RESUMO
BACKGROUND: Currently, the use of probiotics to treat inflammatory bowel diseases (IBD) is widely accepted because of their gut microbiota modulation capabilities and anti-inflammatory potential. OBJECTIVE: The aim of this study is to examine the immunomodulatory outcomes of probiotics and sulfasalazine in the acetic acid-induced colitis murine model. METHODS: The animals were randomly assigned to one of the seven groups. Following the induction of colitis, Lactobacillus acidophilus LA-5, Bifidobacterium animalis subsp. lactis BB-12, and sulfasalazine (SASP) were orally administered for 10 days. Subsequently, the in vitro anti-inflammatory effect on TNF-α and IL-10 in the supernatants of cultured spleen cells was assessed via ELISAs. Relative mRNA expression of ZO-1, MLCK, iNOS, TNFR2, ROR-γt, GATA-3, T-bet, and Foxp3 was determined using quantitative reversetranscription polymerase chain reaction (qRTPCR). RESULTS: The SASP plus probiotic mixture was more effective in alleviating colitis symptoms, and reducing disease activity scores, and mucosal inflammation. qRT-PCR analysis revealed a significant reduction in T-bet and RORγt levels, while Foxp3 and GATA-3 levels increased in the colons of colitis mice. In addition, the selected strains substantially inhibited the release of inflammatory markers. Administration of LA-5 + BB-12 + SASP resulted in considerably higher inhibition of NO production and cell proliferation than in the other groups (p < 0.001). Treatment with LA-5 + BB-12 + SASP also reduced TNF-α-mediated apoptosis in intestinal epithelial cells (IECs). CONCLUSIONS: Survey results highlight that the combination regimen could be a promising strategy for IBD therapy, warranting further study of its clinical application and long-term benefits.
Assuntos
Ácido Acético , Colite , Modelos Animais de Doenças , Probióticos , Sulfassalazina , Animais , Probióticos/farmacologia , Camundongos , Sulfassalazina/farmacologia , Sulfassalazina/uso terapêutico , Colite/induzido quimicamente , Colite/tratamento farmacológico , Ácido Acético/farmacologia , Masculino , Lactobacillus acidophilus , Fator de Necrose Tumoral alfa/metabolismo , Anti-Inflamatórios/farmacologia , Bifidobacterium animalis , Proteínas com Domínio T/genética , Proteínas com Domínio T/metabolismo , Microbioma Gastrointestinal/efeitos dos fármacosRESUMO
RATIONALE: Rheumatoid arthritis (RA) is a systemic inflammatory disease characterized by joint inflammation and various extra-articular manifestations, including rheumatoid nodules (RNs). This case study aims to explore the effectiveness of alternative treatments for RNs, particularly highlighting the therapeutic potential of sulfasalazine. PATIENT CONCERNS: A 52-year-old male with established RA presented with worsening joint pain and firm nodules on his elbows, feet, and fingers. DIAGNOSES: The patient fulfilled the diagnostic criteria for RA and was diagnosed with methotrexate-induced RNs based on their temporal association with methotrexate initiation. INTERVENTIONS: Methotrexate was discontinued and a combination of leflunomide and sulfasalazine was initiated. Sulfasalazine led to improvement in both joint pain and nodule size. However, due to cost concerns, the patient discontinued sulfasalazine, resulting in a resurgence of both symptoms and nodule enlargement. Reintroduction of methotrexate resulted in significant improvement in joint inflammation, and notably, no new nodules developed at 6 months follow-up. OUTCOMES: Sulfasalazine demonstrated efficacy in managing RA nodules, suggesting a potential alternative therapy. LESSONS: The case highlights the complex etiology of nodules in RA and emphasizes the importance of individualized treatment approaches and close monitoring for optimal management.
Assuntos
Antirreumáticos , Artrite Reumatoide , Nódulo Reumatoide , Sulfassalazina , Humanos , Sulfassalazina/uso terapêutico , Pessoa de Meia-Idade , Masculino , Nódulo Reumatoide/tratamento farmacológico , Antirreumáticos/uso terapêutico , Artrite Reumatoide/tratamento farmacológico , Metotrexato/uso terapêuticoRESUMO
Aim: Investigating a novel compound, DMPNP, for treating colitis in mice, a key issue in inflammatory bowel diseases (IBD).Methods: Mice with induced colitis received DMPNP (50, 100, 150 mg/kg) or sulfasalazine (SUL), evaluated via tissue assessment, Disease Activity Index (DAI), myeloperoxidase (MPO), nitric oxide (NO) levels and cytokine analysis.Results: DMPNP significantly reduced colitis symptoms, inflammation and oxidative stress at higher doses, with marked improvements in DAI, MPO, NO and cytokines, comparable to SUL results.Conclusion: DMPNP shows potent anti-inflammatory and immunomodulatory properties, indicating potential as an IBD therapeutic. Further clinical trials are suggested to validate these outcomes.
