Kirsten de Groot

Klinikum Offenbach GmbH, Frankfurt, Hesse, Germany

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Publications (99)603.41 Total impact

  • K de Groot · S M Weiner

    No preview · Article · May 2015 · Zeitschrift für Rheumatologie

  • No preview · Article · Oct 2014 · DMW - Deutsche Medizinische Wochenschrift
  • Ulf Schönermarck · Wolfgang L Gross · Kirsten de Groot
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    ABSTRACT: Antineutrophil cytoplasmic autoantibody (ANCA)-associated diseases are small-vessel vasculitides, encompassing granulomatosis with polyangiitis (formerly Wegener's granulomatosis), microscopic polyangiitis and eosinophilic granulomatosis with polyangiitis. Once considered life-threatening diseases, the introduction of stage-adapted immunosuppressive therapy and medications with decreased toxicity has improved patients' survival. Treatment is biphasic, consisting of induction of remission (3-6 months) for rapid control of disease activity and maintenance of remission (at least 18 months) to prevent disease relapse using therapeutic alternatives that have reduced toxicity. This Review summarizes current treatment strategies for these diseases, with a special focus on long-term follow-up data from key randomized controlled trials and new developments in remission induction and maintenance therapy. Current treatment strategies have substantial short-term and long-term adverse effects, and relapses are frequent; thus, less-toxic and more-effective approaches are needed. Moreover, the optimal intensity and duration of maintenance therapy remains under debate. Clinical trials have traditionally considered ANCA-associated vasculitides as a single disease entity. However, future studies must stratify participants according to their specific disease, clinical features (different types of organ manifestation, PR3-ANCA or MPO-ANCA positivity) and disease severity.
    No preview · Article · Nov 2013 · Nature Reviews Nephrology
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    ABSTRACT: Objectives: To investigate the nature of the relationship between proteinase 3 anti-neutrophil cytoplasm autoantibody (PR3-ANCA) and relapse in patients with early systemic granulomatosis with polyangiitis (Wegener's) (GPA). Methods: Clinical data from 16 relapsing and 12 non-relapsing patients with early systemic GPA from a randomised clinical trial were correlated to monthly PR3-ANCA values over 18 months. Each sample was examined using 9 different enzyme-linked immunosorbent assays (ELISAs) to ensure reliability of ANCA results. PR3-ANCA peaks were identified by the highest sum of logarithmic transformation values from all assays in samples after remission. Results: A PR3-ANCA peak was identified in all relapsing and non-relapsing patients and coincided with relapse in all 14 evaluable relapsing patients. The monthly increment before the peak, however, was similar in relapsing and non-relapsing patients in all assays. Increments from remission to peak were higher in relapsing patients in 2/9 assays. PR3-ANCA values at entry and peak PR3-ANCA values were higher in relapsing patients in 3/9 and 2/9 assays, respectively. However, large overlaps of PR3-ANCA values prevented a distinction between relapsing and non-relapsing patients. The median time to reach peak values was 14 months in relapsing and 12 months in non-relapsing patients with scheduled termination of treatment at 12 months. Conclusions: The predictive value for relapses of PR3-ANCA determinations confirm and extend previous reports. Although all relapses were related to PR3-ANCA increases, reduction or withdrawal of immunosuppression without relapse was also related to increases and may explain the lack of predictive value of sequential PR3-ANCA determinations.
    No preview · Article · Feb 2013 · Clinical and experimental rheumatology
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    No preview · Article · Nov 2012 · Arthritis & Rheumatology
  • Kirsten de Groot
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    ABSTRACT: Glomerulonephritis (GN) is a common manifestation of the antineutrophil cytoplasmic antibody-associated systemic vasculitides (AASV), which include granulomatosis with polyangiitis and microscopic polyangiitis. The level of renal involvement at presentation is highly predictive of survival and should be assessed early so that kidney function can be preserved. AASV patients with urinary sediment but normal function have a twofold greater risk of death than those with no renal involvement. Those with impaired renal function at diagnosis have a fivefold greater risk of death. Renal vasculitis is most prevalent in older patients, who have more severe disease and poorer prognoses. Renal biopsy not only establishes diagnosis but provides information on severity of renal-function impairment and prognosis. Induction of remission with cyclophosphamide is standard treatment. For patients with crescentic, rapidly progressive GN, adjunctive plasma exchange can promote renal recovery. Renal failure occurs in one-fourth of AASV patients after 3 to 4 years; 60% of patients receiving dialysis for acute GN can recover independent renal function. Renal transplant patients with vasculitis fare as well as renal transplant patients without vasculitis. Lastly, renal vasculitis is an independent risk factor for cardiovascular events.
