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35484086 Multifunctional Nanoparticles Co-Loaded with Perfluoropropane, Indocyanine Green, and Meth 2022 Apr 28 Rheumatoid arthritis (RA), a common chronic inflammatory joint disease with features of synovitis and pannus formation, may lead to irreparable joint damage and disability. Methotrexate (MTX) is known as the cornerstone of therapy for RA. However, the therapeutic effects of MTX are unsatisfactory due to its low retention in the inflammatory joints as well as systemic toxic effects. Fortunately, the use of multifunctional nanoparticles for diagnostics and in treatment shows potential for application as a strategy for traceable and targeted RA therapy. This research aims to develop novel nanoparticles that carry with perfluoropropane (PFP), indocyanine green (ICG), and MTX and investigate the corresponding enhancement in multimodal imaging both in vitro and in vivo. A modified double emulsion method was applied for the construction of encapsulated PFP-O(2), ICG, and MTX (OIM@NPs), and the essential properties of the developed NPs were determined. The fluorescence and ultrasonic and photoacoustic imaging characteristics were experimentally evaluated both in in vitro and in vivo models. The OIM@NPs are stable and efficient nanoagents. They enable more targeted distribution in the inflammatory joints in RA rats. Moreover, the NPs play an important role as contrast agents for prominent ultrasound and photoacoustic imaging after laser and low-intensity focused ultrasound excitation, providing precision guidance and monitoring for subsequent treatment. This research may provide a novel and efficient strategy to better enable monitoring in inflammatory joints of RA patients and the developed NPs may be a promising nanoplatform for integrating multimodal image monitoring.
35607639 Pancytopenia Due to Possible Drug-Drug Interactions Between Low-Dose Methotrexate and Prot 2022 Methotrexate (MTX) has been widely used with a wide range of doses in the treatment of certain neoplastic diseases, severe psoriasis, and rheumatoid arthritis. At higher dose, monitoring of serum MTX elimination is performed because delayed elimination can result in serious and potentially life-threatening toxicities. A number of medications, including nonsteroidal anti-inflammatory drugs (NSAIDs), salicylates, phenylbutazone, phenytoin, sulfonamides, and some oral antibiotics, are known to interact with MTX therapy through various mechanisms. Accumulating evidence suggests that concomitant use of MTX (primarily at high doses) and proton pump inhibitors (PPIs) such as omeprazole, esomeprazole, and pantoprazole may decrease MTX clearance. The majority of the reported cases occurred with the administration of high-dose MTX in patients receiving doses of 300 mg/m(2) to 12 g/m(2). However, there were also cases of patients taking PPI and experiencing toxicity at doses as low as 10 mg of MTX per week. Although the dosage of MTX is small, the presence of side effect may be delayed and still dangerous. After literature review, it was found that common toxicities associated with low-dose MTX used for inflammatory arthritis include gastrointestinal adverse effects (>10%; ie nausea, stomatitis) and central nervous system toxicity (~20%; ie fatigue, malaise, dizziness, impaired cognition) with weekly administration. Bone marrow suppression (<3%; ie leukopenia, neutropenia, thrombocytopenia) and hepatotoxicity (~15%; ie reversible elevations in transaminases) are less common, and rarely MTX can also cause pulmonary (<1%) and other toxicities. Here, we report two cases who presented with severe pancytopenia 8 and 13 days after taking low-dose MTX and PPI. We highlight that in absence of risk/benefit ratio correctly set, an assessment of appropriateness of PPI prescription before MTX therapy can limit an iatrogenic risk.