This article focuses on a study testing a new compound, DMPNP, for treating colitis, a challenging aspect of inflammatory bowel disease (IBD). The researchers aimed to determine if DMPNP could alleviate colitis symptoms and serve as an effective treatment option.The study involved mice with induced colitis symptoms, treated with different doses of DMPNP (50, 100, 150 mg/kg). For comparison, another group received sulfasalazine (SUL), a standard IBD medication. The evaluation focused on colon tissue health, disease severity through the Disease Activity Index (DAI) and levels of myeloperoxidase (MPO) and nitric oxide (NO), which are markers of inflammation and oxidative stress. Additionally, the effect of DMPNP on immune cell production and inflammatory gene expression was assessed.The results were encouraging. Mice treated with DMPNP showed significant improvements, particularly at higher doses. Symptoms like inflammation, tissue damage and ulceration in the colon reduced noticeably. The DAI scores, indicative of colitis severity, were substantially lower in the DMPNP group, suggesting reduced disease intensity. Also, decreases in MPO and NO levels indicated less oxidative stress and inflammation. The compound also mirrored sulfasalazine's effects in reducing inflammatory cell and gene production.These findings are crucial as they indicate DMPNP's potential as a new treatment for colitis and possibly other IBD forms. Its effectiveness in reducing inflammation and regulating the immune response, akin to existing treatments but possibly with different advantages, highlights its promise. The study paves the way for more in-depth research and eventual human trials to confirm DMPNP's safety and efficacy in IBD treatment.
Assuntos
Colite , Óxido Nítrico , Piridinas , Animais , Colite/tratamento farmacológico , Colite/induzido quimicamente , Camundongos , Piridinas/química , Piridinas/farmacologia , Piridinas/síntese química , Piridinas/uso terapêutico , Óxido Nítrico/metabolismo , Óxido Nítrico/antagonistas & inibidores , Pirazóis/química , Pirazóis/farmacologia , Pirazóis/síntese química , Citocinas/metabolismo , Citocinas/antagonistas & inibidores , Peroxidase/metabolismo , Sulfassalazina/farmacologia , Sulfassalazina/química , Sulfassalazina/uso terapêutico , Anti-Inflamatórios/química , Anti-Inflamatórios/farmacologia , Anti-Inflamatórios/uso terapêutico , Anti-Inflamatórios/síntese química , Estresse Oxidativo/efeitos dos fármacos , Modelos Animais de Doenças , MasculinoRESUMO
BACKGROUND: Treatments for rheumatoid arthritis (RA) are associated with complex changes in lipids and lipoproteins that may impact cardiovascular (CV) risk. The objective of this study was to examine lipid and lipoprotein changes associated with two common RA treatment strategies, triple therapy or tumor necrosis factor inhibitor (TNFi), and association with CV risk. METHODS: In this secondary data analysis of the TARGET trial, methotrexate (MTX) inadequate responders with RA were randomized to either add sulfasalazine and hydroxychloroquine (triple therapy), or TNFi for 24-weeks. The primary trial outcome was the change in arterial inflammation measured in the carotid arteries or aorta by FDG-PET/CT at baseline and 24-weeks; this change was described as the target-to-background ratio (TBR) in the most diseased segment (MDS). Routine lipids and advanced lipoproteins were measured at baseline and 24-weeks; subjects on statin therapy at baseline were excluded. Comparisons between baseline and follow-up lipid measurements were performed within and across treatment arms, as well as change in lipids and change in MDS-TBR. RESULTS: We studied 122 participants, 61 in each treatment arm, with median age 57 years, 76% female, and 1.5 year median RA disease duration. When comparing treatment arms, triple therapy had on average a larger reduction in triglycerides (15.9 mg/dL, p = 0.01), total cholesterol to HDL-C ratio (0.29, p-value = 0.01), and LDL particle number (111.2, p = 0.02) compared to TNFi. TNFi had on average a larger increase in HDL particle number (1.6umol/L, p = 0.006). We observed no correlation between change in lipid measurements and change in MDS-TBR within and across treatment arms. CONCLUSIONS: Both treatment strategies were associated with improved lipid profiles via changes in different lipids and lipoproteins. These effects had no correlation with change in CV risk as measured by vascular inflammation by FDG-PET/CT. TRIAL REGISTRATION: ClinicalTrials.gov ID NCT02374021.
