The Clinical Relevance of Antifibrillarin (anti-U3-RNP) Autoantibodies in Systemic Sclerosis.

Systemic sclerosis (SSc) is a heterogeneous autoimmune disease associated with several antinuclear autoantibodies useful to diagnosis and prognosis. The aim of the present multicentric study was to determine the clinical relevance of antifibrillarin autoantibodies (AFA) in patients with SSc. The clinical features of 37 patients with SSc positive for AFA (AFA+) and 139 SSc patients without AFA (AFA-) were collected retrospectively from medical records to enable a comparison between AFA- and AFA+ patients. Antifibrillarin autoantibodies were screened by an indirect immunofluorescence technique using HEp2 cells and identified by an in-house Western blot technique and/or an EliA test. Comparing AFA+ and AFA- patients, AFA+ patients were significantly younger at disease onset (36.9 versus 42.9; P = 0.02), more frequently male (P = 0.02) and of Afro-Caribbean descent (65% versus 7.7%; P < 0.001). At diagnosis, the Rodnan skin score evaluating the cutaneous manifestations was higher (13.3 versus 8.7; P = 0.01) and myositis was also more common in the AFA+ group (31.4% versus 12.2%; P < 0.01). Patients with AFA+ were not associated with diffuse cutaneous SSc or with lung involvement and no difference in survival was observed. Antifibrillarin autoantibodies are associated with patients of Afro-Caribbean origin and can identify patients with SSc who are younger at disease onset and display a higher prevalence of myositis.

[Use of pulmonary function tests and biomarkers studies to diagnose and follow-up interstitial lung disease in systemic sclerosis]. / Intérêts des explorations fonctionnelles respiratoires et des études des biomarqueurs dans le diagnostic et le suivi évolutif de la pneumopathie interstitielle diffuse dans la sclérodermie systémique.

Interstitial lung disease (ILD) is becoming one of the main causes of death of patients with systemic sclerosis (SSc). The prevalence of ILD associated with SSc (SSc-ILD) varies from 33% to 100% according to diagnostic methods. Clinical features such as dyspnea on exertion, dry cough, and chest pains are not specific and usually late-appearing, implying more specific tests in the diagnostic, prognosis, and follow-up of ILD in patients with SSc. High resolution thoracic CT scanner (HRCT) is more sensitive than chest X-ray in the detection of SSc-ILD. Pulmonary function tests (PFT) are non-invasive and periodically used to assess the impacts of SSc on respiratory function. Diagnostic values of bronchoalveolar lavage and histological examination on lung biopsy are controversial. However, these techniques are essential for studying cellular and molecular mechanisms underlying the pathophysiology of SSc-ILD. Several biomarkers such as surfactant-A (SP-A), -D (SP-D), mucin-like high molecular weight glycoprotein (KL-6), and chemokine CCL-18 have been implicated in SSc-PID. Serum levels of these proteins are correlated with the severity of SSc-ILD, as assessed by HRCT and/or PFT. Finally, alveolar concentration of exhaled nitric oxide can be used to screen SSc patients with high risk of deterioration of respiratory function, in whom immunosuppressant treatment could be useful in preventing the evolution to irreversible lung fibrosis.

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.

Serum CC chemokine ligand-18 predicts lung disease worsening in systemic sclerosis.

Elevated serum CC chemokine ligand (CCL)18 reflects lung fibrosis activity in systemic sclerosis (SSc) and could be an early marker of lung function worsening. Therefore, we sought to evaluate whether serum CCL18 levels at baseline could predict worsening of lung disease in SSc. In this prospective study, 83 SSc patients were analysed longitudinally over a 4-yr observation period for the risk of occurrence of combined deleterious events, defined as a 10% decrease from baseline of total lung capacity or forced vital capacity % predicted, or death, according to serum CCL18 at inclusion. Receiver operating characteristic (ROC) curve analysis was performed for prediction of events during the first year after inclusion. The best cut-off level of serum CCL18 for prediction of a combined event within the follow-up period was 187 ng · mL(-1), with 53% sensitivity and 96% specificity (area under the ROC curve 0.86; p < 0.001). After a mean ± SD follow-up of 33.7 ± 10.8 months, a higher rate of disease progression occurred in the group with serum CCL18 levels >187 ng · mL(-1). The adjusted hazard ratio was 5.36 (95% CI 2.44-11.75; p < 0.001). In summary, serum CCL18 is an accurate predictive biomarker for the identification of patients with a higher risk of subsequent scleroderma lung disease worsening.

[Salmonella bredney: a rare cause of mycotic aneurysm]. / Salmonella bredney: une cause rare d'anévrisme mycotique.

Mycotic aneurysms are rare, remain asymptomatic for a long time, and may be life threatening by their rupture if therapy is delayed. Historically associated with Streptococcus pyogenes and Staphylococcus aureus, they now frequently involve Salmonella species in elderly or immunodeficient patients, and complicate vascular investigation or surgical procedures. Frequently located in the abdominal aorta, they can also be found rarely in other location. Therapy associates antibiotics and surgical debridement with reestablishment of vascular continuity. We report a case of ruptured popliteal aneurysm with Salmonella bredney bacteraemia.

