Accuracy of power Doppler ultrasonography in the diagnosis and monitoring of idiopathic inflammatory myopathies.

OBJECTIVES: No clear-cut guidelines exist for the use of imaging procedures for the diagnosis of idiopathic inflammatory myopathies (IIM). The aim of the present study was to assess the diagnostic accuracy of power Doppler ultrasonography (PDUS) score in IIM patients compared with a control group and its usefulness during follow-up. METHODS: All patients evaluated in the Vasculitis and Myositis Clinic, Rheumatology Unit, University of Siena were prospectively collected. All patients underwent US examination of both thighs in axial and longitudinal scans, which were also performed twice (T1) or three times (T2). RESULTS: Forty-five patients with IIM (median [interquartile range] age 55 [45-66] years; 35 female) were enrolled. Receiver operating characteristic curves distinguished patients and controls based on ∑power Doppler (PD), ∑oedema, ∑atrophy and CRP. The best cut-off value for ∑PD was 0.5, ∑oedema 1.5, ∑atrophy 0.5 and CRP 0.22 mg/dl. In a logistic regression analysis, the variables that most influenced diagnosis of IIM were ∑PD and ∑oedema (P = 0.017 and P = 0.013, respectively). ∑Oedema was lower at T1 (P = 0.0108) and T2 (P = 0.0012) than at T0. Likewise, ∑PD was lower at T1 (P = 0.0294) and T2 (P = 0.0420) than at T0. Physician global assessment was lower at T1 (P = 0.0349) and T2 (P = 0.0035) than at baseline. CONCLUSION: Our findings show that PDUS is a reliable diagnostic tool in the differential diagnosis between inflammatory and non-inflammatory myopathies. Moreover, PDUS can be employed also during the follow-up of patients with IIM. A reduction in disease activity, measured by physician global assessment, led to a concomitant decrease in both oedema and PD, which was directly correlated with their rate of change. This underlines the close link between clinical assessment and PDUS findings, not only at diagnosis but also during monitoring.

The measurement of fibromyalgia severity: converting scores between the FIQR, the PSD and the FASmod.

OBJECTIVES: The revised Fibromyalgia Impact Questionnaire (FIQR) is a widely used fibromyalgia severity assessment tool that was introduced in 2009 prior to the publication of the American College of Rheumatology (ACR) preliminary fibromyalgia criteria in 2010 and its revision in 2016. In 2020, the modified Fibromyalgia Assessment Scale (FASmod) was published. The Polysymptomatic Distress scale (PSD) of the fibromyalgia criteria and FASmod include assessments of pain location severity and can be used for diagnosis as well as in non-fibromyalgia patients. The aim of this study is to provide equations for the conversion of the FIQR scores to PSD and FASmod as an aid to understanding and sharing fibromyalgia severity information. METHODS: 3089 patients with fibromyalgia, diagnosed according to the ACR 2010/2011 criteria and belonging to the Italian Fibromyalgia Registry completed FIQR, FASmod and PSD questionnaires. Pearson's correlation coefficient was used to test the correlations between indices. The least square regression approach was used to produce predictive equations for each scale based on the remaining scales. RESULTS: FIQR was correlated with PSD (r=0.714) and FASmod (r=0.801); PSD and FASmod showed the highest correlation (r=0.897), expected since they assess the same constructs. Predictive equations showing a linear model were effective in producing mean cohort values, but individual predictions deviated substantially, precluding prediction in the individual patient. CONCLUSIONS: Conversion equations that allow for interconversion of multiple scales fibromyalgia severity assessment scales are produced. These can be useful in obtaining mean values for cohorts but are not accurate enough for use in individual patients.

Determining the PASS cut-off points for the FIQR, FASmod and PSD in patients with fibromyalgia: a registry-based study.

