Distinct Single Cell Gene Expression in Peripheral Blood Monocytes Correlates With Tumor Necrosis Factor Inhibitor Treatment Response Groups Defined by Type I Interferon in Rheumatoid Arthritis.

Previously, we demonstrated in test and validation cohorts that type I IFN (T1IFN) activity can predict non-response to tumor necrosis factor inhibitors (TNFi) in rheumatoid arthritis (RA). In this study, we examine the biology of non-classical and classical monocytes from RA patients defined by their pre-biologic treatment T1IFN activity. We compared single cell gene expression in purified classical (CL, n = 342) and non-classical (NC, n = 359) monocytes. In our previous work, RA patients who had either high IFNß/α activity (>1.3) or undetectable T1IFN were likely to have EULAR non-response to TNFi. In this study comparisons were made among patients grouped according to their pre-biologic treatment T1IFN activity as clinically relevant: "T1IFN undetectable (T1IFN ND) or IFNß/α >1.3" (n = 9) and "T1IFN detectable but IFNß/α ≤ 1.3" (n = 6). In addition, comparisons were made among patients grouped according to their T1IFN activity itself: "T1IFN ND," "T1IFN detected and IFNß/α ≤ 1.3," and "IFNß/α >1.3." Major differences in gene expression were apparent in principal component and unsupervised cluster analyses. CL monocytes from the T1IFN ND or IFNß/α >1.3 group were unlikely to express JAK1 and IFI27 (p < 0.0001 and p 0.0005, respectively). In NC monocytes from the same group, expression of IFNAR1, IRF1, TNFA, TLR4 (p ≤ 0.0001 for each) and others was enriched. Interestingly, JAK1 expression was absent in CL and NC monocytes from nine patients. This pattern most strongly associated with the IFNß/α>1.3 group. Differences in gene expression in monocytes among the groups suggest differential IFN pathway activation in RA patients who are either likely to respond or to have no response to TNFi. Additional transcripts enriched in NC cells of those in the T1IFN ND and IFNß/α >1.3 groups included MYD88, CD86, IRF1, and IL8. This work could suggest key pathways active in biologically defined groups of patients, and potential therapeutic strategies for those patients unlikely to respond to TNFi.

Patient-provider discordance between global assessments of disease activity in rheumatoid arthritis: a comprehensive clinical evaluation.

BACKGROUND: Discordance between patients with rheumatoid arthritis (RA) and their rheumatology health care providers is a common and important problem. The objective of this study was to perform a comprehensive clinical evaluation of patient-provider discordance in RA. METHODS: A cross-sectional observational study was conducted of consecutive RA patients in a regional practice with an absolute difference of ≥ 25 points between patient and provider global assessments (possible points, 0-100). Data were collected for disease activity measures, clinical characteristics, comorbidities, and medications. In a prospective substudy, participants completed patient-reported outcome measures and underwent ultrasonographic assessment of synovial inflammation. Differences between the discordant and concordant groups were tested using χ2 and rank sum tests. Multivariable logistic regression was used to develop a clinical model of discordance. RESULTS: Patient-provider discordance affected 114 (32.5%) of 350 consecutive patients. Of the total population, 103 patients (29.5%) rated disease activity higher than their providers (i.e., 'positive' discordance); only 11 (3.1%) rated disease activity lower than their providers and were excluded from further analysis. Positive discordance correlated with negative rheumatoid factor and anticyclic citrullinated peptide antibodies, lack of joint erosions, presence of comorbid fibromyalgia or depression, and use of opioids, antidepressants, or anxiolytics, or fibromyalgia medications. In the prospective study, the group with positive discordance was distinguished by higher pain intensity, neuropathic type pain, chronic widespread pain and associated polysymptomatic distress, and limited functional health status. Depression was found to be an important mediator of positive discordance in low disease activity whereas the widespread pain index was an important mediator of positive discordance in moderate-to-high disease activity states. Ultrasonography scores did not reveal significant differences in synovial inflammation between discordant and concordant groups. CONCLUSIONS: The findings provide a deeper understanding of patient-provider discordance than previously known. New insights from this study include the evidence that positive discordance is not associated with unrecognized joint inflammation by ultrasonography and that depression and fibromyalgia appear to play distinct roles in determining positive discordance. Further work is necessary to develop a comprehensive framework for patient-centered evaluation and management of RA and associated comorbidities in patients in the scenario of patient-provider discordance.

