Association of immunological parameters with aortic dilatation in giant cell arteritis: a cross-sectional study.

Aortic dilatation (AD) occurs in up to 30% of patients with giant cell arteritis (GCA). Reliable biomarkers for AD development, however, are still absent. The aim of this exploratory study was to evaluate whether immunological parameters are associated with the occurrence of AD in GCA. Cross-sectional study on 20 GCA patients with AD, 20 GCA patients without AD, and 20 non-GCA controls without AD measuring leukocytes, neutrophils, lymphocytes, C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), serum amyloid A (SAA), interferon (IFN)-α, IFN-γ, IFN-γ-induced protein 10 (IP-10), interleukin (IL) 5, IL-8, IL-10, IL-17A, IL-18, IL-1 receptor antagonist, tumor necrosis factor (TNF)-α, platelet-derived growth factor (PDGF), L-selectin, P-selectin, and soluble intercellular adhesion molecule 1 (sICAM-1). AD was measured by aortic contrast-enhanced computed tomography and defined by enlargement of the aorta above population-based aortic diameters adjusted by age, gender, and body surface area. No significant differences were observed between GCA patients with AD and GCA patients without AD concerning levels of leukocytes, neutrophils, lymphocytes, CRP, ESR, SAA, IL-8, IL-18, PDGF, IP-10, selectins, and sICAM-1. Values of IFN-α, IFN-γ, IL-5, IL-10, IL-17A, IL-1 receptor antagonist, and TNF-α were all below the detection limits in more than 70% of subjects. Lymphocytes and CRP revealed positive correlations with the diameter of the thoracic descending aorta. Immunological parameters were not useful to conclude on the presence of AD in GCA. Further studies are required to test if CRP and lymphocytes may be useful to predict future development of AD in GCA.

Ultrasound for diagnosis of carpal tunnel syndrome: comparison of different methods to determine median nerve volume and value of power Doppler sonography.

OBJECTIVE: To compare ultrasound measurement of median nerve cross-sectional area (CSA) at different anatomical landmarks and to assess the value of power Doppler signals within the median nerve for diagnosis of carpal tunnel syndrome (CTS). METHODS: A prospective study of 135 consecutive patients with suspected CTS undergoing two visits within 3 months. A final diagnosis of CTS was established by clinical and electrophysiological findings. CSA was sonographically measured at five different levels at forearm and wrist; and CSA wrist to forearm ratios or differences were calculated. Intraneural power Doppler signals were semiquantitatively graded. Diagnostic values of different ultrasound methods were compared by receiver operating characteristic curves using SPSS. RESULTS: CTS was diagnosed in 111 (45.5%) wrists; 84 (34.4%) had no CTS and 49 (20.1%) were possible CTS cases. Diagnostic values were comparable for all sonographic methods to determine median nerve swelling, with area under the curves ranging from 0.75 to 0.85. Thresholds of 9.8 and 13.8 mm(2) for the largest CSA of the median nerve yielded a sensitivity of 92% and a specificity of 92%. A power Doppler score of 2 or greater had a specificity of 90% for the diagnosis of CTS. Sonographic median nerve volumetry revealed a good reliability with an intraclass correlation coefficient of 0.90 (95% CI 0.79 to 0.95). CONCLUSIONS: Sonographic assessment of median nerve swelling and vascularity allows for a reliable diagnosis of CTS. Determination of CSA at its maximal shape offers an easily reproducible tool for CTS classification in daily clinical practice.

Early endoscopy in systemic sclerosis without gastrointestinal symptoms.

Investigation into the upper GI-tract of patients suffering from systemic sclerosis [SSc] and mixed connective tissue disease [MCTD] without symptoms of GI-tract involvement early in the course of the disease to diagnose inflammatory and motility disorders. We retrospectively analysed patients with SSc and MCTD who underwent oesophago-gastro-duodenoscopy [OGD] within a year of the first diagnosis. Patients with a Rodnan skin score above 5, proton pump inhibitors and treatment regimes potentially harmful to the mucosa of the upper GI-tract were excluded. Mucosal damage of the oesophagus was classified according to the Los Angeles Classification. Oesophageal dysmotility was assessed during OGD and confirmed by video cineradiography. A total of thirteen patients with SSc and six with MCTD fulfilled the inclusion criteria. OGD revealed reflux-oesophagitis in 77%, dysmotility of the distal oesophagus in 85%, gastritis in 92% [31% erosive gastritis] and Helicobacter pylori positivity in 38% of our patients suffering from SSc. Patients with MCTD showed features of reflux-oesophagitis, dysmotility of the distal oesophagus, gastritis and dysmotility of the stomach in 0.6%. In all thirteen patients with SSc, significant pathology of the upper GI-tract was found. The results of this study might indicate that OGD should be performed early in patients diagnosed with SSc, even if they do not report typical symptoms. An early diagnose of GI involvement might be followed by an effective therapy and therefore subsequently may improve the prognosis.

