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Acute monoarthritis can be the initial manifestation of many joint disorders. The first step in diagnosis is to verify that the source of pain is the joint, not the surrounding soft tissues. The most common causes of monoarthritis are crystals (i.e., gout and pseudogout), trauma, and infection. A careful history and physical examination are important because diagnostic studies frequently are only supportive. Examination of joint fluid often is essential in making a definitive diagnosis. Leukocyte counts vary widely in septic and sterile synovial fluids and should be interpreted cautiously. If the history and diagnostic studies suggest an infection, aggressive treatment can prevent rapid joint destruction. When an infection is suspected, culture and Gram staining should be performed and antibiotics should be started. Light microscopy may be useful to identify gout crystals, but polarized microscopy is preferred. Blood tests alone never confirm a diagnosis, and radiographic studies are diagnostic only in selected conditions. Referral is indicated when patients have septic arthritis or when the initial evaluation does not determine the etiology. [ABSTRACT FROM AUTHOR]

Renewable, low-carbon biofuels offer the potential opportunity to decarbonize marine transportation. This paper presents a comparative techno-economic analysis and process sustainability assessment of four conversion pathways: (1) hydrothermal liquefaction (HTL) of wet wastes such as sewage sludge and manure; (2) fast pyrolysis of woody biomass; (3) landfill gas Fischer-Tropsch synthesis; and (4) lignin-ethanol oil from the lignocellulosic ethanol biorefinery utilizing reductive catalytic fractionation. These alternative marine biofuels have a modeled minimum fuel selling price between $1.68 and $3.98 per heavy fuel oil gallon equivalent in 2016 U.S. dollars based on a mature plant assessment. The selected pathways also exhibit good process sustainability performance in terms of water intensity compared to the petroleum refineries. Further, the O and S contents of the biofuels vary widely. While the non-HTL biofuels exhibit negligible S content, the raw biocrudes via HTL pathways from sludge and manure show relatively high S contents (>0.5 wt %). Partial or full hydrotreatment can effectively lower the biocrude S content. Additionally, co-feeding with other low-sulfur wet wastes such as food waste can provide another option to produce raw biocrude with lower S content to meet the target with further hydrotreatment. This study indicates that biofuels could be a cost-effective fuel option for the marine sector. Marine biofuels derived from various feedstocks and conversion technologies could mitigate marine biofuel adoption risk in terms of feedstock availability and biorefinery economics.

Objectives: The Scleroderma: Cyclophosphamide or Transplantation (SCOT) trial compared hematopoietic stem cell transplant to CYC treatment in patients with early SSc with progressive skin and lung or kidney involvement. Here we describe lymphocyte phenotype abnormalities at study entry and the relation to prior DMARD therapy., Methods: Lymphocyte subsets (n = 26) measured by flow cytometry were compared in 123 heathy controls and 71 SCOT participants, including those given (n = 57) or not given (n = 14) DMARDs within 12 months of randomization., Results: Compared with healthy controls, individuals with SSc showed significant reductions in central memory CD8 T cells, activated total and CD4 T cells, γ/δ T cells, memory B cells, myeloid and plasmacytoid dendritic cells and FOXP3+CD25+ Treg cells and increases in naïve CD4 T cells, effector memory CD4 T cells and effector CD8 T cells. A greater bias towards a IL-4+ Th2/T cytotoxic 2 (Tc2) phenotype based on the Th2:Th1 CD4 ratio and Tc2:Tc1 CD8 T cells was also found. Notably, no difference in any lymphocyte subset was observed between those given or not given prior DMARDs., Conclusions: In patients with early, severe SSc, significant lymphocyte subset abnormalities were observed. Prior treatment with immunosuppressive therapy did not impact the immunophenotype, suggesting that lymphocyte disturbances in scleroderma appeared to be due to the disease itself., Trial Registration: ClinicalTrials.gov (https://clinicaltrials.gov), NCT00114530., (© The Author(s) 2022. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Purpose: To report the successful use of tofacitinib in the treatment of refractory ocular mucous membrane pemphigoid (MMP)., Observations: Two patients with ocular MMP presented with refractory disease after failure of multiple therapies. Treatment with tofacitinib led to durable control of conjunctival inflammation within 8 weeks and no apparent progression of sub-conjunctival fibrosis. One patient maintained absence of apparent disease activity over 16 months of follow-up. Cessation of tofacitinib in the other patient led to disease relapse which was reversed by re-initiation of therapy., Conclusions and Importance: Small molecule inhibitors of Janus kinases, such as tofacitinib, may offer an effective treatment option for refractory ocular MMP., Competing Interests: The following authors have no financial disclosures: H.J., G.L.P., T.P.M., and M.A.P. R.B. receives speaking fees from Pfizer. P.L.C. owns stocks in Pfizer., (© 2021 The Authors.)