Assuntos
Antirreumáticos , Artrite Reumatoide , Quimioterapia Combinada , Hidroxicloroquina , Lipídeos , Metotrexato , Humanos , Artrite Reumatoide/tratamento farmacológico , Artrite Reumatoide/sangue , Feminino , Pessoa de Meia-Idade , Masculino , Antirreumáticos/uso terapêutico , Hidroxicloroquina/uso terapêutico , Lipídeos/sangue , Metotrexato/uso terapêutico , Idoso , Sulfassalazina/uso terapêutico , Adulto , Inibidores do Fator de Necrose Tumoral/uso terapêutico , Resultado do Tratamento , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada/métodos , Vasculite/tratamento farmacológico , Vasculite/sangueRESUMO
BACKGROUND: Despite the high prevalence of neuropathic pain, treating this neurological disease remains challenging, given the limited efficacy and numerous side effects associated with current therapies. The complexity in patient management is largely attributed to an incomplete understanding of the underlying pathological mechanisms. Central sensitization, that refers to the adaptation of the central nervous system to persistent inflammation and heightened excitatory transmission within pain pathways, stands as a significant contributor to persistent pain. Considering the role of the cystine/glutamate exchanger (also designated as system xc-) in modulating glutamate transmission and in supporting neuroinflammatory responses, we investigated the contribution of this exchanger in the development of neuropathic pain. METHODS: We examined the implication of system xc- by evaluating changes in the expression/activity of this exchanger in the dorsal spinal cord of mice after unilateral partial sciatic nerve ligation. In this surgical model of neuropathic pain, we also examined the consequence of the genetic suppression of system xc- (using mice lacking the system xc- specific subunit xCT) or its pharmacological manipulation (using the pharmacological inhibitor sulfasalazine) on the pain-associated behavioral responses. Finally, we assessed the glial activation and the inflammatory response in the spinal cord by measuring mRNA and protein levels of GFAP and selected M1 and M2 microglial markers. RESULTS: The sciatic nerve lesion was found to upregulate system xc- at the spinal level. The genetic deletion of xCT attenuated both the amplitude and the duration of the pain sensitization after nerve surgery, as evidenced by reduced responses to mechanical and thermal stimuli, and this was accompanied by reduced glial activation. Consistently, pharmacological inhibition of system xc- had an analgesic effect in lesioned mice. CONCLUSION: Together, these observations provide evidence for a role of system xc- in the biochemical processes underlying central sensitization. We propose that the reduced hypersensitivity observed in the transgenic mice lacking xCT or in sulfasalazine-treated mice is mediated by a reduced gliosis in the lumbar spinal cord and/or a shift in microglial M1/M2 polarization towards an anti-inflammatory phenotype in the absence of system xc-. These findings suggest that drugs targeting system xc- could contribute to prevent or reduce neuropathic pain.
Assuntos
Sistema y+ de Transporte de Aminoácidos , Neuralgia , Doenças Neuroinflamatórias , Animais , Feminino , Camundongos , Sistema y+ de Transporte de Aminoácidos/antagonistas & inibidores , Sistema y+ de Transporte de Aminoácidos/deficiência , Sistema y+ de Transporte de Aminoácidos/genética , Sistema y+ de Transporte de Aminoácidos/metabolismo , Biomarcadores/metabolismo , Proteína Glial Fibrilar Ácida/genética , Proteína Glial Fibrilar Ácida/metabolismo , Gliose/complicações , Gliose/tratamento farmacológico , Gliose/fisiopatologia , Ácido Glutâmico/metabolismo , Hiperalgesia/tratamento farmacológico , Camundongos Transgênicos , Microglia/efeitos dos fármacos , Microglia/metabolismo , Microglia/patologia , Neuralgia/complicações , Neuralgia/tratamento farmacológico , Neuralgia/fisiopatologia , Neuralgia/prevenção & controle , Doenças Neuroinflamatórias/complicações , Doenças Neuroinflamatórias/tratamento farmacológico , Doenças Neuroinflamatórias/fisiopatologia , Doenças Neuroinflamatórias/prevenção & controle , Fenótipo , Reprodutibilidade dos Testes , RNA Mensageiro/efeitos dos fármacos , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Neuropatia Ciática/complicações , Neuropatia Ciática/fisiopatologia , Medula Espinal/efeitos dos fármacos , Medula Espinal/patologia , Medula Espinal/fisiopatologia , Sulfassalazina/farmacologia , Sulfassalazina/uso terapêuticoRESUMO
BACKGROUND: Etanercept has been studied in doses up to 0.8 mg/kg/week (max 50 mg/week) in juvenile idiopathic arthritis (JIA) patients. In clinical practice higher doses are used off-label, but evidence regarding the relation with outcomes is lacking. We describe the clinical course of JIA-patients receiving high-dose etanercept (1.6 mg/kg/week; max 50 mg/week) in the BeSt for Kids trial. METHODS: 92 patients with oligoarticular JIA, RF-negative polyarticular JIA or juvenile psoriatic arthritis were randomised across three treat-to-target arms: (1) sequential DMARD-monotherapy (sulfasalazine or methotrexate (MTX)), (2) combination-therapy MTX + 6 weeks prednisolone and (3) combination therapy MTX + etanercept. In any treatment-arm, patients could eventually escalate to high-dose etanercept alongside MTX 10mg/m2/week. RESULTS: 32 patients received high-dose etanercept (69% female, median age 6 years (IQR 4-10), median 10 months (7-16) from baseline). Median follow-up was 24.6 months. Most clinical parameters improved within 3 months after dose-increase: median JADAS10 from 7.2 to 2.8 (p = 0.008), VAS-physician from 12 to 4 (p = 0.022), VAS-patient/parent from 38.5 to 13 (p = 0.003), number of active joints from 2 to 0.5 (p = 0.12) and