The objective of this study was to identify specific histopathological features of skeletal muscle involvement in systemic sclerosis (SSc) patients.
A total of 35 out of 112 SSc-patients (32%, including 81% female and 68% diffuse scleroderma) presenting clinical, biological and electromyographic (EMG) features of muscle weakness, were included. Patients underwent vastus lateralis biopsy, assessed for individual pathologic features including fibrosis [type I collagen (Coll-I), transforming growth factor β (TGF-β)], microangiopathy [cluster of differentiation 31 (CD31), pro-angiogenic vascular endothelial growth factor A (VEGF-A), anti-angiogenic VEGF-A165b], immune/ inflammatory response [CD4, CD8, CD20, human leucocyte antigens ABC (HLA-ABC)], and membranolytic attack complex (MAC). SSc biopsies were compared with biopsies of (n = 35) idiopathic inflammatory myopathies (IIMs) and to (n = 35) noninflammatory myopathies (NIMs). Ultrastructural abnormalities of SSc myopathy were also analyzed by transmission electron microscopy (TEM).
Fibrosis in SSc myopathy (81%) is higher compared with IIM (32%, p < 0.05) and with NIM (18%, p < 0.05). Vascular involvement is dominant in SSc muscle (92%), and in IIM (78%) compared with NIM (21%, p < 0.05). In particular, CD31 shows loss of endomysial vessels in SSc myopathy compared with IIM (p < 0.05) and with NIM (p < 0.01). VEGF-A is downregulated in SSc myopathy compared with IIM (p < 0.05) and NIM (p < 0.05). Conversely, VEGF-A165b is upregulated in SSc myopathy. The SSc immune/inflammatory response suggested humoral process with majority (85%) HLA-ABC fibral neoexpression and complement deposits on endomysial capillaries MAC, compared with IIM (p < 0.05), characterized by CD4+/CD8+/B-cell infiltrate, and NIM (p < 0.05). TEM analysis showed SSc vascular alterations consisting of thickening and lamination of basement membrane and endothelial cell ‘swelling’ coupled to endomysial/perimysial fibrosis.
Fibrosis, microangiopathy and humoral immunity are predominant in SSc myopathy, even if it is difficult to identify specific histopathological hallmarks of muscle involvement in SSc, since they could be present also in other (IIM/NIM) myopathies.
Sarcoidosis is known as a Th1-mediated disease, which can mimic many primary rheumatologic diseases or sometimes co-exist with them. Clinical characteristics of sarcoid arthropathy are not well described and the studies reported in the literature so far are mostly based on data from referrals. The aim of this study was to evaluate the incidence and clinical characteristics of sarcoid arthropathy.
All our patients were prospectively evaluated in our rheumatology outpatient center from 2011 to 2015. A total of 114 (32 male) patients with sarcoidosis who were admitted to our clinic were included in the study. Clinical, demographical, laboratory, radiological and histological data of these patients obtained during 4-year follow-up and treatment period were compiled and analyzed.
The mean patient age was 48.1 years (range, 20–82 years), and the mean disease duration was 40.5 months (range, 1–300 months). Sarcoid arthritis was observed in 71 (62.3%), and arthralgia in 106 (92.9%) patients. Out of the 71 patients with arthritis, 61 (85.9%) had involvement of ankle, 7 (9.8%) knee, 2 (2.8%) wrist, MCP and PIP joints, and 1 (1.4%) had shoulder periarthritis. Oligoarthritis (two to four joints) was the most common pattern followed by monoarthritis and polyarthritis. Arthritis and erytjhema nodosum and arthritis and female sex was found to be correlated (p = 0.03 and p = 0.001). Again, in patients with arthritis, even higher levels of CRP/ESR as well as ANA and RF positivity were observed (p = 0.03, p = 0.01, p = 0.01, and p = 0.02, respectively). A total of 11 patients had another rheumatic pathology concurrent with sarcoidosis.
Inflammatory arthritis occurs in a majority of patients with sarcoidosis. Acute arthritis with bilateral ankle involvement is the most common pattern of sarcoid arthropathy. Sarcoidosis can mimic many primary rheumatic diseases or may coexist with them. Sarcoidosis should be considered not only as a mimicker but also as a Th1-mediated primary rheumatologic pathology.
We conducted an exploratory analysis of osteoarthritis progression among medication users in the Osteoarthritis Initiative to identify interventions or pathways that may be associated with disease modification and therefore of interest for future clinical trials.
We used participants from the Osteoarthritis Initiative with annual medication inventory data between the baseline and 36-month follow-up visit (n = 2938). Consistent medication users were defined for each medication classification as a participant reporting at all four annual visits that they were regularly using an oral prescription medication at the time of the visit. The exploratory analysis focused on medication classes with 40 or more users. The primary outcome measures were medial tibiofemoral joint space width change and the Western Ontario and McMaster Universities Arthritis Index (WOMAC) knee pain score change (12–36-month visits). Within each knee, we explored eight comparisons between users and matched or unmatched nonusers (defined two ways). An effect size of each comparison was calculated. Medication classes had potential signals if (a) both knees had less progression among users compared with nonusers, or (b) there was less progression based on structure and symptoms in one knee.
