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ID PMID Title PublicationDate abstract
29922065 Current treatment options for psoriatic arthritis: spotlight on abatacept. 2018 Psoriatic arthritis (PsA) is a chronic inflammatory disease of joints, tendon sheaths, and entheses affecting patients with established skin psoriasis, or, less frequently, patients without a personal history of psoriasis with a positive familial history. Many treatment options are now available to deal with the different aspects of the disease, including traditional and biological disease-modifying antirheumatic drugs and the recently released targeted synthetic disease-modifying antirheumatic drugs. However, ~40% of patients still fail to achieve a meaningful clinical response to first-line biologic therapy advocating the development of novel medications. It is now well accepted that T-cells participate in the immunopathogenesis of several autoimmune diseases. For this reason, the potential intervention on T-cells represented an attractive therapeutic target for a long time, becoming a clinical reality with the development of abatacept. Abatacept is a biologic agent selectively targeting the T-cell costimulatory signal delivered through the CD80/86-CD28 pathway and was approved in December 2005 by the US Food and Drug Administration and in May 2007 by European Medicines Agency for the treatment of patients with rheumatoid arthritis in combination with methotrexate. Based on the relevant role of T-cells in PsA pathogenesis and following the positive results obtained in a phase III clinical trial, abatacept recently received approval for treatment of patients with PsA. In this review, we will focus on the current knowledge about the emerging role of abatacept in treatment of PsA.
30498353 Personalization of biologic therapy in patients with rheumatoid arthritis: less frequently 2018 OBJECTIVE: To propose appropriate statements that drive the choice of biologic therapies in patients with rheumatoid arthritis (RA), factoring in their impact on the following issues: anti-drug antibody (ADAb) formation, suspicion and management of infections, lupus-like syndrome (LLS), effects on bone mass and sexual sphere, and relationship between RA and periodontal disease (PD). METHODS: An overview of existing evidence was undertaken by an expert panel on behalf of the Italian board for the TAilored BIOlogic therapy (ITABIO). Data were extracted from controlled trials, national registries, national health care databases, post-marketing surveys, and, when required by the paucity of controlled studies, from open-label clinical series. Anti-tumor necrosis factor (anti-TNF) and non-anti-TNF-targeted biologics approved for RA were investigated. RESULTS: ADAb formation is chiefly associated with anti-TNFs, and it is reduced by combination therapy with methotrexate. To date, ADAb titration is not advisable for clinical practice, and, in case of anti-TNF secondary failure, a non-anti-TNF biologic is indicated. LLS is observed in anti-TNF receivers and, in most cases, resolves without anti-TNF withdrawal. A non-anti-TNF biologic is advisable in patients experiencing LLS. Non-anti-TNFs demonstrated a low or absent infection risk and are preferable in patients with comorbidities. Due to their positive effects on bone mass, anti-TNFs are indicated in women at osteoporosis risk, whereas non-anti-TNF have been poorly investigated. The emerging evidence of the relationship between RA and PD and the effects on anti-TNF efficacy should lead clinicians to consider the periodontal status in RA patients. Anti-TNFs may exert a positive effect on fertility and sexuality, and clinicians should explore these aspects in RA patients. CONCLUSION: The optimization of biologic therapies by taking into proper account the above issues would improve patient outcomes.
28877615 Clinicopathologic investigation of methotrexate-induced lymphoproliferative disorders, wit 2018 May Although recent accumulative data reveal the clinicopathogenesis of regression in methotrexate-induced lymphoproliferative disorders (MTX-LPDs), the precise understanding including this category remains controversial. In this study, we analyzed 62 patients with MTX-LPD. Forty-three patients showed regression (Reg group), with high rates of Hodgkin lymphoma (HL) and LPD (90 and 88%, respectively). Among the 43 patients of the Reg group, 14 patients (33%) relapsed. The median duration before relapse in the Reg group was 10.6 months. Although the difference of OS between the Reg and Non-Reg groups was not significantly different, relapse-free patients in the Reg group had a superior overall survival (OS). MTX duration had a significant impact on Epstein-Barr virus (EBV) infection (p = .00131). Furthermore, EBV infection was significantly related to clinical manifestations, including spleen invasion, in the regression phenomenon. Some human leukocyte antigens (HLA) alleles might affect MTX-LPD development via EBV infection, although A*2402 and DRB1*0405 might be affected as fundamental factors.
