Nürnberg, Germany
Nürnberg, Germany

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Hauser W.,Klinikum Saarbrucken GGmbH | Hauser W.,TU Munich | Biewer W.,Rheumatology Practice | Gesmann M.,Psychosomatic Medicine Practice | And 5 more authors.
European Journal of Pain | Year: 2011

Background: The "funnel hypothesis" of fibromyalgia syndrome (FMS) assumes that the high levels of somatic and psychological symptoms reported by FMS-patients are due to a selection bias of patients seeking for medical specialist care. We tested the hypothesis by comparing FMS-patients from a general population sample and different clinical settings. Methods: From a cross-sectional survey of a representative sample of the German general population, persons meeting FMS-criteria were selected. Consecutive in- and outpatients from German rheumatology, pain medicine, psychosomatic medicine and integrative medicine settings with established or initial diagnosis of FMS were recruited. FMS was diagnosed in all samples by the survey criteria of the regional pain scale. Somatic symptom intensity was measured by 13 items of the Patient Health Questionnaire PHQ 15, depressed mood by the 9-items PHQ 9. Results: 96 persons of the general population, 86 of the rheumatology, 80 of the pain medicine, 69 of the psychosomatic medicine and 58 of the integrative medicine setting were included into the comparison. Patients of the clinical settings reported more pain sites and more somatic and depressive symptoms than FMS-persons of the general population. Patients of the different clinical settings did not differ in the number of pain sites and the intensity of depressive and somatic symptoms. Conclusions: We found a "funnel" between FMS-persons of the general population and FMS-patients of clinical settings, but not between patients of different levels of care. Patients contacting the health care system did not differ in clinical features. © 2011 Elsevier Inc. All rights reserved.


PubMed | Arthritis and Rheumatism Associates Group Practice, Rheumatology Practice, Georgetown University, University of Kansas and 2 more.
Type: Journal Article | Journal: Clinical and experimental rheumatology | Year: 2015

The robustness of findings on retrospective self-reports of childhood maltreatment and lifetime traumatic experiences of adults with fibromyalgia syndrome (FMS) has not been demonstrated by transcultural studies. This is the first transcultural study to focus on the associations between FMS, childhood maltreatment, lifetime psychological traumas, and potential differences between countries adjusting for psychological distress.71 age-and sex-matched US and German FMS outpatients were compared. Childhood maltreatment were assessed by the Childhood Trauma Questionnaire and potential, traumatic experiences by the trauma list of the Munich Composite International Diagnostic Interview. Potential posttraumatic stress disorder (PTSD) was diagnosed according to the Diagnostic and Statistical Manual of Mental Disorders IV-TR symptom criteria by the Posttraumatic Diagnostic Scale. Potential depressive and anxiety disorder were assessed by the Patient Health Questionnaire PHQ 4.US and German patients did not significantly differ in the amount of self-reported childhood maltreatment (emotional, physical and sexual abuse or neglect) or in the frequency of lifetime traumatic experiences. No differences in the frequency of potential anxiety, depression, and PTSD were seen. Psychological distress fully accounted for group differences in emotional and sexual abuse and emotional and physical neglect.The study demonstrated the transcultural robustness of findings on the association of adult FMS with self-reports of childhood maltreatment and lifelong traumatic experiences. These associations are mainly explained by current psychological distress.


Furnrohr B.G.,Friedrich - Alexander - University, Erlangen - Nuremberg | Wach S.,Friedrich - Alexander - University, Erlangen - Nuremberg | Kelly J.A.,Oklahoma Medical Research Foundation | Haslbeck M.,TU Munich | And 15 more authors.
Annals of the Rheumatic Diseases | Year: 2010