VAS-pain from 35.5 to 15 (p = 0.030). Functional impairments (CHAQ-score) improved more gradually and ESR remained stable. A comparable pattern was observed in 11 patients (73% girls, median age 8 (IQR 6-9)) who did not receive high-dose etanercept despite eligibility (comparison group). In both groups, 56% reached inactive disease at 6 months. No severe adverse events (SAEs) occurred after etanercept dose-increase. In the comparison group, 2 SAEs consisting of hospital admission occurred. Rates of non-severe AEs per subsequent patient year follow-up were 2.27 in the high-dose and 1.43 in the comparison group. CONCLUSIONS: Escalation to high-dose etanercept in JIA-patients who were treated to target was generally followed by meaningful clinical improvement. However, similar improvements were observed in a smaller comparison group who did not escalate to high-dose etanercept. No SAEs were seen after escalation to high-dose etanercept. The division into the high-dose and comparison groups was not randomised, which is a potential source of bias. We advocate larger, randomised studies of high versus regular dose etanercept to provide high level evidence on efficacy and safety. TRIAL REGISTRATION: Dutch Trial Register; NTR1574; 3 December 2008; https://onderzoekmetmensen.nl/en/trial/26585 .
Assuntos
Antirreumáticos , Artrite Juvenil , Quimioterapia Combinada , Etanercepte , Metotrexato , Humanos , Artrite Juvenil/tratamento farmacológico , Etanercepte/administração & dosagem , Etanercepte/uso terapêutico , Etanercepte/efeitos adversos , Feminino , Masculino , Criança , Antirreumáticos/administração & dosagem , Antirreumáticos/uso terapêutico , Metotrexato/administração & dosagem , Metotrexato/uso terapêutico , Pré-Escolar , Relação Dose-Resposta a Droga , Resultado do Tratamento , Prednisolona/administração & dosagem , Sulfassalazina/administração & dosagem , Sulfassalazina/uso terapêuticoRESUMO
OBJECTIVE: There are various combination conventional synthetic disease-modifying-antirheumatic drug (csDMARD) treatment strategies used in rheumatoid arthritis (RA). A commonly used csDMARD combination is triple therapy with methotrexate (MTX), sulfasalazine (SSZ) and hydroxychloroquine (HCQ). Another approach is double therapy with MTX and leflunomide (LEF). We compared the real-world retention of these two treatment combinations. METHODS: Patients with RA from the Ontario Best Practices Research Initiative (OBRI) who received triple or double therapy on or after OBRI enrolment were included. Retention rates were compared between these two groups. We also analyzed which medication in the combination was discontinued and the reasons for treatment discontinuation. Disease activity was assessed at baseline, 6 and 12 months after treatment initiation as well as at time of discontinuation. Risk factors for treatment discontinuation were also examined. RESULTS: Six hundred and ninety-two patients were included (258 triple and 434 double therapy). There were 175 (67.8%) discontinuations in the triple therapy group and 287 (66.1%) discontinuations in patients on double therapy. The median survival for triple therapy was longer (15.1 months; 95% CI: 11.2-21.2) compared to double therapy (9.6 months; 95%CI: 7.03-12.2). However, this was not statistically significant. Disease activity at 6 and 12 months, measured by 28-joint count Disease Activity Score based on erythrocyte sedimentation rate (DAS28-ESR) was lower with triple therapy (mean DAS28 at 6 months 3.4 vs. 3.9, P<0.0001 and at 12 months 3.2 vs. 3.5, P=0.0005). CONCLUSION: Patients on triple therapy remained on treatment longer than patients on double therapy. However, this difference was not statistically significant.
Assuntos
Antirreumáticos , Artrite Reumatoide , Quimioterapia Combinada , Hidroxicloroquina , Leflunomida , Metotrexato , Sulfassalazina , Humanos , Artrite Reumatoide/tratamento farmacológico , Hidroxicloroquina/uso terapêutico , Hidroxicloroquina/administração & dosagem , Leflunomida/uso terapêutico , Leflunomida/administração & dosagem , Sulfassalazina/uso terapêutico , Sulfassalazina/administração & dosagem , Metotrexato/uso terapêutico , Metotrexato/administração & dosagem , Feminino , Masculino , Pessoa de Meia-Idade , Antirreumáticos/uso terapêutico , Antirreumáticos/administração & dosagem , Idoso , Resultado do Tratamento , Adulto , Estudos Retrospectivos , Isoxazóis/uso terapêutico , Isoxazóis/administração & dosagem , Índice de Gravidade de DoençaRESUMO
We report a 9-year-old Japanese girl with chronic non-bacterial osteomyelitis (CNO) accompanied by recurrent erythema nodosum (EN) which was successfully treated with salazosulfapyridine (SASP). She was referred to our hospital because of recurrent erythema on her lower extremities and persistent knee and ankle arthralgia, which had been present for approximately 1 year. Although naproxen, a nonsteroidal anti-inflammatory drug, was initiated, her symptoms frequently recurred. Magnetic resonance imaging demonstrated multiple distinct high-intensity signals in the talus bones suggestive of multiple bone oedemas. Additionally, a histological examination of erythematous lesions was consistent with the histopathological findings of EN. She was diagnosed as having CNO complicated by EN, and received 250 mg/day of SASP as a second-line treatment, which showed partial response of both skin and bone lesions. Following increase in the dose of SASP to 500 mg/day resulted in complete remission of her skin and bone lesions. In conclusion, our findings suggest that SASP is effective not only for CNO bone lesions but also for EN. SASP could serve as a second-line therapeutic option at least for some cases of CNO complicated by EN refractory to nonsteroidal anti-inflammatory drugs.
