Patients Receiving Methotrexate Therapy Research Articles

Revisiting the safety profile: Understanding the link between Methotrexate and skin cancer in psoriasis patients

Madam, Methotrexate (MTX) is an antimetabolite (formerly known as amethopterin) proven t effective in managing autoimmune diseases by suppressing the hyperactive immune response, reducing inflammation, and alleviating associated symptoms. In the case of psoriasis, a chronic autoimmune skin disorder characterized by red, scaly patches on the skin, MTX is among the available treatment options. It is proven beneficial for moderate to severe psoriasis that does not respond adequately to other treatments by reducing the severity and extent of the skin lesions, relieving itching, and improving the overall quality of life. A recent study by Ravi Bharadwaj et al. found that MTX exerts its therapeutic effect on psoriatic skin inflammation by inhibiting the activity of the muropeptide transporter SLC46A21. This mechanism interferes with two key inflammatory responses, namely the NOD1 and NOD2 pathways. It is administered orally, intramuscularly, intravenously, or subcutaneously. Doctors opt for a once-weekly oral dosage, which initiates at a low level to minimize adverse effects. Subsequently, the dosage is incrementally raised to attain the desired efficacy2. Although MTX can be an effective treatment choice, its usage has raised concerns regarding the potential elevation of skin cancer risk. In recently published studies, researchers have concluded that the use of this drug in psoriatic patients might be doing more harm than good. In a meta-analysis performed by Margaret et al., It was found that psoriasis patients receiving MTX therapy have a 2.8-fold greater likelihood of developing non-melanoma skin cancer (NMSC) in comparison to those who do not undergo MTX treatment3. Moreover, there is evidence that prolonged use of MTX may be associated with an increased probability of developing basal cell carcinoma (BCC) and cutaneous squamous cell carcinoma (cSCC), following a dose-dependent trend4. Individuals with psoriasis who may require long-term systemic treatment could face a significantly elevated risk of developing skin cancer. Despite multiple studies confirming the link between MTX and different skin malignancies, its usage remains alarmingly high in treating psoriasis. In resource-limited settings such as Pakistan, this drug is a cost-effective and efficient therapeutic option for managing various forms of psoriasis, including extensive plaque-type psoriasis, acute pustular psoriasis, and erythrodermic psoriasis5. Nevertheless, healthcare workers in Pakistan must prioritize establishing an accurate drug administration plan, to reduce morbidity and mortality rates, as well as the heightened risk of non-melanoma skin cancer (NMSC) among psoriasis patients receiving this treatment.

The expression of interferon-stimulated genes (interferon “signature”) in patients with rheumatoid arthritis (Preliminary results)

Objective. To assess the expression of interferon-stimulated genes in patients with rheumatoid arthritis (RA). Material and methods . Twenty patients with RA were examined. All patients received methotrexate therapy at a stable dose (Me 15 [10-17.5] mg) for at least 4 weeks. To assess the Type I IFN gene signature (IFNGS) we selected five genes (IFI44L, MX1, IFIT1, RSAD2, EPSTI1). The expression of IFI44L and IFIT1 could not be determined, and further analysis took into account three genes - MX1, EPSTI1, RSAD2. Results . Baseline level of MX1 expression - 11.48 [5.45-19.38], EPSTI1 - 12.83 [5.62-19.64], RSAD2 - 5.16 [2.7310.4] and IFN score - 10.3 [5.18-17.12] in patients with rheumatoid arthritis was significantly higher compared with healthy donors - 1.26 [0.73-1.6], 1.06 [0.81-1.48], 0.93 [0.72-1.19], and 1.09 [0.92-1.42] respectively, p<0.05. IFN signature was found in 15 (75%) patients, was absent - in 5 (15%) patients. A positive correlation was found between the IFNGS and the level of EPSTI1 expression with the duration of methotrexate therapy (r=0.46, p=0.03). Among patients who received methotrexate therapy for more than one year, there was a tendency to a higher level of EPSTI1 expression (10.74 [12.6-32.8]) and IFNGS (16.2 [8.9-38.3]) compared with patients taking methotrexate for less than a year (9.67 [5.4-14.2] and 7.9 [4.5-13.4]), (p=0.06). Conclusion . Preliminary results on the assessment of IFNGS indicate an increased expression of IFN-stimulated genes in patients with RA, which may be important for predicting the course of the disease and personalizing therapy.