We screened 28 medication classes. Six medication classes had signals for fewer structural changes and better knee pain changes: alpha-adrenergic blockers, antilipemic (excluding statins and fibric acid), anticoagulants, selective serotonin reuptake inhibitors, antihistamines, and antineoplastic agents. Four medication classes had signals for structural changes alone: anti-estrogen (median effect size = 0.28; range = –0.41–0.64), angiotensin-converting enzyme inhibitors (median effect size = 0.13; range = –0.08–0.28), beta-adrenergic blockers (median effect size = 0.09; range = 0.01–0.30), and thyroid agents (median effect size = 0.04; range = –0.05–0.14). Thiazide diuretics had evidence for symptom modification (median effect size = –0.12; range = –0.24–0.04).
Users of neurovascular, antilipemic, or hormonal interventions may have less disease progression compared with nonusers.
In resource-constrained settings where biologic agents are not widely available, there are limited therapeutic options for patients with rheumatoid arthritis (RA) refractory to other synthetic disease modifying antirheumatic (DMARD) therapies. The aim of this study is to evaluate the effectiveness and safety of leflunomide (LEF) with methotrexate (MTX) in refractory RA.
A retrospective record review of adult RA patients treated with LEF/MTX. Demographic details, adverse reactions, and the 3-variable 28 joint disease activity score (DAS28-3) were recorded at initiation of LEF/MTX therapy, and after 4 and 12 months of treatment.
Of 194 patients, most were middle-aged seropositive Black African females, with established disease [mean (standard deviation, SD) disease duration 9.4 (8.2) years] and time on previous DMARDs of 7.0 (5.5) years. Before adding LEF, the mean (SD) dose of MTX was 21.7 (3.5) mg/week, and 87.6% of patients used low dose oral corticosteroids.
A good or moderate EULAR response was achieved by 44% and 42% of patients, and the retention rate was 71%. Major infections were seen in 6 patients: comprising 2 deaths, 3 cases of leucopaenia and septicaemia and 1 case of tuberculosis. Hepatotoxicity (n = 3), intolerable gastrointestinal symptoms (n = 3), and hypertension (n = 17) were the most common problems. Predictors of remission or low disease activity at 12 months was a baseline DAS28-3 <= 5.5 [odds ratio (OR) = 2.7; 95% confidence interval (CI) 1.1–5.6; p = 0.01].
LEF/MTX was effective in the majority of patients in this cohort of mainly Black African women who failed other combination synthetic DMARDs, particularly in those with moderate disease activity at the time of addition of LEF. Infections and hypertension were important complications. In a setting where biologic DMARDs are not readily accessible, the combination of LEF/MTX is a cost-effective approach.
We evaluated agreement among several definitions of accelerated knee osteoarthritis (AKOA) and construct validity by comparing their individual associations with injury, age, obesity, and knee pain.
We selected knees from the Osteoarthritis Initiative that had no radiographic knee osteoarthritis [Kellgren–Lawrence (KL) 0 or 1] at baseline and had high-quality quantitative medial joint space width (JSW) measures on two or more consecutive visits (n = 1655 knees, 1143 participants). Quantitative medial JSW was based on a semi-automated method and was location specific (x = 0.25). We compared six definitions of AKOA: stringent JSW (averaged): average JSW loss greater than 1.05 mm/year over 4 years; stringent JSW (consistent): JSW loss greater than 1.05 mm/year for at least 2 years; lenient JSW (averaged): average JSW loss greater than 0.25 mm/year over 4 years; lenient JSW (consistent): JSW loss greater than 0.25 mm/year for at least 2 years; comprehensive KL based: progression from no radiographic osteoarthritis to advance-stage osteoarthritis (KL 3 or 4; development of definite osteophyte and joint space narrowing) within 4 years; and lenient KL based: an increase of at least two KL grades within 4 years.
Over 4 years the incidence rate of AKOA was 0.4%, 0.8%, 15.5%, 22.1%, 12.4%, and 7.2% based on the stringent JSW (averaged and consistent), lenient JSW (averaged and consistent), lenient KL-based definition, and comprehensive KL-based definition. All but one knee that met the stringent JSW definition also met the comprehensive KL-based definition. There was fair substantial agreement between the lenient JSW (averaged), lenient KL-based, and comprehensive KL-based definitions. A comprehensive KL-based definition led to larger effect sizes for injury, age, body mass index, and average pain over 4 years.
A comprehensive KL-based definition of AKOA may be ideal because it represents a broader definition of joint deterioration compared with those focused on just joint space or osteophytes alone.
Osteoporosis is characterized by a low bone-mineral density associated with skeletal fractures. The decrease in bone-mineral density is the consequence of an unbalanced bone-remodeling process, with higher bone resorption than bone formation. The orchestration of the bone-remodeling process is under the control of the most abundant cell in bone, the osteocyte. Functioning as an endocrine cell, osteocytes are also a source of soluble factors that not only target cells on the bone surface, but also target distant organs. Therefore, any drugs targeting the osteocyte functions and signaling pathways will have a major impact on the bone-remodeling process. This review discusses potential advances in drug therapy for osteoporosis, including novel osteocyte-related antiresorptive and anabolic agents that may become available in the coming years.