30013407 Treatment of rheumatoid arthritis in the USA: premature use of tumor necrosis factor inhib 2018 PURPOSE: The objective of this study was to assess the treatment for patients with rheumatoid arthritis (RA) in the USA. PATIENTS AND METHODS: This study entailed analysis of claims data for patients with RA who initiated treatment with oral methotrexate (MTX) or a biologic in 2009 (n=48,910) or 2012 (n=107,636) and had follow-up for 4 years (2009 cohort) or 2 years (2012 cohort). RESULTS: A biologic was initiated before MTX for 27% of the 2009 cohort and 36% of the 2012 cohort. Concomitant use of MTX and a biologic declined from 74.1% (2009 cohort) to 45.4% (2012 cohort). CONCLUSION: MTX is underused in the treatment of RA in the USA.
30349273 Additional effect of etanercept or infliximab on the liver function tests of patients with 2018 PURPOSE: One of the most important long-term side effects of therapy for rheumatoid arthritis (RA) is the elevation of liver function tests, with earlier studies reporting an elevation of more than 1× the upper limit of normal (>1 × ULN). The current study expands the literature by comparing the trends of transaminase changes caused by conventional and biologic disease-modifying antirheumatic drugs (DMARDs). PATIENTS AND METHODS: The drug categories examined were methotrexate (MTX) and all other nonbiologic DMARDs. Where RA patients exhibited inadequate response to conventional DMARDs (cDMARDs), we added biologic DMARDs (bDMARDs) to the treatment. We compared the trend of changes in alanine aminotransferase (ALT) and aspartate aminotransferase (AST) in the patients receiving MTX with the trend observed in the patients whose treatment encompassed both bDMARDs and MTX. The comparison was conducted using random intercept models, which are a type of linear mixed effects model. RESULTS: This work involved 512 RA patients (MTX: 450, MTX + infliximab [INF]: 26, MTX + etanercept [ETA]: 36), whose ALT and/or AST levels were measured in 1,786 visits (MTX: 1,543, MTX + INF: 107, MTX + ETA: 136). ALT and/or AST elevations greater than 1 × ULN were observed in 344 (19.3%) visits (MTX: 295 [19.1%], MTX + INF/ETA: 49 [20.2%]). In this study, the trends of ALT and AST changes increased when receiving MTX, while the INF/ETA addition decreased these trends. The random intercept models indicated that changes in the mean ALT levels were significantly different over the time for MTX and MTX + INF/ETA groups (β [SE] =-0.190 [0.093], P= 0.040) but changes in the mean AST levels were nonsignificantly different over the time for such groups (β [SE] =-0.099 [0.064], P=0.120). CONCLUSION: Despite a higher incidence of elevated transaminases during the use of MTX + INF/ETA, the combination of INF/ETA with MTX reduced transaminase levels and returned ALT levels to normal concentrations.
29667047 Investigation of the Mechanism of Therapeutic Protein-Drug Interaction Between Methotrexat 2018 Apr 17 A prominent example of human therapeutic protein-drug interaction (TP-DI) is between methotrexate (MTX) and anti-TNFα mAbs. One plausible mechanism for this TP-DI is through the pharmacodynamic effect of MTX on immunogenicity. However, there is no definitive evidence to substantiate this mechanism, and other competing hypotheses, such as MTX suppressing FcγRI expression thereby affecting mAb PK, have also been proposed. In order to understand this mechanism, a cynomolgus monkey study was conducted using golimumab as a model compound. Golimumab elicited high incidences of immunogenicity in healthy cynomolgus monkeys. Concomitant dosing of MTX delayed the onset and reduced the magnitude of anti-drug antibody (ADA) formation. The impact of MTX on golimumab PK correlated with the ADA status. Prior to ADA formation, MTX has no discernable effect on golimumab PK. Additionally, no alteration in FcγRI expression was observed following MTX treatment. The impact of MTX on golimumab immunogenicity and PK has been observed in patients with rheumatoid arthritis, psoriatic arthritis (PsA), and ankylosing spondylitis. In a representative phase 3 study of golimumab in patients with PsA, patients not receiving concomitant MTX was reported to have ~ 30% lower steady-state trough golimumab levels compared to those who received MTX. However, further analysis showed that PsA patients who were negative for ADA in both treatment groups had comparable trough levels of golimumab. Taken together, our results suggest that the mechanism of TP-DI between MTX and golimumab can mostly be attributed to the pharmacodynamic effect of MTX, i.e., the lowering of immunogenicity and immunogenicity-mediated clearance of mAbs.
