Rheumatoid Arthritis: Lange U

Lange U, Müller-Ladner U. · Klinische Immunologie, Kerckhoff-Klinik, Justus-Liebig-Universität Giessen, Benekestr. 2-8, 61231, Bad Nauheim, Deutschland. · Z Rheumatol. · Pubmed #19002473 No free full text.

Abstract: Inflammatory rheumatic disorders usually progress towards morphologic and functional deficits and thus cause substantial impairment of physical health. Amongst the therapeutic options physiotherapeutic strategies are essential and are often required to maintain the individual's quality of life. Because of the large variety of physiotherapeutical approaches, differentiated clinical examination is needed in order to implement physiotherapeutics in a treatment plan that is based on pathophysiologic and regeneration-specific aspects. The article presents a current overview of evidence-based physiotherapeutic strategies for musculoskeletal pain reduction in daily practice.

Klett R, Lange U, Haas H, Voth M, Pinkert J. · Department of Nuclear Medicine, University Hospital Giessen and Marburg, Giessen, Germany. · Rheumatology (Oxford). · Pubmed #17596287 No free full text.

Abstract: Hypertrophy and inflammation of the synovium with various underlying pathologies - such as rheumatoid arthritis, osteoarthritis, haemophilia and spondyloarthropathy - can be treated successfully by radiosynoviorthesis (RSO). For medium-sized joints (shoulder, elbow, wrist, hip and ankle), the radionuclide of choice is rhenium-186. We review the evidence for the efficacy of this local, relatively non-invasive therapy and evaluate its benefits and risks. We conclude good evidence of rhenium-186 RSO in rheumatoid arthritis and haemophilic arthropathy. In the remaining pathologies, up to now, the therapeutic efficacy has not been confirmed by today's most stringent criteria for clinical studies. The available data support rhenium-186 RSO as a suitable second-line treatment for patients in whom other therapies (including locally injected corticoids) have failed, as long as proper attention is paid to correct administration - including post-treatment immobilization and the co-administration of corticoids.

Strunk J, Lange U, Müller-Ladner U. · Lehrstuhl für Innere Medizin mit Schwerpunkt Rheumatologie der Justus-Liebig Universität Giessen, Abteilung für Rheumatologie und Klinische Immunologie, Kerckhoff-Klinik Bad Nauheim. · Dtsch Med Wochenschr. · Pubmed #16049881 No free full text.

Abstract: The development of novel anti-rheumatic drugs revolutionizes currently therapeutic strategies and diagnostic management of patients with rheumatoid arthritis, facilitating the goal of true remission instead of only symptomatic treatment as in former years. Since early treatment is known to be crucial for the longterm outcome, imaging modalities such as magnetic resonance imaging and high-frequency ultrasonography including Doppler sonography, which allow direct visualization of very early pathologic alterations of synovitis, or even initial destruction, become increasingly important. Besides the established therapy with methotrexate, new drugs such as leflunomide or the use of various combination therapies have been successfully introduced into the therapeutic armamentarium. Especially the introduction of cytokine-antagonists such as TNF-a inhibitors target the aim of remission. In addition, the upcoming therapeutic agents, which influence very effectively the inflammatory and destructive process need also to be integrated into the concert of different therapeutic strategies in the management of patients with rheumatoid arthritis, which includes the mandatory complementary factors such as physiotherapy, ergotherapy and orthopedic surgery.

Lange U, Schumann C, Schmidt KL. · Zentrum für Innere Medizin, Universität Giessen, Kerckhoff Klinik-Rheumatologie, Bad Nauheim. · Z Arztl Fortbild Qualitatssich. · Pubmed #11921607 No free full text.

Abstract: The complex actions of colchicine, which are attributable to its stabilising action on the cytoskeleton and cell membranes and its special pattern of distribution, form the basis of the results presented here; results that relating to the prophylactic and/or therapeutic actions of colchicine in a whole range of other diseases.

