Nutritional status and anxious and depressive symptoms in anorexia nervosa: a prospective study.

The interweaving of malnutrition and symptoms of anxiety and depression in anorexia Nervosa (AN) is mentioned without any consensus regarding the course of anxious-depressive symptoms in relation to nutritional status in the course of treatment of patients with AN. The objectives of the current study in a large sample of AN inpatients were to assess the relationships between anxiety and depression symptoms and nutritional status both over the course of inpatient treatment and at discharge. 222 consecutive inpatients with AN (DSM-IV TR) were assessed (entrance and discharge) for duration of illness, psychiatric treatments, sociodemographic data and with psychometric scales for different psychopathological symptoms [depressive (BDI), anxiety and depressive (HAD scale), obsessive-compulsive (MOCI) and social phobia (LSAS fear score)]. Nutritional status was assessed with Body Mass Index (BMI) and body composition by bioelectrical impedance. The Fat free mass index [FFMI = FFM (kg)/height (m2)] was considered for the analysis. Two models were developed where the dependent variables were each psychopathological score at discharge (BDI, HAD anxiety, MOCI, and LSAS fear) in the cross-sectional model, and their variation in the longitudinal model (where a positive score reflected symptom decrease at discharge). A fixed set of predictors, defined on presumed clinical and statistical relevance (FFMI in the cross-sectional model and Variation of FFMI in the longitudinal model), were considered in each model, without any model selection procedure. This is the first study to confirm a positive relationship between the course of eating disorder symptoms and that of anxious-depressive symptoms during inpatient treatment of AN even after adjustment on a vast array of possibly confounding factors.

International validation of the Bullous Pemphigoid Disease Area Index severity score and calculation of cut-off values for defining mild, moderate and severe types of bullous pemphigoid.

BACKGROUND: The Bullous Pemphigoid Disease Area Index (BPDAI) score has been proposed to provide an objective measure of bullous pemphigoid (BP) activity. OBJECTIVES: The objective of this study was to calculate BPDAI cut-off values defining mild, moderate and severe BP. We also aimed to assess the interrater reliability and correlation with the number of daily new blisters, and anti-BP180 and anti-BP230 antibodies. METHODS: Severity scores were recorded by two blinded investigators. Anti-BP180 and anti-BP230 antibodies were measured using an enzyme-linked immunosorbent assay (ELISA). Cut-off values defining mild, moderate and severe subgroups were calculated based on the 25th and 75th percentiles of the BPDAI score. RESULTS: In total, 285 patients with BP were enrolled from 50 dermatology departments in Europe. Median BPDAI activity was 37·5 points (range 0-164). Cut-off values corresponding to the first and third quartiles of the BPDAI score were 20 and 57, respectively; thus, these values were used to define mild (≤ 19), moderate (≥ 20 and ≤ 56) and severe (≥ 57) BP. The median BPDAI score for patients with ≤ 10 daily new blisters was 26 [interquartile range (IQR) 17-45], and for patients with > 10 daily new blisters the median score was 55 (IQR 39-82). The BPDAI intraclass correlation coefficient measured at baseline was 0·97 and remained higher than 0·90 up to month 6. The improvement in the BPDAI score was correlated with the absolute decrease in anti-BP180 ELISA value (Spearman's rank r = 0·34, P < 0·004), but not with anti-BP230 antibodies (r = 0·17, P = 0·15). CONCLUSIONS: This study suggests cut-off values of 20-57 for BPDAI to distinguish mild, moderate and severe BP, and confirms that it is a robust tool to assess BP severity precisely.

French expert opinion for the management of juvenile dermatomyositis.

A guideline group consisting of a pediatric rheumatologist, internists, rheumatologists, immunologists, a physiotherapist and a patient expert elaborated guidelines related to the management of juvenile dermatomyositis on behalf of the rare autoimmune and autoinflammatory diseases network FAI2R. A systematic search of the literature published between 2000 and 2015 and indexed in PubMed was undertaken. Here, we present the expert opinion for diagnosis and treatment in juvenile dermatomyositis.