Background: Heat shock proteins (Hsps) play a role in the delivery and presentation of antigenic peptides and are thought to be involved in the pathogenesis of multifactorial diseases. Objective: To investigate genes encoding cytosolic Hsp70 proteins for associations of allelic variants with systemic lupus erythematosus (SLE). Methods: Case-control studies of two independent Caucasian SLE cohorts were performed. In a haplotype-tagging single-nucleotide polymorphism approach, common variants of HspA1L, HspA1A and HspA1B were genotyped and principal component analyses were performed for the cohort from the Oklahoma Medical Research Foundation (OMRF). Relative quantification of mRNA was carried out for each Hsp70 gene in healthy controls. Conditional regression analysis was performed to determine if allelic variants in Hsp70 act independently of HLA-DR3. Results: On analysis of common genetic variants of HspA1L, HspA1A and HspA1B, a haplotype significantly associated with SLE in the Erlangen-SLE cohort was identified, which was confirmed in the OMRF cohort. Depending on the cohorts, OR ranging from 1.43 to 1.88 and 2.64 to 3.16 was observed for individuals heterozygous and homozygous for the associated haplotype, respectively. Patients carrying the risk haplotype or the risk allele more often displayed autoantibodies to Ro and La in both cohorts. In healthy controls bearing this haplotype, the amount of HspA1A mRNA was significantly increased, whereas total Hsp70 protein concentration was not altered. Conclusions: Allelic variants of the Hsp70 genes are significantly associated with SLE in Caucasians, independently of HLA-DR3, and correlate with the presence of autoantibodies to Ro and La. Hence, the Hsp70 gene locus appears to be involved in SLE pathogenesis.


Rech J.,Friedrich - Alexander - University, Erlangen - Nuremberg | Manger B.,Friedrich - Alexander - University, Erlangen - Nuremberg | Lang B.,Rheumatology Practice | Schett G.,Friedrich - Alexander - University, Erlangen - Nuremberg | And 2 more authors.
Rheumatology International | Year: 2012

Still's disease and chronic recurrent multifocal osteomyelitis (CRMO) are febrile rheumatic diseases of unknown etiology, which predominantly affect children but can also have their initial manifestation in adults. Both can present as intermittent, relapsing episodes and are considered potential candidates within the expanding spectrum of autoinflammatory disorders, although no genetic abnormalities have been described for either of them. Here, we describe a man with an initial manifestation of abacterial multifocal osteitis at the age of 41. During a relapsing- remitting course of his illness, he increasingly developed symptoms of adult-onset Still's disease (AOSD), and the diagnosis was established according to the Yamaguchi criteria. When treated with anakinra, not only the acute symptoms disappeared promptly, but also the osteitis went into complete remission. This is to our knowledge the first description of a simultaneous occurrence of these two manifestations of autoinflammation in adulthood. © Springer-Verlag 2011.


Haschka J.,Friedrich - Alexander - University, Erlangen - Nuremberg | Haschka J.,Saint Vincent Hospital | Englbrecht M.,Friedrich - Alexander - University, Erlangen - Nuremberg | Hueber A.J.,Friedrich - Alexander - University, Erlangen - Nuremberg | And 22 more authors.
Annals of the Rheumatic Diseases | Year: 2016

Objective: To prospectively analyse the risk for disease relapses in patients with rheumatoid arthritis (RA) in sustained remission, either continuing, tapering or stopping disease-modifying antirheumatic drugs (DMARDs) in a prospective randomised controlled trial. Methods: Reduction of Therapy in patients with Rheumatoid arthritis in Ongoing remission is a multicentre, randomised controlled, parallel-group phase 3 trial evaluating the effects of tapering and stopping all conventional and/or biological DMARDs in patients with RA in stable remission. Patients (disease activity score 28 (DAS28)<2.6 for least 6 months) were randomised into three arms, either continuing DMARDs (arm 1), tapering DMARDs by 50% (arm 2) or stopping DMARDs after 6 months tapering (arm 3). The primary endpoint was sustained remission during 12 months. Results: In this interim analysis, the first 101 patients who completed the study were analysed. At baseline, all patients fulfilled DAS28 remission and 70% also American College of Rheumatology-European League Against Rheumatism Boolean remission. 82.2% of the patients received methotrexate, 40.6% biological DMARDs and 9.9% other DMARDs. Overall, 67 patients (66.3%) remained in remission for 12 months, whereas 34 patients (33.7%) relapsed. The incidence of relapses was related to study arms (p=0.007; arm 1: 15.8%; arm 2: 38.9%; arm 3: 51.9%). Multivariate logistic regression identified anticitrullinated protein antibodies (ACPA) positivity (p=0.038) and treatment reduction (in comparison to continuation) as predictors for relapse (arm 2: p=0.012; arm 3: p=0.003). Conclusions: This randomised controlled study testing three different treatment strategies in patients with RA in sustained remission demonstrated that more than half of the patients maintain in remission after tapering or stopping conventional and biological DMARD treatment. Relapses occurred particularly in the first 6 months after treatment reduction and were associated with the presence of ACPA.


