Regulation of peripheral classical and non-classical monocytes on infliximab treatment in patients with rheumatoid arthritis and ankylosing spondylitis.

OBJECTIVE To investigate the regulatory effect of tumour necrosis factor (TNF) blockade with infliximab on the distribution of peripheral blood monocyte subpopulations in patients with rheumatoid arthritis (RA) and ankylosing spondylitis (AS). METHODS Purified CD11b+CD14+ monocytes from 5 patients with RA and 5 AS were analysed ex vivo before and after infliximab treatment by flow cytometry for CD16, CD163, CD11b, C-C chemokine receptor type 2 (CCR2) and CXC chemokine receptor 4 (CXCR4) at baseline and at days 2, 14, 84 and 168 after the first infliximab administration. Serum levels of the stromal cell-derived factor (SDF)-1 and monocyte chemotactic peptide (MCP)-1 at different time points were measured in either patient group before and on infliximab treatment. RESULTS Anti-TNF treatment with infliximab led to a significant increase of circulating CD11b+ non-classical and a concomitantly decrease of CD11b+ classical monocytes, to a decline in SDF-1 levels and reduced expression of CCR2 and CXCR4 on non-classical monocyte subpopulation. CONCLUSIONS Our study shows, that TNFα blockade by infliximab resulted in a dichotomy of the regulation of classical and non-classical monocytes that might have substantial impact on inhibition of osteoclastogenesis and of subsequent juxta-articular bone destruction and systemic bone loss in RA and AS.

Hepatoprotective effect of tumour necrosis factor alpha blockade in psoriatic arthritis: a cross-sectional study

Objective To evaluate the impact of tumour necrosis factor α (TNFα) blockers on the presence of liver fibrosis in patients with rheumatoid arthritis (RA) and psoriatic arthritis (PsA) treated with methotrexate (MTX). Methods Participants were consecutive patients with RA and PsA who had undergone MTX treatment for at least 1 year ± TNF blockade for over 6 months. Liver fibrosis was assessed using non-invasive transient elastography (FibroScan). Regression models were used to compare FibroScan values of patients with RA and patients with PsA receiving TNFα blockers with those who were not. Results FibroScan assessments were performed on 51 patients with RA and 43 patients with PsA. Compared to patients with RA, those with PsA were predominantly young men, received lower cumulative dosages of MTX and exhibited a higher incidence of liver steatosis and hyperlipidaemia. An abnormal result was observed in 7.1% of the anti-TNFα-naïve and in 13% of the anti-TNFα-treated patients in the RA group and in 30% of the anti-TNFα-naïve and 4.3% of the anti-TNFα-treated patients in the PsA group (OR=0.11, 95% CI 0.02 to 0.98). Results of the PsA group were robust when adjusted for baseline characteristics. Conclusion The results suggest a protective effect of TNFα inhibitors against the development of liver fibrosis in patients with PsA.

[Ultrasound and arthritis]

Musculoskeletal ultrasonography (US) is an established and validated imaging technique in rheumatology. Ultrasonography is able to directly visualize soft tissue pathologies such as synovial tissue changes. Pathological findings in superficial cartilage, bone lesions and synovial tissue changes in the context of rheumatoid arthritis, spondyloarthritis or crystal arthropathies may only be seen by sonography or detected earlier by ultrasonography compared to conventional imaging techniques. The activity of an inflammatory arthropathy can be visualized using Doppler and power Doppler US. US is helpful in the detection of early inflammatory changes, particularly in patients with undifferentiated arthritis and/or unremarkable conventional radiography. In addition to diagnosis in early arthritis and monitoring of therapy in rheumatoid arthritis, sonography is able to detect pivotal pathologies in spondyloarthritis and crystal deposition diseases such as gout, pseudogout and apatite deposition disease. Ultrasound-guided diagnostic and therapeutic interventions are characterized by their excellent accuracy and improvement of clinical effectiveness compared to unguided procedures. In conclusion, ultrasonography plays a pivotal role in the assessment and monitoring of therapy in rheumatic diseases.