Treatment of refractory adult-onset Still's disease with tocilizumab: report of two cases and review of the literature.

Adult-onset Still's disease (AOSD) is empirically treated with nonsteroidal anti-inflammatory drugs, corticosteroids, conventional disease-modifying antirheumatic drugs, tumor necrosis factor-blocking agents or anakinra. The monoclonal anti-interleukin (IL)-6 antibody tocilicumab (TOC) has recently been approved for the treatment of rheumatoid arthritis and may be an attractive therapeutic option for AOSD as well. We report two AOSD patients treated with TOC and review of the current data on the use of TOC in AOSD. TOC was applied to the first patient after failure of cloroquin, methotrexate, adalimumab and etanercept. The second patient received TOC because of inefficacious methotrexate treatment. TOC was well tolerated by both the patients, and no clinically significant side effects occurred. Including these two cases, a total of seven AOSD patients have been successfully treated with TOC so far. TOC may be a promising treatment option for AOSD patients refractory to conventional disease-modifying antirheumatic drugs anakinra and tumor necrosis factor-[Formula: see text].

Prevalence and prognostic factors for aortic dilatation in giant cell arteritis - a longitudinal study.

OBJECTIVES: Predictive data for the development of aortic dilatation (AD) in giant-cell arteritis (GCA) are controversial. The aim was to investigate by computed tomography (CT) the prevalence of AD in a consecutive cohort of GCA patients and controls, and to identify possible predictors for AD. METHODS: GCA patients and controls were identified by electronic search and underwent aortic contrast enhanced CT defining AD by aortic diameter adjusted to age, gender and body surface area. Pulse-wave velocity, intima-media thickness (IMT) and laboratory studies including lymphocyte subsets were conducted identifying potential factors associated with AD. Clinical and laboratory parameters at disease onset, occurrence of aortic rupture/dissection before and up to five years after study visit were retrieved by chart review. RESULTS: 144 GCA patients and 115 controls were included. GCA patients developed more frequently AD of the ascending and thoracic descending aorta compared to controls (OR 2.60, p = 0.016; OR 3.65, p = 0.005, respectively). Factors associated with AD development of thoracic descending aorta, but not of the ascending aorta, were higher percentages of circulating CD3+CD4+ cells, higher CD4/CD8 ratio, presence of polymyalgia rheumatica and increased carotid IMT at disease onset (OR range 1.10-3.11, all with p < 0.05). During follow-up, no GCA patient required surgical aortic repair or suffered aortic rupture/dissection. CONCLUSIONS: Thoracic but not abdominal ADs occur more commonly in GCA patients, however, the subsequent risk for aortic repair, rupture or dissection is low. Changes of T-cell subsets, presence of polymyalgia rheumatica and increased carotid IMT at disease onset are associated with AD development.

The Value of Median Nerve Sonography as a Predictor for Short- and Long-Term Clinical Outcomes in Patients with Carpal Tunnel Syndrome: A Prospective Long-Term Follow-Up Study.