Side Effects of Methotrexate for Psoriasis Therapy

Background: Psoriasis is a chronic and relapsing inflammatory disease of the skin, characterized by the presence of well-defined erythematous plaque covered by silvery-white scales. Methotrexate is a folic acid antimetabolic for psoriasis therapy and given systemically so unexpected effects can occur. Purpose: To evaluate the side effects of methotrexate as therapy in psoriasis. Methods: The descriptive research based on the medical record of psoriasis patients who were treated for hospitalization on at Kemuning I and II ward Dr. Soetomo General Academic Hospital Surabaya during the period January 2017 – December 2018. The sampling method used was total sampling. Result: Twenty two psoriasis patients receiving methotrexate therapy with the dose of methotrexate is 10-15 mg once weekly, there were 4.5% low erythrocyte level, 27.3% high leukocyte level, 13.6% high thrombocyte level, 18.2% high SGOT level, 22.8% high SGPT level, 18% nausea, 9.1% vomiting, 4.6% headache, and 4.6% shortness of breath. Conclusion: Methotrexate for psoriasis therapy may cause several side effects even not the severe ones, therefore careful dosing and side effect monitoring are necessary.

An Exploration of the Pulmonary Complication of the Treatment in Psoriatic Patients Receiving Topical, PUVA and Methotrexate Therapy

Background: In Bangladesh the prevalence rate of psoriasis is 1.49%. Although this rate of prevalence rate is not so high but in patient’s traditional treatment procedure, physicians have to aware about the exploration of the pulmonary complication of the treatment in psoriatic patients receiving topical, PUVA and Methotrexate Therapy. Aim of the study: The aim of this study was to compare the lung function test results among the psoriatic patients receiving topical, PUVA and Methotrexate therapy in order to explore the pulmonary complication of the treatment. Methods: This cross-sectional study was carried out in the Department of Physiology of Bangabandhu Sheikh Mujib Medical University (BSMMU), Shahbag, Dhaka, from July 2012 to June 2013. A total number of 120 subjects were selected, among which 30 were apparently healthy subjects (control group-A) for comparison and 90 were diagnosed male Psoriatic patients (study Group-B). Controls were selected from the community and the patients from the Indoor and Out Patient Department (OPD) of Dermatology and Venereology, BSMMU, Dhaka. Based on treatment, these study subjects were further divided into three groups consists of 30 male subjects in each group. These were group B1 (30 diagnosed male Psoriatic patient receiving only topical therapy), B2 (30 male Psoriatic patients receiving PUVA therapy, B3 (30 male Psoriatic patients receiving Methotrexate therapy). Results: In this study, all the control subjects (A) were with normal lung function tests (LFT). On the contrary, 19, 20 and 29 psoriatic patients were with abnormal lung function tests in the experimental groups B1, B2 and B3 respectively. The results were shown in Table IV. Decreased FVC was detected in patients of Psoriasis belonged to total 48(53.33%) out of 90 patients. Among them 10(33.33%) were in group B1, 13 (43.33%) in group B2 and 25 (83.33%) in group B3. Decreased FEV1 was detected in patients of Psoriasis belonged to total 43(47.78%) out of 90 patien

Association between malignancy and methotrexate and biological disease-modifying antirheumatic drugs in patients with rheumatoid arthritis .

This study was aimed at investigating the risk of malignancies in rheumatoid arthritis patients treated with methotrexate (MTX), and whether the addition of biological disease-modifying antirheumatic drugs (bDMARDs) further increases the risk of malignancies in patients receiving MTX therapy, by using data from a spontaneous adverse reaction database. Patient data from the U.S. Food and Drug Administration's Adverse Event Reporting System (FAERS) from the first quarter of 2004 to the end of 2015 were analyzed. A data subset analysis was performed to investigate whether the use of bDMARDs further increased the risk of malignancies in patients receiving MTX therapy. MTX showed significant associations with all malignancies except liver cancer. bDMARDs showed significant associations with stomach cancer, colorectal cancer, prostate cancer, ovarian cancer, malignant melanoma, and lung cancer. In addition, bDMARD use increased the risk of breast, ovarian, and lung cancers in rheumatoid arthritis patients receiving MTX therapy. MTX use was significantly associated with various malignancies. Moreover, concomitant use of bDMARDs further increased the risk of breast, ovarian, and lung cancers in MTX-treated patients with rheumatoid arthritis.