Competing Interests: The authors declare no conflict of interest.

Introduction: The objective of this study was to assess efficacy and safety of repository corticotropin injection (RCI) in subjects with active rheumatoid arthritis (RA) despite treatment with a corticosteroid and one or two disease-modifying antirheumatic drugs (DMARDs)., Methods: All subjects received open-label RCI (80 U) twice weekly for 12 weeks (part 1); only those with low disease activity [LDA; i.e., Disease Activity Score 28 joint count and erythrocyte sedimentation rate (DAS28-ESR) < 3.2] were randomly assigned to receive either RCI (80 U) or placebo twice weekly during the 12-week double-blind period (part 2). The primary efficacy endpoint was the proportion of subjects who achieved LDA at week 12. Secondary efficacy endpoints included proportions of subjects who maintained LDA during weeks 12 through 24 and achieved Clinical Disease Activity Index (CDAI) ≤ 10 at weeks 12 and 24. Safety was assessed via adverse event reports., Results: Of the 259 enrolled subjects, 235 completed part 1; 154 subjects (n = 77 each for RCI and placebo) entered part 2, and 127 (RCI, n = 71; placebo, n = 56) completed. At week 12, 163 subjects (62.9%) achieved LDA and 169 (65.3%) achieved CDAI ≤ 10 (both p < 0.0001). At week 24, 47 (61.0%) RCI-treated and 32 (42.1%) placebo-treated subjects maintained LDA (p = 0.019); 66 (85.7%) RCI-treated and 50 (65.8%) placebo-treated subjects maintained CDAI ≤ 10 (p = 0.004). No unexpected safety signals were observed., Conclusions: RCI was effective and generally safe in patients with active RA despite corticosteroid/DMARD therapy. By week 12, > 60% of patients achieved LDA, which was maintained with 12 additional weeks of treatment. Most patients who achieved LDA maintained it for 3 months after RCI discontinuation., Trial Registration: Clinicaltrials.gov identifier NCT02919761.

Background: Despite current therapies, diffuse cutaneous systemic sclerosis (scleroderma) often has a devastating outcome. We compared myeloablative CD34+ selected autologous hematopoietic stem-cell transplantation with immunosuppression by means of 12 monthly infusions of cyclophosphamide in patients with scleroderma., Methods: We randomly assigned adults (18 to 69 years of age) with severe scleroderma to undergo myeloablative autologous stem-cell transplantation (36 participants) or to receive cyclophosphamide (39 participants). The primary end point was a global rank composite score comparing participants with each other on the basis of a hierarchy of disease features assessed at 54 months: death, event-free survival (survival without respiratory, renal, or cardiac failure), forced vital capacity, the score on the Disability Index of the Health Assessment Questionnaire, and the modified Rodnan skin score., Results: In the intention-to-treat population, global rank composite scores at 54 months showed the superiority of transplantation (67% of 1404 pairwise comparisons favored transplantation and 33% favored cyclophosphamide, P=0.01). In the per-protocol population (participants who received a transplant or completed ≥9 doses of cyclophosphamide), the rate of event-free survival at 54 months was 79% in the transplantation group and 50% in the cyclophosphamide group (P=0.02). At 72 months, Kaplan-Meier estimates of event-free survival (74% vs. 47%) and overall survival (86% vs. 51%) also favored transplantation (P=0.03 and 0.02, respectively). A total of 9% of the participants in the transplantation group had initiated disease-modifying antirheumatic drugs (DMARDs) by 54 months, as compared with 44% of those in the cyclophosphamide group (P=0.001). Treatment-related mortality in the transplantation group was 3% at 54 months and 6% at 72 months, as compared with 0% in the cyclophosphamide group., Conclusions: Myeloablative autologous hematopoietic stem-cell transplantation achieved long-term benefits in patients with scleroderma, including improved event-free and overall survival, at a cost of increased expected toxicity. Rates of treatment-related death and post-transplantation use of DMARDs were lower than those in previous reports of nonmyeloablative transplantation. (Funded by the National Institute of Allergy and Infectious Diseases and the National Institutes of Health; ClinicalTrials.gov number, NCT00114530 .).