Clinical and immunological features and outcome of anti-p200 pemphigoid.

BACKGROUND: Anti-p200 pemphigoid is a rare autoimmune blistering disease (AIBD) of the dermoepidermal junction, characterized by autoantibodies to laminin γ1. The clinical course of anti-p200 pemphigoid in patients remains poorly investigated. OBJECTIVES: We aimed to describe the clinical and immunological features and the course of a series of patients with anti-p200 pemphigoid. METHODS: We conducted a retrospective study by immunoblotting detection of sera on 200-kDa dermal protein extracts from the register of the French reference centre for AIBD. We recorded the clinical and immunological features and the course of patients. RESULTS: A total of 14 patients with a mean age 81·6 ± 6·5 years were included. Only one patient had an associated neurological condition and one had psoriasis. Twelve patients had atypical clinical presentation, including eczematous, urticarial, prurigo-like, dyshydrosis-like and rosette-like skin lesions. Eight patients (57%) had mucosal involvement. Immunoblot analysis of sera on dermal and epidermal extracts showed a 200-kDa band in 14 and 10 cases, respectively. All eight of the sera tested by enzyme-linked immunosorbent assay detected recombinant human laminin γ1. Disease control was obtained in six of nine patients treated with topical corticosteroids, and four of five patients who received systemic treatment. Seven patients relapsed (50%) and five patients (36%) died during the median follow-up time of 12·6 months. At the end of the study, only one of the nine living patients was in complete remission off therapy. CONCLUSIONS: Many patients with anti-p200 pemphigoid had heterogeneous clinical presentation and a more severe prognosis than previously suspected.

Long term outcome of patients with low level of cryoglobulin (<0.05g/L).

OBJECTIVES: To date, no studies have yet assessed the characteristics of non-HCV patients with low level of cryoglobulin (≤0.05 g/L). The aims of the current study were thus to: 1) determine the prevalence of cryoglobulin ≤0.05 g/L in patients with non-HCV cryoglobulin; and 2) compare clinical features and long term outcome, including organ complications and mortality rate, between non-HCV patients with cryoglobulin level ≤0.05 g/L and those exhibiting cryoglobulin level >0.05 g/L. METHODS: Among 6379 cryoglobulin testing, cryoglobulin was detected in 618 patients (9.69% of cases); of these 618 patients, 453 non-HCV patients were included in the study. The medical records of these patients were reviewed. RESULTS: Of the 453 non-HCV cryoglobulin-positive patients, 265 (58.6%) exhibited cryoglobulin level ≤0.05 g/L. We showed that patients with cryoglobulin level ≤0.05 g/L had: 1) less commonly: palpable purpura (p<0.001), digital ulcers (p=0.006), peripheral neurologic involvement (p=0.03) and renal impairment (p=0.03); and 2) lower median values of ESR (p<0.001) and C-reactive protein (p=0.001). The patients with cryoglobulin level ≤0.05 g/L less often experienced infections (p=0.04) and hematological malignancies (p=0.01); both groups did not differ regarding prevalence of connective tissue diseases and solid tumors. Mortality rate was as high as 13.6% in patients with cryoglobulin level ≤0.05 g/L; death was mainly due to: solid tumors (16.6%), cardiovascular complications (13.8%), hematological malignancies (11.1%), infections (8.3%), pulmonary/renal complications of cryoglobulin (8.3%) and connective tissue diseases (8.3%). CONCLUSION: Our study shows a high prevalence of cryoglobulin level ≤0.05 g/L in clinical practice. Our findings further underscore that non-HCV cryoglobulin level ≤0.05 g/L may be responsible for severe renal and neurological complications, leading to high morbidity and mortality in these patients. Thus, our data suggest that both appropriate therapy and close follow-up may be required to improve such patients' outcome.

Immune-mediated necrotizing myopathy.