OBJECTIVES: To determine the cut-off values of Patient Acceptable Symptom State (PASS) for the revised Fibromyalgia Impact Questionnaire (FIQR), the modified Fibromyalgia Assessment Scale (FASmod), and the Polysymptomatic Distress scale (PSD) and to determine the predictors of PASS in patients with fibromyalgia (FM). METHODS: FM patients belonging to the Italian Fibromyalgia Registry (IFR) completed the FIQR, the FASmod and the PSD. The PASS was assessed using a dichotomous answer. The cut-off values were obtained through the receiver operating characteristic curve (ROC) analyses. A multivariate logistic regression analysis was performed to determine predictors of achieving the PASS. RESULTS: 5545 women (93.7%) and 369 males (6.3%) were included in the study. The 27.8% of patients reported an acceptable symptom state. Patients in PASS differed in all patient-reported outcome measures (p <0.001). The FIQR PASS threshold was ≤58 (area under the ROC curve [AUC] = 0.819). The FASmod PASS threshold was ≤23 (AUC = 0.805) and the PSD PASS threshold was ≤16 (AUC = 0.773). In the pairwise AUC comparison, the discriminatory power of the FIQR PASS outperforms both FASmod PASS (p = 0.0124) and PSD PASS (p <0.0001). Multivariate logistic analysis showed that FIQR items related to memory and pain were the only predictors of PASS. CONCLUSIONS: The FIQR, FASmod, and PSD PASS cut-off points for FM patients have never been determined before. This study provides additional information to facilitate interpretation of the severity assessment scales in daily practice and clinical research related to FM patients.

Sociodemographic factors in fibromyalgia: results from the Italian Fibromyalgia Registry.

OBJECTIVES: Fibromyalgia (FM) is a chronic musculoskeletal pain syndrome of unknown aetiopathogenesis. Its development and maintenance are related to the interplay of biological, psychological, and contextual factors. Among the contextual factors, sociodemographic aspects are poorly elucidated. This study aimed to evaluate the relationships between sociodemographic/clinical factors and symptom severity measures using a web-based registry of patients with FM. METHODS: Adult patients with an ACR 2010/2011 diagnosis of FM underwent a clinical evaluation and were asked to complete questionnaires covering their sociodemographic data (gender, age, marital status, educational level), and disease-specific measures (the revised Fibromyalgia Impact Questionnaire (FIQR), and the Polysymptomatic Distress Scale (PDS)). RESULTS: Data relating to 3,221 patients (3001 women and 220 men) was collected. The ANOVA showed significant difference in mean FIQR scores when the five marital conditions (cohabiter, married, separated/divorced, single, widowed) were compared (F 3.321, p<0.01). While males and females were found to have comparable FIQR scores, the interaction between gender and marital status indicated that separated/divorced males have higher FIQR scores (F 5.684, p=0.001). The multiple regression analysis demonstrated that patients who reported lower educational level experienced more severe FM symptoms, as scored with FIQR (p<0.0001). CONCLUSIONS: Our results indicated that being male and separated/divorced is associated to higher severity of FM symptoms, as rated with FIQR. Furthermore, a relationship between educational level and FIQR scores has been detected. This study supports the importance of collecting simple SES measures to identify environmental risk factors for FM severity.

Fibromyalgia severity according to age categories: results of a cross-sectional study from a large national database.

OBJECTIVES: The role of age in influencing the severity of fibromyalgia (FM) is still controversial. The aim of this study is to define the contribution of age in the severity of FM from data from a large national database. METHODS: This cross-sectional study included adult patients with FM diagnosed according to the 2010/2011 American College of Rheumatology criteria. Disease severity was assessed with the revised Fibromyalgia Impact Questionnaire (FIQR) and the modified Fibromyalgia Assessment Status (FAS 2019mod). Patients were grouped into five age categories (between 18-40 years, between 41-50 years, between 51-60 years, between 61-70 years, and ≥71 years). Differences in disease severity between groups were assessed by one-way analysis of variance (ANOVA). RESULTS: The study included 2889 patients (199 males and 2690 females), mean age of 52.58 (±11.82) years, with a mean FIQR score of 59.22 (±22.98) and a mean FAS 2019mod of 25.50 (±8.66). Comparing the mean values of the various indices between age categories, there were no statistically significant differences between the groups for FIQR total score and FAS 2019mod. However, the 60-70 years category showed the lowest scores for both scales. The main difference emerged for the FIQR physical function subscale, where the ≥71 years category showed significantly higher scores (p<0.05) compared the 18-40 years category. CONCLUSIONS: The severity of FM has a significant level of stationarity according to age categories. Patients between 60-70 years have a lower disease burden. Physical function is the health domain with the most significant difference between the groups.

