Pharmacomicrobiology of Methotrexate in Rheumatoid Arthritis: Gut Microbiome as Predictor of Therapeutic Response

Rheumatoid arthritis (RA) is a disabling autoimmune disease with invasive arthritis as the main manifestation and synovitis as the basic pathological change, which can cause progressive destruction of articular cartilage and bone, ultimately leading to joint deformity and loss of function. Since its introduction in the 1980s and its widespread use in the treatment of RA, low-dose methotrexate (MTX) therapy has dramatically changed the course and outcome of RA treatment. The clinical use of this drug will be more rational with a better understanding of the pharmacology, anti-inflammatory mechanisms of action and adverse reaction about it. At present, the current clinical status of newly diagnosed RA is that MTX is initiated first regardless of the patients’ suitability. But up to 50% of patients could not reach adequate clinical efficacy or have severe adverse events. Prior to drug initiation, a prognostic tool for treatment response is lacking, which is thought to be the most important cause of the situation. A growing body of studies have shown that differences in microbial metagenomes (including bacterial strains, genes, enzymes, proteins and/or metabolites) in the gastrointestinal tract of RA patients may at least partially determine their bioavailability and/or subsequent response to MTX. Based on this, some researchers established a random forest model to predict whether different RA patients (with different gut microbiome) would respond to MTX. Of course, MTX, in turn, alters the gut microbiome in a dose-dependent manner. The interaction between drugs and microorganisms is called pharmacomicrobiology. Then, the concept of precision medicine has been raised. In this view, we summarize the characteristics and anti-inflammatory mechanisms of MTX and highlight the interaction between gut microbiome and MTX aiming to find the optimal treatment for patients according to individual differences and discuss the application and prospect of precision medicine.

Evaluation of sexual dysfunction and its predictive factors in female and male patients with rheumatoid arthritis

Background Rheumatoid arthritis (RA) is a common disabling joint disease affecting both males and females. Sexual dysfunction (SD) is a common association with RA. The aim of this work was to study the prevalence and predictors of sexual dysfunction in male and female patients with rheumatoid arthritis. Results The mean age of female patients was 32.1 years and 39.7 years for males. The prevalence of sexual dysfunction was higher in RA female patients than controls, 62.1% versus 41.2% respectively (P ≤ 0.05). The prevalence of global sexual dysfunction was higher in RA male patients than controls, 63.8% versus 47.5% respectively (P ≤ 0.05). Predictors of sexual dysfunction in female RA patients were the number of children, BMI, disease duration, DAS score, HADs-D score, HAQ score, VAS score, joint deformity, and the number of drugs. Predictors of sexual dysfunction in male RA patients were age, disease duration, DAS score, HAQ score, VAS score, and the number of drugs. Conclusion SD is prevalent in RA patients. Disease activity, pain, depression, and disturbed quality of life affect nearly all domains of sexual functions in female and male patients.

Staged Joint Arthrodesis in the Treatment of Severe Septic Ankle Arthritis Sequelae: A Case Report

Septic ankle arthritis is a devastating clinical entity with high risks of morbidity and mortality. Prompt treatment is necessary because delayed or inadequate treatment can lead to irreversible damage that may occur on the articular surface, resulting in cartilage erosion, infective synovitis, osteomyelitis, joint deformity, and pain and joint dysfunction. An aggressive surgical approach is required when a joint infection causes severe limb-threatening arthritis. A 58-year-old woman visited our clinic with increasing pain in the right ankle, which had been present for the previous 2 months. She complained of discomfort in daily life due to deformity of the ankle; limping; and severe pain in the ankle even after walking a little. The patient reported a history of right-ankle injury while exiting a bus in her early 20s. Plain radiographs of the right ankle joint revealed that the medial malleolus was nearly absent in the right ankle joint on the anteroposterior view, and severe varus deformity was observed with osteoarthritic changes because of joint space destruction. Magnetic resonance imaging revealed diffuse synovial thickening of the destroyed tibiotalar joint with joint effusion. Hybrid 99mTc white blood cell single-photon emission computed tomography/computed tomography showed increased uptake along the soft tissue around the ankle joint; uptake was generally low in the talocrural and subtalar joints. A two-stage operation was performed to remove the infected lesions and correct the deformity, thus enabling limb salvage. The patient was nearly asymptomatic at the 6-month follow-up, with no discomfort in her daily life and nearly normal ability to carry out full functional activities. She had no complications or recurrent symptoms at the 1-year follow-up. We have described a rare case of a staged limb salvage procedure in a patient with chronic septic arthritis sequelae. For patients with severe joint deformity because of septic ankle sequelae, staged arthrodesis is a reliable method to remove infected lesions, solve soft tissue problems, correct deformities, and maintain leg length.