Determinants of Disability in Rheumatoid Arthritis: A Community-Based Cohort Study.

Longitudinal care of a community-based cohort of patients with rheumatoid arthritis (RA) was evaluated retrospectively. Candidate determinants of disability included visual analog scales (VAS) for patient global assessment and pain, comorbidities, and medications. The outcome was the 'patient-acceptable symptom state' for disability as defined by the Health Assessment Questionnaire (HAQ) disability index, using a cutoff of <1.04. Two-sample t tests and multivariable logistic regression were used to determine odds ratios (OR) for associations between predictor variables and disability. Out of a total of 99 patients, 28 (28%) patients had HAQ ≥1.04 at their last visit. The greatest odds of not attaining the patient-acceptable symptom state in a multivariable model was associated with corticosteroids (OR: 5.1; p=0.02), antidepressants (OR: 5.3; p=0.02), and female sex (OR: 6.5; p=0.05). In the era of biologic therapy, female sex, corticosteroids, and antidepressants remain profound determinants of disability highlighting the need to understand the underlying mechanisms.

Unusual etiology of upper extremity ischemia in a scleroderma patient: thoracic outlet syndrome with arterial embolization.

Although the causes of digital ischemia and necrosis are diverse in women, the most common etiology is connective tissue disease. We describe a patient with scleroderma who presented with arm ischemia secondary to arterial embolization from thoracic outlet syndrome. Her sublavian artery was compressed by the anterior scalene muscle and a cervical rib, leading to a stenosis with poststenotic dilation of the artery. Within the aneurysmal formation was a thrombus, which was probably the source of the distal embolization. The patient underwent surgical resection of the cervical and first rib. The abnormal portion of the subclavian artery was resected and replaced with an interposition graft.

Eosinophilic fasciitis: spectrum of MRI findings.

OBJECTIVE: Our objective was to describe the spectrum of MRI features of eosinophilic fasciitis. CONCLUSION: MRI findings in eosinophilic fasciitis are characteristic and consist of abnormal fascial signal intensity and enhancement, both of which are directly proportional to disease activity. MRI provides a useful aid for diagnosis and a marker for disease activity and response to treatment.

Whipple's disease with destructive arthritis, abdominal lymphadenopathy, and central nervous system involvement.

We describe a patient with Whipple's disease who had an unusual erosive and destructive polyarthritis, massive abdominal lymphadenopathy, asymptomatic central nervous system involvement, and rare manifestations of orbital pseudotumor and orchitis with epididymitis. Taking oral therapy with trimethoprim-sulfamethoxazole he had recurrent flares of orbital pseudotumor, an episode of orchitis with epididymitis, and persistent polymerase chain reaction T. whipplei-positive cerebrospinal fluid. Resolution was achieved with a one month course of intravenous ceftriaxone and a 6 month course of azithromycin, and no relapse occurred during 24 months of followup.

Temporal artery bruits in a patient with giant cell arteritis.

Giant cell arteritis (GCA) is a disease of unknown etiology characterized by granulomatous inflammation of medium and large arteries. A 69-year-old man presented with right jaw claudication, intermittent scalp tenderness without headache, and visibly swollen temporal arteries. Results of a right temporal artery biopsy were positive for GCA. Auscultation revealed audible bruits of the temporal arteries. We believe this is the first reported example of bruits of the temporal arteries as a manifestation of GCA. The condition resolved with corticosteroid therapy.