Preservation of lesser metatarsophalangeal joints in rheumatoid forefoot reconstruction

A standard rheumatoid forefoot reconstruction consists of arthrodesis of the first metatarsophalangeal (MTP) joint and resection arthroplasty of the lesser metatarsal heads. However, preservation of the metatarsal heads has gained renewed interest since the medical treatment of rheumatoid arthritis has improved dramatically.

Prospective study of fetal DNA in serum and disease activity during pregnancy in women with inflammatory arthritis

OBJECTIVE: Rheumatoid arthritis (RA) usually improves during pregnancy and recurs postpartum. Fetal cells and cell-free DNA reach the maternal circulation during normal pregnancy. The present study investigated dynamic changes in levels of fetal DNA in serum from women with RA and inflammatory arthritis during and after pregnancy to test the hypothesis that the levels of circulating fetal DNA correlate with arthritis improvement. METHODS: Twenty-five pregnant patients were prospectively studied. A real-time quantitative polymerase chain reaction panel targeting unshared, paternally transmitted HLA sequences, a Y chromosome-specific sequence, or an insertion sequence within the glutathione S-transferase M1 gene was used to measure cell-free fetal DNA. Results were expressed as fetal genomic equivalents per milliliter (gE/ml) of maternal serum. Physical examinations were conducted during and after pregnancy. RESULTS: Levels of fetal DNA in women with improvement in or remission of arthritis were higher than those in women with active disease, especially in the third trimester. Overall, an inverse relationship between serum fetal DNA levels and disease activity was observed (P < 0.001). Serum fetal DNA increased with advancing gestation, reaching median levels of 24 gE/ml (range 0-334), 61 gE/ml (range 0-689), and 199 gE/ml (range 0-2,576) in the first, second, and third trimesters, respectively, with fetal DNA clearance observed postpartum. Arthritis improvement was initially noted in the first trimester for most patients, increased further or was sustained with advancing gestation, and was active postpartum. CONCLUSION: Changes in serum fetal DNA levels correlated with arthritis improvement during pregnancy and recurrence postpartum. Immunologic mechanisms by which pregnancy might modulate RA activity are described.

Induction of complete and sustained remission of rheumatoid pachymeningitis by rituximab

Aseptic pachymeningitis is a rare and serious complication of rheumatoid arthritis (RA). Herein, we describe a patient with rheumatoid factor-positive and anti-cyclic citrullinated peptide-positive RA who experienced a focal seizure, with aphasia and convulsions of the right side of the body. The findings of magnetic resonance imaging and histologic analysis led to a diagnosis of rheumatoid pachymeningitis. Because the patient had a large number of CD20-expressing B lymphocytes, therapy with rituximab was started and has resulted in complete and sustained remission of both the pachymeningitis and the RA for >2 years. Despite a decrease in immunoglobulins, the patient has remained free of infections, which illustrates the favorable outcome that can result from therapeutic B cell depletion in this potentially lethal manifestation of RA.

Inter- and intraobserver reliability of the COFAS end-stage ankle arthritis classification system

End-stage ankle arthritis should have an appropriate classification to assist surgeons in the management of end-stage ankle arthritis. Outcomes research also requires a classification system to stratify patients appropriately.

[Osteoporosis - whom to treat? The importance of FRAX® in Switzerland]