Assuntos
Eritema Nodoso , Osteomielite , Sulfassalazina , Humanos , Feminino , Eritema Nodoso/tratamento farmacológico , Eritema Nodoso/diagnóstico , Eritema Nodoso/etiologia , Osteomielite/tratamento farmacológico , Osteomielite/diagnóstico , Osteomielite/etiologia , Criança , Resultado do Tratamento , Sulfassalazina/uso terapêutico , Sulfassalazina/administração & dosagem , Doença Crônica , Imageamento por Ressonância MagnéticaRESUMO
BACKGROUNDS: Acute anterior uveitis (AAU) is the most common extra-musculoskeletal manifestation in axial spondyloarthritis (axSpA). OBJECTIVES: The aim of the study is to evaluate the factors associated with AAU attacks in patients with axSpA during a 36-month follow-up period. METHODS: In total, 469 patients with axSpA were included in this observational study. Demographic data, clinical characteristics, disease activity measurements, and treatment patterns were compared between patients with and without a history of AAU. The development of AAU and its related factors were investigated using generalized estimating equations, which is a technique for longitudinal data analysis. RESULTS: Overall, 99 (21%) out of 469 patients experienced at least one AAU attack, with 77 patients (78%) having a history of AAU and 53 patients (58% of whom had a history of AAU) experiencing AAU attacks during the follow-up period. At baseline, patients with a history of AAU were found to be older (p = .001), be more likely to have peripheral arthritis (p < .001), have higher serum CRP levels (p = .016), have a higher frequency of sulfasalazine (SLZ) and tumor necrosis factor inhibitors (TNFi) use (p < .001 and p < .001, respectively). In the longitudinal analysis, having a history of AAU was identified as the only independent determinant of the development of AAU. CONCLUSIONS: AAU history might be a risk factor for the development of AAU attacks in patients with axSpA. Although TNFi and SLZ were prescribed more frequently to patients with a history of AAU, the effectiveness of these agents in preventing further AAU attacks was not demonstrated.
Assuntos
Espondiloartrite Axial , Espondilartrite , Espondilite Anquilosante , Uveíte Anterior , Humanos , Estudos Longitudinais , Espondilartrite/diagnóstico , Espondilartrite/tratamento farmacológico , Espondilartrite/epidemiologia , Espondilite Anquilosante/tratamento farmacológico , Uveíte Anterior/diagnóstico , Uveíte Anterior/tratamento farmacológico , Uveíte Anterior/epidemiologia , Sulfassalazina/uso terapêutico , Doença AgudaRESUMO
OBJECTIVE: Ferroptosis has been reported to play a role in rheumatoid arthritis (RA). Sulfasalazine, a common clinical treatment for ankylosing spondylitis, also exerts pathological influence on the progression of rheumatoid arthritis including the induced ferroptosis of fibroblast-like synoviocytes (FLSs), which result in the perturbated downstream signaling and the development of RA. The aim of this study was to investigate the underlying mechanism so as to provide novel insight for the treatment of RA. METHODS: CCK-8 and Western blotting were used to assess the effect of sulfasalazine on FLSs. A collagen-induced arthritis mouse model was constructed by the injection of collagen and Freund's adjuvant, and then, mice were treated with sulfasalazine from day 21 after modeling. The synovium was extracted and ferroptosis was assessed by Western blotting and immunofluorescence staining. RESULTS: The results revealed that sulfasalazine promotes ferroptosis. Compared with the control group, the expression levels of ferroptosis-related proteins such as glutathione peroxidase 4, ferritin heavy chain 1, and solute carrier family 7, member 11 (SLC7A11) were lower in the experimental group. Furthermore, deferoxamine inhibited ferroptosis induced by sulfasalazine. Sulfasalazine-promoted ferroptosis was related to a decrease in ERK1/2 and the increase of P53. CONCLUSIONS: Sulfasalazine promoted ferroptosis of FLSs in rheumatoid arthritis, and the PI3K-AKT-ERK1/2 pathway and P53-SLC7A11 pathway play an important role in this process.
