Isabelle Marie

Correlation of anti–signal recognition particle autoantibody levels with creatine kinase activity in patients with necrotizing myopathy

OBJECTIVE Anti-signal recognition particle (anti-SRP) autoantibodies are associated with severe acquired necrotizing myopathies. The role of these autoantibodies remains elusive, and the evolution of anti-SRP levels over time is unknown. In this study, we developed an addressable laser bead immunoassay (ALBIA) technique to investigate a correlation between anti-SRP levels, serum creatine kinase (CK) levels, and muscle strength in patients with necrotizing myopathy. METHODS The diagnostic value of the ALBIA assay was determined by comparing serum levels of anti-SRP autoantibodies in 31 anti-SRP immunodot-positive patients to those in 190 healthy blood donors and 199 control patients with different inflammatory/autoimmune conditions or polyclonal hypergammaglobulinemia. Among the 31 anti-SRP-positive patients, serum samples from 8 patients were monitored over time for levels of anti-SRP autoantibodies and levels of CK (determined at least 3 times, consecutively, over a mean followup period of 783 days). The relationship between levels of anti-SRP autoantibodies and levels of CK was tested using a linear mixed model. RESULTS The assay yielded positive results for anti-SRP in all anti-SRP immunodot-positive serum samples tested, while all control sera tested negative. The 8 anti-SRP-positive patients who were followed up longitudinally were found to have normalized CK levels and improved muscle strength. There was a striking correlation between the degree of myolysis, as measured by CK levels, in patients receiving therapy and the anti-SRP54 autoantibody levels in these same patients (P = 0.002). CONCLUSION Anti-SRP-positive myositis appears to be one of the few autoimmune diseases in which specific autoantibody levels are correlated with surrogate disease activity markers. These results reveal the usefulness of monitoring anti-SRP autoantibody levels in patients receiving therapy, and may also suggest a possible pathogenic role for anti-SRP autoantibodies in the necrotizing myopathies.

Short-term and long-term outcomes of interstitial lung disease in polymyositis and dermatomyositis: a series of 107 patients.

OBJECTIVE This study was undertaken to assess the characteristics and outcome of interstitial lung disease (ILD) in polymyositis/dermatomyositis (PM/DM) and to determine variables predictive of ILD deterioration in PM/DM. METHODS Among 348 consecutive patients with PM/DM, 107 patients with ILD were identified by medical records search in 4 medical centers. All patients underwent pulmonary function tests (PFTs) and pulmonary high-resolution computed tomography (HRCT) scan. RESULTS ILD onset preceded PM/DM clinical manifestations in 20 patients, was identified concurrently with PM/DM in 69 patients, and occurred after PM/DM onset in 18 patients. Patients with ILD could be divided into 3 groups according to their presenting lung manifestations: patients with acute lung disease (n = 20), patients with progressive-course lung signs (n = 55), and asymptomatic patients with abnormalities consistent with ILD evident on PFTs and HRCT scan (n = 32). We observed that 32.7% of the patients had resolution of pulmonary disorders, whereas 15.9% experienced ILD deterioration. Factors that predicted a poor ILD prognosis were older age, symptomatic ILD, lower values of vital capacity and diffusing capacity for carbon monoxide, a pattern of usual interstitial pneumonia on HRCT scan and lung biopsy, and steroid-refractory ILD. The mortality rate was higher in patients with ILD deterioration than in those without ILD deterioration (47.1% versus 3.3%). CONCLUSION Our findings indicate that ILD results in high morbidity in PM/DM. Our findings also suggest that more aggressive therapy may be required in PM/DM patients presenting with factors predictive of poor ILD outcome.

Comparison of long-term outcome between anti-Jo1- and anti-PL7/PL12 positive patients with antisynthetase syndrome.

The aims of the present study were to: compare the characteristics between antisynthetase syndrome (ASS) patients with anti-Jo1 antibody and those with anti-PL7/PL12 antibody. The medical records of 95 consecutive patients with ASS were reviewed. Seventy-five of these patients had anti-Jo1 antibody; the other patients had anti-PL7 (n=15) or anti-PL12 (n=5) antibody. At ASS diagnosis, the prevalence of myalgia (p=0.007) and muscle weakness (p=0.02) was significantly lower in the group of anti-PL7/PL12-positive patients than in those with anti-Jo1 antibody; median value of CK (p=0.00003) was also lower in anti-PL7/PL12 patients. Anti-Jo1 positive patients developed more rarely myositis resolution (21.3% vs. 46.2%); in addition, the overall recurrence rate of myositis was higher in anti-Jo1 positive patients than in patients with anti-PL7/PL12 antibody (65.9% vs. 19.4%). Anti-Jo1-positive patients, compared with those with anti-PL7/PL12 antibody, more often experienced: joint involvement (63.3%vs. 40%) and cancer (13.3% vs. 5%). By contrast, anti-PL7/PL12 positive patients, compared with those with anti-Jo1 antibody, more commonly exhibited: ILD (90% vs. 68%); in anti-PL7/PL12 positive patients, ILD was more often symptomatic at diagnosis, and led more rarely to resolution of lung manifestations (5.6% vs. 29.4%). Finally, the group of anti-PL7/PL12 positive patients more commonly experienced gastrointestinal manifestations related to ASS (p=0.02). Taken together, although anti-Jo1 positive patients with ASS share some features with those with anti-PL7/PL12 antibody, they exhibit many differences regarding clinical phenotype and long-term outcome. Our study underscores that the presence of anti-Jo1 antibody results in more severe myositis, joint impairment and increased risk of cancer. On the other hand, the presence of anti-PL7/PL12 antibody is markedly associated with: early and severe ILD, and gastrointestinal complications. Thus, our study interestingly indicates that the finding for anti-Jo1 and anti-PL7/PL12 antibodies impacts both the long-term outcome and prognosis of patients with ASS.