Should nitrous oxide ever be used in oncology patients receiving methotrexate therapy?

Nitrous oxide (N2 O) is frequently used for short anesthesia/analgesia in children undergoing painful or repetitive procedures. Children with acute lymphoblastic leukemia (ALL) require repeated lumbar punctures with direct instillation of intrathecal chemotherapy, usually the anti-folate agent methotrexate, during their treatment. These procedures are frequently performed under anesthesia. Concerns have been intermittently raised about a drug interaction between methotrexate and N2 O that may potentiate the undesirable side effects of methotrexate, including neurotoxicity. However, the clinical evidence consists mainly of isolated case reports leading to a lack of consensus among pediatric anesthetists about the relative risk benefits of using N2 O in children with ALL. In this article, we review the biochemical basis and scientific observations that suggest a significant interaction between N2 O and methotrexate due to their dual inhibition of the key enzyme methionine synthase. The possible role of this interaction in potentiating neurotoxicity in children with cancer is discussed, and arguments and counterarguments about the clinical significance of this largely theoretical relationship are explored. Following comprehensive review of all the available data, we make the case for the circumstantial evidence being sufficiently compelling to prompt a review of practice by pediatric anesthetists and call for a precautionary approach by avoiding the use of N2 O in children receiving concurrent methotrexate.

Effectiveness and tolerability of methotrexate in pulmonary sarcoidosis: A single center real-world study.

Pulmonary sarcoidosis patients who get disease progression despite corticosteroid treatment or can't tolerate corticosteroid required second-line drug. Methotrexate (MTX) is the most widely used in our clinical practice. Data on its safety and efficacy at different doses are still limited, especially for those without folic acid supplements. To report effectiveness of different MTX dosages and tolerability of MTX in pulmonary sarcoidosis without folic acid supplements. A retrospective study on pulmonary sarcoidosis patients receiving MTX therapy with various dose ≥3 months was conducted. The primary outcome was change in high-resolution computed tomography (HRCT) before and after MTX therapy. Other efficacy parameters included SGRQ score, prednisone dose change, discontinuation and relapse-free survival. Response-linked factors and safety outcomes were also analyzed. Overall, 49 patients (81.7%) were assessed as MTX responders by HRCT and there was no significant difference in clinical response rate among three groups with different doses. The health-related quality of life (HRQL) of the responders improved obviously, which was evidenced by SGRQ score declining from 16.7(IQR: 7.9-26.4) to 10.7(IQR: 4.8-19.3) (P=0.029). The corticosteroids sparing effect was confirmed in "responders" group (P<0.001). When MTX was discontinued in 11 responders with complete improvement, 2 patients experienced relapses within 15.5 (range: 1-30) months (mean follow-up time of these 11 responders: 13.5±13.0 months). No clinical characteristics were found related to MTX effectiveness. Adverse events occurred in 31.7% of the patients, with gastrointestinal-related being the commonest. Drug discontinuation owing to adverse events occupied 6.7% of the subjects. Nearly 80% of the sarcoidosis subjects had well response to MTX. Its effectiveness was irrelevant to the treatment dosages and baseline characteristics. A quite low relapse rate was witnessed in those complete responders discontinuing MTX therapies. The steroid-sparing effect, well drug tolerability and low drug withdrawal rate were observed in these patients even without folic acid supplements in clinical practice.

Risk of malignant lymphoma in patients with rheumatoid arthritis treated with biological disease-modifying antirheumatic drugs and methotrexate .

