy (single agent low-dose). The patient received first course of therapy with MTX (50 mg/m², intra muscular). Unfortunately, after two days of treatment she developed uncommon severe toxicity, fever, severe nausea and vomiting, tachycardia, and generalized weakness. Also, we found hematologic abnormality (WBC: -14000-15000 µI, platelet- 540 µI and sever neutropenia), and abnormal rising in liver function test (SGOT, SGPT) (three to four times) and renal function test (BUN and Creatinine) (two times). In addition, she had disseminated erosive lesion in all of body especially in face. Due to the fatal side effects of chemotherapy, she was admitted to intensive care unit (ICU). Fortunately, after two to three weeks, she was improved by conservative management. After few weeks beta-hCG titer was in normal limit. However she had normal serial beta-hCG in one year of follow-up. Conclusion: It is important to emphasis unpredictable side effects of chemotherapy with low-dose methotrexate.
Volume 75, Issue 9 (12-2017)
Methods: This cross-sectional descriptive study carried out in Emam Sajjad Hospital, Ramsar, Iran from June 2016 to July 2017. Doses more than 500 mg/m2 of MTX was considered as a high-dose. Hydration status, evaluation of the renal and hepatic function, blood tests, urine pH, doses and frequencies of leucovorin administration, measurement of serum levels of MTX and side effects were evaluated. Recommendations of UpToDate 2017 were considered as standards of administration of HDMTX.
Results: Forty-four courses of HDMTX were evaluated in this study. HDMTX were prescribed for lymphoma (30 cases), ALL (8 cases) and osteosarcoma (6 cases). In all patients, hydration was done with 1340.9±894 normal saline plus 25 ml sodium bicarbonate 8.4%, one to two hours before HDMTX. The solution used for dilution of MTX was 5% dextrose (1022.7±105.5 ml). Urine pH was not measured in any patient. The frequency of leucovorin administration was 5.64±3.03 times with doses of 17.6±1.7 mg/m2 every 6 hours. Serum levels of MTX were not measured in any patient. Blood urea nitrogen and creatinine measurement was carried out before administration of HDMTX in all patients. The most common adverse effects were nausea (64.4%), anxiety (44%) and headache (43.2%).
Conclusion: The appropriate aspects of HDMTX usage were good hydration, urine alkalinization with bicarbonate and administration of leucovorin in patients receiving HDMTX, whereas monitoring of serum levels of MTX and administration of bicarbonate based on urinary pH were not done in any of the patients.
Volume 77, Issue 5 (8-2019)
Case Presentation: The patient was a 77 years old woman, Aryan race, who was known a case of severe and progressive rheumatoid arthritis. She previously was treated by multiple drugs such as salicylates, gold, corticosteroids, because of unresponsiveness to these drugs, physician prescribed methotrexate once a day, but patient misunderstands and use three times per day for days. Patient with this history referred to a poisoning emergency. In a physical exam, she had oral and throat erythema and swelling of mucosa. In the funduscopy of eyes, bottom of the eyes was normal and conjunctival eyes were prurient she had multiple petechiae at the upper part of chest and base of neck and shoulders and arms with no swelling around petechiae. The lesion had no itching. She had no other sign besides laboratory analysis showed a high level of creatinine, leukopenia, decreased the level of platelets, patient with high suspicious of methotrexate poisoning underwent to granulocyte-macrophage colony-stimulating factor (GM-CSF) and folic acid treatment. After treatment all of her signs recovered and laboratory tests became normal.
Conclusion: At the time of taking methotrexate by the patient, even with appointment of a specialist physician, with any skin signs such as maculopapular rash without itching, we should consider poisoning with methotrexate, and think appropriately about it. This suggests that methotrexate can cause side effects even at low doses.
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