35016227 Multifocal Oral Epstein-Barr Virus-Positive Mucocutaneous Ulcers Associated with Dual Meth 2022 Jan 11 Epstein-Barr virus (EBV)-positive mucocutaneous ulcer (EBVMCU) is a unique clinicopathologic entity of lymphoproliferative disorder, occurring in immunosuppressed patients. Due to its rarity, EBVMCU may be under-recognized by clinicians as well as pathologists. In addition, its clinical and histopathologic features overlap with other benign and malignant conditions, making a diagnosis challenging. This report presents an unusual case of multifocal oral EBVMCUs in a 52-year-old female patient with rheumatoid arthritis, receiving the combination of methotrexate and leflunomide for 5 years. The patient presented with persistent multiple large painful ulcers involving her palate and gingiva for 6 months. The histopathologic examination revealed extensive ulceration with diffuse polymorphic inflammatory infiltrate admixed with scattered atypical lymphoid cells showing occasional Hodgkin and Reed/Sternberg-like cell features. These atypical cells showed immunoreactivity for CD20, CD30 and MUM1/IRF4. EBV-encoded small RNA in situ hybridization was positive, validating the presence of EBV-infected cells. Two months after discontinuation of both immunosuppressive medications, oral lesions gradually regressed. At 9-month follow-up, no evidence of relapsing oral EBVMCU has been observed. The multifocal presentation of EBVMCU is rare and could be resulted from the overwhelming immune suppression by long-term use of dual immunosuppressants. Its diagnosis requires comprehensive correlation of patient history, clinical findings, histopathologic, and immunophenotypic features. The ability of EBVMCU to regress following removal of immunosuppressive causes is in drastic contrast to a variety of its potential clinical and histopathologic mimics. Therefore, accurate diagnosis is crucial to avoid unnecessary patient management and achieve optimal patient outcomes.
35115328 Acute respiratory distress syndrome precipitated by granulocyte colony-stimulating factor 2022 Feb 3 We present the case of a 62-year-old man with rheumatoid arthritis who developed a leukaemoid reaction and acute respiratory distress syndrome (ARDS) following granulocyte colony-stimulating factor (G-CSF) administration that had been given to treat neutropenia secondary to methotrexate and leflunomide toxicity. Later it was established that he had Pneumocystis jirovecii pneumonia, which was treated to complete resolution with a course of corticosteroids and antibiotics. This case highlights the potential risk of G-CSF administration in an immune compromised individual in the midst of bone marrow recovery in the context of active infection. Recognition of immune escape syndromes is vital and requires an understanding of potential triggers and risk factors.
34731869 Infective Necrotizing Scleritis After XEN Gel Stent With Mitomycin-C. 2022 Feb 1 PURPOSE: The purpose of this study was to report a case of infective necrotizing scleritis following XEN Gel Stent with mitomycin-C. METHODS: Case report. This is a case report of a 68-year-old woman. RESULTS: XEN Gel Stent glaucoma surgery enhanced with mitomycin-C 0.04% and combined with cataract surgery was performed at a regional center to manage the patient's primary open-angle glaucoma. Past medical history was significant for rheumatoid arthritis requiring treatment with methotrexate and adalimumab. Periocular pain and swelling developed 14 months after the initial operation, followed by a rapid deterioration of visual acuity to 20/60, intraocular pressure of 4 mm Hg, and worsening pain 5 months later. On initial presentation to Sydney Eye Hospital, 180 degrees of scleral necrosis was evident with a moderate anterior segment inflammatory reaction and a large temporal choroidal effusion due to hypotony. Empirical hourly topical ofloxacin and cephalothin 5% drops, with oral moxifloxacin, were initiated. Conjunctival swab grew Staphylococcus aureus and Staphylococcus lugdunensis. Significant clinical improvement occurred, but the XEN Gel Stent became exposed after 9 days of treatment with worsening hypotony. Urgent surgical revision was performed to remove the XEN Gel Stent and apply a tutoplast plug with overlying amniotic membrane graft. Intraocular pressure gradually improved over 6 weeks to 15 mm Hg with reversal of hypotonous changes, and visual acuity stabilized at 20/40. CONCLUSIONS: To our knowledge, this is the first reported case of necrotizing scleritis following XEN Gel Stent insertion. It is a reminder that infection should always be the primary differential diagnosis in patients with surgical-induced necrotizing scleritis.