Assuntos
Artrite Reumatoide , Ferroptose , Camundongos , Animais , Sulfassalazina/farmacologia , Sulfassalazina/uso terapêutico , Proteínas Proto-Oncogênicas c-akt/metabolismo , Proteína Supressora de Tumor p53/metabolismo , Sistema de Sinalização das MAP Quinases , Fosfatidilinositol 3-Quinases/metabolismo , Artrite Reumatoide/metabolismo , Células Cultivadas , Proliferação de CélulasRESUMO
In the past two decades, the treatment of juvenile idiopathic arthritis (JIA) has evolved markedly, owing to the availability of a growing number of novel, potent and relatively safe therapeutic agents and the shift of management strategies towards early achievement of disease remission. However, JIA encompasses a heterogeneous group of diseases that require distinct treatment approaches. Furthermore, some old drugs, such as methotrexate, sulfasalazine and intraarticular glucocorticoids, still maintain an important therapeutic role. In the past 5 years, information on the efficacy and safety of drug therapies for JIA has been further enriched through the accomplishment of several randomized controlled trials of newer biologic and synthetic targeted DMARDs. In addition, a more rational therapeutic approach has been fostered by the promulgation of therapeutic recommendations and guidelines. A multinational collaborative effort has led to the development of the recommendations for the treat-to-target strategy in JIA. There is currently increasing interest in establishing the optimal time and modality for discontinuation of treatment in children with JIA who achieve sustained clinical remission. The aim of this Review is to summarize the current evidence and discuss the therapeutic approaches to the management of non-systemic phenotypes of JIA, including oligoarthritis, polyarthritis, enthesitis-related arthritis and psoriatic arthritis.
Assuntos
Antirreumáticos , Artrite Juvenil , Artrite Psoriásica , Criança , Humanos , Artrite Juvenil/tratamento farmacológico , Antirreumáticos/uso terapêutico , Metotrexato/uso terapêutico , Sulfassalazina/uso terapêutico , Artrite Psoriásica/tratamento farmacológico , Resultado do TratamentoRESUMO
Sulfasalazine is a prodrug known to be effective for the treatment of inflammatory bowel disease (IBD)-associated peripheral spondyloarthritis (pSpA), but the mechanistic role for the gut microbiome in regulating its clinical efficacy is not well understood. Here, treatment of 22 IBD-pSpA subjects with sulfasalazine identifies clinical responders with a gut microbiome enriched in Faecalibacterium prausnitzii and the capacity for butyrate production. Sulfapyridine promotes butyrate production and transcription of the butyrate synthesis gene but in F. prausnitzii in vitro, which is suppressed by excess folate. Sulfasalazine therapy enhances fecal butyrate production and limits colitis in wild-type and gnotobiotic mice colonized with responder, but not non-responder, microbiomes. F. prausnitzii is sufficient to restore sulfasalazine protection from colitis in gnotobiotic mice colonized with non-responder microbiomes. These findings reveal a mechanistic link between the efficacy of sulfasalazine therapy and the gut microbiome with the potential to guide diagnostic and therapeutic approaches for IBD-pSpA.
Assuntos
Colite , Microbioma Gastrointestinal , Doenças Inflamatórias Intestinais , Humanos , Camundongos , Animais , Sulfassalazina/farmacologia , Sulfassalazina/uso terapêutico , Doenças Inflamatórias Intestinais/tratamento farmacológico , Resultado do Tratamento , ButiratosRESUMO
Pyoderma gangrenosum manifests as recurrent deep ulceration of the skin and is associated with a variety of disorders. We report a 40-year-old man who developed ulcers on the flexor surface of his right lower limb following a trauma 10 years prior to the current presentation. He was diagnosed with ulcerative colitis 20 years ago, and was previously placed on sulfasalazine and prednisolone. He also developed an enterocutaneous fistula at the right iliac fossa following an appendectomy he had 16 years previously. Mayo score of his ulcerative colitis was severe (11/12), and he received three courses of intravenous infliximab at irregular intervals as it was difficult to access Infliximab in Nigeria. He was stepped down to tablet Mesalazine after the third course due to cost considerations, and skin grafting was done for the extensive leg ulcer to achieve wound healing after failed steroid and sulfasalazine therapy.