29936438 Methotrexate and BAFF interaction prevents immunization against TNF inhibitors. 2018 Oct OBJECTIVES: TNF inhibitors (TNFi) can induce anti-drug antibodies (ADA) in patients with autoimmune diseases (AID) leading to clinical resistance. We explored a new way of using methotrexate (MTX) to decrease this risk of immunisation. METHODS: We treated BAFF transgenic (BAFFtg) mice, a model of AID in which immunisation against biologic drugs is high, with different TNFi. We investigated the effect of a single course of MTX during the first exposure to TNFi. Wild-type (WT) and BAFFtg mice were compared for B-Cell surface markers involved in MTX-related purinergic metabolism, adenosine production and regulatory B-cells (Bregs).We translated the study to macaques and patients with rheumatoid arthritis from the ABIRISK cohort to determine if there was an interaction between serum BAFF levels and MTX that prevented immuniation. RESULTS: In BAFFtg but not in WT mice or macaques, a single course of MTX prevented immunisation against TNFi and maintained drug concentration for over 52 weeks. BAFFtg mice B-cells expressed more CD73 and CD39 compared to WT mice. MTX induced adenosine release from B cells and increased Bregs and precursors. Use of CD73 blocking antibodies reversed MTX-induced tolerance. In patients from the ABIRISK cohort treated with TNFi for chronic inflammatory diseases, high BAFF serum level correlated with absence of ADA to TNFi only in patients cotreated with MTX but not in patients on TNFi monotherapy. CONCLUSION: MTX and BAFF interact in mice where CD73, adenosine and regulatory B cells were identified as key actors in this phenomenon. MTX and BAFF also interact in patients to prevent ADA formation.
29103180 Safety of weekly adalimumab in the treatment of juvenile idiopathic arthritis and pediatri 2018 Feb Weekly adalimumab dosing is used to treat juvenile idiopathic arthritis (JIA), uveitis, and other pediatric rheumatic diseases, but the safety of such dosing has not previously been studied. A retrospective chart review was conducted to assess the safety of weekly adalimumab. Demographic and clinical data were collected. Basic descriptive analysis was performed to assess for adverse events from weekly adalimumab. Sixty-nine patients at the University of Minnesota or Gillette Children's Hospital were identified as treated with weekly adalimumab. Sixty (87%) were eligible for the chart review. Weekly adalimumab was used most commonly to treat uveitis (28%, 17/60) and rheumatoid factor-negative polyarticular JIA (25%, 15/60). Mean age at the start of weekly dosing was 13.9 years. The majority of patients were concurrently treated with a non-steroidal anti-inflammatory drug and methotrexate. Fifty-three (90%) patients continued weekly dosing for greater than 3 months. The mean duration of weekly adalimumab was 2 years. Throughout the duration of weekly dosing, 24/60 (40%) patients had documented minor infections not requiring antimicrobials and 24/60 (40%) had documented infections requiring antimicrobial treatment. Only three patients (5%) had an infection requiring hospitalization. Two patients (3%) developed autoimmune disease. Laboratory abnormalities and injection site reactions were rare. Weekly adalimumab was used most commonly to treat uveitis and rheumatoid factor-negative polyarticular JIA, and mean duration of weekly dosing was 2 years. Serious adverse events were rare.