35359225 Rheumatic Diseases in Reproductive Age-the Possibilities and the Risks. 2022 Mar 31 The most common systemic connective tissue diseases (CTD), such as rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), antiphospholipid syndrome (APS), systemic sclerosis (SSc), and Sjögren's syndrome (SjS), affect many women of reproductive age. These diseases may strongly impact the course of pregnancy and increase the risk factors of incompatibility. A literature search was done on MEDLINE, PubMed, and Google Scholar in 2011-2021. The analysis included meta-analysis, randomized control trials, prospective and retrospective studies, and systematic reviews. The literature search allowed us to form conclusions and underline recommendations regarding pregnancy's risk and treatment possibilities in the course of rheumatic disease. Optimal control of CTD activity should be reached at least 6 months before conception. High-risk pregnancies are often accompanied by maternal-placental syndrome, which manifests as preeclampsia, eclampsia, fetal growth restriction, and prematurity. The flare of rheumatic disease can coexist with obstetrical complications, and differential diagnosis can be difficult. Medications that do not influence the risk of fetus complications should be applied before and during pregnancy. Teratogenic drugs (e.g., methotrexate, leflunomide, cyclophosphamide) must be withdrawn before pregnancy. Conventional medications such as hydroxychloroquine, sulfasalazine, colchicine, and the TNFα inhibitor certolizumab can be used safely at any stage of pregnancy. Corticosteroids should be tapered, and other biologics should be avoided due to teratogenicity or carefully administered due to the impact on the fetal immune system. Distinguishing between disease flare and obstetrical complications can be difficult in clinical practice; however, some clinical symptoms and serological markers can be helpful in the differential diagnosis.
34515135 Evaluation and Differential Diagnosis of Hypereosinophilia in Rheumatology Practice. 2022 BACKGROUND: There has been no investigation so far on the prevalence or causes of hypereosinophilia during rheumatic diseases. OBJECTIVES: The study aimed to identify the prevalence and causes of hypereosinophilia among the patients followed in a rheumatology department. METHODS: The patients aged 18 years or over followed in our rheumatology department between January 2010 and December 2019 who had at least one AEC ≥1,500/µL measurement in their peripheral blood count were identified retrospectively. RESULTS: Over the 10 years, a total of 130,769 peripheral blood counts were performed, of which 3.9% showed eosinophilia and 0.065% showed hypereosinophilia. Hypereosinophilia was identified in 85 patients. The underlying rheumatic disease was determined in 89.4% (n = 76) of patients. Of these, the most frequent one was rheumatoid arthritis at a ratio of 40.8%, followed by eosinophilic granulomatosis with polyangiitis (EGPA) at a ratio of 10.5%. Hypereosinophilia was in primary form in 3.5% of the patients, whereas secondary to another condition in 91.8% (n = 78) of the cases and idiopathic in 4.7% (n = 4) of patients. The most common cause of secondary hypereosinophilia was drug induced, as detected in 61.2%, followed by allergic conditions in 11.5% and EGPA in 9.4%. In 15.2% (n = 13) of the cases, hypereosinophilia was associated with an underlying rheumatic disease. In the cases with drug-induced hypereosinophilia, most often (in 28.8%) methotrexate was the offending agent. CONCLUSIONS: Rheumatologists should be cognizant that hypereosinophilia concurrent to rheumatic diseases is usually not due to the underlying rheumatic disease, except for the conventional eosinophil-related rheumatic diseases.
35355725 Biological and Methotrexate Survival after Pregnancy in Patients With a Rheumatic Disease. 2022 Objective: Patients with a rheumatic disease who discontinue their disease-modifying anti-rheumatic drug (DMARD) due to pregnancy often wonder if treatment will be as effective after pregnancy. This study investigates the effect of a temporary discontinuation of DMARDs due to pregnancy on the effectiveness of the same DMARD postpartum in patients with a rheumatic disease. Methods: Pregnant, rheumatic patients were derived from the Preconceptional Counseling in Active Rheumatoid Arthritis (PreCARA) cohort. DMARD-survival after pregnancy, for biological and methotrexate (MTX) therapy, was analyzed and compared to controls with stable DMARD-treatment from a retrospective cohort. Results: In total, 234 patients were included, of whom 114 patients had stable biological or MTX treatment before their pregnancy. After pregnancy, 40 out of 56 (71%) patients restarted their biological, for MTX this was 49%. One year after restart, and censoring for a following pregnancy, 88.9% of patients were still using their biological, and 85% still used their MTX (p = 0.92). Compared to the matched controls the survival after pregnancy was significantly lower 1 year after restart for both biologicals (98.3%) and MTX (99.6%); p = 0.002 and p < 0.001 respectively; 3 years after restart this significant difference was no longer observed (p = 0.50 and p = 0.33, respectively). Conclusion: Effective DMARD (biological or MTX) treatment before pregnancy that was discontinued due to pregnancy seems effective after pregnancy. Although DMARD-survival was higher in the control group 1 year after restart, the percentage of patients with effective treatment was still very good (>85%). In addition, this difference was no longer observed after 3 years.