Genetic markers for psoriatic arthritis in patients with psoriasis. Part I: non-HLA genes

Psoriatic arthritis often develops in patients with psoriasis and can lead to joint deformity, stiffness, dysfunction, and disability. Psoriatic arthritis is a polygenic disease. and the issue of personalizing the prognosis of its development can only be resolved taking into account the variability of plenty genomic loci associated with the development of the disease. The personification of the prognosis of the disease can be solved taking into account the variability of the set of genomic loci with which its development is associated. The review examines genomic polymorphisms associated with the development of psoriatic arthritis not psoriasis, except of HLA polymorphisms. Genome regions containing polymorphisms, allelic variants of which are associated both with the development of psoriatic arthritis and reducing the likelihood of its occurrence, are described. It has been reported that the predisposition to the development of psoriatic arthritis in patients with psoriasis is determined by genes encoding proteins involved in inflammation and bone metabolism.

Distal transradial artery access for coronary angiography in a patient having rheumatoid arthritis-related severe arthropathies

Conventional radial access has become the default access for coronary angiography. Sometime, it is difficult to take a conventional radial access, especially in patients having severe arthropathies leading to limited wrist joint mobility. In such scenarios, distal transradial access (dTRA) can be adopted. We describe a case of an elderly male patient having rheumatoid arthritis with arthropathies. He presented to us with unstable angina; coronary angiogram was advised for ischaemia assessment. Right dTRA was adopted due to severe joint deformity at wrist joint, limiting joint extension. A successful coronary angiogram was performed via the right dTRA without major discomfort and complications. Haemostasis was secured with TR band radial artery compression device. In this case report, we have evaluated the importance of practising dTRA in a patient with severe arthropathies.

The Combination of Modified Mitchell’s Osteotomy and Shortening Oblique Osteotomy for Patients with Rheumatoid Arthritis: An Analysis of Changes in Plantar Pressure Distribution

The present study aims to evaluate changes in plantar pressure distribution after joint-preserving surgery for rheumatoid forefoot deformity. A retrospective study was performed on 26 feet of 23 patients with rheumatoid arthritis (RA) who underwent the following surgical combination: modified Mitchell’s osteotomy (mMO) of the first metatarsal and shortening oblique osteotomy of the lateral four metatarsals. Plantar pressure distribution and clinical background parameters were evaluated preoperatively and one year postoperatively. A comparison of preoperative and postoperative values indicated a significant improvement in the visual analog scale, Japanese Society for Surgery of the Foot scale, and radiographic parameters, such as the hallux valgus angle. A significant increase in peak pressure was observed at the first metatarsophalangeal joint (MTPJ) (0.045 vs. 0.082 kg/cm2; p < 0.05) and a significant decrease at the second and third MTPJs (0.081 vs. 0.048 kg/cm2; p < 0.05, 0.097 vs. 0.054 kg/cm2; p < 0.05). While overloading at the lateral metatarsal heads following mMO has been reported in previous studies, no increase in peak pressure at the lateral MTPJs was observed in our study. The results of our study show that this surgical combination can be an effective and beneficial surgical combination for RA patients with mild to moderate joint deformity.