Definition of fibromyalgia severity: findings from a cross-sectional survey of 2339 Italian patients.

OBJECTIVE: To establish optimal cut-off values for the scores of the revised Fibromyalgia Impact Questionnaire (FIQR), the modified Fibromialgia Assessment Scale (FAS 2019mod), and the Polysymptomatic Distress Scale (PDS) in order to distinguish five levels of FM disease severity. METHODS: Consecutive FM patients were evaluated with the three clinimetric indices, and each patient was required to answer the anchor question: 'In general, would you say your health is 1 = very good, 2 = good, 3 = fair, 4 = poor, or 5 = very poor?'-which represented the external criterion. Cut-off points were established through the interquartile reconciliation approach. RESULTS: The study sample consisted of 2181 women (93.2%) and 158 men (6.8%), with a mean age of 51.9 (11.5) years, and mean disease duration was 7.3 (6.9) years. The overall median FIQR, FAS 2019 mod and PDS scores (25th-75th percentiles) were respectively 61.16 (41.16-77.00), 27.00 (19.00-32.00) and 19.0 (13.00-24.00). Reconciliation of the mean 75th and 25th percentiles of adjacent categories defined the severity states for FIQR: 0-23 for remission, 24-40 for mild disease, 41-63 for moderate disease, 64-82 for severe disease and >83 for very severe disease; FAS 2019 mod: 0-12 for remission, 13-20 for mild disease, 21-28 for moderate disease, 29-33 for severe disease and >33 for very severe disease; PDS: 0-5 for remission, 6-15 for mild disease, 16-20 for moderate disease, 21-25 for severe disease and >25 for very severe disease. CONCLUSIONS: Disease severity cut-offs can represent an important improvement in interpreting FM.

Functional avidity-driven activation-induced cell death shapes CTL immunodominance.

Immunodominance is a complex phenomenon that relies on a mere numerical concept, while being potentially influenced at every step of the immune response. We investigated the mechanisms leading to the establishment of CTL immunodominance in a retroviral model and found that the previously defined subdominant Env-specific CD8(+) T cells are endowed with an unexpectedly higher functional avidity than is the immunodominant Gag-recognizing counterpart. This high avidity, along with the Env Ag overload, results in a supraoptimal TCR engagement. The overstimulation makes Env-specific T lymphocytes more susceptible to apoptosis, thus hampering their expansion and leading to an unintentional "immune kamikazing." Therefore, Ag-dependent, hyperactivation-induced cell death can be regarded as a novel mechanism in the establishment of the immunodominance that restrains and opposes the expansion of high-avidity T cells in favor of lower-affinity populations.

Giant Soft Tissue Leiomyosarcoma of the Left Lower Extremity: Case Presentation With a Review of the Literature.

Leiomyosarcoma (LMS) accounts for approximately 5-10% of soft tissue sarcomas, with an estimated incidence in the United States (US) of less than one case/200,000 persons, more frequent in women than men. Approximately two-thirds of LMSs are retroperitoneal, abdominal, and mediastinal. Localized, soft tissue LMSs represent a lower percentage, with the lower limbs and trunk being the most frequently involved sites. LMSs larger than 5 cm (so-called giants) are even rarer, and to date have been little reported in the literature. In this paper, we present the case of a giant LMS of the left lower limb in a 73-year-old patient, who had a mass for about two years, and who, after the first diagnostic biopsy, underwent limb amputation. Macroscopic and microscopic examinations confirmed the infiltration of the underlying tibial bone. We briefly discuss eight other cases described in the literature with similar size, pointing out that the parameters with the greatest impact on prognosis proved to be size >5 cm and depth of invasion. Due to the rarity of this neoplasm, little has yet been done in relation to the most suitable therapeutic treatment of such patients, and larger case series are mandated in order to be able to conduct broader-spectrum studies.

Mature Triphyllic Cystic Teratoma of the Posterior Mediastinum in a Fetus: A Case Report and Literature Review.