BACKGROUND: Immune-mediated necrotizing myopathy (IMNM) is a newly identified subgroup of idiopathic inflammatory myopathies. It is defined as a rare and severe disease, with symmetrical and proximal muscle weakness and a characteristic histology. An autoimmune aspect of IMNM is suggested by its association with autoantibodies directed against signal recognition particle (SRP) and 3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMGCR) in the majority of patients. Statin use is strongly associated with anti-HMGCR-positive IMNM. The pathophysiological mechanisms of this disease are still poorly understood, and as a result, no therapeutic strategy has been validated to date. OBJECTIVE: The aim of this article is to provide an overview of the current knowledge about epidemiology, clinical features, and pathophysiology of IMNM, as well as treatment strategies. RESULTS AND CONCLUSION: IMNM is a subject of widespread interest, with quick and meaningful advances being made. In recent years, huge progress has been made in terms of diagnosis and patient management. However, the understanding of pathophysiological mechanisms and treatment strategies still requires further investigation.

Clinical manifestations and outcome of anti-PL7 positive patients with antisynthetase syndrome.

BACKGROUND: The aims of the present study were to determine both clinical manifestations and outcome of anti-PL7 patients with antisynthetase syndrome (ASS). METHODS: The medical records of 15 consecutive anti-PL7 patients with biopsy proven ASS were retrospectively analyzed without prior selection. RESULTS: Anti-PL7 patients exhibited polymyositis (n=14) and dermatomyositis (n=1); extra-pulmonary manifestations of ASS included: Raynaud's phenomenon (40%), mechanic's hands (33.3%), joint impairment (26.7%), pericardial effusion (20%) and esophageal/gastrointestinal involvement (20%). The outcome of myositis was as follows: remission/improvement (91.7%) and deterioration (8.3%). Fourteen patients (93.3%) experienced interstitial lung disease (ILD). ILD preceded ASS diagnosis (n=5), was identified concomitantly with ASS (n=8) and occurred after ASS diagnosis (n=1). Patients could be divided into 3 groups according to their presenting lung manifestations: acute onset of lung disease (n=1), progressive onset of lung signs (n=11) and asymptomatic patients exhibiting abnormalities consistent with ILD on PFT and HRCT-scan (n=2). No patient had resolution of ILD, whereas 64.3% and 35.7% experienced improvement and deterioration of ILD, respectively. ILD resulted in respiratory insufficiency requiring O2 therapy in 14.3% of cases. Two patients died. Predictive parameters of ILD deterioration were: DLCO<45% at ILD diagnosis and HRCT-scan pattern of usual interstitial pneumonia (UIP). CONCLUSION: Our series mainly underscores that ILD is frequent in anti-PL7 patients, leading to high morbidity. Our study further suggests that patients with predictive factors of ILD deterioration may require more aggressive therapy, especially the group of patients with DLCO<45% at ILD diagnosis and UIP pattern on HRCT-scan.

Interstitial lung disease in anti-Jo-1 patients with antisynthetase syndrome.

OBJECTIVE: 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. METHODS: Ninety-one anti-Jo-1 patients were identified by medical records search in 4 medical centers. All of these patients had undergone pulmonary function tests (PFTs) and high-resolution computed tomography (HRCT) scans. RESULTS: Sixty-six patients (72.5%) had ILD. Patients could be divided into 3 groups according to their presenting lung manifestations: acute onset of lung disease (n = 12), progressive onset of lung signs (n = 35), and asymptomatic patients exhibiting abnormalities consistent with ILD on PFTs and HRCT scans (n = 19). Sixteen patients had resolution of ILD; 39 and 11 patients experienced improvement and deterioration of ILD, respectively. ILD led to decreased functional status, since 29.8% of patients exhibited a marked reduction of activities due to ILD and 13.6% had respiratory insufficiency requiring oxygen therapy; 5 of 6 patients died due to ILD complications. Predictive parameters of ILD deterioration were HRCT scan pattern of usual interstitial pneumonia, respiratory muscle involvement, and age ≥55 years. Furthermore, anti-Jo-1 patients with ILD, compared with those without, more frequently exhibited mechanic's hands and lower creatine kinase levels. CONCLUSION: Our findings confirm that ILD is a frequent complication in anti-Jo-1 patients, resulting in high morbidity. We suggest that patients with predictive factors of ILD deterioration may require more aggressive therapy. Finally, anti-Jo-1 patients with ILD, compared with those without, may exhibit a particular clinical phenotype.