This study investigated whether using biological disease-modifying antirheumatic drugs (bDMARDs) further increases the risk of malignant lymphoma in patients with rheumatoid arthritis undergoing methotrexate therapy using spontaneous adverse reaction databases in different countries. Patient data were acquired from the US Food and Drug Administration's Adverse Event Reporting System (FAERS), the Japanese Adverse Drug Event Report (JADER), and the Canada Vigilance Adverse Reaction Online Database (CVARD) from the first quarter of 2004 to the end of 2015. Data subset analysis was performed to investigate whether the use of bDMARDs further increased the risk of malignant lymphoma in patients receiving methotrexate therapy. The FAERS subset data indicated a significant association between Hodgkin lymphoma and methotrexate with infliximab (reporting odds ratio (ROR): 8.28. 95% CI: 5.70-12.02; information component (IC): 2.04, 95% CI: 1.59-2.49). In addition, signal scores suggested that methotrexate with infliximab (ROR: 3.26. 95% CI: 2.68-3.98; IC: 1.31, 95% CI: 1.04-1.58) was significantly associated with non-Hodgkin lymphoma (NHL). The CVARD subset data also indicated a significant association between NHL and methotrexate with infliximab (ROR: 22.82. 95% CI: 5.02-103.78; IC: 1.77, 95% CI: 0.13-3.41). However, the JADER subset data revealed no significant associations. The present study shows that using infliximab further increases the risk of malignant lymphoma in patients receiving methotrexate therapy. .

Study of Keratinocyte Proliferation, Apoptosis and Dermal Inflammation in Psoriatic Skin Lesions Before and After Methotrexate Therapy: Which Change Is Contributing More to Clinical Severity of the Disease?

Objective: The pathogenesis of psoriasis involves T-cell mediated immunologic response, keratinocytes hyperproliferation, and resistance to apoptosis. Methotrexate is one of the most reliable modalities in the treatment of psoriasis that target those changes. The study of those variables before and after methotrexate therapy may answer the question: Which of those variables contributes more to the clinical severity of the disease and is more valuable to be targeted in psoriasis treatment. Patients and Methods: A total of 50 cases of psoriasis vulgaris were included, 25 patients received methotrexate therapy. Skin biopsies of psoriatic skin lesions before and after treatment were examined histologically for measurement of epidermal thickness and grading of dermal inflammation. Immunostaining for Ki-67 and p53 was done for assessment of keratinocyte proliferation and apoptosis. Results were correlated with clinical severity of the disease, assessed by psoriatic area and severity index (PASI) score. 15 biopsies of normal skin were included as control. Results: Dermal inflammation, Ki-67%, and p53% were significantly higher in psoriatic skin lesion than in normal skin. Those changes were significantly correlated with PASI score. Multiple logistic regression models revealed that Ki-67 was the most significant variable contributing to clinical severity. One unit change in ki-67% can explain 1.2 unit changes in PASI score with 97% sensitivity, 40% specificity and 25% cut-off value. PASI score, dermal inflammation, Ki-67% and P53% were significantly reduced after methotrexate therapy. No significant difference was detected between the percent reduction in PASI score (81%) and that of Ki-67% (70%). Conclusion: Keratinocyte proliferation was the most significant variable contributing to the clinical severity of psoriasis and it was the single parameter that showed parallel changes to PASI score after methotrexate therapy. Keratinocyte proliferation may be considered as the stimulus that induces all other pathological and clinical changes in psoriasis and should be targeted by therapy.

Study of Keratinocyte Proliferation, Apoptosis and Dermal Inflammation in Psoriatic Skin Lesions Before and After Methotrexate Therapy: Which Change Is Contributing More to Clinical Severity of the Disease?