A teratoma is a neoplasm composed of cell populations or tissues that are reminiscent, in their appearance, of normal elements derived from at least two embryonic layers. Fetal mature teratomas are normally benign, cystic, and typically occur along the midline, while they are rare in the posterior mediastinum. Teratomas are frequently solitary; however, they may sometimes be associated with other congenital anomalies and/or with chromosomal abnormalities. Clinically, they are often asymptomatic but can occasionally cause compression symptoms. Prenatal diagnoses are uncommon and made with ultrasonography; differential diagnosis with other congenital conditions is mandatory. We report the case of a 21 weeks of gestational age old fetus with a mature triphyllic fetal cystic teratoma, grade 0, located in the right posterior mediastinum. The tumor presented as a 3 cm wide cystic mass that caused a contralateral shift of the surrounding structures. Histological examination later revealed the presence of derivatives of the three germ layers, such as hyaline cartilage, smooth muscle, nervous tissue, and a respiratory-type epithelium.

Blastic Plasmocytoid Dendritic Cell Neoplasm (BPDCN): Clinical Features and Histopathology with a Therapeutic Overview.

Blastic Plasmacytoid Dendritic Cell Neoplasms (BPDCNs) are a rare, highly aggressive hematological malignant neoplasm that primarily involve the skin, bone marrow, lymph nodes and even extra-nodal sites. The rarity and relative poor description of cases in the literature make it necessary to review and further studies that deeply investigate this entity not only in a histopathological but also molecular field. In August-September 2023, we searched MEDLINE, PubMed and Scopus for randomized controlled trials (RCTs), narrative and systematic reviews, meta-analyses, observational studies (either longitudinal or retrospective), and case series published in English in the last 25 years using the keywords BPDCN, PDCs, Blastic NK-cell lymphoma, agranular CD4+ NK leukemia/lymphoma, agranular CD4+ CD56+ hematodermic neoplasm/tumor. Despite the progress made in recent years in the diagnosis and biological understanding of the disease, until 2018 there was no clear consensus regarding its treatment and the main therapeutic schemes used were based on chemotherapy regimens already used in the treatment of lymphomas, acute lymphoblastic leukemia (ALL) and/or acute myeloid leukemia (AML). In this narrative review, we address the definition and epidemiological features of BPDCN, provide the different theories on the etiopathogenesis with particular attention to the presumed cell of origin, discuss the main clinical manifestations that provide a sign of its presence, summarize the main histopathological and immunophenotypic characteristics with special attention to the most important markers, and finally, we provide some of the most effective information on the therapeutic treatment modalities of BPDCN.

Anti-Cytosolic 5'-Nucleotidase 1A in the Diagnosis of Patients with Suspected Idiopathic Inflammatory Myopathies: An Italian Real-Life, Single-Centre Retrospective Study.

BACKGROUND: Anti-cytosolic 5'-nucleotidase 1A (anti-cN1A) antibodies were proposed as a biomarker for the diagnosis of inclusion body myositis (IBM), but conflicting specificity and sensitivity evidence limits its use. Our study aimed to assess the diagnostic accuracy of anti-cN1A in a cohort of patients who underwent a myositis line immunoassay for suspected idiopathic inflammatory myopathies (IIM). We also assessed the agreement between two testing procedures: line immunoassay (LIA) and enzyme-linked immunoassay (ELISA). MATERIALS AND METHODS: We collected retrospective clinical and serological data for 340 patients who underwent a myositis antibody assay using LIA (EUROLINE Autoimmune Inflammatory Myopathies 16 Ag et cN-1A (IgG) line immunoassay) and verification with an anti-cN1A antibody assay using ELISA (IgG) (Euroimmun Lubeck, Germany). RESULTS: The serum samples of 20 (5.88%) patients (15 females, 5 males, mean age 58.76 ± 18.31) tested positive for anti-cN1A using LIA, but only two out of twenty were diagnosed with IBM. Seventeen out of twenty tested positive for anti-cN1A using ELISA (median IQR, 2.9 (1.9-4.18)). CONCLUSIONS: Our study suggests excellent concordance between LIA and ELISA for detecting anti-cN1A antibodies. LIA may be a rapid and useful adjunct, and it could even replace ELISA for cN1A assay. However, the high prevalence of diseases other than IBM in our cohort of anti-cN1A-positive patients did not allow us to consider anti-cN1A antibodies as a specific biomarker for IBM.