35509787 Epstein-Barr virus-related diffuse large B-cell lymphoma type methotrexate-associated lymp 2022 May INTRODUCTION: Methotrexate-associated lymphoproliferative disorders appear during treatment with methotrexate as an immunosuppressive drug. However, the mechanism and frequency are still unknown, and the treatment is undefined. CASE PRESENTATION: A 76-year-old woman was admitted to the hospital with back pain, and magnetic resonance imaging showed a tumor in the right adrenal region. She had received methotrexate for rheumatoid arthritis. Enhanced computed tomography showed a tumor of 90 mm in diameter on the dorsal side of the liver abutting to the inferior vena cava. The preoperative diagnosis was a hepatic invasion of right adrenocortical carcinoma and right adrenalectomy was performed. The histopathological diagnosis was diffuse large B-cell lymphoma. The final diagnosis was methotrexate-associated lymphoproliferative disorders. CONCLUSION: It is important to consider methotrexate-associated lymphoproliferative disorders before surgery when neoplastic lesions are found in patients taking methotrexate.
31986916 Naringenin: a potential natural remedy against methotrexate-induced hepatotoxicity in rats 2022 Mar Hepatotoxicity is an adverse side effect of methotrexate (MTX) administration for the treatment of different malignancies, psoriasis, and rheumatoid arthritis (RA). Naringenin (NAR) is a citrus flavone with multiple pharmacological characteristics. In this study, we aimed to investigate the protective effects of NAR on MTX-induced hepatotoxicity in rats. For this purpose, 32 Wistar rats were randomly divided into four experimental groups as group 1 Control, group 2 NAR (50 mg/kg/d, o.p.), group 3 MTX (20 mg/kg/d, i.p.), group 4 NAR + MTX. NAR was administrated for 10 consecutive days and MTX was injected on the ninth day. The results indicated that MTX significantly increased malondialdehyde (MDA), NO, TNF-α, and IL-6 levels in the liver. On the other hand, administration of MTX reduced the GSH content, as well as CAT, SOD, and GPx levels. NAR administration remarkably improved MTX-induced alteration of biochemical biomarkers. Our findings were confirmed by the histopathological examination of the liver. Based on our findings, NAR may inhibit MTX-induced hepatotoxicity through scavenging reactive free radicals and inducing anti-inflammatory effects.
35049423 Antibody response in patients with autoimmune inflammatory rheumatic disease after pneumoc 2022 Jan 20 OBJECTIVE: The aim of the study was to assess the pneumococcal antibody response in autoimmune inflammatory rheumatic disease (AIIRD) patients receiving 23-valent pneumococcal polysaccharide vaccine (PPV23) as a prime vaccination or revaccination. METHOD: Antibodies to 12 serotypes occurring in the commonly applied pneumococcal vaccines in Denmark were measured in AIIRD patients receiving biological disease-modifying anti-rheumatic drug (bDMARD) treatment for rheumatoid arthritis, spondyloarthritis, or psoriatic arthritis. Patients with a non-protective level of pneumococcal antibodies (geometric mean pneumococcal antibody level < 1 μg/mL) were invited to receive vaccination with PPV23 followed by control of antibody titre 3 months later. RESULTS: In total, 224 (74%) of 301 patients were included in the analyses, of whom 126 patients had previously received PPV23 vaccination. Post-vaccination antibody measurement revealed that only 80 patients (36%) achieved a protective level of antibodies. In a multivariable logistic regression analysis, significantly more patients without a previous PPV23 vaccination history achieved a protective antibody level compared with patients with a history of PPV23 vaccination less than 5 years ago (p = 0.005). This difference was not seen when comparing the former group with patients vaccinated 5 years ago or more. Methotrexate (MTX) treatment at the time of vaccination was associated with a non-protective antibody level (p < 0.001). CONCLUSION: Only 36% of patients with a non-protective antibody level achieved a protective level in response to pneumococcal vaccination. Pneumococcal vaccination within the last 5 years and MTX treatment at the time of vaccination were independently associated with a poor antibody response.