Intravenous immunoglobulins for steroid‐refractory esophageal involvement related to polymyositis and dermatomyositis: A series of 73 patients

To assess the long‐term outcome of esophageal complications in the group of patients receiving intravenous immunoglobulins (IVIG) for the treatment of severe steroid‐refractory esophageal involvement related to polymyositis/dermatomyositis (PM/DM).

Oesophageal mucosal involvement in patients with systemic sclerosis receiving proton pump inhibitor therapy

Aim  To assess the prevalence of oesophagitis, Barretts oesophagus (BE) and other oesophageal mucosal abnormalities in patients with systemic sclerosis (SSc) without prior selection on digestive clinical presentation. We also investigated the association between oesophageal endoscopic and manometric data with clinical manifestations of SSc.

Prospective study to evaluate the association between systemic sclerosis and occupational exposure and review of the literature.

INTRODUCTION Systemic sclerosis (SSc) has complex pathogenesis and likely multifactorial causes. Environmental exposures have been suggested to play a role in SSc pathogenesis, including occupational exposure to pollutants and chemicals as well as use of drugs leading to modulation of immune response. Thus, this case-control study aimed to assess: the relationship between SSc and occupational exposure; and the risk of SSc related to occupational exposure in male and female patients. METHODS From 2005 to 2008, 100 patients with a definite diagnosis of SSc were included in the study; 3 age, gender, and smoking habits matched controls were selected for each patient. A committee of experts evaluated blindly occupational exposure to crystalline silica, white spirit, organic solvents, ketones, welding fumes, epoxy resins, and pesticides; an occupational exposure score was calculated for all subjects. Our findings were compared with previous data in the literature. RESULTS Increased ORs for SSc were found for: crystalline silica (p<0.0001), white spirit (p<0.0001), aromatic solvents (p=0.0002), chlorinated solvents (p=0.014), trichlorethylene (p=0.044), ketones (p=0.002) and welding fumes (p=0.021). Elevated risk associated with high final cumulative score in SSc was observed for: crystalline silica, white spirit, chlorinated solvents, trichlorethylene, aromatic solvents, any type of solvents, ketones and welding fumes. A marked association between SSc and occupational exposure was further found for: 1) crystalline silica, chlorinated solvents, trichloroethylene, white spirit, ketones and welding fumes in male patients; and 2) white spirit, aromatic solvents, any type of solvent and ketones in female patients. Finally, we did not find an association between SSc and: 1) the use of drugs that have been speculated to play a role in SSc onset (anorexigens, pentazocine, bromocriptine, l-tryptophan); 2) implants - that are prosthesis, silicone implants, and contact lenses; and 3) dyeing hair. In the literature, SSc has been associated with occupational exposure to silica and solvents, while the association between SSc and specific organic solvents and welding fumes has been anecdotally reported. CONCLUSION The following occupational factors have an impact in the development of SSc: crystalline silica, white spirit, aromatic solvents, chlorinated solvents, trichlorethylene, ketones and welding fumes. The risk of SSc appears to be markedly associated with high cumulative exposure. Finally, the association between SSc and occupational exposure may be variable according to gender.

Efficacy of Biological-Targeted Treatments in Takayasu Arteritis Multicenter, Retrospective Study of 49 Patients