Mammals have evolved neurophysiologic reflexes, such as coughing and scratching, to expel invading pathogens and noxious environmental stimuli. It is well established that these responses are also associated with chronic inflammatory diseases, including asthma and atopic dermatitis. However, the mechanisms by which inflammatory pathways promote sensations such as itch remain poorly understood. Here, we show that type 2 cytokines directly activate sensory neurons in both mice and humans. Further, we demonstrate that chronic itch is dependent on neuronal IL-4Rα and JAK1 signaling. We also observe that patients with recalcitrant chronic itch that failed other immunosuppressive therapies markedly improve when treated with JAK inhibitors. Thus, signaling mechanisms previously ascribed to the immune system may represent novel therapeutic targets within the nervous system. Collectively, this study reveals an evolutionarily conserved paradigm in which the sensory nervous system employs classical immune signaling pathways to influence mammalian behavior., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Objective: The Sjögren's Syndrome Foundation clinical practice guidelines (CPGs) are designed to improve quality and consistency of care in Sjögren's syndrome by offering recommendations for management., Methods: Management questions for the systemic manifestations of Sjögren's syndrome were posed by the CPG committee with input from patients and rheumatologists. Clinical questions were assigned to a topic review group that performed systematic reviews and data extraction and drafted guidelines. Quality of evidence and strength of recommendation were rated using the American Society of Clinical Oncology's modification of the Grading of Recommendations Assessment, Development, and Evaluation. Guideline recommendations were reviewed by a consensus expert panel (CEP) composed of 30-40 clinicians from academia and community practices, as well as registered nurses and patients, using a modified Delphi process. A CEP agreement level of 75% was set as a minimum for adoption of a guideline recommendation., Results: Consensus was achieved for 19 recommendations; for 11 additional modules, available data were insufficient to allow a recommendation to be formulated. Of the 19 recommendations, 15 required 1 Delphi round, 2 required 2 rounds, and 2 required 3 rounds., Conclusion: Key recommendations include a decision tree for the use of oral disease-modifying antirheumatic drugs for inflammatory musculoskeletal pain, use of self-care measures and advice regarding exercise to reduce fatigue, and the use of rituximab in selected clinical settings for oral and ocular dryness and for certain extraglandular manifestations, including vasculitis, severe parotid swelling, inflammatory arthritis, pulmonary disease, and mononeuritis multiplex. The CPG committee strongly discouraged the use of tumor necrosis factor inhibitors for sicca symptoms and for the majority of clinical contexts in primary Sjögren's syndrome., (© 2016, American College of Rheumatology.)

Background Context: No previous cases of atlantoaxial instability due to granulomatosis with polyangiitis have been reported., Purpose: The aim of this study was to report a case of granulomatosis with polyangiitis causing atlantoaxial instability., Study Design: This is a case report., Patient Sample: A 45-year-old woman participated in this study., Outcome Measures: The patient's pain and atlantoaxial instability were resolved., Methods: A 45-year-old Caucasian woman with a large ulcerative lesion in her oropharynx initially presented with chronic sinusitis, pharyngitis, and severe odynophagia. Years after her original symptoms began, she developed neck pain radiating into her upper trapezial region and shoulders., Results: Atlantoaxial fusion was performed on the patient, resolving her neck, upper trapezial, and shoulder pain. She was diagnosed with granulomatosis with polyangiitis (formerly Wegener's granulomatosis) and treated with cyclophosphamide., Conclusions: Granulomatosis with polyangiitis should be part of the working differential diagnosis for non-traumatic cervical spine injury. The atlantoaxial instability can be managed with stabilization, and the disease process itself can be treated with cyclophosphamide., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Granulomatosis polyangiitis (GPA, formerly Wegener granulomatosis) is a vasculitis that typically involves the upper respiratory tract, lungs, and kidneys. The 2 established methods to confirm a suspicion of GPA are the antineutrophil cytoplasmic antibody (ANCA) test and biopsy. However, ANCA-negative cases have been known to occur, and it can be difficult to find biopsy evidence of granulomatous disease.We report a case of suspected granulomatosis with polyangiitis limited to the nasopharynx. With a negative ANCA and no histological evidence, our diagnosis was founded on the exclusion of other diagnoses and the response to cyclophosphamide therapy. This case is unique because the patient's lesion resulted in atlantoaxial instability, which required a posterior spinal fusion at C1-C2. This is the first reported case of suspected GPA producing damage to the cervical spine and threatening the spinal cord.