35196176 Case 303. 2022 Mar History A 54-year-old man was found by paramedics in his home face-down at his computer desk with a substantially reduced level of consciousness. He had not contacted his family for more than 50 hours. The patient lived alone and was a heavy smoker with a history of alcohol abuse. His medical history was otherwise unremarkable, and there was no history of cancer, psoriasis, or rheumatoid arthritis, nor was there a history of methotrexate administration. On presentation to the emergency department, he was mildly hypotensive and was experiencing hypercapnic respiratory failure and acute renal failure with rhabdomyolysis. His toxicology screen was mildly positive for opiates. He received naloxone (Narcan; Emergent) with minimal effect. An unenhanced CT scan of the head was obtained (Fig 1A). Of note, this patient's presentation predated the COVID-19 pandemic. He was admitted to the intensive care unit for decreased level of consciousness and respiratory failure. The decreased level of consciousness was thought to be secondary to seizure, as he developed seizurelike movements prior to intubation, probably in the context of intoxication or alcohol withdrawal. Electroencephalography revealed moderate bilateral cerebral dysfunction and encephalopathy, with no evidence of nonconvulsive seizures. He had a short course of intermittent hemodialysis and was discharged home 8 days later with an appointment for neurology follow-up. At discharge, he was at his cognitive and functional baseline. Approximately 3 weeks later, the patient was brought back to the emergency department for progressive confusion and decrease in balance. He became apathetic with reduced psychomotor activity and was no longer able to perform basic daily activities, such as cooking or bathing. He displayed bizarre behavior, such as staring at a wall for hours, and was somnolent, irritable, and inattentive. He eventually became incontinent of urine and stool. Results of a neurologic examination of the cranial nerves, motor function, sensation, and reflexes were normal. The results of blood work-up were grossly normal, and the results of an extensive toxicology work-up were negative. Repeat head CT was performed (Fig 1B). MRI was ordered to further investigate the patient's encephalopathic presentation (Figs 2-3).
35619835 Treatment of COVID-19 in a Patient With Maple Syrup Urine Disease. 2022 Apr Maple syrup urine disease (MSUD) is an inborn error of metabolism caused by a defect in the branched-chain alpha-ketoacid dehydrogenase complex (BCKDC). This leads to the accumulation of the branched-chain amino acids (BCAAs) leucine, isoleucine, and valine, which can cause neurotoxicity. Patients with MSUD are carefully managed from birth with dietary restrictions and can acutely decompensate in the setting of infections or injury. We present the case of a 29-year-old female with a history of MSUD and rheumatoid arthritis on methotrexate and adalimumab who presented to our emergency department with symptoms suggestive of a metabolic crisis including nausea, vomiting, and presyncope. She was diagnosed with coronavirus disease 2019 (COVID-19) and admitted. An initial leucine level was mildly elevated at 253 μmol/L, consistent with her underlying metabolic condition. She was placed on an infusion of normal saline and 10% Dextrose (D10) in addition to a protein-restricted sick-day diet. Remdesivir therapy was initiated due to her immunocompromised status and high risk for decompensation but had to be discontinued due to nausea and vomiting that negatively impacted the patient's oral intake. Her leucine level peaked at 647 μmol/L; however, her neurologic examination remained benign without signs of cerebral edema. With prompt involvement of our metabolic genetics team and initiation of intravenous fluids and the sick-day diet protocol, we avoided a metabolic crisis. The patient was discharged on day 5 of hospitalization with no complications from COVID-19 infection. This case highlights the individualized approach to the treatment of COVID-19 infection in a patient with a metabolic disorder. COVID-19 infection in the setting of MSUD has only been reported in two prior publications, one being a severe metabolic crisis with neurologic involvement. Fortunately, our patient experienced a mild case of COVID-19 without significant respiratory symptoms, and we were able to prevent a metabolic crisis during admission.