Clinical, laboratory and ultrasonographic findings at baseline predict long-term outcome of polymyalgia rheumatica: a multicentric retrospective study : Polymyalgia rheumatica predicted by ultrasonographic findings polymyalgia rheumatica outcome predicted early by ultrasound.

To assess the rate of PMR who, during the follow-up, undergo a diagnostic shift as well as to assess which clinical, laboratory and US findings are associated to a diagnostic shift and predict the long-term evolution of PMR. All PMR followed-up for at least 12 months were included. According to the US procedures performed at diagnosis, patients were subdivided into four subgroups. Clinical data from follow-up visits at 12, 24, 48 and 60 months, including a diagnostic shift, the number of relapses and immunosuppressive and steroid treatment, were recorded. A total of 201 patients were included. During the follow-up, up to 60% had a change in diagnosis. Bilateral LHBT was associated with persistence in PMR diagnosis, whereas GH synovitis and RF positivity to a diagnostic shift. Patients undergoing diagnostic shift had a higher frequency of GH synovitis, shoulder PD, higher CRP, WBC, PLT and Hb and longer time to achieve remission, while those maintaining diagnosis had bilateral exudative LHBT and SA-SD bursitis, higher ESR, lower Hb and shorter time to remission. Cluster analysis identified a subgroup of older patients, with lower CRP, WBC, PLT and Hb, lower PD signal or peripheral synovitis who had a higher persistence in PMR diagnosis, suffered from more flares and took more GCs. Most PMR have their diagnosis changed during follow-up. The early use of the US is associated with a lower dosage of GCs. Patients with a definite subset of clinical, laboratory and US findings seem to be more prone to maintain the diagnosis of PMR.

The association between body mass index and fibromyalgia severity: data from a cross-sectional survey of 2339 patients.

OBJECTIVE: Various studies have shown that overweight and obesity are central features of FM, but the real impact of a high BMI on clinical severity in patients with FM is still controversial. The aim of this study was to analyse the relationships between BMI categories and measures of symptom severity and functional impairment using data from a Web-based registry of patients with FM. METHODS: Adult patients with an ACR 2010/2011 diagnosis of FM underwent a complete physical examination and laboratory tests and were asked to complete a package of questionnaires covering their sociodemographic and treatment details, in addition to the following disease-specific questionnaires: the revised Fibromyalgia Impact Questionnaire (FIQR), the modified Fibromyalgia Assessment Status questionnaire (ModFAS) and the Polysymptomatic Distress Scale (PDS). RESULTS: A total of 2339 patients were recruited and divided into two weight categories, underweight/normal (U/N, n = 1127, 48.2%) and overweight/obese (O/O, n = 1212, 51.8%). The total and subscales of FIQR, ModFAS and PSD scores were significantly higher in the O/O patients, as were all the mean scores of the individual FIQR items (P < 0.001 for all). CONCLUSION: Our findings demonstrate that O/O patients with FM are significantly more impaired than U/N patients in all the symptomatological and functional domains as measured using the FIQR, ModFAS and PDS, thus suggesting that being O/O has an additional effect on symptoms and function.

Predictors of psychological distress and well-being in women with chronic musculoskeletal pain: two sides of the same coin?

OBJECTIVE: To date, few results on well-being in chronic-pain patients have been published, while several studies in patients without pain have indicated that well-being may not be equivalent to absence of psychological distress. The aim of the present study was to investigate the relationship between psychological distress and well-being and to identify the predictors of each in patients with chronic nonmalignant pain. METHODS: Sixty-nine women with chronic multiregional musculoskeletal pain, 41 of whom met American College of Rheumatology criteria for fibromyalgia, completed questionnaires on pain, fatigue, stiffness, physical disability (Fibromyalgia Impact Questionnaire), psychological distress [Multidimensional Affect and Pain Survey (MAPS), Symptom Check List-90 (SCL-90), State-Trait Anxiety Inventory Form Y2 (STAI-Y2)], and hedonic and eudaimonic well-being (MAPS). RESULTS: Patients reported increased amounts of psychological distress (STAI-Y2 and SCL-90) compared to healthy people. Multiple regression analysis of patient data demonstrated that higher psychological distress was related to higher age, more intense pain, a higher positive tender point count, and more physical disability. Well-being (both hedonic and eudaimonic aspects) decreased with higher disability, but was independent of age, pain intensity, and number of positive tender points. Bivariate correlations showed that psychological distress was moderately related to eudaimonic well-being and strongly related to positive affect, an aspect of hedonic well-being. CONCLUSION: In patients with chronic musculoskeletal pain, self-reports of well-being and low psychological distress only partially overlap with each other and are differently related to major patient symptoms, supporting the relevance of the concept of well-being to chronic-pain research and a need for further studies in this field.