Lange U, Teichmann J, Müller-Ladner U, Strunk J. · Kerckhoff Clinic and Foundation, Department of Rheumatology, Clinical Immunology and Osteology, Sprudelhof 11, 61231 Bad Nauheim, Germany. · Rheumatology (Oxford). · Pubmed #16263785 links to  free full text

Abstract: OBJECTIVE: To determine the changes in bone mineral density (BMD) in patients with rheumatoid arthritis (RA; without osteoporosis) treated with infliximab. METHODS: Twenty-six patients (19 women, seven men) aged 54.2 yr (range 27-75), with persistently active RA despite a high dose of non-steroidal anti-inflammatory drugs and/or treatment with methotrexate or leflunomide, were studied. Mean duration of disease was 9.8 yr. Patients receiving or having received bisphosphonates or hormone replacement therapy were excluded. The patients were treated with 3.5 mg/kg infliximab at weeks 0, 2, 6 and then every 6-8 weeks. Lumbar and femoral BMD was measured by dual-energy X-ray absorptiometry at baseline and 12 months later. Serum osteocalcin and serum crosslaps were measured at baseline (week 0) and after 12 months. Twelve patients were taking calcium (1 g/day) and vitamin D (800 IU/day). Twenty patients were receiving methotrexate (mean dose 12.5 mg/day), six patients were receiving leflunomide (mean dose 20 mg/day) and nine patients were concomitantly receiving corticosteroids at a mean daily dose of 10 mg. RESULTS: After 12 months of infliximab therapy, there was a significant increase in BMD in the spine (BMD, P < 0.001; T-score, P < 0.001; Z-score, P < 0.001) and the femoral neck (BMD, P < 0.001; T-score, P < 0.001; Z-score, P < 0.01). With regard to the root mean square average, there was a significant increase in BMD at the left femoral neck (11.6% for a root mean square of 6%) but only a trend towards improvement in the spine (2.7% for a root mean square of 4%) during the study period. There was a significant increase in osteocalcin serum levels between baseline and after 12 months (P < 0.01) and a significant decrease in the marker for bone resorption (P < 0.01) but no change in serum calcium was observed. However, the changes in markers of bone metabolism and BMD were not correlated. CONCLUSION: The data support the hypothesis that anti-TNF therapy may exert beneficial effects on bone metabolism in RA patients.

Lange U, Illgner U, Teichmann J, Schleenbecker H. · Kerckhoff Clinic and Foundation, Department of Rheumatology, University Giessen, Bad Nauheim, Germany. · Int J Clin Pharmacol Res. · Pubmed #15689049 No free full text.

Abstract: Glucocorticoid therapy is an important risk factor for osteoporosis in rheumatoid arthritis. Reduction in fracture risk is the most important endpoint for osteoporosis treatments. The aim of this study was to evaluate whether skeletal benefit (increases in osteosonogrammetry parameters, reduction in bone turnover and fracture incidence) are maintained during a follow-up of 1 year with risedronate therapy (5 mg/day). During the study period osteosonogrammetry parameters showed a significant increase and no new osteoporotic fractures were reported, suggesting an antifracture effect of risedronate therapy. Urine crosslinks (as a bone resorption marker) significantly decreased during the follow-up, suggesting a positive balance in the bone remodeling process. The tolerability of risedronate was good and only seven out of 51 patients presented minimal adverse effects. In summary, risedronate significantly decreased new osteoporotic fractures in patients with rheumatoid arthritis and glucocorticoid-induced osteoporosis and is an effective and well-tolerated treatment.

Strunk J, Lange U, Kürten B, Schmidt KL, Neeck G. · Department of Rheumatology, Kerckhoff Clinic and Foundation, University of Giessen, Ludwigstrasse. 37-39, 61231 Bad Nauheim, Germany. · Arthritis Rheum. · Pubmed #12847675 links to  free full text