PubMed | University of Tübingen, Institute Reumatologia Of Sao Paulo, Rheumatology Practice, Clinic Burghausen and 7 more.
Type: Journal Article | Journal: Annals of the rheumatic diseases | Year: 2016

To perform a detailed analysis of the autoantibody response against post-translationally modified proteins in patients with rheumatoid arthritis (RA) in sustained remission and to explore whether its composition influences the risk for disease relapse when tapering disease modifying antirheumatic drug (DMARD) therapy.Immune responses against 10 citrullinated, homocitrullinated/carbamylated and acetylated peptides, as well as unmodified vimentin (control) and cyclic citrullinated peptide 2 (CCP2) were tested in baseline serum samples from 94 patients of the RETRO study. Patients were classified according to the number of autoantibody reactivities (0-1/10, 2-5/10 and >5/10) or specificity groups (citrullination, carbamylation and acetylation; 0-3) and tested for their risk to develop relapses after DMARD tapering. Demographic and disease-specific parameters were included in multivariate logistic regression analysis for defining the role of autoantibodies in predicting relapse.Patients varied in their antimodified protein antibody response with the extremes from recognition of no (0/10) to all antigens (10/10). Antibodies against citrullinated vimentin (51%), acetylated ornithine (46%) and acetylated lysine (37%) were the most frequently observed subspecificities. Relapse risk significantly (p=0.011) increased from 18% (0-1/10 reactivities) to 34% (2-5/10) and 55% (>5/10). With respect to specificity groups (0-3), relapse risk significantly (p=0.021) increased from 18% (no reactivity) to 28%, 36% and finally to 52% with one, two or three antibody specificity groups, respectively.The data suggest that the pattern of antimodified protein antibody response determines the risk of disease relapse in patients with RA tapering DMARD therapy.2009-015740-42; Results.


PubMed | University of Tübingen, Institute Reumatologia Of Sao Paulo, Rheumatology Practice, Asklepios Medical Center and 5 more.
Type: Journal Article | Journal: Annals of the rheumatic diseases | Year: 2016

To analyse the role of multibiomarker disease activity (MBDA) score in predicting disease relapses in patients with rheumatoid arthritis (RA) in sustained remission who tapered disease modifying antirheumatic drug (DMARD) therapy in RETRO, a prospective randomised controlled trial.MBDA scores (scale 1-100) were determined based on 12 inflammation markers in baseline serum samples from 94 patients of the RETRO study. MBDA scores were compared between patients relapsing or remaining in remission when tapering DMARDs. Demographic and disease-specific parameters were included in multivariate logistic regression analysis for defining predictors of relapse.Moderate-to-high MBDA scores were found in 33% of patients with RA overall. Twice as many patients who relapsed (58%) had moderate/high MBDA compared with patients who remained in remission (21%). Baseline MBDA scores were significantly higher in patients with RA who were relapsing than those remaining in stable remission (N=94; p=0.0001) and those tapering/stopping (N=59; p=0.0001). Multivariate regression analysis identified MBDA scores as independent predictor for relapses in addition to anticitrullinated protein antibody (ACPA) status. Relapse rates were low (13%) in patients who were MBDA-/ACPA-, moderate in patients who were MBDA+/ACPA- (33.3%) and MBDA-ACPA+ (31.8%) and high in patients who were MBDA+/ACPA+ (76.4%).MBDA improved the prediction of relapses in patients with RA in stable remission undergoing DMARD tapering. If combined with ACPA testing, MBDA allowed prediction of relapse in more than 80% of the patients.EudraCT 2009-015740-42.


PubMed | University of Tübingen, Rheumatology Practice, Asklepios Medical Center, University of Heidelberg and 3 more.
Type: Clinical Trial, Phase III | Journal: Annals of the rheumatic diseases | Year: 2015