Replicative verification of susceptibility genes previously identified from families with segregating developmental dysplasia of the hip

Background Developmental dysplasia of the hip (DDH) is a complex hip joint deformity with effects ranging from acetabulum malformation to irreversible hip dislocation. Previous studies suggest a significant association of four variations, teneurin transmembrane protein 3 (TENM3, OMIM * 610083) (chr4:183721398), heparan sulfate proteoglycan 2 (HSPG2, OMIM * 142461) (chr1:22201470), ATPase plasma membrane Ca2+ transporting 4 (ATP2B4, OMIM * 108732) (chr1:203682345), and prostaglandin F receptor (PTGFR, OMIM * 600563) (chr1:79002214), with DDH susceptibility in families with segregating DDH. However, the association was not validated in sporadic cases and remains controversial. To confirm the association of the reported variations in these four genes with DDH, we conducted replicative verification in 250 sporadic samples with DDH from a Chinese Han population. Methods We conducted Sanger sequencing after amplifying the variation sites. The results were compared with the reference sequence from the GRCh37 assembly in UCSC (http://genome.ucsc.edu). Results Replication analysis of 250 sporadic samples by Sanger sequencing indicated that the four variations, TENM3 (OMIM * 610083, chr4:183721398), HSPG2 (OMIM * 142461, chr1:22201470), ATP2B4 (OMIM * 108732, chr1:203682345), and PTGFR (OMIM * 600563, chr1:79002214), were not associated with the susceptibility to DDH in the Chinese Han population. Conclusions Further studies should be performed to identify other variations of these four genes that are potentially associated with DDH by whole-exome sequencing and the results should be verified in different populations.

The Neurasthenic Nipper-Juvenile Idiopathic Arthritis

Juvenile Idiopathic Arthritis (JIA) is a heterogeneous group of paediatric, idiopathic, inflammatory arthritis exceeding >six weeks duration and commonly arising in children beneath <16 years. International League of Associations for Rheumatology (ILAR) has categorized juvenile idiopathic arthritis into distinctive subclasses as pauciarticular variant or oligoarthritis, Rheumatoid Factor (RF) positive polyarthritis, Rheumatoid Factor (RF) negative polyarthritis, systemic arthritis, psoriatic arthritis, enthesitis-related arthritis and undifferentiated arthritis. The condition is posited to arise from environmental factors, viral or bacterial infection or demonstrates a genetic predisposition. Juvenile idiopathic arthritis depicts decimated joint function with reduced Range of Motion (ROM), joint pain, morning stiffness, limping due to pain in the lower extremities, joint deformity and joint swelling commonly discerned within the knee, hand or foot, anomalous limb growth with leg length discrepancies,, uveitis, reoccurring pyrexia, cutaneous rash, myalgia, weight loss and disorders of skeletal growth. An intense, synovial infiltration of T lymphocytes, B lymphocytes, plasma cells, macrophages and dendritic cells is observed along with villous hyperplasia and hypertrophy, endothelial activation and hyperplasia and hyperplasia of synoviocytes.

Current review of surgical management options for total knee arthroplasty in the rheumatoid knee

Rheumatoid arthritis (RA) represents a condition that can erode cartilage and damage joints, leading to inflammation and loss of movement, characterized by inflammatory synovitis. While the widespread use of potent disease-modifying medications has increased opportunities for RA patients, orthopedic surgery and complete joint arthroplasty remain an important option in end-stage joint treatment. The knee is one of the most frequently affected joints in chronic rheumatoid arthritis patients. The severity of RA ranges from a moderate illness to a serious, rapidly progressing, destructive version, gradually leading to incessant pain and joint deformity. Despite recent advances in biological agents and therapeutic modalities in the field of rheumatology, certain patients with RA, who ultimately undergo joint surgery, tend to experience progressive joint damage. Though, TKA can be performed in these patients, increased complications and poorer outcomes may result after total knee arthroplasty, because of the particularities given by RA. They are associated with extended operating time, specifically resulting in increased infection, blood loss and deep vein thrombosis. However, because RA patients present additional risk factors for complications, certain critical preoperative examination and surgical aspects need to be considered in order to maximize TKA outcomes in this subgroup of patients.