Seronegative polyarthritis revealing antisynthetase syndrome: a multicentre study of 40 patients.

OBJECTIVE: The aim of this study was to determine the frequency and characteristics of antisynthetase syndrome (ASS) revealed by polyarthritis. METHODS: First we conducted a retrospective single-centre study to assess the frequency of ASS patients who presented with polyarthritis without pulmonary and/or muscle symptoms. Secondly, we conducted a larger, multicentre study in order to describe the clinical characteristics of these patients. Exclusion criteria were the presence of RF, the presence of ACPA and overlap with another CTD. RESULTS: In the single-centre study, polyarthritis was the first manifestation in 12 of 45 ASS patients (27%). An additional 28 patients were collected for the multicentre study, resulting in a total population of 40 ASS patients who presented with polyarthritis. The mean delay from polyarthritis onset to ASS diagnosis was 27 months (s.d. 40). Pulmonary and muscle symptoms were uncommon at ASS diagnosis (40% and 32.5%, respectively) and were dramatically delayed [mean delay after polyarthritis onset of 41 months (s.d. 53) and 21 months (s.d. 14), respectively]. Mechanic's hands and cutaneous signs of DM occurred in 25% and 22.5%, respectively, with a mean delay of 10 months (s.d. 10) and 31 months (s.d. 21), respectively. When present (32%), RP was the earliest non-articular manifestation [mean delay 3 months (s.d. 23) after polyarthritis onset]. On HEp-2 cells, antinuclear and/or cytoplasmic fluorescence was found in 70% of cases, with specificity for various anti-aminoacyl tRNA synthetase (anti-ARS) antibodies. CONCLUSION: ASS may be revealed by polyarthritis. To decrease the delay in diagnosis of ASS, pulmonary and muscle symptoms and anti-ARS antibodies might usefully be searched for in seronegative polyarthritis patients, especially in those with RP.

Pattern of demyelination occurring during anti-TNF-α therapy: a French national survey.

OBJECTIVE: To determine the pattern of demyelinating disorders (DDs) occurring during anti-TNF-α therapy. METHODS: Between June 2005 and April 2008, 1800 French rheumatologists and internists were contacted to report cases of DDs occurring in patients treated with anti-TNF-α. RESULTS: After a median of 10.2 (1.5-39.9) months of treatment, 33 patients developed DDs: 22 had CNS and 11 peripheral nervous system (PNS) involvement. Underlying diseases were RA (n = 16), AS (n = 11), PsA (n = 4), JIA (n = 1) and PM (n = 1). Anti-TNF-α was infliximab (n = 15), etanercept (n = 12) or adalimumab (n = 6). CNS involvement was encephalic lesions (n = 16), transverse myelitis (n = 8) or retrobulbar optic neuritis (n = 5). Cerebrospinal fluid (CSF) analysis in 16 patients and MRI in 20 patients were abnormal. All patients discontinued anti-TNF-α. Fifteen patients required steroids. Twenty patients initially improved. Five patients developed multiple sclerosis. PNS involvement was chronic (n = 9) or acute inflammatory demyelinating polyneuropathy (n = 2). CSF analysis revealed an increased protein level in nine patients. Nerve conduction studies confirmed DD in all these patients. Anti-TNF-α was discontinued in 10 patients and 8 received i.v. immunoglobulins. Two patients relapsed after introduction of another anti-TNF-α. Overall, a causal relationship between anti-TNF-α and DD was considered as probable in 31 patients and definite in 2 who had positive rechallenge. CONCLUSION: Causal relationship between anti-TNF-α and induction of DD remains unclear, but in some cases the chronology of clinical events is suggestive. Nevertheless, DD might persist despite treatment discontinuation, suggesting that anti-TNF-α could trigger the demyelinating process, which further evolves independently.

Open-Label Pilot Study of a Single Intra-Articular Injection of Mannitol-Modified Cross-Linked Hyaluronic Acid (HANOX-M-XL) for the Treatment of the First Metatarsophalangeal Osteoarthritis (Hallux Rigidus): The REPAR Trial.