Le pyoderma gangrenosum se manifeste par des ulcères profonds récurrents de la peau et est associé à divers troubles. Nous rapportons le cas d'un homme de 40 ans qui a développé des ulcères sur la face antérieure de sa jambe droite suite à un traumatisme survenu 10 ans avant la présentation actuelle. Il a été diagnostiqué d'une rectocolite hémorragique il y a 20 ans et avait précédemment été traité par sulfasalazine et prednisolone. Il a également développé une fistule entérocutanée à la fosse iliaque droite suite à une appendicectomie subie 16 ans auparavant. Le score de Mayo de sa rectocolite hémorragique était sévère (11/12), et il a reçu trois cures d'infliximab par voie intraveineuse à des intervalles irréguliers en raison de la difficulté d'accès à l'infliximab au Nigeria. Il est passé à la mésalazine en comprimés après la troisième cure en raison de considérations budgétaires, et une greffe de peau a été réalisée pour l'ulcère étendu de la jambe afin d'obtenir une cicatrisation après l'échec du traitement par stéroïdes et sulfasalazine. Mots-clés: pyoderma gangrenosum, Rectocolite hémorragique, Infliximab, Africain, Ulcères aphteux.
Assuntos
Colite Ulcerativa , Pioderma Gangrenoso , Masculino , Humanos , Adulto , Colite Ulcerativa/complicações , Colite Ulcerativa/tratamento farmacológico , Colite Ulcerativa/diagnóstico , Pioderma Gangrenoso/diagnóstico , Pioderma Gangrenoso/tratamento farmacológico , Pioderma Gangrenoso/etiologia , Sulfassalazina/uso terapêutico , Úlcera/complicações , Infliximab/uso terapêuticoRESUMO
Ulcerative colitis is a chronic inflammatory disease with high mortality and morbidity worldwide. It causes inflammation in the lining of the colon, resulting in several symptoms that negatively impact the quality of life. Unfortunately, there is currently no known cure for this condition. Therefore, it is crucial to explore alternative treatment approaches. This research aimed to investigate the anti-inflammatory and antioxidative effects of a combination therapy involving Sulfasalazine+Ezetimibe compared to Sulfasalazine alone in a rat model of ulcerative colitis. Forty adult rats were divided into four groups for this study. The groups consisted of a control group (negative control), an acetic acid group (positive control), an acetic acid+Sulfasalazine (100 mg/kg per day) group, and an acetic acid+Sulfasalazine (50 mg/kg)+Ezetimibe (5 mg/kg) group. Rats were treated for one week, and colitis was induced by administering 2 ml of 4% (v/v) acetic acid inter-rectally. After sacrifice, the colonic tissue homogenate was analyzed for several markers, including proinflammatory cytokines (TNF-α, IL-1ß, NF-κB), oxidative stress markers (malondialdehyde, myeloperoxidase), and adhesive molecule markers (E-selectin, ICAM-1). Sulfasalazine and the combination of Sulfasalazine+Ezetimibe significantly reduced the colonic levels of TNF-α, IL-1ß, NF-κB, MDA, and E-selectin in the homogenate. However, the combination therapy of Sulfasalazine and Ezetimibe demonstrated a superior effect.
Assuntos
Colite Ulcerativa , Colite , Ratos , Animais , Sulfassalazina/uso terapêutico , Sulfassalazina/farmacologia , Colite Ulcerativa/tratamento farmacológico , Selectina E , NF-kappa B/farmacologia , Fator de Necrose Tumoral alfa , Qualidade de Vida , Colite/induzido quimicamente , Colo , Biomarcadores , Acetatos/efeitos adversosRESUMO
OBJECTIVE: We sought to investigate the reasons why spondyloarthritis (SpA) patients failed to respond to non-steroidal anti-inflammatory drugs (NSAIDs) and conventional synthetic disease-modifying antirheumatic drugs (cDMARDs) and the influences of different initial cDMARDs on the likelihood of a switch to biologics. METHODS: SpA patients were divided into a conventional drug maintenance group and a biologics conversion group to determine the causes of conversion to biologics. Then, we divided all patients into three groups according to different initial cDMARDs, NSAID monotherapy, NSAID + (sulfasalazine or thalidomide) double combination, and NSAID + sulfasalazine + thalidomide triple combination therapy groups, to clarify the influence of initial treatment on later conversion to biologics. RESULTS: This study includes 202 patients, including 97 patients in the conventional drug maintenance group and 105 patients in the biologics conversion group. The mean age of the conventional drug maintenance group was higher than that of the biologics conversion group (40.8 ± 14.3 vs. 33.8 ± 12.3 years, P < 0.05). Uveitis (OR 5.356, P < 0.05) is positively correlated with conversion to biological therapy, while age (OR 0.940, P < 0.05) is negatively correlated. The proportion of NSAID monotherapy, double combination, and triple combination groups converted to biological agents was 80%, 51.1%, and 23.2%, respectively (P < 0.05). CONCLUSION: Age and uveitis are related to conversion to biologics therapy. The early combination of sulfasalazine and thalidomide with NSAIDs may lower the probability of conversion to biologics therapy in the later stage and offer a new option for patients with limited use of biologics in SpA patients. Key Points ⢠Patients' move to biologics may be caused mostly by inadequate disease control by conventional oral medications. ⢠Regardless of axial vs. peripheral joint involvement, combination drug therapy was superior to single drug therapy in controlling SpA and decreasing the probability of conversion to a biological agent. ⢠For SpA patients who are not candidates for biologics due to contraindications or other reasons, early combination application of NSAIDs, sulfasalazine, and thalidomide may be a new choice.
