Gait abnormalities differentially indicate pain or structural joint damage in monoarticular antigen-induced arthritis

Gait abnormalities have been suggested to provide an objective measure for joint pain in animal models. Here, we aimed to assess whether parameters of gait analysis correlate with measures of pain-related behavior in experimental monoarthritis. For this purpose, antigen-induced arthritis was induced in the left knee joints of 68 female Lewis rats, of which 30 were treated with tumor necrosis factor-alpha(TNF)-neutralizing compounds. During the course of arthritis, paw print analysis parameters and measures for mechanical and thermal hyperalgesia were obtained. Knee joints harvested on either day 3 or day 21 were scored histologically for signs of inflammation and cartilage and bone destructions. Data were compared to those obtained from 33 immunized control rats and correlated for days 3 and 21. Arthritic rats showed distinct asymmetric gait abnormalities. In the acute stage of antigen-induced arthritis, but not in the chronic phase, there was a significant correlation between the gait parameter ‘left–right distance’ and measures of primary and secondary hyperalgesia. Both in the acute and chronic phases, however, the gait parameter ‘angle between paws’ indicating outward rotation of paws mainly correlated with joint destruction as assessed using histology. Etanercept treatment exhibited pronounced anti-nociceptive and pro-locomotional effects, but the described correlations remained. In conclusion, some parameters of gait analysis may represent a good measure for arthritis pain, mainly in acute inflammation, while others are increasingly influenced by mechanical joint deformation as indicated by cartilage and bone destructions. Thus, gait abnormalities may not unequivocally be suitable for objective pain assessment in all stages of experimental arthritis.     

Endoscopic Facet Debridement for the treatment of facet arthritic pain - a novel new technique

Study design: Retrospective, observational, open label.Objective: We investigated the efficacy of facet debridement for the treatment of facet joint pain.Summary of background data: Facet joint disease, often due to degenerative arthritis, is common cause of chronic back pain. In patients that don''t respond to conservative measures, nerve ablation may provide significant improvement. Due to the ability of peripheral nerves to regenerate, ablative techniques of the dorsal nerve roots often provide only temporary relief. In theory, ablation of the nerve end plates in the facet joint capsule should prevent reinnervation.Methods: All patients treated with endoscopic facet debridement at our clinic from 2003-2007 with at least 3 years follow-up were included in the analysis. Primary outcome measure was percent change in facet-related pain as measured by Visual Analog Scale (VAS) score at final follow-up visit.Results: A total of 174 people (77 women, 97 men; mean age 64, range 22-89) were included. Location of facet pain was cervical in 45, thoracic in 15, and lumbar in 114 patients. At final follow-up, 77%, 73%, and 68% of patients with cervical, thoracic, or lumbar disease, respectively, showed at least 50% improvement in pain. Mean operating time per joint was 17 minutes (range, 10-42). Mean blood loss was 40 ml (range, 10-100). Complications included suture failure in two patients, requiring reclosure of the incision. No infection or nerve damage beyond what was intended occurred.Conclusions: Our results demonstrate a comparable efficacy of endoscopic facet debridement compared to radiofrequency ablation of the dorsal nerve branch, with durable results. Large scale, randomized trials are warranted to further evaluate the relative efficacy of this surgical treatment in patients with facet joint disease.     

Gustatory sweating due to autonomic neuropathy in a patient with amyloidosis secondary to rheumatoid arthritis

Abstract

Autonomic neuropathy, although often reported to occur in patients with AL (amyloid of light chain of immunoglobulin) amyloidosis, is extremely rare in AA (amyloid A) amyloidosis. We describe a patient with AA amyloidosis secondary to rheumatoid arthritis (RA) in whom autonomic neuropathy resulted in gustatory sweating during the end stage of RA. We discuss the importance of gustatory sweating as a characteristic sign of autonomic nervous system dysfunction in AA amyloidosis secondary to RA, and stress the availability of cardiovascular autonomic tests as an indicator of autonomic neuropathy in not only AL amyloidosis but also AA amyloidosis.     

Radiographic comparative evaluation of the Sauve-Kapandji procedure and the Darrach procedure for rheumatoid wrist reconstruction

Abstract

For surgical treatment of rheumatoid wrists, we have routinely selected the Sauve-Kapandji (S-K) procedure or the Darrach procedure based on predetermined indications. In this study, we conducted a retrospective radiographic comparative evaluation of the changes in the carpus after the two procedures. The S-K group and the Darrach group each consisted of 13 wrists of 10 patients (all women). The indications for the Darrach procedure were the presence of radiolunate fusion, radial shelf formation, and old age. The carpal height ratio (CHR) and the ulnocarpal distance ratio (UCDR) were determined on wrist radiograms obtained before operation and at the final follow-up. The mean follow-up period was 4 years. Fisher’s test was used to analyze the differences between the two groups. Both groups showed a decrease in mean CHR and an increase in mean UCDR at the final follow-up compared to the values before the operation, and there were no statistically significant differences. Furthermore, in the Darrach group, no significant differences in changes of the carpus were observed between patients with or without a radial shelf. We concluded that the present results do not support the superiority of the S-K method over the Darrach procedure for rheumatoid wrist reconstruction based on a radiographic evaluation.     