Purpose: The purpose of this study was to obtain information on safety and short-term efficiency of a single intra-articular injection of mannitol-modified cross-linked hyaluronic acid (HANOX-M-XL) in patients with painful first metatarsophalangeal joint osteoarthritis (1stMTPJ-OA). Methods: The study involved an observational, single-arm, prospective multicentre trial, with a 3-month follow-up. Inclusion criteria were patients with symptomatic 1st MTPJ-OA not relieved by analgesics and / or non-steroidal-anti-inflammatory drugs and / or foot orthotic. All patients received a single, imaging-guided intra-articular (IA) injection of 1 mL of HANOX-M-XL in the 1st MTPJ. The primary outcome was the change in pain between the date of injection and month 3. The secondary outcomes were the patient assessment of effectiveness, the decrease in painkiller use and the influence of the radiographic score on the clinical efficacy. Results: Sixty-five participants (72.3% women, mean age = 60) were included in the trial. Coughlin-Shurnas radiological grade was 1 in 28 patients, 2 in 29, and 3 in 6. At baseline and month 3, the average pain (0-10) was 6.5 ± 1.8 and 2.8 ± 2.3, respectively. The change in pain score was highly significant (-3.1 ± 2.9; P < .0001). At baseline there was no statistically difference in pain between the radiological stages (P = .69). At endpoint, the average pain score was 2.0 ± 1.9 in x-ray stage 1, 3.1 ± 2.3 in stage 2 and 3.3 ± 2.4 in stage 3 (P = .001). Mild to moderate adverse reactions were reported by 15 patients. All were a transient increase of the hallux pain that occurred immediately and up to 6 hours after injection and resolved in 1 to 7 days. Conclusion: This pilot study suggests that a single IA injection of HANOX-M-XL is safe and mainly benefits patients with mild moderate 1st MTPJ-OA. Further randomized controlled trials are necessary to confirm these preliminary encouraging results.

Safety and Predictive Factors of Short-Term Efficacy of a Single Injection of Mannitol-Modified Cross-Linked Hyaluronic Acid in Patients with Trapeziometacarpal Osteoarthritis. Results of a Multicentre Prospective Open-Label Pilot Study (INSTINCT Trial).

PURPOSE: To assess safety and search predictive factors of efficacy of a single intra-articular injection of a mannitol-modified hyaluronic acid (HA) viscosupplement, in patients having trapeziometacarpal (TMC) osteoarthritis (OA). METHODS: Patients with symptomatic TMC OA, not adequately relieved by analgesic therapy and/or by the use of a thumb splint, were included in a 3-month prospective multicentre open-label trial. All underwent plain radiographs with the Kapandji incidences allowing the Dell radiological grade assessment (1-4). Primary end point was the variation between injection (D0) and day 90 (D90) of the thumb pain (11-point Likert scale). Treatment consisted in a single injection of 0.6 to 1 mL of a viscosupplement made of a cross-linked HA combined with mannitol. All injections were performed under imaging guidance. Predictive factors of pain decrease were studied in univariate and multivariate analysis. RESULTS: A total of 122 patients (76% women, mean age 60, mean disease duration 36 months) were included and 120 (98%) were assessed at 3 months. The TMC OA was of Dell's grade 1, 2, 3, and 4 in 23%, 36.8%, 36.8%, and 3.5% of cases, respectively. At D0, the average (SD) pain level was 6.5 ± 1.6 without significant difference between Dell groups (P = .21). At day 90, pain decreased from 6.5 ± 1.6 to 3.9 ± 2.5 (difference -2.7 ± 2.5; -42%; P < .0001) without significant difference between Dell grade (P = .055), despite a seemingly smaller number of responders in stage 2 patients. The average analgesic consumption decreased in more than 1 out of 2 patients. In multivariate analysis, no predictor of response was identified. There was no safety issue. All adverse events (11%) were transient increase in pain during or following HA administration and resolved without sequel within 1 to 7 days. CONCLUSIONS: This study suggests that a single course of HANOX-M-XL injection is effective in relieving pain in patients with TMC OA, without safety concern. Patients with advanced stage of OA benefit the treatment as much as those with mild or moderate OA.