35127323 A case of Epstein-Barr virus-positive mucocutaneous ulcer of the hypopharynx: a mimicker o 2022 Jan Epstein-Barr virus-positive mucocutaneous ulcer (EBVMCU) is a new disease, described by the World Health Organization in 2017. It has been recognized as a specific type of immunodeficiency-associated lymphoproliferative disorder. Since patients with EBVMCU present with only cutaneous or mucosal ulcers, it is difficult to clinically distinguish them from carcinoma. A 72-year-old man, who took methotrexate (MTX) (12 mg/week) for rheumatoid arthritis, was referred to our hospital because endoscopy revealed an ulcerated mass in the left pyriform sinus, suggesting hypopharyngeal squamous cell carcinoma. Contrast-enhanced computed tomography and magnetic resonance imaging revealed an ill-defined mass in the left pyriform sinus without lymphadenopathy in the head and neck region. A biopsy of the ulcerative lesion in the hypopharynx was performed, and lymphoproliferative disease was suspected, based on the histopathological findings. Two weeks after MTX withdrawal, the lesions in the hypopharynx disappeared. The patient was diagnosed with EBVMCU, based on the clinical and histopathological findings. This is the first case report of EBVMCU of the hypopharynx. EBVMCU should be considered as a differential diagnosis in immunocompromised patients with hypopharyngeal mucosal ulcers without lymph node or organ involvement.
35655424 Protective effect of dexpanthenol against methotrexate-induced liver oxidative toxicity in 2022 Jun 2 Methotrexate is a familiar chemotherapeutic preferred in a wide range of clinical fields such as leukemia, psoriasis, rheumatoid arthritis, neoplastic and autoimmune disorders. However, methotrexate therapy has limitations as it causes severe side effects from which liver damage is the most important one. Several antioxidant compounds have been studied against methotrexate related liver toxicity, but dexpanthenol has not been experienced. Vitamin B5-derived dexpanthenol is a usual therapeutic having a potent anti-inflammatory and antioxidant effect. In this study, we aimed to evaluate the ameliorating effect of dexpanthenol against methotrexate-induced hepatotoxicity. We performed our experiments on Wistar albino rats divided randomly into four groups involving control, dexphantenol, dexpanthenol + methotrexate and methotrexate applied animals. After this experimental work on rats, for the first time, we showed dexpanthenol improvement effect on ROS-caused hepatotoxicity initiated by methotrexate administration in terms of liver tissue antioxidant/oxidant enzymes, liver function tests, and histological changes. We suggest that dexpanthenol might be applied during methotrexate treatment in order to reduce the liver toxicity. However, further studies are needed to find out the optimal dose regimen and to understand the mechanism of action.
35471956 Accelerated waning of immunity to SARS-CoV-2 mRNA vaccines in patients with immune mediate 2022 Apr 26 BACKGROUND: Limited information is available on the impact of immunosuppressants on COVID-19 vaccination in patients with immune-mediated inflammatory diseases (IMID). METHODS: This observational cohort study examined the immunogenicity of SARS-CoV-2 mRNA vaccines in adult patients with inflammatory bowel disease, rheumatoid arthritis, ankylosing spondylitis, or psoriatic disease, with or without maintenance immunosuppressive therapies. Antibody and T cell responses to SARS-COV-2, including neutralization against SARS-CoV-2 variants were determined before and after 1 and 2 vaccine doses. RESULTS: We prospectively followed 150 subjects, 26 healthy controls, 9 IMID patients on no treatment, 44 on anti-TNF, 16 on anti-TNF with methotrexate/azathioprine (MTX/AZA), 10 on anti-IL-23, 28 on anti-IL-12/23, 9 on anti-IL-17, and 8 on MTX/AZA. Antibody and T cell responses to SARS-CoV-2 were detected in all participants, increasing from dose 1 to dose 2 and declining 3 months later, with greater attrition in IMID patients compared to healthy controls. Antibody levels and neutralization efficacy against variants of concern were substantially lower in anti-TNF treated patients than in healthy controls and were undetectable against Omicron by 3 months after dose 2. CONCLUSIONS: Our findings support the need for a third dose of mRNA vaccine and for continued monitoring of immunity in these patient groups. FUNDING: Funded by a donation from Juan and Stefania Speck and by Canadian Institutes of Health (CIHR) /COVID-Immunity Task Force (CITF) grants VR-1 172711 and VS1-175545 (T.H.W. and A.C.G); CIHR FDN-143250 (T.H.W.), GA2- 177716 (V.C., A.C.G., T.H.W.), GA1-177703 (A.C.G.) and the CIHR rapid response network to SARS-CoV-2 variants, CoVaRR-Net (to A.C.G.).