To prospectively analyse the risk for disease relapses in patients with rheumatoid arthritis (RA) in sustained remission, either continuing, tapering or stopping disease-modifying antirheumatic drugs (DMARDs) in a prospective randomised controlled trial.Reduction of Therapy in patients with Rheumatoid arthritis in Ongoing remission is a multicentre, randomised controlled, parallel-group phase 3 trial evaluating the effects of tapering and stopping all conventional and/or biological DMARDs in patients with RA in stable remission. Patients (disease activity score 28 (DAS28)<2.6 for least 6 months) were randomised into three arms, either continuing DMARDs (arm 1), tapering DMARDs by 50% (arm 2) or stopping DMARDs after 6 months tapering (arm 3). The primary endpoint was sustained remission during 12 months.In this interim analysis, the first 101 patients who completed the study were analysed. At baseline, all patients fulfilled DAS28 remission and 70% also American College of Rheumatology- European League Against Rheumatism Boolean remission. 82.2% of the patients received methotrexate, 40.6% biological DMARDs and 9.9% other DMARDs. Overall, 67 patients (66.3%) remained in remission for 12 months, whereas 34 patients (33.7%) relapsed. The incidence of relapses was related to study arms (p=0.007; arm 1: 15.8%; arm 2: 38.9%; arm 3: 51.9%). Multivariate logistic regression identified anticitrullinated protein antibodies (ACPA) positivity (p=0.038) and treatment reduction (in comparison to continuation) as predictors for relapse (arm 2: p=0.012; arm 3: p=0.003).This randomised controlled study testing three different treatment strategies in patients with RA in sustained remission demonstrated that more than half of the patients maintain in remission after tapering or stopping conventional and biological DMARD treatment. Relapses occurred particularly in the first 6 months after treatment reduction and were associated with the presence of ACPA.2009-015740-42.


Mandel D.R.,Rheumatology Practice | Demarco P.J.,Rheumatology Practice | Demarco P.J.,Georgetown University
International Journal of Clinical Rheumatology | Year: 2014

Dupuytren's disease (DD) is a fibroproliferative disorder affecting palmar and digital fascial structures of the hand that the rheumatologist is apt to encounter in the clinical setting and is well positioned to first identify. The etiology of DD is unknown and multiple genetic and environmental factors are thought to be involved. Histological and biochemical changes include increased fibroblasts and expression of extracellular matrix proteins, such as collagen, and the presence of contractile myofibroblasts. Development of fibrous cords is common and joint contractures can develop as the skin fuses with the underlying fascia and cords. Surgery is widely used treatment for contractures. A minimally invasive procedure, collagenase clostridium histolyticum injection, has been approved for adult patients with Dupuytren's contracture with a palpable cord. © 2014 Future Medicine Ltd.


Detert J.,Charité - Medical University of Berlin | Bastian H.,Charité - Medical University of Berlin | Listing J.,German Rheumatism Research Center | Weiss A.,German Rheumatism Research Center | And 15 more authors.
Annals of the Rheumatic Diseases | Year: 2013

Objective: To investigate the long-term effects of induction therapy with adalimumab (ADA) plus methotrexate (MTX) in comparison with placebo (PBO) plus MTX in DMARD-naïve patients with active early rheumatoid arthritis (RA). Methods: Patients with active early RA (disease duration of ≤12 months) were randomly assigned to receive 40 mg ADA subcutaneously every other week (eow) plus MTX 15 mg/week subcutaneously or PBO plus MTX subcutaneously at 15 mg/week over 24 weeks. Thereafter, all patients received MTX monotherapy up to week 48. The primary outcome was the Disease Activity Score 28 (DAS28) at week 48. Secondary outcomes included proportions of patients in remission (DAS28<2.6), ACR responses, Health Assessment Questionnaire (HAQ) score and radiographic progression. Results: 87 patients were assigned to ADA/MTX and 85 patients to PBO/MTX. At baseline, DAS28 was 6.2 ±0.8 in the ADA/MTX and 6.3±0.9 in the PBO/MTX groups. At week 24, treatment with ADA/MTX compared with PBO/MTX resulted in a greater reduction in DAS28 (3.0±1.2 vs 3.6±1.4; p=0.009) and other secondary outcomes such as DAS28 remission rate (47.9% vs 29.5%; p=0.021) and HAQ (0.49±0.6 vs 0.72±0.6; p=0.0014). At week 48, the difference in clinical outcomes between groups was not statistically significant (DAS28: 3.2±1.4 vs 3.4 ±1.6; p=0.41). Radiographic progression at week 48 was significantly greater in patients administered PBO/MTX (Sharp/van der Heijde score: ADA/MTX 2.6 vs PBO/MTX 6.4; p=0.03, Ratingen score: 1.7 vs 4.2; p=0.01). Conclusions: A greater reduction in radiographic progression after initial combination therapy with ADA and MTX was seen at week 48, even after discontinuation of ADA treatment at week 24. This sustained effect was not found at the primary endpoint (DAS28 reduction).

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