[Peripheral neuropathy with autonomous nervous system involvement in the course of dermatomyositis]. / Neuropathie périphérique avec atteinte du système nerveux autonome au cours d'une dermatomyosite.

A peripheral neuropathy occurs rarely during the course of an inflammatory myopathy. Once the classical aetiologies of peripheral neuropathies are ruled out, the diagnosis of neuromyositis can be accepted. We report a patient with dermatomyositis who presented a peripheral neuropathy revealed by dysautonomia. The presence of associated vasculitis led us to consider that this constituted the mechanism of the neurological involvement.

[Recurrent fever and skin eruption revealing chronic meningococcemia]. / Fièvre prolongée associée à une éruption cutanée diffuse révélant une méningococcémie chronique.

INTRODUCTION: Chronic meningococcemia is an unusual clinical presentation within the spectrum of infections due to Neisseria meningitidis. CASE REPORT: We report a 32-year-old man who presented with a 15-day history of fever and maculopapular skin rash, in the absence of meningeal irritation or severe sepsis manifestation. Blood culture identified N. meningitidis. Clinical course was uneventful after antibiotic treatment was initiated. CONCLUSION: Early diagnosis of chronic meningococcemia is crucial for optimal management of the patient and his/her contacts. Such a diagnosis should be suspected in the presence of the characteristic clinical triad (recurrent fever, skin rash and arthralgia), and this clinical presentation should be distinguished from systemic vasculitis as inadequate prescription of corticosteroids may be deleterious.

Diagnostic value of exhaled nitric oxide to detect interstitial lung disease in systemic sclerosis.

BACKGROUND AND AIM: Increased alveolar concentration of nitric oxide (CA(NO)) is related to the severity of interstitial lung disease (ILD) in systemic sclerosis (SSc). However, cut-off levels of CA(NO) to rule out, or to rule in, the presence of ILD in individual patients are unknown. We aimed to assess the validity of CA(NO) for the diagnosis of ILD in SSc and to determine the thresholds of CA(NO) that can be used in clinical practice to predict the likelihood of ILD in SSc. METHODS: Lung HRCT scan, PFTs and partitioned exhaled NO measurements were performed in 65 consecutive SSc patients. ILD was diagnosed on pulmonary HRCT according to the presence of ground glass or reticular opacities. Diagnostic performance of CANo for ILD diagnosis was assessed using ROC curves. RESULTS: 38 out of 65 SSc patients had ILD. CA(NO), at a cut-off level of 4.3 ppb, had a sensitivity and specificity for the diagnosis of ILD of 87% (95% CI: 77 to 99) and 59% (95% CI: 41 to 78), respectively. The same cut-off level of CA(NO) could detect impairment of gas exchange with a sensitivity and specificity of 78% (95% CI: 67 to 90) and 73% (95% CI: 46 to 99), respectively. Moreover, ILD could be ruled in (positive predictive value > 95%) when CA(NO) > or = 10.8 ppb, and ruled out C(ANO) values < or = 3.8 ppb (negative predictive value > 95%). CONCLUSION: CA(NO) could be a valid non-invasive biological marker of ILD in SSc, and be of use in clinical practice.

[Increase of CXCL10 serum level in systemic sclerosis interstitial pneumonia]. / Augmentation de CXCL10 dans le sérum au cours de la pneumopathie interstitielle de la sclérodermie systémique.

INTRODUCTION: CXCL10, a gamma-interferon-induced chemokine seems to play a relevant role in lung involvement that occurs in systemic sclerosis (SSc). The objective of this study was to assess the serum level of CXCL10 in interstitial lung disease (ILD) associated with SSc. METHODS: Serum level of CXCL10 was assayed in 23 healthy volunteers (60.0 years; 58.0-67.3) and 29 SSc patients (63.1 years; 60.1-69.4) by ELISA method. Pulmonary function tests (PFTs), lung CT-scan and echocardiogram were also performed in the patients. Serum levels from patients and healthy controls were compared and a comparison among SSc patients between those with and without ILD, as documented by lung CT-scan, was also performed. RESULTS: Median CXCL10 level from patients with SSc was significantly higher than that from healthy volunteers (110.0 pg/ml; 60.8-223.8 versus 52.0; 41.3-65.8; p<0.001). Fifteen out of the 29 patients had ILD on lung CT-scan; the median CXCL10 level from SSc patients with ILD was significantly higher than that from SSc patients without ILD (210.0 pg/ml; 115.0-307.5 versus 76.0; 55.0-110.0; p=0.02). CONCLUSION: Our findings suggest that CXCL10 is specifically increased in the lung involvement of SSc and plays a role in scleroderma lung disease.

Localized scleroderma: a series of 52 patients.