Background— The goal of this work was to assess the safety and efficacy of biologics (ie, tumor necrosis factor-&agr; antagonists and tocilizumab) in patients with Takayasu arteritis. Methods and Results— This was a retrospective, multicenter study of the characteristics and outcomes of 49 patients with Takayasu arteritis (80% female; median age, 42 years [20–55 years] treated by tumor necrosis factor-&agr; antagonists [80%] or tocilizumab [20%]) and fulfilling American College of Rheumatology or Ishikawa criteria. Factors associated with complete response were assessed. Eighty-eight percent of patients with Takayasu arteritis were inadequately controlled with or were intolerant to conventional immunosuppressive therapy (median number, 3 [1–5]). Overall response (ie, complete and partial) to biological-targeted treatments at 6 and 12 months was 75% and 83%, respectively. There were significantly lower C-reactive protein levels at the initiation of biological-targeted treatments (22 mg/L [10–46 mg/L] versus 58 mg/L [26–76 mg/L]; P=0.006) and a trend toward fewer immunosuppressants drugs used before biologics (P=0.054) in responders (ie, complete or partial responders) relative to nonresponders to biological-targeted treatments. C-reactive protein levels and daily prednisone dose significantly decreased after 12 months of biological-targeted treatments (30 versus 6 mg/L [P<0.05] and 15 versus 7.5 mg [P<0.05] at baseline and 12 months, respectively). The 3-year relapse-free survival was 90.9% (83.5%–99%) over the biological treatment period compared with 58.7% (43.3%–79.7%; P=0.0025) with disease-modifying antirheumatic drugs. No difference in efficacy was found between tumor necrosis factor-&agr; antagonists and tocilizumab. After a median follow-up of 24 months (2–95 months), 21% of patients experienced adverse effects, with biological-targeted treatments discontinued in 6.6% of cases. Conclusion— This nationwide study shows a high efficacy of biological-targeted treatments in refractory patients with Takayasu arteritis with an acceptable safety profile.Background— The goal of this work was to assess the safety and efficacy of biologics (ie, tumor necrosis factor-α antagonists and tocilizumab) in patients with Takayasu arteritis. Methods and Results— This was a retrospective, multicenter study of the characteristics and outcomes of 49 patients with Takayasu arteritis (80% female; median age, 42 years [20–55 years] treated by tumor necrosis factor-α antagonists [80%] or tocilizumab [20%]) and fulfilling American College of Rheumatology or Ishikawa criteria. Factors associated with complete response were assessed. Eighty-eight percent of patients with Takayasu arteritis were inadequately controlled with or were intolerant to conventional immunosuppressive therapy (median number, 3 [1–5]). Overall response (ie, complete and partial) to biological-targeted treatments at 6 and 12 months was 75% and 83%, respectively. There were significantly lower C-reactive protein levels at the initiation of biological-targeted treatments (22 mg/L [10–46 mg/L] versus 58 mg/L [26–76 mg/L]; P =0.006) and a trend toward fewer immunosuppressants drugs used before biologics ( P =0.054) in responders (ie, complete or partial responders) relative to nonresponders to biological-targeted treatments. C-reactive protein levels and daily prednisone dose significantly decreased after 12 months of biological-targeted treatments (30 versus 6 mg/L [ P <0.05] and 15 versus 7.5 mg [ P <0.05] at baseline and 12 months, respectively). The 3-year relapse-free survival was 90.9% (83.5%–99%) over the biological treatment period compared with 58.7% (43.3%–79.7%; P =0.0025) with disease-modifying antirheumatic drugs. No difference in efficacy was found between tumor necrosis factor-α antagonists and tocilizumab. After a median follow-up of 24 months (2–95 months), 21% of patients experienced adverse effects, with biological-targeted treatments discontinued in 6.6% of cases. Conclusion— This nationwide study shows a high efficacy of biological-targeted treatments in refractory patients with Takayasu arteritis with an acceptable safety profile. # CLINICAL PERSPECTIVE {#article-title-34}

Interstitial Lung Disease in Anti–Jo‐1 Patients With Antisynthetase Syndrome

To assess the outcome of interstitial lung disease (ILD) in anti–Jo‐1 patients with antisynthetase syndrome, determine predictive variables of ILD deterioration in these patients, and compare features of anti–Jo‐1 patients with and without ILD.

Watermelon stomach in systemic sclerosis: its incidence and management

Background  To date, there are no large endoscopic studies in systemic sclerosis (SSc), and both prevalence and characteristics of watermelon stomach in SSc have not been determined.

The Relapsing Polychondritis Disease Activity Index: Development of a disease activity score for relapsing polychondritis

OBJECTIVE The rarity of relapsing polychondritis (RP) has hindered the development of standardized tools for clinical assessment. Here, we describe the development of a preliminary score for disease assessing activity in RP, the Relapsing Polychondritis Disease Activity Index (RPDAI). METHODS Twenty-seven RP experts participated in an international collaboration. Selection and definition of items for disease activity were established by consensus during a 4-round internet-based Delphi survey. Twenty-six experts assessed the Physicians Global Assessment (PGA) of disease activity on 43 test cases on a 0-100 scale, yielding a total of 1118 PGA ratings. The weight of each item was estimated by multivariate regression models with generalized estimating equation, using PGA as the dependent variable. RESULTS Experts decided in consensus that the RPDAI should consider the 28-day period before each RPDAI assessment. Inter-rater reliability assessed by the intra-class correlation coefficient for the 1118 PGA ratings was 0.51 (CI95%: 0.41-0.64). The final RPDAI score comprised 27 items with individual weights ranging from 1 to 24 and a maximum theoretical RPDAI score of 265. Correlation between the RPDAI scores calculated based on the weights derived from the final multivariate model, and the 1118 PGA ratings was good (r=0.56, p<0.0001). CONCLUSION We have developed the first consensus scoring system to measure disease activity in relapsing polychondritis (see www.RPDAI.org for online scoring). This tool will be valuable for improving the care of patients with this rare disease.