30203153 [Value of combining biologics with methotrexate for treatment of psoriatic arthritis-quest 2018 Nov BACKGROUND: Concomitant methotrexate (MTX) improves the therapeutic effect of biologic therapies in rheumatoid arthritis treatment. However, the influence of MTX on biologic therapy in psoriasis arthritis (PsA) has not yet been fully clarified, as data from randomized clinical studies are lacking. So far, it is only known, that PsA patients with inadequate response to MTX or non-steroidal anti-inflammatory drugs alone respond equally well to a subsequent biologic therapy. OBJECTIVES: The aim of this study is to investigate whether MTX-naive patients achieve greater disease improvement with the combination of MTX and a biologic than with biologic monotherapy alone, and whether patients on MTX in whom a biologic therapy is additionally started would worsen if MTX is discontinued. METHODS: The current data situation and its limitations are presented. Furthermore, an investigator-initiated multicenter randomized clinical study in patients with active PsA is introduced (MUST study), which investigates the influence of placebo-controlled MTX combination therapy with the interleukin 12/23 inhibitor ustekinumab (UST) in order to close the existing evidence gap. RESULTS: The primary objective of the study is to demonstrate the non-inferiority of UST monotherapy compared to MTX/UST combination therapy as measured by mean DAS28 values at week 24. Of 196 planned patients, 77 have been included so far. Recruitment is still open. CONCLUSION: The MUST study offers the ideal opportunity to investigate the influence of concomitant MTX in a controlled study design and to assess whether the addition of MTX to UST therapy or its continuation is beneficial for PsA patients.
30046349 Anti-Inflammatory, Antioxidative, and Hepatoprotective Effects of Trans Δ9-Tetrahydrocann 2018 Rheumatoid arthritis (RA) is a painful chronic autoimmune disease affecting the joints. Its first-line therapy, Methotrexate (MTX), although effective in ameliorating the progress of the disease, induces hepatotoxicity over long-term usage. Thus, seeking natural compounds with fewer side effects could be an alternative therapeutic approach. This study aimed to investigate the anti-inflammatory, antiarthritic, and antioxidative effects of synthetic trans-Δ9-tetrahydrocannabinol (Δ9-THC) dissolved in sesame oil (Dronabinol) against MTX in adjuvant-induced arthritis (AIA) rat model. Daily oral administration of Δ9-THC/sesame oil, over a period of 21 days, was well tolerated in arthritic rats with no particular psychoactive side effects. It markedly attenuated the severity of clinical manifestations, recovered the histopathological changes in tibiotarsal joints, and repressed the splenomegaly in arthritic rats. Δ9-THC/sesame oil therapy showed similar effects to MTX in neutralizing the inflammatory process of AIA, through attenuating erythrocyte sedimentation rate (ESR) scores and proinflammatory cytokines, including tumor necrosis factor-alpha (TNF-α), interleukin 1-beta (IL-1β), and interleukin-6 (IL-6) levels, to normal values. As opposed to MTX, this natural combination markedly protected the liver of arthritic rats and downregulated the induced oxidative stress by increasing the antioxidant defense system such as activities of catalase and superoxide dismutase (SOD) and levels of glutathione (GSH). These results suggest promising effects for the clinical use of Δ9-THC/sesame oil therapy in alleviating arthritic clinical signs as well as arthritis-induced liver injury.
29721441 Indolent, T-cell, large granular lymphocytic leukaemia in a dog presenting with severe neu 2018 In humans, large granular lymphocytic leukaemia (LGLL) is a low-grade, indolent lymphoproliferative disorder of large granular lymphocytes (LGL) associated with autoimmune disorders; including rheumatoid arthritis and single or multiple cytopenias; particularly neutropenia. Therapy largely centres around immunosuppression which aims to resolve the immune-mediated secondary pathology, often without eradicating the neoplastic clone. The most effective agents appear to be cyclophosphamide, cyclosporine and methotrexate. This case report describes the presentation, diagnostics, therapeutic approach and outcome of a 6 year-old Golden Retriever presenting with severe neutropenia. Chlorambucil, prednisolone and cyclosporine failed to improve the neutropenia but subsequent cyclophosphamide resulted in a sustained albeit temporary improvement in neutrophil count and the ability to withdraw prophylactic antibacterials. This case closely mirrors the diagnostics and therapeutic response in human LGLL.