Cervical spine involvement in patients with rheumatoid arthritis (RA) and other inflammatory arthropathies is common. While the radiographic features can be dramatic in untreated disease, patients may remain asymptomatic making treatment decisions challenging. Further, subtle clinical presentations can belie serious myelopathy because peripheral joint involvement can make interpreting the physical exam difficult. While new pharmacologic therapies have drastically reduced the morbidity of the widespread joint destruction that occurs in RA, patients remain at risk for symptomatic occipitocervical, atlantoaxial, or subaxial instability causing myelopathy, deformity, and premature death. In this review, we discuss the clinical presentation of RA patients with cervical spine disease as well as the indications and outcomes of surgical treatment.

Purpose: The research goal of improving patient adherence was assessed in this randomized controlled trial of the outcomes of a 15-min multimedia educational program when compared to educational literature for rheumatoid arthritis (RA) patients., Data Sources: One hundred eight RA patients from a Midwestern rheumatology outpatient clinic completed the self-reported Medication Adherence Questionnaire (MAQ), the Brief Illness Perception Questionnaire (BIPQ), and Health Assessment Questionnaire (HAQ) at baseline and 1 month after education. A paired samples t-test was use for data analyses to determine if there was a significant difference in the change between the groups at preintervention and 1-month postintervention., Conclusions: There were no significant differences in the scores between the two groups from pretest to posttest. Results from this study showed that medication adherence, illness perception, and disability were not improved by use of multimedia or the literature within 1 month., Implications for Practice: Findings from this research study showed that a short multimedia educational program is as effective as printed materials to educate patients with RA about their disease and treatment. However, neither multimedia nor literature affects medication adherence, illness perception, or disability as self-reported by patients with RA., (©2013 American Association of Nurse Practitioners.)

The past decade has brought increasing evidence to support aggressive therapeutic intervention in early rheumatoid arthritis (RA). Treat-to-target strategies that focus on frequent monitoring and treatment adjustments to achieve states of low disease activity or clinical remission have shown superior long-term results. Both oral disease-modifying antirheumatic drugs and biologic agents are effective in treating early RA. It remains unclear if initial combination therapy or biologic use is more effective in early active disease as compared with the traditional approach. The authors review various studies on the treatment of early RA with a focus on studies with a treat-to-target approach., (Copyright © 2012 Elsevier Inc. All rights reserved.)

Objective: To examine whether polymorphisms in genes coding for drug-metabolizing enzymes (DMEs) have an impact on rheumatoid arthritis (RA) risk due to cigarette smoking in African Americans., Methods: Smoking status was evaluated in African American patients with RA compared with non-RA controls, with smoking exposure categorized as heavy smoker (≥10 pack-years) versus never smoker/<10 pack-years. Individuals were genotyped for a homozygous deletion polymorphism in the M1 gene loci of glutathione S-transferase (GSTM1-null) in addition to tagging single-nucleotide polymorphisms (SNPs) in N-acetyltransferase 1 (NAT1), NAT2, and epoxide hydrolase 1 (EPXH1). Associations of these genotypes with RA risk were examined using logistic regression, and gene-smoking interactions were assessed., Results: There were no significant associations of any DME genotype with RA. After adjustment for multiple comparisons, there were significant additive interactions between heavy smoking and the NAT2 SNPs rs9987109 (P(additive) = 0.000003) and rs1208 (P(additive) = 0.00001); the attributable proportion due to interaction ranged from 0.61 to 0.67. None of the multiplicative gene-smoking interactions examined remained significant with regard to overall disease risk, after adjustment for multiple testing. There was no evidence of significant gene-smoking interactions in analyses of GSTM1-null, NAT1, or EPXH1. DME gene-smoking interactions were similar when cases were limited to those patients who were positive for anti-citrullinated protein antibodies., Conclusion: Among African Americans, RA risk imposed by heavy smoking appears to be mediated in part by genetic variation in NAT2. While further studies are needed to elucidate the mechanisms underpinning these interactions, these SNPs appear to identify African American smokers at a much higher risk for RA, in whom the relative risk is at least 2-fold higher when compared to nonsmokers lacking these risk alleles., (Copyright © 2012 by the American College of Rheumatology.)