Reactivity to superficial and deep stimuli in patients with chronic musculoskeletal pain.

In this study, we evaluated pain sensitivity in patients with fibromyalgia or other types of chronic, diffuse musculoskeletal pain to establish whether fibromyalgia represents the end of a continuum of dysfunction in the nociceptive system. One hundred and forty five patients and 22 healthy subjects (HS) completed an epidemiological questionnaire to provide information about fatigue, stiffness, sleep, the intensity of pain (VAS 0-100) and its extent both at onset and at present. Algometry was performed at all American College of Rheumatology (ACR) tender points and at ten control points. Patients were divided into five main groups: fibromyalgia (FS) patients, secondary-concomitant fibromyalgia (SCFS) patients, patients with widespread pain (WP) but not reaching the ACR criterion of 11 tender points, patients with diffuse multiregional pain (MP) not reaching the ACR criteria (widespread pain, tender point counts), and patients with multiregional pain associated with at least 11 tender points (MPTE). von Frey monofilaments were used to assess superficial punctate pressure pain thresholds. Heat and cold pain thresholds were determined with a thermal stimulator. Ischemic pain was assessed by the cold pressure test and the submaximal effort tourniquet test. The scores for stiffness and present pain intensity gradually increased concomitantly with the increase in tender point count and pain extent. The pressure pain thresholds for positive tender and positive control points were significantly lower in the SCFS, FS and MPTE groups than in HS, MP and WP groups, the latter three groups displaying similar values. In all groups, there were no differences in pain thresholds between positive tender and positive control points. The heat pain threshold and the pain threshold in the cold pressure test were lower in the FS and SCFS groups than in HS. The cold pressure tolerance was lower in patients with widespread pain than in HS. In the von Frey test, all patient groups except MP had similar values, which were significantly lower than in HS. Finally, all patient groups displayed lower tourniquet tolerance than HS. In each psychophysical test, patients with widespread pain and patients with multiregional pain showed similar thresholds; however, the thresholds in the MP or MPTE groups differed from those in the FS and SCFS groups. In the FS group, pain thresholds and pain tolerance did not differ according to the presence of ongoing pain at the stimulated site and were not correlated to ongoing pain. The results indicate that dysfunction in the nociceptive system is already present in patients with multiregional pain with a low tender point count; it becomes more and more severe as the positive tender point count and pain extent increase and it is maximal in fibromyalgia patients.

The MBP-reactive repertoire is shaped by recognition of minor histocompatibility antigens.

While it is known that the degeneracy of T-cell antigen recognition is involved in many aspects of T cell-immunology, its importance in the selection of the T cell repertoire remains an aspect to be better investigated. Here we examined if an intrathymic degenerate T cell recognition mechanism shapes the myelin basic protein (MBP)-reactive repertoire inducing resistance to experimental autoimmune encephalomyelitis (EAE) in some MHC and/or minor histocompatibility antigens (MiHAs) heterozygous F1 mice bearing the H-2(s) susceptibility allele. We found a considerable degree of cross-reactivity between MBP and MiHAs encoded in various EAE resistant mouse strains: (1) MBP-specific T cells can be re-stimulated in vitro by cells expressing these MiHAs and maintain their encephalitogenic activity, and (2) lymphoid cells from parental strains that generate EAE resistant F1 hybrids can induce disease relapse when injected into EAE-susceptible hosts. The results suggest that heterozygosity, through the degeneracy of T cell antigen recognition mechanism, may provide further means to constrain the potential autoreactive repertoire.

The clinical impact of interferon beta antibodies in relapsing-remitting MS.