30025850 Comparative study of anti-VEGF Ranibizumab and Interleukin-6 receptor antagonist Tocilizum 2018 Oct 1 Although the precise etiology of Rheumatoid arthritis (RA) remains obscure, heightened immune response is thought to play a vital role in provoking joint inflammation and bone erosion. This study aims at comparatively evaluating the effects of two monoclonal antibodies Ranibizumab (RANI) as anti-VEGF antibody and Tocilizumab (TCZ) as interleukin-6 receptor (IL-6R) antagonist, against adjuvant induced arthritis in rats. CFA-induced arthritic rats were treated for three consecutive weeks with Methotrexate (MTX), TCZ and RANI monotherapy. Clinical assessment of RA, bone erosion, inflammatory, angiogenic and apoptotic markers were determined to assess the anti-arthritic effect. Liver enzymes and histopathological examination of liver and spleen were assessed to evaluate the toxicity profile of the tested therapeutic agents. MTX, TCZ and RANI monotherapy significantly enhanced the anti-arthritic parameters in comparison with the Complete Freund's Adjuvant (CFA)-induced arthritic rats through significant reduction of ankle and paw swelling. Also, they significantly reduced inflammatory, angiogenic and apoptotic markers. Importantly, Ranibizumab showed better effect than the standard anti-rheumatic drugs Methotrexate (MTX) or Tocilizumab (TCZ) in bone protection and cartilage health; hence proves to be a promising new therapeutic agent for RA.
29231165 Polyvalent immunoglobulins with vitamin D3 and vitamin B12 in the treatment of Sjogren's s 2018 Jan BACKGROUND: Sjogren's syndrome, involving sicca symptoms with xerostomia, stomatitis, and considerable pain is a difficult-to-treat autoimmune disease where the treatment options are limited and, as in the case of methotrexate, have a low therapeutic index. CASE REPORT: This case report concerns a male patient, aged 75 years and vegetarian, with Sjogren's syndrome subsequently confirmed by salivary gland biopsy. Serum antinuclear antibodies (ANA) were elevated (1 : 320). Low serum vitamin B12 and iron levels could be improved after 20 days using vitamin B12 and iron oral supplements. Despite symptomatic treatment, xerostomia, glossitis, and glossodynia were still present, at times marked, after 12 months when the ANA titer was unchanged. Following treatment with an anti-inflammatory polyvalent immunoglobulin formulation (Lactobin®N, 7 g daily), a bovine colostrum concentrate given orally in combination with oral vitamin D3 (2,000 IU daily), sicca symptoms and xerostomia progressively decreased and at day 750 were confined to occasional and minor glossitis of the upper lip. CONCLUSION: This case report demonstrates the satisfactory control of Sjogren's syndrome using oral polyvalent immunoglobulins with vitamin D3. In contrast to treatment options involving antimalarial drugs and methotrexate, there are no safety issues in patients tolerant to milk products.
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29982962 Novel Anti-arthritic Mechanisms of Polydatin in Complete Freund's Adjuvant-Induced Arthrit 2018 Oct Articular manifestations are the main hall mark for rheumatoid arthritis; inflammation and oxidative stress are involved in its pathogenesis. This study was designed to figure out the possible therapeutic potential of polydatin on experimentally induced arthritis in rats. Polydatin (POLY) was administered (200 mg/kg, p.o.) for 21 days to complete Freund's adjuvant (CFA; 0.1 ml, s.c.)-induced arthritic rats. Meanwhile, methotrexate (MTX; 0.75 mg/kg, i.p.) was given as a reference standard disease-modifying anti-rheumatic drug (DMARD). Both POLY and MTX significantly attenuated articular damage associated with CFA-induced arthritis. This was manifested by reducing levels of tumor necrosis factor alpha (TNF-α), interleukin-6 (IL-6), interleukin-17 (IL-17), and matrix metalloproteinase-3 (MMP-3), paralleled with marked decrease in hind paw and ankle diameters. Moreover, POLY and MTX downregulated gene expressions of receptor activator of nuclear factor kappa-B ligand (RANKL) as well as signal transducer and activator of transcription-3 (STAT3) besides hampering immunohistochemical staining of vascular endothelial growth factor (VEGF) and nuclear factor kappa-B (NF-κB). Furthermore, substantial decline in myeloperoxidase (MPO) activity and malondialdehyde (MDA) level associated with significant rise in reduced glutathione content (GSH) was observed. These findings provide an innovative therapeutic approach of POLY as a natural anti-arthritic drug through modulating IL-6/STAT-3/IL-17/NF-кB cascade. Graphical Abstract ᅟ.