Objective: The pathogenesis of psoriasis involves T-cell mediated immunologic response, keratinocytes hyperproliferation, and resistance to apoptosis. Methotrexate is one of the most reliable modalities in the treatment of psoriasis that target those changes. The study of those variables before and after methotrexate therapy may answer the question: Which of those variables contributes more to the clinical severity of the disease and is more valuable to be targeted in psoriasis treatment. Patients and Methods: A total of 50 cases of psoriasis vulgaris were included, 25 patients received methotrexate therapy. Skin biopsies of psoriatic skin lesions before and after treatment were examined histologically for measurement of epidermal thickness and grading of dermal inflammation. Immunostaining for Ki-67 and p53 was done for assessment of keratinocyte proliferation and apoptosis. Results were correlated with clinical severity of the disease, assessed by psoriatic area and severity index (PASI) score. 15 biopsies of normal skin were included as control. Results: Dermal inflammation, Ki-67%, and p53% were significantly higher in psoriatic skin lesion than in normal skin. Those changes were significantly correlated with PASI score. Multiple logistic regression models revealed that Ki-67 was the most significant variable contributing to clinical severity. One unit change in ki-67% can explain 1.2 unit changes in PASI score with 97% sensitivity, 40% specificity and 25% cut-off value. PASI score, dermal inflammation, Ki-67% and P53% were significantly reduced after methotrexate therapy. No significant difference was detected between the percent reduction in PASI score (81%) and that of Ki-67% (70%). Conclusion: Keratinocyte proliferation was the most significant variable contributing to the clinical severity of psoriasis and it was the single parameter that showed parallel changes to PASI score after methotrexate therapy. Keratinocyte proliferation may be considered as the stimulus that induces all other pathological and clinical changes in psoriasis and should be targeted by therapy.

LO079: Prevalence and geographic variability of ectopic pregnancy in Ontario using inpatient and outpatient data: a 12-year surveillance study

Introduction: It is estimated that 6% to 13% of patients presenting to the emergency department (ED) with vaginal bleeding or abdominal pain will have ectopic pregnancy. Risk factors such as previous pelvic infections, assisted reproductive technologies and previous tubal surgery as well as prevalence of ectopic pregnancy vary geographically. To date, the surveillance of ectopic pregnancy in Canada has been limited to hospitalized patient data, excluding patients receiving methotrexate therapy, day surgery or expectant management, possibly underestimating the true prevalence. The objective of this study was to determine Ontario’s ectopic pregnancy rate and geographic variability using both inpatient and outpatient data sources. Methods: Data from the Canadian Institute for Health Information Discharge Abstract Database, Same Day Surgery Database, National Ambulatory Care Reporting System, and Ontario Health Insurance Plan (OHIP) Claims Database was retrieved for all females with valid OHIP coverage aged 15 to 45 years from July 2002 to August 2014. Using ICD-10 and OHIP codes for ectopic pregnancy, abortions and deliveries, the rates and distribution of ectopic pregnancy (per 1000 reported pregnancies) by age group and public health unit (PHU) were documented. These data were also compared to the rate of ectopic pregnancy documented using only hospitalized patient data. Results: Using inpatient and outpatient data sources, the rate of ectopic pregnancy in Ontario increased from 20.5 to 27.5 per 1000 reported pregnancies from 2002 to 2014, respectively. The rate of ectopic pregnancy using only hospitalized patient data decreased from 12.6 to 9.5 per 1000 reported pregnancies from 2002 to 2014, respectively. The median (IQR) rate of ectopic pregnancy over the 12-year study period varied across public health units in Ontario, ranging from 14.9 (12.5, 17.5) to 37.7 (29.1, 55.8) per 1000 reported pregnancies. Conclusion: The rate of ectopic pregnancy is increasing in Ontario and has been previously underreported using only hospitalized patient data. Further research is needed to identify the factors resulting in this increase as well as the outcomes of ectopic pregnancies in Ontario.

The effect of mirtazapine on methotrexate-induced oxidative damage and infertility in rats

Methotrexate (MTX) is a folic acid antagonist and common chemotherapeutic drug. This study investigated the effectiveness of mirtazapine in preventing infertility developed by MTX-associated oxidative damage. In addition, we demonstrate an association between oxidative stress in ovarian tissue induced by MTX and infertility. Rats were divided into three groups: MTX control, mirtazapine+ MTX, and healthy control. At the end of the procedures the reproductive function was noted and ovaries extracted to determine malondialdehyde (MDA), myeloperoxidase (MPO), and total glutathione (GSH) levels. MDA concentration in ovarian tissue in the control group given MTX was 13.7 2.1 µmol/g protein. In the mirtazapine + MTX group and healthy control group the levels were 7.5 1.9 and 4.0 1.4 µmol/g protein, respectively. MPO activity in the control group given MTX, mirtazapine + MTX, and healthy control groups was 17.8 4.7, 7.5 2.4, and 5.2 1.7 µmol/g protein, and GSH levels 4.5 2.1, 11.8 3.9, and 14.7 4.7 nmol/g protein, respectively. The study also demonstrated an association between oxidative stress induced by MTX in ovarian tissue and infertility. The mirtazapine used prevented MTX-associated infertility. There were no live births in the control group given MTX alone. However, only one of the 10 rats kept for reproduction did not give birth in the mirtazapine + MTX (end of the procedure only given mirtazapine) group. In conclusion, mirtazapine can be used to prevent infertility appearing in patients receiving MTX therapy.