We analysed the kinetics and clinical impact of binding antibodies (BAbs) and neutralizing antibodies (NAbs) to three interferon beta (IFNbeta) products in patients with relapsing-remitting MS (RRMS). Patients with RRMS received IFNbeta-1b 8 MIU subcutaneously (SC) every other day, intramuscular (IM) IFNbeta-1a 30 mcg once weekly, or SC IFNbeta-1a 22 mcg three times weekly for up to 4 years. The changes of BAbs and IFNbeta were measured using enzyme-linked immunosorbent assay (ELISA), and positive BAb samples were then analysed for neutralizing activity using an antiviral cytopathic effect assay. Patients were considered BAb+ if they had a positive sample with an optical density (OD)>mean + 3SD of the OD of the control sample; high BAb titers were defined as >1:500. Patients were considered NAb+ if they had titers > or =20 LU/mL, with high NAb titers defined as >1:100. The impact of BAbs and NAbs on relapses and Expanded Disability Status Scale (EDSS) score also was evaluated. Thirty patients were enrolled in each treatment group. Over the course of the study, 83% of patients developed BAbs to IFNbeta-1b, 13% to IM IFNbeta-1a, and 47 % to SC IFNbeta-1a. Forty percent of patients developed NAbs to IFNbeta-1b, 6.7% to IM IFNbeta-1a, and 26.7% to SC IFNbeta-1a. Of 22 NAb+ patients, 10 patients (45.5%) demonstrated high titers of both NAbs and BAbs (20% IFNbeta-1b, 3.3% IM IFNbeta-1a, 10% SC IFNbeta-1a). The relapse rate significantly increased after the appearance of high NAb titers (p=0.03); however, an even higher significance level (p<0.001) was observed in patients with high titers of both NAbs and BAbs. In 10 patients with high titers of both NAbs and BAbs, an increase in mean EDSS score from 2.2 +/- 0.8 at baseline to 3.6 +/- 1.2 at year 2 (p<0.01) was observed. NAb-negative patients showed no significant change in EDSS score at year 2. These findings demonstrate that high titers of both BAbs and NAbs reduce the clinical efficacy of IFNbeta in patients with RRMS, which is important for the long-term efficacy of these drugs.

Linear scleroderma associated with progressive brain atrophy.

Linear scleroderma (LS) is characterized by scleroatrophic lesions affecting limbs and legs, unilaterally. Neurological involvement may be associated with ipsilateral facial and skull involvement in disorders referred to clinically as LS 'en coup de sabre', and Parry-Romberg syndrome. We report a child with LS presenting with a severe neurological disorder characterized by epilepsy, progressive mental deterioration and a rapid process of atrophy involving the ipsilateral cerebral hemisphere, but not associated with an overlying facial structure involvement. Functional brain studies showed a reduction in the diameter of the left internal carotid and of the left middle cerebral artery. Our observations suggest that neuroimaging studies should be considered in all patients with linear scleroderma, and such studies become necessary when neurological symptoms occur.

Pain Symptoms in Fibromyalgia Patients with and without Provoked Vulvodynia.

Objective. The aim of the study was to compare the pain symptoms of fibromyalgia patients exhibiting (FMS+PVD) and not exhibiting (FMS) comorbidity with provoked vulvodynia. Study Design. The case control study was performed in 39 patients who had been diagnosed with FMS and accepted to undergo gynaecological examination and in 36 healthy women (C). All patients completed standardized questionnaires for pain intensity, pain area, and psychological functioning. The gynaecological examination included vulvar pain pressure reactivity (Q-tip), pelvic tone assessment (Kegel manoeuver), and a semistructured interview collecting detailed information about pelvic symptoms and sexual function. Results. FMS+PVD patients displayed a higher number of associated symptoms than FMS patients. The vulvar excitability was significantly higher in FMS+PVD than in FMS and in both groups than in Controls. Half of FMS+PVD patients were positive to Kegel manoeuver and displayed higher scores in widespread pain intensity, STAI-Y2, and CESD levels than Kegel negative patients. Conclusions. The study reveals that increased vulvar pain excitability may occur in FMS patients independently of the presence of coital pain. Results suggest that coital pain develops in patients with higher FMS symptoms severity due to the cooperative effects of peripheral and central sensitization mechanisms.