29298172 Psoriatic Arthritis in Nigeria: Case Series and Literature Review. 2018 Jun BACKGROUND: Psoriatic arthritis (PsA) is an extracutaneous manifestation of psoriasis occurring in 6% to 42% of patients. Both conditions are common among whites but rarely reported among black Africans.Few African studies, however, have reported PsA frequencies of 0% to 4.6%, with a previous case report of 2 patients from a Nigerian rheumatology clinic. METHODS: Case records of PsA patients from the Lagos State University Teaching Hospital Rheumatology Clinic seen over a 5-year period from January 2012 to December 2016 were retrieved and documented.Psoriatic arthritis was diagnosed using the Classification Criteria for Psoriatic Arthritis. Data on demography, clinical features, laboratory parameters, imaging, and treatment were extracted from case records. RESULTS: Twelve PsA cases were identified out of 2330 patients (0.5%) seen during the study period. There were 9 males and 3 females. Age range was 24 to 67 years (mean, 45.3 ± 15.1 years). Duration of psoriasis ranged between 11 and 96 months (mean, 46.8 ± 33.6 months), whereas median duration of arthritis at presentation was 15 months (range, 4-72 months).Oligoarthritis was the commonest presentation (58.3%). Dactylitis (66.7%) and enthesitis (44.7%) were frequent extra-articular features. All patients were negative for rheumatoid factor and human immunodeficiency virus. HLAB27 was negative in 5 patients tested.Treatment was mostly with nonsteroidal anti-inflammatory drugs (100%) and methotrexate (75%). Only 1 patient received the biologic etanercept. Eight subjects (66.6%) showed initial improvement in skin and joint symptoms, of which 6 had a relapse within 6 to 12 months. CONCLUSIONS: Psoriatic arthritis is rare among Nigerians and predominantly affects males in their fourth decade. Oligoarthritis is common, and extra-articular manifestations are frequent.
30232853 [Fire-needle Acupuncture Intervention Relieves Ankle-joint Inflammatory Reactions Possibly 2018 Aug 25 OBJECTIVE: To observe the effect of fire-needle acupuncture of "Zusanli" (ST 36) and "Kunlun" (BL 60) on ankle-joint swelling and serum tumor necrosis factor-α (TNF-α) and anti-cyclic citrullinated peptide antibody (ACPA) contents in collagen-induced arthritis (CIA) rats, so as to study its mechanism underlying improvement of rheumatoid arthritis (RA)．. METHODS: Thirty-two male Wistar rats were randomized into control, model, medication (Methotrexate) and fire-needling groups (n＝8 in each). The RA model was established by injecting type Ⅱ chicken collagen (0.1 mol/L) plus Freund's complete adjuvant (primary immunization) and Freund's incomplete adjuvant (immunization once more) into the subcutaneous tissues of the right foot bottom, back and tail root of rats. Fire-needling was applied to the left and right "Zusanli" (ST 36) and "Kunlun" (BL 60) alternatively for 3 times in each acupoint, once daily for 10 days. For rats of the medication group, Methotrexate sodium chloride solution (0.1 mg/100 g) was administrated by gavage, once every 5 days, twice together. The rats' right hind ankle diameter was measured before and after the treatment. The X-ray film of the right ankle was taken, and the contents of serum TNF-α and ACPA were assayed by ELISA. RESULTS: The ankle diameter and serum concentrations of TNF-α and ACPA were significantly increased in the model group compared to the control group (P<0.05), and X-ray film showed swollen and deformed tarsus joints, and narrowing of the joint space. After the intervention, the ankle diameter, serum TNF-α and ACPA levels were considerably decreased in both medication and fire-needle groups compared with the model group (P<0.05). Meanwhile, the joint swelling and bone deformity became relatively milder. There were no significant differences between the medication and fire-needling groups in the ankle diameter and the contents of serum TNF-α and ACPA (P>0.05). CONCLUSION: Fire-needling stimulation of ST 36 and BL 60, similar to Methotrexate, can relieve the inflammatory reactions of hind-ankle joint in CIA rats, which may be related to its effect in down-regulating ACPA and TNF-α levels.