Abstract: OBJECTIVE: To compare power Doppler sonography (PDS) findings inside the bicipital tendon sheath in patients with rheumatoid arthritis (RA) and degenerative disorders of the shoulder, in order to evaluate the diagnostic value of PDS in distinguishing between inflammatory and noninflammatory shoulder pain. METHODS: The glenohumeral joints of 41 consecutive patients with shoulder pain were examined by ultrasound. Using ventral transverse and longitudinal scanning, the vascularity near and/or inside the bicipital tendon sheath was visualized by PDS. One fully trained and experienced examiner performed the sonography. Representative images were digitally stored and were read, under blinded conditions, by 2 independent investigators, who categorized the Doppler signals as being either inside or outside the tendon sheath. RESULTS: Biceps tendon sheath effusion, represented by the typical hypoechoic rim, was found in 95.8% of the RA patients (23 of 24) and in 58.8% of the patients with degenerative disorders (10 of 17). PDS signals were localized to inside the tendon sheath in 22 of the RA patients (91.7%) and in none of the patients with degenerative disorders. Although no PDS signal was found inside the tendon sheath in patients with degenerative disorders, in 9 of these patients (52.9%), signals could be localized to the environment of the tendon sheath. CONCLUSION: PDS demonstrates vascularity in the long bicipital tendon sheath of patients with RA, but not in those with degenerative shoulder disorders.

Albrecht K, Albert C, Lange U, Müller-Ladner U, Strunk J. · No affiliation provided · Ann Rheum Dis. · Pubmed #19525412 No free full text.

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Lange U, Uhlemann C, Müller-Ladner U. · Abteilung Rheumatologie, Klinische Immunologie, Physikalische Medizin und Osteologie (Innere Medizin mit Schwerpunkt Rheumatologie, Justus-Liebig-Universität Giessen), Kerckhoff-Klinik, Bad Nauheim. · Med Klin (Munich). · Pubmed #18548207 No free full text.

Abstract: BACKGROUND AND PURPOSE: Local as well as whole-body cryotherapy is used to relieve pain and inflammation in rheumatic diseases. In comparison with a chamber-based whole-body cryotherapy, the novel criostream whole-body therapy (single-person cabin with cold air cooled by liquid nitrogen) as an innovative technique offers not only a rapid therapeutic effect but also a considerable reduction in costs. The aim of this study was to compare the effect of whole-body cryotherapy in the criostream on pain reduction, disease activity and pro-inflammatory cytokines (tumor necrosis factor-[TNF-]alpha and interleukin-[IL-]1), and improvement in functional scores. PATIENTS AND METHODS: Ten patients with different active inflammatory rheumatic diseases (four patients with rheumatoid arthritis, three patients with ankylosing spondylitis, and three patients with psoriatic arthritis/spondylitis) underwent nine sessions of whole-body cryotherapy in 5 days for a short time period (at first 90 s, with step-up in each application to 2.5 min total time). RESULTS: Pain and disease activity scores decreased significantly, and, subsequently, also the functional scores showed a significant amelioration. Furthermore, there was a significant reduction in TNF-alpha (p < 0.01) and IL-1 (p < 0.05). Side effects were reported only after the first application in two cases (headache and sensation of cold). CONCLUSION: The criostream offers an elegant and, from the patient's point of view, attractive therapeutic agent in the multimodal treatment concept for inflammatory rheumatic diseases.

Strunk J, Strube K, Rumbaur C, Lange U, Müller-Ladner U. · Rheumatology, Kerckhoff-Clinic/University of Giessen. · Ultraschall Med. · Pubmed #17680519 No free full text.

Abstract: PURPOSE: To compare the interobserver agreement in qualitative and quantitative two- (2D) and three-dimensional (3D) power Doppler ultrasonographic assessment of joint vascularity in wrist arthritis of patients with rheumatoid arthritis (RA) during anti-inflammatory therapy. MATERIALS AND METHODS: Tender and swollen wrists of 15 patients with RA were examined by two independent ultrasound investigators before and at day 3, 7, 14 and 42 after the initiation of an anti-inflammatory therapy. Besides the assessment of clinical and laboratory disease activity parameters, a linear array transducer was used to produce grey-scale images of synovitis and effusion as well as 2D and 3D power Doppler sonographic images and movies of synovial vascularity. Interobserver agreement was evaluated with regard to the obtained qualitative information such as grading of synovitis and Doppler signal intensity and compared with the correlations of quantitative assessments such as measurement of synovial thickening, resistance index (RI), 3D blood vessel count, computerized pixel count and first described computerized voxel count. RESULTS: High interobserver agreement was found for the measurement of synovial thickening (r = 0.86), the computerized voxel count (r = 0.85) and the 3D blood vessel count (r = 0.83) in contrast to significantly lower levels of agreement for RI measurement, the computerized pixel count, the grading of synovitis and the 2D and 3D Doppler grading. A significant decrease of synovial perfusion could be demonstrated by means of 2D and 3D Doppler ultrasound under the anti-inflammatory treatment in accordance with an improvement in clinical and laboratory disease activity. CONCLUSION: Quantification of 3D power Doppler images (voxel count) showed higher interobserver agreement compared with 2D quantitative analyses as well as with 2D and 3D semiquantitative grading, indicating this method as a reliable approach to measure synovial perfusion as sign of inflammatory activity in arthritis.