Preliminary analysis of mortality associated with rituximab use in autoimmune diseases

Abstract

Normal antibodies and pathogenic autoantibodies are produced by B-cells and plasma cells. Rituximab is a chimeric monoclonal antibody that targets the CD20 molecule on cells that express them on their surface and kills them. Rituximab has been increasingly used to treat several autoimmune diseases. Studies on fatal outcomes associated with rituximab therapy are lacking. A comprehensive and detailed analysis in which the multiple factors that could contribute to a fatal outcome in all the autoimmune diseases in which rituximab has been used would be cumbersome, lack uniformity and would prove difficult in making certain definitive conclusions and comparisons, but more importantly it would not allow to provide specific precautions and recommendations to prevent mortality. Hence, autoimmune mucocutaneous blistering diseases (AMBD) were used as model to study fatal outcomes in patients treated with rituximab between 2000 and 2013, using uniform 13 criteria. Fatal outcomes were found in 14 patients with autoimmune blistering diseases out of 134 patients (10.4%). Patients died due to infections (75%), gastrointestinal (17%) and cardiac events (8%). Causes of death were reported in 101 patients with other autoimmune diseases out of 4320 with a mortality rate of 2.4%. Among them, 44 patients (43.6%) died from infections. A statistical analysis of the data demonstrated that a statistically significant higher mortality rate was observed in patients with AMBD compared to patients with other autoimmune diseases. Similarly, a statistically significant higher rate of death due to infections was reported in patients with AMBD compared to patients with other autoimmune diseases. Use of systemic corticosteroids and immunosuppressive agents as concomitant therapy with rituximab enhanced immunosuppression. In many patients, B-cells were depleted for prolonged periods, even after clinical recovery was observed. Although its main action is depletion of B-cells, rituximab has a significant impact on the immune and inflammatory systems, directly and indirectly and thus enhances susceptibility to infection. These preliminary data suggests that physicians using rituximab to treat autoimmune diseases should monitor their patients closely, especially their B-cell levels until they return to normal, be vigilant for possible sources of infection, and be aware of potential fatal outcomes.     

IL-1β at the crossroad between rheumatoid arthritis and type 2 diabetes: may we kill two birds with one stone?

Although in the past the prevention of joint destruction in rheumatoid arthritis (RA) was strongly emphasized, now a great interest is focused on associated comorbidities in these patients. Multiple data suggest that a large percentage of RA patients are affected by Type 2 Diabetes (T2D), whose incidence has reached epidemic levels in recent years, thus increasing the health care costs. A better knowledge about the pathogenesis of these diseases as well as the mechanisms of action of drugs may allow both policy designers and physicians to choose the most effective treatments, thus lowering the costs. This review will focus on the role of Interleukin (IL)-1β in the pathogenesis of both the diseases, the efficacy of IL-1 blocking molecules in controlling these diseases, and will provide information suggesting that targeting IL-1β, in patients affected by both RA and T2D, may be a promising therapeutic choice.     

Adalimumab: a review of side effects

Adalimumab (Humira^®) is a human monoclonal TNF-α antibody that blocks the effects of TNF-α. It is administered by subcutaneous injection. It has been approved alone or in combination with methotrexate for the treatment of rheumatoid arthritis in the EU and US. Approval for its use for the treatment of psoriasis, psoriatic arthritis and ankylosing spondylitis is expected in the near future. Its side effect profile is favourable when compared with traditional systemic treatments for these diseases. It does not require laboratory monitoring. The most common side effects of adalimumab are injection site reactions. Adalimumab increases the risk of rare serious infections. There is a two-fold risk of serious infections with the use of adalimumab, as reported in the Premier trial. This risk should not be minimised in this way. It should not be used during periods of active infection. Its most notable infectious complication is the reactivation of tuberculosis. Tuberculosis screening should be according to country standards and may or may not include purified protein derivative test or chest X-ray. Deep fungal and other serious and atypical infection can also be promoted by adalimumab. It has been associated infrequently with skin rashes. Rare side effects include: worsening or initiation of congestive heart failure, a lupus-like syndrome, a promotion of lymphoma, medically significant cytopenias, and worsening or initiation of a multiple sclerosis/neurological disease. There has been reported pancytopenia and elevated transamines with the use of adalimumab, which suggest that laboratory monitoring blood counts and liver functions, at least intermittently, are useful. In patients with any of the foregoing problems, its use should be extremely carefully considered. Adalimumab is a useful medication which can be safely used if its side effects are recognised.