Two Cases of Severe Pancytopenia Associated with Low-Dose Methotrexate Therapy in Patients with Chronic Kidney Disease and Rheumatoid Arthritis

Due to its efficacy and tolerability, low dose oral methotrexate (MTX) therapy has been widely used for treatment of rheumatoid arthritis (RA). However, it can rarely cause serious, life-threatening hematologic toxicities, such as pancytopenia. We report here on two patients with chronic kidney disease (CKD), who developed severe pancytopenia after 5 years (cumulative dose 1,240 mg) and 4 years (cumulative dose 1,320 mg) of low dose MTX therapy for treatment of RA, respectively. Both patients presented with renal insufficiency, hypoalbuminemia, concurrent use of nonsteroidal anti-inflammatory drugs, and elevated mean corpuscular volume of red blood cells (RECs), all of which are known as risk factors of MTX-induced pancytopenia. Despite receiving treatment, which included REC and platelet transfusions, antibiotic therapy, granulocyte colony stimulating factor, and leucovorin rescue, one patient died of sepsis. Based on our case study, prompt investigation of risk factors associated with MTX toxicity is required for all patients receiving MTX therapy. MTX treatment, even at a low dose, should be discontinued in patients with advanced CKD.

Atypical Lymphoplasmacytic and Immunoblastic Proliferation of Autoimmune Disease : Clinicopathologic and Immunohistochemical Study of 9 Cases

Atypical lymphoplasmacytic immunoblastic proliferation (ALPIB) is a rare lymphoproliferative disorder (LPD) associated with autoimmune disease (AID). To further clarify the clinicopathologic, immunohistological, and genotypic findings of ALPIB in lymph nodes associated with well-documented AIDs, 9 cases are presented. These 9 patients consisted of 4 patients with systemic lupus erythematosus, 3 patients with rheumatoid arthritis, and one case each with Sjögren's syndrome and dermatomyositis. All 9 patients were females aged from 25 to 71 years with a median age of 49 years. Four cases presented with lymphadenopathy as the initial manifestation. In 4 patients, immunosuppressive drugs were administered before the onset of lymph node lesion. However, none of the 9 patients received methotrexate therapy. The present 9 cases were characterized by : (i) prominent lymphoplasmacytic and B-immunoblastic infiltration ; (ii) absence of pronounced arborizing vascular proliferation ; (iii) absence of CD10(+) "clear cells" ; (iv) presence of hyperplastic germinal center in 7 cases ; (v) immunohistochemistry, flow cytometry, and polymerase chain reaction demonstrated a reactive nature of the T- and B-lymphocytes ; and (vi) on in situ hybridization, there were no Epstein-Barr virus -infected lymphoid cells in any of the 9 cases. Overall 5-year survival of our patients was 83%. The combination of clinical, immunophenotypic, and genotypic findings indicated that the present 9 cases can be regarded as having an essentially benign reactive process. Finally, we emphasized that ALPIB should be added to the differential diagnostic problems of atypical LPDs, particularly lymph node lesions of IgG4-related diseases.

Accelerated Cutaneous Nodulosis During Infliximab Therapy in a Patient With Rheumatoid Arthritis

Up to one fourth of patients with rheumatoid arthritis (RA) may have extraarticular findings such as subcutaneous nodules. These are discrete subcutaneous granulomatous nodules located on extensor surfaces, especially of the elbows. Over the past 10 to 15 years, there have been reports of accelerated cutaneous nodulosis in patients receiving methotrexate therapy. Recently, antitumor necrosis factor alpha (anti-TNFalpha) biologic therapy has become commonplace in the management of RA, especially in methotrexate-resistant or toxic patients. There have been recent reports of accelerated nodulosis in patients with RA on etanercept. We describe what we believe is the first case of accelerated cutaneous nodulosis resulting from infliximab anti-TNFalpha therapy in a patient with RA. One year after the initiation of infliximab, with RA in remission, our patient noted the rapid development of rheumatoid nodules of both hands. A biopsy was characteristic of a rheumatoid nodule, revealing palisading granulomas and fibrinoid necrosis.