Assuntos
Antirreumáticos , Produtos Biológicos , Espondilartrite , Uveíte , Humanos , Produtos Biológicos/uso terapêutico , Sulfassalazina/uso terapêutico , Talidomida/uso terapêutico , Espondilartrite/tratamento farmacológico , Antirreumáticos/uso terapêutico , Anti-Inflamatórios não Esteroides/uso terapêutico , Fatores Biológicos/uso terapêutico , Analgésicos/uso terapêutico , Uveíte/tratamento farmacológicoRESUMO
In patients with suspected phaeochromocytoma, biochemical screening of urine or blood for excess secretion catecholamines and/or their metabolites is performed. Elevated levels of catecholamines and metanephrines help in establishing the diagnosis of phaeochromocytoma. In two patients with adrenal lesions who were subjected to biochemical testing significantly elevated urinary normetanephrines appeared to establish the diagnosis of phaeochromocytoma. However, on subsequent investigations, this was demonstrated to be a 'false positive' finding. Both these patients were on sulfasalazine, an anti-inflammatory drug used in inflammatory bowel disease, rheumatoid arthritis and ankylosing spondylitis. Sulfasalazine can cause analytical interference in some assays for urinary normetanephrine and result in spuriously elevated levels, leading to misdiagnosis of phaeochromocytoma. In this report, one patient underwent adrenalectomy and another had conservative management.Although this has been previously reported, increased awareness of the possibility of false-positive results on urinary metanephrines testing is important to reduce the potential for misdiagnosis and unnecessary treatment.
Assuntos
Neoplasias das Glândulas Suprarrenais , Feocromocitoma , Humanos , Feocromocitoma/diagnóstico , Feocromocitoma/cirurgia , Sulfassalazina/uso terapêutico , Normetanefrina , Neoplasias das Glândulas Suprarrenais/diagnóstico , MetanefrinaRESUMO
Interleukin 17A (IL-17A) inhibitors, such as secukinumab, have been widely used as the mainstream treatment for chronic plaque psoriasis; however, cutaneous adverse events have been reported. Here, we report a 43-year-old Chinese man who developed herpetiform pemphigus (HP) during secukinumab treatment for his psoriasis. He presented with (1) clinical features of HP, which resembled bullous pemphigoid; histopathological features of intraepidermal blisters, eosinophilic/neutrophilic spongiosis, and liquefactive degeneration of the basal cell layer; (3) positive anti-desmoglein 1 antibody by enzyme-linked immunosorbent assay and cell surface IgG reactivity within the epidermis by indirect immunofluorescence assay; and (4) a satisfactory response to salicylazosulfapyridine (sulfasalazine). To the best of our knowledge, this is the first report of the development of HP after the use of secukinumab for psoriasis.
Assuntos
Penfigoide Bolhoso , Pênfigo , Psoríase , Adulto , Humanos , Masculino , Penfigoide Bolhoso/induzido quimicamente , Penfigoide Bolhoso/diagnóstico , Penfigoide Bolhoso/tratamento farmacológico , Pênfigo/patologia , Psoríase/diagnóstico , Psoríase/tratamento farmacológico , Sulfassalazina/uso terapêuticoRESUMO
Ulcerative Colitis (UC) is a chronic idiopathic inflammatory bowel disease in which the colon's lining becomes inflamed. Exploring herbal remedies that can recover mucosal damage is becoming popular in UC. The study aims to investigate the probable colo-protective effect of a natural isoflavone, genistein (GEN), and/or a drug, sulfasalazine (SZ), against acetic acid (AA)-induced UC in rats, in addition to exploring the possible underlying mechanisms. UC was induced by the intrarectal installation of 1-2 ml of 5% diluted AA for 24 h. Ulcerated rats were allocated into the disease group and three treated groups, with SZ (100 mg/kg), GEN (100 mg/kg), and their combination for 14 days, besides the control groups. The anti-colitic efficacy of GEN and/or SZ was evidenced by hindering the AA-induced weight loss, colon edema, and macroscopic scores, besides reduced disease activity index and colon weight/length ratio. Furthermore, treatments attenuated the colon histopathological injury scores, increased the number of goblet cells, and lessened fibrosis. Both treatments reduced the up-regulation of INF-γ/JAK1/STAT1 and INF-γ /TLR-4/ NF-κB signaling pathways and modulated the IRF-1/iNOS/NO and IL-6/JAK2/STAT3/COX-2 pathways and consequently, reduced the levels of TNF-α and IL-1ß. Moreover, both treatments diminished oxidative stress, which appeared by reducing the MPO level and elevating the SOD activity, and hindered apoptosis; proved by the decreased immunohistochemical expression of caspase-3. The current findings offer novel insights into the protective effects of GEN and suggest a superior benefit of combining GEN with SZ, over either drug alone, in the UC management.