Lange U, Piegsa M, Müller-Ladner U, Strunk J. · Kerckhoff Clinic, University of Giessen, Department of Rheumatology and Clinical Immunology, Internal Medicine and Rheumatology, Bad Nauheim, Germany. · Autoimmunity. · Pubmed #16769661 No free full text.

Abstract: Idiopathic inflammatory myopathies (IM), including dermatomyositis (DM) and polymyositis (PM), are a group of systemic rheumatologic diseases of unknown etiology characterized by chronic myositis. Antisynthetase antibodies such as the anti-Jo-1 antibody are known to be highly specific for inflammatory myopathies. Patients with this antibody frequently show a combination of symptoms including interstitial lung disease, fever, polyarthritis, myositis, Raynaud's phenomenon and "mechanic's hands". In the management of PM with anti-Jo-1 antibody, immunosuppressive agents are used to control the disease. Leflunomide is a new immunosuppressive drug recently introduced in the treatment of rheumatoid and psoriatic arthritis. Here, we report two cases of female patients with PM and anti-Jo-1 antibodies, who were successfully treated with leflunomide.

Strunk J, Bundke E, Lange U. · Department of Rheumatology, Kerckhoff-Clinic and Foundation, University of Giessen, Benekestrasse 2-8, 61231 Bad Nauheim, Germany. · Rheumatol Int. · Pubmed #15999273 No free full text.

Abstract: To compare the effect of oral glucocorticoid (GC) therapy with the effect of intravenous anti-TNF-alpha-therapy on serum VEGF levels of patients with rheumatoid arthritis (RA). Five RA patients (5/8) who had no prior treatment with DMARDs (Disease modifying antirheumatic drugs) or GCs were administered 20 mg prednisolone daily. Three patients who failed more than one DMARD therapy received infusion with Infliximab (200 mg). VEGF-serum levels were measured by enzyme-linked immunosorbent assay before treatment,and at day 10 or 13 during prednisolone therapy, or 14 days after the first Infliximab infusion. Serum VEGF levels in therapy naive RA patients (GC group) were higher than those in pretreated patients who received Infliximab (median serum VEGF level: 1106 vs 320 pg/ml; P=0.1). Treatment with Infliximab as well as GCs significantly decreased serum VEGF levels after 10-14 days in RA patients (median serum VEGF level after treatment: GC group 559 pg/ml, Infliximab group 92 pg/ml; P=0.01 vs without treatment or preinfusion). Conclusions: Anti-TNF-alpha antibody Infliximab as well as GC are able to decrease serum VEGF levels in patients with active RA. Whether therapeutic reduction of serum VEGF levels is associated with inhibition of angiogenesis should be evaluated in future by imaging of synovial vasculature.

Strunk J, Heinemann E, Neeck G, Schmidt KL, Lange U. · Department of Rheumatology, Kerckhoff Clinic and Foundation/University of Giessen, Ludwigstrasse 37-39, 61231 Bad Nauheim, Germany. · Rheumatology (Oxford). · Pubmed #15353607 links to  free full text