29650849 [A Case of Resected Reactive Lymphoid Hyperplasia of Liver Suspected of Hepatocellular Car 2018 Apr A 64-year-old woman who had chronic type C viral hepatitis was referred with a liver tumor detected by magnetic resonance imaging(MRI). She had a history of rheumatoid arthritis which was treated by methotrexate. Ethoxybenzyl-MRI(EOBMRI) showed a low signal in the T1-weighted imaging, a high signal in the T2-weighted imaging and a low signal in the hepatobiliary phase. The tumor was 7 millimeters in diameter at S4, and exhibited enhancement in the arterial phase and wash out in the portal phase by contrast enhanced CT. Imaging findings suggested hepatocellular carcinoma, and we performed partial hepatectomy of S4. Histopathological examination confirmed reactive lymphoid hyperplasia(RLH)of liver. RLH of liver is a rare benign lesion and it is necessary to consider RLH as a differential diagnosis of the liver tumor.
29708588 Anti-arthritic properties of crude extract from Chenopodium ambrosioides L. leaves. 2018 Aug OBJECTIVES: To evaluate the effect of hydroalcoholic crude extract (HCE) from Chenopodium ambrosioides leaves on the development of type II collagen-induced arthritis (CIA) and on pro-inflammatory cytokine balance. METHODS: Collagen-induced arthritis was induced in DBA1/J mice. On the 21st day, the mice were treated orally with HCE or methotrexate, daily. Six weeks after beginning the treatment, the following measures were determined: lymphoid organs cell numbers, percentage of blood cells, IL-6, IFN-γ, TNF-α and IL-17 serum concentrations, activity of hepatic and kidney glutathione S-transferase, hepatic 7-ethoxyresorufin-O-deethylase activity, bone density and histopathology. KEY FINDINGS: Treatment of CIA mice with HCE 5 mg/kg (HCE5) reduced the percentage of neutrophils and macrophages and the number of bone marrow cells and increased the lymphocyte numbers and the inguinal lymph node cellularity. This treatment inhibited the serum concentration of IL-6 and TNF-α, which may be related to the preservation of bone density and to the slight thickening of periarticular tissues, with minimal fibrosis and fibroblast proliferation in the joints. The CIA group presented advanced articular erosion and synovial hyperplasia. Phytochemical analysis showed mainly flavonols. CONCLUSIONS: HCE5 presented anti-arthritic potential and reduced IL-6 and TNF-α, which participate directly in the development and maintenance of the inflammatory process in rheumatoid arthritis.
30008749 A Rapidly Fatal Case of Low-Dose Methotrexate Toxicity. 2018 An 82-year-old female presented with multiple oral ulcers and malena for 1 week. Her laboratory tests revealed pancytopenia and acute renal failure. She had history of rheumatoid arthritis for which she was taking 7.5 mg methotrexate weekly and stage 4 chronic kidney disease from diabetic nephropathy. During the hospital stay, she developed pneumonia and septic shock requiring norepinephrine and vasopressin. She underwent continuous venovenous hemodiafiltration. Leucovorin, filgrastim, and multiple packed red blood cell and platelet transfusions were given. She remained hypotensive and pancytopenic despite all interventions. She died on day 6 of hospital stay from acute hypoxic respiratory failure due to septic shock.
30413231 Sunburn Recall Reaction and Mucositis Secondary to Methotrexate Toxicity. 2018 A 59-year-old Native American female presented with a 4-day history of malaise, abdominal pain, nausea, jaundice, and a "sunburn-like rash" on the upper chest and back despite lack of recent sun exposure (Figure 1). Medical history was significant for a twenty-year history of universal vitiligo and a five-year history of rheumatoid arthritis (RA) treated with methotrexate (MTX), adalimumab, prednisone, and naproxen sodium. Cutaneous examination revealed hemorrhagic crusting of upper and lower lips (Figure 2), scleral icterus, diffuse jaundice of the skin, and well-demarcated erythematous patches on mid-upper back and anterior neck. The patient had a few scattered erythematous papules with whitish center on bilateral extensor surfaces of the upper extremities and scattered petechiae on both the trunk and upper extremities.