OBJECTIVES: To investigate the prognostic value of B-mode and Power Doppler (PD) ultrasound of the median nerve for the short- and long-term clinical outcomes of patients with carpal tunnel syndrome (CTS). METHODS: Prospective study of 135 patients with suspected CTS seen 3 times: at baseline, then at short-term (3 months) and long-term (15-36 months) follow-up. At baseline, the cross-sectional area (CSA) of the median nerve was measured with ultrasound at 4 levels on the forearm and wrist. PD signals were graded semi-quantitatively (0-3). Clinical outcomes were evaluated at each visit with the Boston Questionnaire (BQ) and the DASH Questionnaire, as well as visual analogue scales for the patient's assessment of pain (painVAS) and physician's global assessment (physVAS). The predictive values of baseline CSA and PD for clinical outcomes were determined with multivariate logistic regression models. RESULTS: Short-term and long-term follow-up data were available for 111 (82.2%) and 105 (77.8%) patients, respectively. There was a final diagnosis of CTS in 84 patients (125 wrists). Regression analysis revealed that the CSA, measured at the carpal tunnel inlet, predicted short-term clinical improvement according to BQ in CTS patients undergoing carpal tunnel surgery (OR 1.8, p = 0.05), but not in patients treated conservatively. Neither CSA nor PD assessments predicted short-term improvement of painVAS, physVAS or DASH, nor was any of the ultrasound parameters useful for the prediction of long-term clinical outcomes. CONCLUSIONS: Ultrasound assessment of the median nerve at the carpal tunnel inlet may predict short-term clinical improvement in CTS patients undergoing carpal tunnel release, but long-term outcomes are unrelated to ultrasound findings.

Expression of sarcoidosis related genes in lung lavage cells.

BACKGROUND: Sarcoidosis is a systemic granulomatous multiorgan disease of unknown cause. Some facts point to a genetically determined predisposition, like associations with certain Major Histocompatibility Antigens Class I- and II-types (MHC). Mycobacterial DNA has been found in about 30% of sarcoidosis patients within the granulomas, which has been interpreted as a probable trigger mechanism. METHODS: Cells from bronchoalveolar lavage (BAL) of sarcoidosis patients were stimulated with dead Mycobacterium avium and gene expression was studied after six hours. Gene expression was profiled by hybridization to PCR filters (Human UniGene Set RZPD-1). To avoid the detection of effects related to secondary and tertiary inflammatory messages, we compared gene expression in sarcoidosis with that of tuberculosis and extrinsic allergic alveolitis. After normalization genes up- or downregulated for a factor of at least 1.8 were further analyzed. Genes differentially expressed in sarcoidosis as well as in tuberculosis or EAA, respectively, were subtracted. RESULTS AND CONCLUSIONS: Four different genes were exclusively upregulated in sarcoidosis: fatty acid binding protein 4 (FABP4), B-MYB, and two EST's. FABP4 has already been described in some autoimmune diseases, but its function in sarcoidosis is unknown. B-MYB is a potent growth factor for haematopoietic cells including lymphocytes. It might be one of the central genes upregulated in sarcoidosis and by that inducing clonal expansion of sarcoidosis-antigen primed T-helper-lymphocytes. Clonal selection of T-helper cells might be facilitated by c-Akt together with Tcl-1, both also upregulated in sarcoidosis. For the two ESTs neither function nor location is known.

Mastocytic enterocolitis as a rare cause of chronic diarrhea in a patient with rheumatoid arthritis.

The prevalence of chronic diarrhea within the U.S. population has been reported to be as high as five per cent, and numerous causes have been identified. Especially in patients suffering from rheumatoid arthritis drug therapy should be considered as possible cause. We report a case of chronic diarrhea triggered by mastocytic enterocolitis in a patient suffering from rheumatoid arthritis. Systemic mastocytosis and other causes of chronic diarrhea, especially therapy with methotrexate, were carefully ruled out. Treatment with desloratadin and ranitidine was initiated and led to a rapid and persistent amelioration of clinical symptoms. The diagnosis of mastocytic enterocolitis should be considered in patients with chronic diarrhea and normal clinical, laboratory, as well as endoscopical work-up.

omega-3 Fatty acids infusions as adjuvant therapy in rheumatoid arthritis.

BACKGROUND: The present study investigated the efficacy and safety of parenteral omega-3 fatty acids (omega-3 FA) in patients with active rheumatoid arthritis (RA). METHODS: We performed a double-blind, randomized, placebo-controlled study in 23 patients with moderate to severe RA. Patients received either 0.2 g of fish oil emulsion/kg (active) or 0.9% saline (placebo) infusion intravenously for 14 consecutive days, followed by 20 weeks of 0.05 g of fish oil/kg (active) or paraffin wax (placebo) ingested orally as capsules. A decrease in swollen and tender joint counts was the primary efficacy measure. RESULTS: At baseline, both swollen and tender joint counts were not significantly different between patients in the treatment and placebo groups. Twenty patients completed the infusion portion of the study, and 13 completed the oral portion. Swollen joint count was significantly lower in the omega-3 FA group compared with the placebo group after 1 week of infusion (P = .002) as well as after 2 weeks of infusion (P = .046). Tender joint count also tended to be lower in the omega-3 FA group, although this did not reach statistical significance. Both swollen and tender joint counts were significantly lower in the omega-3 FA group compared with the placebo group during and at the end of oral treatment. CONCLUSION: Our pilot study indicates that parenteral omega-3 FAs are well tolerated and improve clinical symptoms of RA. Subsequent oral administration of omega-3 FAs may prolong the beneficial effects of the infusion therapy. These results warrant validation in larger multicenter studies.