Abstract: OBJECTIVE: To evaluate angiogenesis as an essential component of pannus formation and cartilage destruction in rheumatoid arthritis (RA) using power Doppler ultrasonography (PDUS) and serum vascular endothelial growth factor (VEGF) measurement. METHODS: Twenty-one RA patients with a painful and swollen wrist and 12 healthy controls were examined with ultrasound. By means of standard scans, vascularity near and inside the joint capsule was visualized with PDUS. Two trained investigators performed sonography. Representative video clips were stored and read by two independent investigators, under blinded conditions, with regard to the microvascular Doppler flow being either inside or outside the joint capsule and with respect to a qualitative estimate of the intensity of blood flow, according to a grading from 1 to 3. Serum levels of VEGF were measured with a standard quantitative sandwich ELISA. RESULTS: The power Doppler mode identified increased synovial microvascular blood flow inside the joint capsule in 17 of 21 RA patients (81%) vs one of the healthy controls. We found large variation in serum VEGF levels in RA patients and in healthy controls. The degree of synovial vascularity determined by PDUS showed no correlation with the immediate serum VEGF level in the same patient. CONCLUSION: The high correlation between intra-articular microvascular power Doppler flow and clinical synovitis in RA patients (P<0.0001) indicates that PDUS may be helpful in studying the role of synovial blood vessels in rheumatoid inflammation.

Strunk J, Lange U. · Department of Rheumatology, Kerckhoff-Clinic and Foundation, University of Giessen, Ludwigstrasse, Bad Nauheim, Germany. · J Rheumatol. · Pubmed #15124266 No free full text.

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Strunk J, Strube K, Lange U. · Abteilung Rheumatologie der Universität Giessen, Herz- und Rheumazentrum Kerckhoff-Klinik Bad Nauheim. · Internist (Berl). · Pubmed #14689077 No free full text.

Abstract: We report on a 44 year old woman with fever, cutaneous rash, severe sore throat, arthritis, leukocytosis, splenomegaly and liver dysfunction. After exclusion of an infectious or malignant disease, adult onset Still's disease was diagnosed according to the Yamaguchi criteria. Reduction of the initial treatment with corticosteroids after 4 month caused a relapse of disease. Thus methotrexate treatment was started, which resulted in improvement of symptoms and inflammatory activity.

Lange U, Boss B, Teichmann J, Stracke H, Neeck G. · Kerckhoff Clinic and Foundation, Department of Rheumatology, Ludwigstr. 37-39, 61231 Bad Nauheim, Germany. · Z Rheumatol. · Pubmed #11155797 No free full text.

Abstract: In the present prospective study, bone metabolism was examined in 51 patients at the time of diagnosis and 6-7 months later: 29 patients had definitive diagnosis of late onset rheumatoid arthritis (LORA) and 22 patients had polymyalgia rheumatica (PMR). At the time of diagnosis, the patients had not received any medication; during the 6-7 months of follow-up they were treated with corticosteroids and nonsteroidal-antirheumatic drugs (NSAIDs). Serum levels of osteocalcin, alkaline phosphatase and ostase, as markers for bone formation, were tested. Bone density was examined by dual x-ray absorption (DEXA) of the lumbar spine and the left ward triangle. At the time of diagnosis, no signs of bone alterations were seen. After 6-7 months, abnormal values of the serum parameters and bone mineral density were found in 16/51 patients (31%): 10/29 patients with LORA and 6/22 with PMR. Thus, our findings suggest that an alteration of bone metabolism could be observed in a minority of patients during the first few months of glucocorticoid medication, but in the majority of patients an osteoprotective effect seems to be worth discussing. The results suggest from a prophylactic and therapeutic point of view that an additional disease-modifying antirheumatic medication should be considered in the early stages of therapy to reduce the osteoporotic risk of a longterm corticoid therapy.

Lange U, Piegsa M, Teichmann J, Neeck G. · Kerckhoff Clinic and Foundation, Department of Rheumatology, University Giessen, Bad Nauheim,Germany. · Rheumatol Int. · Pubmed #10984136 No free full text.