34843092 Patient-Reported Nausea and Fatigue Related to Methotrexate: A Prospective, Self-Controlle 2022 Feb INTRODUCTION: The magnitude and frequency of temporally related methotrexate (MTX)-associated side effects in rheumatoid arthritis (RA) or psoriatic arthritis (PsA) patients are difficult to quantify using traditional research methods. As proof of concept designed in part to implement digital data collection for remote patient monitoring, we conducted a study implementing self-controlled case series analytic methods to understand MTX-related symptoms in RA or PsA. METHODS: In study phase 1, adults with RA or PsA from the ArthritisPower(®) Registry (past or current oral MTX users) participated in a cross-sectional survey. In phase 2, current MTX users participated in a longitudinal study and completed the Patient-Reported Outcomes Measurement Information System (PROMIS(®)) 1-day nausea/vomiting and fatigue measure. Within-person change in PROMIS scores between risk (6-36 h post-dose) and control (96-144 h post-dose) windows were compared using mixed models. RESULTS: The baseline survey was completed by 671 participants (mean age: 54 years, 88% female, 92% white, 79% with RA). Among current MTX users (353/671 [53%]), most reported MTX-associated side effects (216/353 [61%]), most frequently fatigue (161/353 [46%]). Among phase 2 participants with (n = 39) and without (n = 84) baseline nausea, mean increase in PROMIS nausea was 5.1 units (P < 0.0001) and 0.7 units (P = 0.135), respectively; among those with (n = 51) and without (n = 72) baseline fatigue, mean increase in PROMIS fatigue was 3.9 units (P = 0.0003) and 0.4 units (P = 0.554), respectively. CONCLUSIONS: Digital remote patient monitoring presents an opportunity to detect and address medication tolerability in real time. Using a novel study design to control for between-person confounding, the magnitude of nausea and fatigue experienced by participants with RA and PsA temporally related to weekly MTX use was substantial.
35645413 Association between forkhead box P3 expression level and gender of Iranian juvenile idiopa 2022 OBJECTIVES: Juvenile idiopathic arthritis (JIA) is a childhood autoimmune rheumatoid disease. Past studies have confirmed that JIA is a complex disease, which means that genes and environmental factors affect the aetiology of the disease. In this study, we analysed the expression of interleukin 32, forkhead box P3 (FOXP3), methyl-CpG binding domain protein 1 (MBD1), and methyl-CpG-binding protein 2 (MECP2) in peripheral blood mononuclear cells of children with JIA in comparison with the expression of those in healthy children. Interleukin 32 is an inflammatory factor, FOXP3 is a transcription factor, and MBD1 and MECP2 are binding proteins that bind to the methylated deoxyribonucleic acid (DNA). MATERIAL AND METHODS: We collected blood from JIA patients who had been diagnosed and classified into clinical subtypes by a rheumatologist from the division of paediatric rheumatology. Healthy children, whose clinical and preclinical analysis confirmed they had no disease and just came to the hospital for a check-up or minor surgical procedures were considered as a control group. Age and gender were matched in patients and the control group. Total ribonucleic acid was extracted from blood, and cDNA was synthesized. Eventually, the transcript levels were analysed by quantitative polymerase chain reaction, and statistical analysis was carried out. RESULTS: Statistical analysis of gene expressions in young females affected by JIA demonstrated that MECP2 and FOXP3 were increased significantly (p-value = 0.002 and 0.05, respectively). Interleukin 32 gene expression was also increased (p-value = 0.14), whereas MBD1 gene expression was decreased (p-value = 0.06); however, these changes in the expression of all 4 genes were not significant in young males. CONCLUSIONS: Different expression levels of the mentioned genes between affected young females and males result from hormones in both gender and also methotrexate (MTX) drug. Also, the reason affected young females are more prone to JIA than males can be the lower level of FOXP3 expression in healthy females than healthy males.