BACKGROUND: Localized scleroderma also called morphea is a skin disorder of undetermined cause. The widely recognized Mayo Clinic Classification identifies 5 main morphea types: plaque, generalized, bullous, linear and deep. Whether each of these distinct types has a particular clinical course or is associated with some patient-related features is still unclear. METHODS: We report here a retrospective series of patients with localized scleroderma with an attempt to identify features related to the type of lesion involved. The medical records of all patients with a diagnosis of localized scleroderma were reviewed by skilled practitioners. Lesions were classified according to the Mayo Clinic Classification. The relationship between each lesion type and various clinical features was tested by non-parametrical methods. RESULTS: The sample of 52 patients included 43 females and 9 males. Median age at onset was 30 y (range 1-76). Frequencies of patients according to morphea types were: plaque morphea 41 (78.8%) (including morphea en plaque 30 (57.7%) and atrophoderma of Pasini-Pierini 11 (21.1%)), linear scleroderma 14 (26.9%). Nine patients (17.3%) had both types of localized scleroderma. Median age at onset was lower in patients with linear scleroderma (8 y (range 3-44)) than in others (36 y (range 1-77)) (p=0.0003). Head involvement was more common in patients with linear scleroderma (37.5%) than in other subtypes (11.1%) (p=0.05). Atrophoderma of Pasini-Pierini was never located at the head. Systemic symptoms, antinuclear antibodies and the rheumatic factor were not associated with localized scleroderma types or subtypes. CONCLUSION: These results suggest that morphea types, in adults are not associated with distinct patient features except for age at disease onset (lower) and the localization on the head (more frequent), in patients with lesions of the linear type.

[Short-term effect of dietary-sodium intake on arterial blood pressure of patients treated with systemic corticosteroids: a prospective, randomised, crossover study]. / Effet à court terme des apports sodés sur la pression artérielle des patients recevant une corticothérapie systémique: étude prospective, randomisée, croisée.

INTRODUCTION: It is unknown if the level of dietary-sodium intake influences blood pressure in patients receiving systemic corticosteroids. METHODS: Randomized, single centre, crossover trial involving patients starting systemic corticosteroid therapy and having initial blood pressure less or equals to 159/99 mm Hg. The first period of sodium regimen was randomized (<3 g/j versus >6 g/j) and each period of sodium regimen lasted 3 weeks. No washout period was performed. Blood pressure was recorded for each patient at inclusion and after 3 weeks and 6 weeks. Moreover, all patients were asked to record on a standardized questionnaire everything they ate during 1 week of each period regimen. Questionnaires were analysed by a dietician for mean daily energy and sodium intakes during each period. Mixed models were used to estimate the relationship between sodium intake and blood pressure variations. RESULTS: Between June 2006 and June 2008, 49 patients were randomized, 24 in group 1 (first period regimen=salt<3g/day; women: 63%; mean age: 56+/-21 years; baseline prednisone dosage: 54+/-19 mg/day) and 25 in group 2 (first period regimen=salt>6g/day; women: 56%; mean age: 60+/-19 years; baseline prednisone dosage: 56+/-16 mg/day). Mean daily salt intakes were 2.5+/-1.8 and 9.3+/-1.9 g/day during the first period and 7.8+/-3.2 and 3.8+/-2.9 g/day during the second period, respectively for group 1 and group 2. Blood pressure variations were not significantly associated with daily salt intakes or with randomisation group. No order effect was evidenced. By comparison with baseline, systolic blood pressure increased by greater than 20 mm Hg at week 6 in five patients (2 in group 1 and 3 in group 2). CONCLUSION: At short-term, sodium intake does not seem to influence blood pressure variations in patients starting systemic corticosteroids therapy.

[Long-term systemic corticosteroid-therapy associated measures: description of the French internal medicine physicians' practices]. / Mesures adjuvantes à une corticothérapie systémique prolongée : description des pratiques des médecins internistes français.

INTRODUCTION: Except for the prevention of osteoporosis, no consensual recommendations are available regarding the therapeutic measures associated with the prescription of long-term corticosteroid therapy. The aim of this study was to assess the internal medicine physicians' practices regarding the prescription of long-term corticosteroid therapy. METHODS: In September 2007, we sent, by e-mail, a questionnaire to 813 internal medicine physicians, members of the French National Society of Internal Medicine. With this questionnaire, we assessed the frequency of prescription of measures sometimes associated with systemic corticosteroids and for whom no consensual recommendations were available (dietary advices, physical training, potassium supplementation, gastric protection, influenza vaccination and prescription of hydrocortisone). RESULTS: Three hundred and thirty-six out of 813 internal medicine physicians completed the questionnaire (response rate: 41%). The practitioners were predominantly male (71%) and mainly engaged in tertiary centres (53%). Regarding the dietary measures associated with the prescription of corticosteroids, low-sodium diet was recommended by most of the physicians, 69% of them prescribing such dietary regimen in more than 80% of their corticosteroid-treated patients. The concomitant prescription of caloric restriction, low-carbohydrate diet and/or high-protein diet was not consensual. The prescription of muscular physiotherapy was unusual, 74% of physicians prescribing such reeducation in less than 20% of their patients. The frequency of recommendation for daily physical training varied between physicians as well as for potassium supplementation, gastric protection, influenza vaccination or hydrocortisone prescription. CONCLUSION: There is no consensus between French internal medicine physicians regarding most of the measures, which must be prescribed in association with a long-term corticosteroid therapy.