Accelerated cutaneous nodulosis during methotrexate therapy in a patient with rheumatoid arthritis

Rheumatoid nodulosis is characterized by multiple small subcutaneous granulomatous nodules typically located on the elbows in approximately 20% of patients with rheumatoid arthritis. Accelerated rheumatoid nodulosis, especially involving the hands and feet, has recently been reported in patients receiving methotrexate therapy for rheumatoid arthritis. We describe a woman with seropositive, erosive rheumatoid arthritis who, on two occasions, developed nonperiarticular subcutaneous nodules and new heart murmurs during methotrexate therapy, while her arthritis remained under good control. The nodules resolved after methotrexate was discontinued and recurred after methotrexate was reintroduced. They again resolved after methotrexate was stopped and colchicine was added. Her DNA oligotyping was positive for HLA- DRB1 * 0401 , a genetic risk factor associated with accelerated rheumatoid nodulosis. Cutaneous biopsy specimens revealed palisading granulomas and giant cells consistent with rheumatoid nodulosis. (J Am Acad Dermatol 1998;39:359-62.)

METHOTREXATE IN THE TREATMENT OF CHILDREN WITH CHRONIC ARTHRITIS — LONG‐TERM OBSERVATIONS OF EFFICACY AND SAFETY

SUMMARY In a study to investigate the efficacy and toxicity of long‐term methotrexate (MTX) therapy in children with chronic arthritis, the medical records of 26 children (seven boys and 19 girls) with juvenile rheumatoid arthritis (JRA) were reviewed retrospectively. The patients received MTX therapy for a mean of three years (range, six months to six years). A clinically significant response occurred in 19 children (73.1%): remission in ten (38.5%) and improvement (25% reduction in the number of actively inflamed joints) in nine (34.6%). Concomitant prednisolone therapy was reduced in 13 out of 14 children (93%). Haemoglobin levels and erythrocyte sedimentation rates were statistically significantly improved over baseline after MTX therapy. Six (23%) children experienced toxic effects during MTX therapy. One patient discontinued the MTX treatment after 18 months because of jaundice and raised liver enzymes. It is concluded that the study confirms the efficacy, and acceptable toxicity profile, of MTX given over a period of several years to children with JRA.

An enzyme immunoassay design using labelled antibodies for the determination of haptens. Application to methotrexate assay

A competitive enzyme immunoassay with labelled antibodies has been developed for methotrexate (MTX). Methotrexate in the sample and a constant quantity of this hapten physically absorbed to polystyrene spheres through a methylated bovine albumin carrier were allowed to compete for a limiting amount of peroxidase labelled antibody. After washing, the residual enzyme activity bound to the solid phase was measured. This test was able to detect 10 fm of MTX per sample. A comparative study of this test with a commercial radioimmunoassay kit using the same antiserum and a high pressure liquid chromatography method showed that the sensitivity, specificity and precision of this test were as good as of the radioimmunoassay. The high pressure liquid chromatography method was 500 times less sensitive. Good agreement was found among the 3 methods on 83 serum samples from patients receiving methotrexate therapy.

AUTOIMMUNITY TO HUMAN SWEAT. I. Demonstration of Antigens in Sweat Reactive with Autologous and Homologous Sera

Antigens reactive with autologous and homologous sera have been demonstrated in human sweat, but not in serum, amniotic fluid, urine, or secretions of other glands investigated. The antisweat precipitins (IgG) were demonstrated in 33% of adult hospital staff and 40% of adult blood donors. While the incidence of positive antisweat precipitin tests (ASP) was elevated in many skin disorders, it was depressed in diabetes and patients receiving methotrexate therapy for psoriasis.