Assessment of pulmonary arterial pressure during exercise in collagen vascular disease: echocardiography vs right-sided heart catheterization.

BACKGROUND: This study compared the results of exercise Doppler echocardiography (EDE) with right-sided heart catheterization (RHC) and evaluated the combination of EDE and cardiopulmonary exercise testing (CPET) as a screening method for early pulmonary vasculopathy in patients with connective tissue disease. METHODS: Patients (N = 52) with connective tissue disease (predominantly systemic sclerosis) and without known pulmonary arterial hypertension underwent both EDE and CPET. If systolic pulmonary arterial pressure (SPAP) was > 40 mm Hg during exercise or peak oxygen uptake (Vo(2)) was < 75% predicted, RHC was suggested. RESULTS: EDE showed an SPAP > 40 mm Hg during exercise in 26/52 patients. Additionally, CPET showed a peak Vo(2) < 75% predicted in 10/26 patients with SPAP 40 mm Hg in 25 patients (n = 1 at rest, n = 24 during exercise). SPAP values assessed by EDE showed no significant difference vs RHC at rest, 25 W, 50 W, and maximal exercise (difference [95% CI]: 0.3 [-2.7; 3.2], -1.3 [-7.1; 4.4], 0.9 [-7.7; 5.9], and -5.6 [-13.5; 2.2] mm Hg). Eight patients with exercise SPAP > 40 mm Hg had an exercise pulmonary arterial wedge pressure > 20 mm Hg, suggesting exercise-induced left ventricular diastolic dysfunction not detectable by EDE. CONCLUSIONS: EDE appears to be a reasonable noninvasive method to detect SPAP increase during exercise in connective tissue disease. In combination with CPET, it may be a useful screening tool for early pulmonary vasculopathy, although RHC remains the gold standard for hemodynamic assessment. TRIAL REGISTRATION: clinicaltrials.gov; Identifier: NCT00609349 (Early Recognition of Pulmonary Arterial Hypertension).

Steroid hormone receptor in pleural solitary fibrous tumours and CD34+ progenitor stromal cells.

Solitary fibrous tumours (SFT), originally described in the pleura, were subsequently recognized in numerous extrapleural sites. This suggests that a common stem cell, present in various organs and tissues, may be at the origin of SFT and that specific factors may be involved in the proliferation of such cells. Recently it has been described that steroid hormone receptors, progesterone receptors in particular, are expressed by extrapleural SFT. In addition, progesterone may participate as growth factor in many CD34(+) stromal neoplasms, which express low levels of the hormone receptors. The present study analysed the expression of androgen (AR), oestrogen (ER) and progesterone (PR) receptors in a series of 32 pleural SFT, 10 mesotheliomas and in reactive tissue of chronic pleuritis. ER and AR were never expressed by SFT or by chronic pleuritis, whereas PR were demonstrated in 2/16 "large" (>8 cm) and in 6/16 "small" (< or =8 cm) pleural SFT (all expressing CD34, bcl-2 and CD99). PR(+) SFT had a significantly higher proliferative activity (p = 0.04) (Ki-67 mean value 6.5%) and lower p27(kip1) (mean value 51.5%) expression than the PR(-) cases (Ki-67 mean value 3.81% and p27(kip1) mean value 57.86%). One of the cases expressing a high level of PR (80%) recurred 1 year after first surgery and the recurrence was PR(+) as well, but with a lower percentage of nuclear receptor expression (12%). In addition, in chronically inflamed subserosal tissue, a subpopulation of CD34(+) endothelial and interstitial dendritic cells was identified, which also expressed PR. These findings suggest that the CD34(+) submesothelial interstitial dendritic cells, activated during reactive processes, may be the stem cells that give rise to SFT, and that progesterone might participate in the growth of SFT through modulation of its specific receptors.