Abstract: In a prospective study, the glenohumeral joints of 51 patients (aged 60 or above) were examined, using ultrasonography. Twenty-two patients were suffering from characteristic polymyalgia rheumatica (PMR) symptoms. In contrast, 29 other patients initially had similar complaints, but were diagnosed as having elderly onset rheumatoid arthritis (EORA, rheumatoid factor negative) upon development of typical symptoms. Ultrasound examination revealed glenohumeral joint inflammation in 40.9% (9/22) of the patients with PMR and 65.5% (19/29) of the patients with EORA. A discrete symmetrical biceps tendon sheath effusion was found in only three patients and unilateral in six patients with PMR. In contrast, 12 patients with EORA presented a massive effusion of the biceps tendon sheath, in some cases combined with a bilateral subdeltoid bursitis, and an intraarticular (i.a.) effusion/synovitis. To summarize our results: an i.a. effusion/synovitis, subdeltoid bursitis and biceps tendon sheath effusion were more frequent in patients with EORA, with a predominate symmetry and signs for massive inflammation. The typical ultrasonographic result in patients with PMR was a unilateral inflammation of the glenohumeral joint with predominate discrete biceps tendon sheath effusion and, in comparison with the EORA group, with signs of a low grade inflammation. We conclude that the results of our prospective study might be helpful in the differentiation of PMR and a rheumatoid factor negative subgroup of EORA at the first time of manifestation where clinical overlaps can be observed. However, ultrasonography of the glenohumeral joints might be a good and helpful instrument of differentiation in both diseases.

Klett R, Grau K, Puille M, Matter HP, Lange U, Steiner D, Bauer R. · Klinik für Nuklearmedizin, Klinikum der Justus-Liebig-Universität Giessen, Deutschland. · Nuklearmedizin. · Pubmed #10726255 No free full text.

Abstract: AIM: Because of a similar tracer accumulation, we assumed to get the same information about synovitis in arthritic joint disease with HIG scintigraphy and bloodpool scintigraphy using HDP. Therefore, we compared retrospectively 23 patients. METHODS: In HIG scintigraphy, synovitis was diagnosed according to increasing activity from early to late image. In bloodpool scintigraphy according to an increased activity in comparison to the surrounding tissues. RESULTS: In 694 joints comparison of both scintigraphic modalities was possible, resulting in a 2 x 2 kappa coefficient of 0.93 or 0.97 by using late-phase bone scintigraphy as an anatomical marker. For intra- and interobserver agreement, 2 x 2 kappa coefficients of 0.93 and 0.88 in HIG scintigraphy, respectively 0.96 and 0.90 in blood-pool scintigraphy were calculated. CONCLUSION: This study shows an excellent agreement in the visualization of synovitis by HIG and bloodpool scintigraphy. Because of its higher objectivity and lower cost, investigation of synovitis should be performed by bloodpool scintigraphy.

Lange U, Boss B, Teichmann J, Klett R, Stracke H, Bretzel RG, Neeck G. · Kerckhoff Clinic and Foundation, Department of Rheumatology, Ludwig Str. 37-39, D-61231 Bad Nauheim, Germany. · Eur J Med Res. · Pubmed #10585302 No free full text.

Abstract: The association between rheumatological and thyroid disorders has long been known, the most common being the association of rheumatoid arthritis and autoimmune thyroiditis. Little is known as to possible thyroid involvement in ankylosing spondylitis (AS). In 22 female patients with AS and 22 healthy age-matched control subjects parameters of thyroid gland function, rheumatic activity, as well as a subtle drug anamnesis of the rheumatic medication, and an ultrasonographic examination of the thyroid gland were determined. Thyroid function was tested by intravenous injection of 400 microg thyrotropin-releasing hormone (TRH). In parallel basal levels of reverse-T3 (rT3), calcium and anti-thyroid antibodies were estimated. In the AS-group an enlarged thyroid volume was seen in 10 cases, basal FT4, FT3 and TT3 were significantly lower, TSH and TT4 were found to be in the normal range and rT3 was significantly increased. The prevalence of anti-thyroid antibodies was significantly higher in the AS-group. The AS-patients responded as well as the controls with thyroid hormone secretion to TRH, within an observation period of 2 hours. No differences were observed in TSH response. Free serum calcium showed in both groups no significant difference. To summarize our results, female patients with AS showed a

Strunk J, Strube K, Müller-Ladner U, Lange U. · No affiliation provided · Ann Rheum Dis. · Pubmed #16474035 links to  free full text

This publication has no abstract.