Objective: To examine the associations of cigarette smoking with rheumatoid arthritis (RA) in African Americans, and to determine whether this association is impacted by the HLA-DRB1 shared epitope (SE)., Methods: Smoking status, cumulative smoking exposure, and SE status were determined in African American patients with RA and African American healthy controls. Associations of smoking with RA were examined using age- and sex-adjusted logistic regression analyses. Additive and multiplicative SE-smoking interactions were examined., Results: After adjustment for age and sex, ever smoking (odds ratio [OR] 1.45, 95% confidence interval [95% CI] 1.07, 1.97) and current smoking (OR 1.56, 95% CI 1.07, 2.26), relative to never smoking, were more common in African American patients with RA (n = 605) than in controls (n = 255). The association of smoking with RA was limited to those with a cumulative exposure exceeding 10 pack-years, associations that were evident both in autoantibody-positive and in autoantibody-negative disease. There was evidence of a significant additive interaction between SE status and heavy smoking (≥10 pack-years) in relation to RA risk (attributable proportion [AP] due to interaction 0.58, P = 0.007), with similar results for the additive interaction between SE status and ever smoking (AP 0.47, P = 0.006). There was no evidence of multiplicative interactions., Conclusion: Among African Americans, cigarette smoking is associated not only with the risk of autoantibody-positive RA but also with the risk of autoantibody-negative disease. The risk of RA attributable to smoking is limited to African Americans with more than 10 pack-years of exposure and is more pronounced among individuals positive for the HLA-DRB1 SE., (Copyright © 2010 by the American College of Rheumatology.)

Objective: To describe radiographic changes in African Americans with rheumatoid arthritis (RA) from the Consortium for the Longitudinal Evaluations of African Americans with Early Rheumatoid Arthritis (CLEAR) Registry, a multicenter observational study., Methods: Self-declared African American patients were enrolled in CLEAR I, a longitudinal cohort of early RA (disease duration of <2 years) from 2000 to 2005, or in CLEAR II, a cross-sectional cohort (any disease duration) from 2006 to the present. Demographic and clinical data were obtained, and sets of hand/wrist and foot radiographs were scored using the modified Sharp/van der Heijde scoring system., Results: A total of 357 and 418 patients were enrolled in CLEAR I and CLEAR II, respectively. We report here an interim analysis of radiographic severity in these patients. For the CLEAR I cohort, 294 patients had a mean radiographic score of 2.89 at the baseline visit; 32.0% showed either erosions (25.9%) or joint space narrowing (JSN; 19.4%). At the 36-month visit, the mean score was 5.65; 44.2% had erosions, 41.5% had JSN, and 54.4% had either. Among those patients without radiographic damage at baseline, 18.9% had progressed at the 36-month visit, compared with 57.1% of those with baseline damage (P < 0.0001). For the CLEAR II cohort, of 167 patients with RA of any duration, 65.3% exhibited joint erosions, 65.3% exhibited JSN, and 74.8% exhibited either. The mean radiographic score was 33.42., Conclusion: To our knowledge, this is the largest radiographic study of African American RA patients. Damage occurs early in the disease and is associated with radiographic progression at 3 years of disease duration. The CLEAR Registry will provide a valuable resource for future analyses of genetic, clinical, and environmental factors associated with radiographic severity of RA in African Americans.

We provide the basics for clinicians who might be called on to consider the diagnosis of diseases such as systemic lupus erythematosus (SLE) or rheumatoid arthritis (RA) in their practice. We will emphasize clinical recognition and first-line laboratory testing. Only characteristics of the classic rheumatic inflammatory diseases (ie, RA, seronegative spondyloarthropathy, SLE, antiphospholipid syndrome, Sjögren syndrome, scleroderma, and polymyositis/dermatomyositis) will be covered. In the past decade, treatment for RA and seronegative spondyloarthropathy has substantially improved. Their treatment has been revolutionized by the use of methotrexate and, more recently, TNF inhibitors, T-cell costimulation modulators, and B-cell depletion. The goal of RA treatment today is to induce a complete remission as early as possible in the disease process, with the mantra being "elimination of synovitis equals elimination of joint destruction." The hope is that if the major mediators of Sjögren syndrome, SLE, or scleroderma can be identified and then blocked, as in the example of TNF inhibitors in patients with RA, more specific treatments will become available. Thus RA has become an excellent model of this evolving paradigm. Through the identification of major mediators in its pathogenesis, novel and highly efficacious therapeutic agents have been developed., (Copyright 2010 American Academy of Allergy, Asthma & Immunology. Published by Mosby, Inc. All rights reserved.)