35543332 COVID-19 outcomes among rheumatic disease patients in Kuwait: Data from the COVID-19 Globa 2022 May 11 PURPOSE: We aimed to assess the characteristics of inflammatory rheumatic disease (IRD) patients in Kuwait diagnosed with COVID-19 and the factors linked with hospitalization, complications, and mortality. METHODS: Data of IRD patients from Kuwait diagnosed with COVID-19 between March 2020 and March 2021, submitted to the COVID-19 Global Rheumatology Alliance physician-reported registry, were included in our analysis. Data on patients' age, gender, smoking, diagnosis, IRD activity, and other comorbidities were collected. Statistical Package for the Social Sciences (SPSS), version 25, was used for statistical analysis. RESULTS: A total of 52 patients were included, with a mean age of 55 years (±14). The majority of patients were ≤65 years (77%), female (77%), non-smokers (80.8%), and diagnosed with rheumatoid arthritis (67.0%). Of the included patients, 19.2%, 9.6%, and 7.7% reported having methotrexate monotherapy, antimalarials monotherapy, and interleukin-6 inhibitors monotherapy immediately before COVID-19, respectively. Most of the included patients (92.3%) were either in remission or had minimal/low disease activity, while others (7.7%) had moderate disease activity. Forty-three patients (82.7%) were hospitalized, while 11 patients (25.6%) required ventilation (invasive or non-invasive). Ten of the ventilated patients (90.9%) received glucocorticoids as part of the local protocol to treat severe COVID symptoms, and 4 patients (7.69%) died. The duration till symptom-free ranged between 0 to 30 days, with a mean value of 10 days (±6.5). CONCLUSION: The current study provides timely real-world evidence regarding characteristics and potential risk factors linked to poor COVID-19-related outcomes in the IRD population in Kuwait.
35057671 Inhibition of methotrexate induced toxicity in the adult rat spleen by adalimumab. 2022 Jan 20 Methotrexate (MTX) has been in use for the treatment of rheumatoid arthritis (RA), psoriasis, and cancer since 1948. Its toxic side effects on tissues and organs have been well documented but splenotoxicity has not been addressed. This study set out to investigate this issue by examining the effectiveness of anti-TNFα agents against MTX-induced toxicity in T lymphocytes and macrophages via the regulation of CD3, CD68, and CD200R. Twenty-four Sprague Dawley rats were allocated to three groups: control (received saline solution only), MTX (20 mg/kg of single-dose of MTX), and Ada + MTX (single dose of 10 mg/kg Adalimumab before MTX administration). The spleens were removed 5 days after MTX administration. The number of CD3+/mm3cells for the control, MTX and Ada + MTX groups were, respectively, 2.69 ± 0.86, 20.51 ± 2.7, (p = 0.000) and 11.07 ± 2.01 (p = 0.000). The number of CD68+ macrophages/mm3 in the control, MTX and Ada + MTX groups were, respectively, 8.62 ± 1.08, 38.19 ± 1.37 (p = 0.000), and 16.87 ± 12.57 (p = 0.000). The number of macrophages that were CD200R+/mm3 in the control, MTX, and Ada + MTX groups were 3.33 ± 1.66, 25.77 ± 2.37 (p = 0.000), and 8.68 ± 2.66 (p = 0.000), respectively. We also observed that Ada reduced the numerical densities of these cells following MTX administration (p < 0.05). Ada may, therefore, be a promising candidate for the prevention of the deleterious effects on T lymphocytes and macrophages of MTX-induced toxicity.
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