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.

[Idiopathic inflammatory myopathies with anti-PM-Scl antibodies: case series and literature review]. / Myopathies inflammatoires et anticorps anti-PM-Scl: à propos d'une série et revue de la littérature.

PURPOSE: The objectives of this study were to evaluate: (1) the prevalence of anti-PM-Scl antibodies within the framework of antinuclear antibodies detection; and (2) the clinical features and outcome of patients with isolated polymyositis/dermatomyositis. METHODS: Nine thousand and sixty-four consecutive antinuclear testing data allowed us to evaluate anti-PM-Scl antibody prevalence. Second, we also assessed the characteristics of patients with isolated dermatomyositis/polymyositis and associated anti-PM-Scl antibody. RESULTS: Over 9064 consecutive antinuclear samples tested for antinuclear antibodies, 3263 (36%) were positive; anti-PM-Scl antibody were positive in nine patients: 0.1% of all sera, 0.2% of sera positive for antinuclear antibodies, 1.2% of sera positive for anti-ENA antibodies. Four of the nine patients with anti-PM-Scl antibody had dermatomyositis (n=3) and polymyositis (n=1). Patients with dermatomyositis/polymyositis and anti-PM-Scl antibody exhibited severe complications, as follows: ventilatory insufficiency (n=2) requiring mechanical ventilation in one case, esophageal involvement requiring enteral feeding (n=1); also, two of these patients had cancer. CONCLUSION: Our case series suggests that the presence of anti-PM-Scl antibody is not a favorable prognostic factor in patients with dermatomyositis/polymyositis. This type of antibody appears to be associated with lung and esophageal involvement; in addition, anti-PM-Scl antibody may co-exist with malignancy in PM/DM patients. Taken together, we suggest that patients with dermatomyositis/polymyositis and anti-PM-Scl antibody require both initial evaluation for lung/digestive manifestations and cancer and close surveillance.

Long-term outcome of patients with polymyositis/ dermatomyositis and anti-PM-Scl antibody.

BACKGROUND: To date, no series has analysed long-term outcome in patients with polymyositis/dermatomyositis (PM/DM) with anti-PM-Scl antibody. OBJECTIVES: The aims of the present study were: (i) to assess clinical features and long-term outcome, including organ complications, functional course and mortality rate, in patients with isolated PM/DM with anti-PM-Scl antibody; and (ii) to evaluate prevalence, characteristics and long-term outcome of interstitial lung disease (ILD) in patients with isolated PM/DM with anti-PM-Scl antibody. METHODS: The medical records of 20 consecutive patients with isolated PM/DM with anti-PM-Scl antibody were reviewed. RESULTS: Two patients (10%) achieved remission of PM/DM, whereas 14 (70%) improved and four (20%) had a worsened clinical status. Short-term recurrences (during tapering of therapy) occurred in nine patients and long-term recurrences (after discontinuation of therapy) in three patients. Moreover, patients with PM/DM with anti-PM-Scl antibody exhibited severe complications, as follows: oesophageal involvement (n = 4) requiring enteral feeding in three cases, ventilatory insufficiency (n = 3) requiring mechanical ventilation in two cases; three other patients had cancer. Interestingly, patients with PM/DM with anti-PM-Scl antibody often presented symptoms that are usually found in antisynthetase syndrome, i.e. hyperkeratotic rhagadiform hand symptoms (n = 2; 10%), Raynaud's phenomenon (n = 8; 40%), arthralgia/arthritis (n = 7; 35%) and ILD (n = 12; 60%). In our cohort, the associated ILD often required combined therapy of steroids and immunosuppressive agents. CONCLUSIONS: Our series suggests that the presence of anti-PM-Scl antibody is not a good prognostic factor in patients with PM/DM, as there appears to be an association with lung and oesophageal involvement; in addition, anti-PM-Scl antibody may coexist with malignancy in patients with PM/DM. Furthermore, anti-PM-Scl antibody-positive patients with PM/DM often exhibit 'mechanic's hands', Raynaud's phenomenon and joint involvement. Our latter findings raise the possibility that the immunogenetic background influences the autoantibody status of these patients; HLA-DR3 has, in fact, been found in association with antisynthetase syndrome antibodies and with anti-PM-Scl antibodies.