The WHO fracture risk assessment tool FRAX® is a computer based algorithm that provides models for the assessment of fracture probability in men and women. The approach uses easily obtained clinical risk factors (CRFs) to estimate 10-year probability of a major osteoporotic fracture (hip, clinical spine, humerus or wrist fracture) and the 10-year probability of a hip fracture. The estimate can be used alone or with femoral neck bone mineral density (BMD) to enhance fracture risk prediction. FRAX® is the only risk engine which takes into account the hazard of death as well as that of fracture. Probability of fracture is calculated in men and women from age, body mass index, and dichotomized variables that comprise a prior fragility fracture, parental history of hip fracture, current tobacco smoking, ever long-term use of oral glucocorticoids, rheumatoid arthritis, other causes of secondary osteoporosis, daily alcohol consumption of 3 or more units daily. The relationship between risk factors and fracture probability was constructed using information of nine population-based cohorts from around the world. CRFs for fracture had been identified that provided independent information on fracture risk based on a series of meta-analyses. The FRAX® algorithm was validated in 11 independent cohorts with in excess of 1 million patient-years, including the Swiss SEMOF cohort. Since fracture risk varies markedly in different regions of the world, FRAX® models need to be calibrated to those countries where the epidemiology of fracture and death is known. Models are currently available for 31 countries across the world. The Swiss-specific FRAX® model was developed very soon after the first release of FRAX® in 2008 and was published in 2009, using Swiss epidemiological data, integrating fracture risk and death hazard of our country. Two FRAX®-based approaches may be used to explore intervention thresholds. They have recently been investigated in the Swiss setting. In the first approach the guideline that individuals with a fracture probability equal to or exceeding that of women with a prior fragility fracture should be considered for treatment is translated into thresholds using 10-year fracture probabilities. In that case the threshold is age-dependent and increases from 16 % at the age of 60 ys to 40 % at the age of 80 ys. The second approach is a cost-effectiveness approach. Using a FRAX®-based intervention threshold of 15 % for both, women and men 50 years and older, should permit cost-effective access to therapy to patients at high fracture probability in our country and thereby contribute to further reduce the growing burden of osteoporotic fractures.

Interaction of pregnancy and autoimmune rheumatic disease

During pregnancy, the fetus represents a natural allograft that is not normally rejected. While the maternal immune system retains the ability to respond to foreign antigens, tolerance mechanisms are up-regulated to protect the fetus from immunologic attacks by the mother. The profound immunologic adaptations during and after pregnancy do influence maternal autoimmune rheumatic diseases in several ways. One is triggering the onset of a rheumatic disease in the post partum period, the other influencing disease activity of established rheumatic disease. The review will discuss the mechanisms of increased susceptibility of rheumatoid arthritis (RA) in the first year post partum with a specific emphasis on the role of fetal cells or antigens persisting in the maternal circulation (so called microchimerism). Furthermore, the different influences of pregnancy on established rheumatic diseases will be highlighted. A marked beneficial effect of pregnancy is observed on RA whereas several other rheumatic diseases as ankylosing spondylitis (AS) and systemic lupus erythematosus (SLE) show either no particular effect or an aggravation of symptoms during pregnancy. Differences emerging in regard to modulation of disease symptoms during pregnancy seem related to response to hormones, the type of cytokine profile and immune response prevailing as well as further downstream interactions of molecular pathways that are important in disease pathogenesis.

[Proteins in rheumatology and clinical immunology]

Twelve years ago the tumour necrosis factor (TNF) inhibitors revolutionised the therapy of rheumatoid arthritis and other inflammatory rheumatic diseases. Today, in addition to anti-cytokine strategies, immunosuppressive biologicals have been developed that delete B-lymphocytes or inhibit the activation of T-lymphocytes. The spectrum of indications for these protein drugs will broaden substantially in the near future and will likely include also diseases with orphan status (incidence below 1:10'000). Used in the right indication and with knowledge of molecular effects as well as clinical adverse effects these new drugs do not appear to be more dangerous than conventional disease modifying agents (DMARDs).

Hand and Wrist Surgery

Despite improved medical treatment of rheumatoid arthritis, carpal tunnel compression, caput ulnae syndrome and palmar and dorsal tenosynovitis with potential tendon rupture represent urgent surgical indications. While diagnostic and therapeutic synovectomy may guide medical treatment, it should be performed before joint instability and destructive arthritis are established. Swan-neck and Boutonniere deformities as well as ulnar or radial drift of metacarpophalangeal (MCP) joints or the wrist can only be corrected when the involved joints are supple and intact. In the presence of destructive arthritis, partial and total wrist fusion, arthroplasties of the MCP joints and arthrodeses of the distal interphalangeal joints are recommended.

Elevated laser flare values correlate with complicated course of anterior uveitis in patients with juvenile idiopathic arthritis

To evaluate the prognostic value of anterior chamber (AC) laser flare (LF) in uveitis associated with juvenile idiopathic arthritis (JIA).