Impact of three anti-TNFalpha biologics on existing and emergent autoimmunity in rheumatoid arthritis and spondylarthropathy patients.

OBJECTIVE: The objective of this study was to analyze the effects of 3 anti-TNFalpha agents on markers of autoimmunity in rheumatoid arthritis (RA) and spondylarthropathy (SPA) patients. METHODS: First-time anti-TNFalpha biologics (infliximab, etanercept, or adalimumab) were prescribed to 156 RA and 95 SPA (58 ankylosing spondylarthritides, 37 psoriatic arthritides). During 1-2 years of follow-up, clinical, biological [antinuclear (ANA) and anti-double-stranded (dsDNA) antibodies, rheumatoid factors (RF), and anti-cyclic citrullinated peptide (CCP) for RA], and therapeutic data were collected biannually. RESULTS: ANA appeared or ANA and anti-dsDNA titers increased significantly (P < 0.001) more under infliximab than etanercept in both rheumatisms and than adalimumab in RA patients. During the 2-year follow-up, ANA appeared more in RA patients taking adalimumab than etanercept (P = 0.003), but independently of the anti-TNFalpha used; anti-dsDNA titers rarely became positive. Under etanercept or infliximab, ANA and anti-dsDNA were not influenced by the underlying pathology nor were they affected by infliximab intensification over 18 months. Only one case of cutaneous lupus was observed in a patient having IgG anti-dsDNA. The therapeutic responses were independent of ANA and anti-dsDNA titers for all rheumatisms and biologics. In RA patients, RF titers, but not anti-CCP levels, declined with the therapeutic response for all biologics. CONCLUSION: This is the first study that has evaluated the impact of three TNFalpha blockers on ANA and anti-dsDNA antibodies in RA and SPA patients. Autoimmunity was more induced with infliximab than etanercept and to a lesser degree to adalimumab but, more importantly, this emergent autoimmunity was exceptionally associated to clinical manifestations of lupus.

Contribution of PTPN22 1858T, TNFRII 196R and HLA-shared epitope alleles with rheumatoid factor and anti-citrullinated protein antibodies to very early rheumatoid arthritis diagnosis.

OBJECTIVES: To evaluate the predictive value of TNFRII 196R, PTPN22 1858T and HLA-shared epitope (SE) alleles, RFs and anti-citrullinated protein antibodies (ACPAs) for RA diagnosis in a cohort of patients with very early arthritis. METHODS: We followed up 284 patients who had swelling of at least two joints that had persisted for longer than 4 weeks but had been evolving for <6 months. At 2 yrs, patients were classified as having RA or non-RA rheumatic diseases according to the ACR criteria. Patients were genotyped with respect to TNFRII 196M/R and PTPN22 1858C/T polymorphisms and HLA-SE. The presence of IgA, IgG and IgM RF isotypes and ACPA was sought in sera collected at disease onset. RESULTS: HLA-SE alleles alone, concomitant presence of TNFRII 196R and PTPN22 1858T alleles, IgA, IgG and IgM RF alone and ACPA were found to be significantly associated with RA diagnosis. Using logistic regression analysis, the concomitant presence of RF and ACPA at disease onset was the best association to predict RA diagnosis. In patients (n = 34) who did not fulfil the ACR criteria for RA at inclusion but who progressed to ACR positivity, the study of the genetic risk markers did not contribute to predict RA diagnosis at 2 yrs. CONCLUSIONS: PTPN22 1858T, TNFRII 196R and HLA-SE alleles do not improve the predictive value of RF and ACPA for RA diagnosis in our cohort, and do not contribute to an earlier diagnosis in undifferentiated patients initially negative for RF and ACPA.