    No preview · Article · Nov 2012 · Cleveland Clinic Journal of Medicine
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    ABSTRACT: The NORAM (Nonrenal Wegener's Granulomatosis Treated Alternatively with Methotrexate [MTX]) trial demonstrated that MTX can replace cyclophosphamide (CYC) as remission-inducing treatment for patients with newly diagnosed early systemic antineutrophil cytoplasmic antibody-associated vasculitis. Duration of relapse-free survival was longer among CYC-treated patients than among MTX-treated patients during short-term followup. The aim of the present study was to describe the long-term outcome in patients enrolled in the randomized clinical trial. Outcome questionnaires were sent to investigators who had recruited patients for the NORAM trial. Patients treated with MTX for induction of remission (n = 49) were compared to CYC-treated patients (n = 46) with respect to immunosuppressive therapy during followup, relapse-free survival, mortality, and occurrence of other clinical events. The median duration of followup was 6 years (range 0.1-10.8 years). One patient developed end-stage renal disease, and 11 died. The number of patients affected by serious infection, malignancy, or severe organ failure did not differ between treatment groups, and no difference in survival rate was observed. The duration of corticosteroid therapy was longer in the MTX group during the 18 months of the trial (P = 0.005). During subsequent followup, patients who were in the MTX group in the NORAM trial received corticosteroids, CYC, and other immunosuppressive agents (azathioprine, MTX, and/or mycophenolate mofetil) for longer periods than those who were in the CYC group (P = 0.004, P = 0.037, and P = 0.031, respectively). The cumulative relapse-free survival tended to be lower in the MTX group (P = 0.056). In the NORAM cohort, no difference in occurrence of major adverse events was observed between treatment groups during long-term followup. However, first-line treatment with MTX was associated with less effective disease control than CYC-based induction therapy.
    Full-text · Article · Oct 2012 · Arthritis & Rheumatology
  • K de Groot · E Märker-Hermann
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    ABSTRACT: Secondary vasculitis is a form of vasculitis for which an underlying disease is known. Diseases associated with secondary vasculitis include infections, drug hypersensitivity, malignancy, rheumatoid arthritis, collagen vascular disease and sarcoidosis. Moreover, there are numerous conditions that can mimic vasculitis clinically, in laboratory testing, radiographically and in histopathology. It is evident that distinguishing primary vasculitis from secondary vasculitis and also vascular inflammation from non-vasculitic disorders (vasculitis mimics) has significant therapeutic implications.
    No preview · Article · Sep 2012 · Zeitschrift für Rheumatologie
  • B. Hellmich · K. de Groot
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    ABSTRACT: Cryoglobulinemic vasculitis consists of a group of immune complex-mediated diseases of small and medium-sized vessels, which mainly occur in association with hepatitis C infections or connective tissue diseases. Typical symptoms include purpuric skin changes, arthralgia and polyneuropathy often in conjunction with membranoproliferative glomerulonephritis. Classification criteria have recently been established which encompass serological and clinical parameters after detection of cryoglobulins in serum. Therapy is based on treatment of the underlying primary disease, e.g. antiviral treatment of hepatitis C with pegylated interferon-alpha and ribavirin. Corticosteroids and cyclophosphamide are administered for life or organ function threatening manifestations (e.g. large skin ulcers, severe motor neuropathy, rapid progressive glomerulonephritis), however they can slow down virus elimination and thus constitute the primary treatment in cases of non-virus-associated cryoglobulinemia. The B-cell depleting drugs (e.g. rituximab) have proven very effective for hepatitis C-associated as well as essential cryoglobulinemia and have shown to be superior to steroids plus additional immunosuppressants. Since the introduction of rituximab plasma exchange is only used in cases with hyperviscosity due to cryoglobulins.
    No preview · Article · May 2012 · Der Nephrologe
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    ABSTRACT: The previously reported randomised controlled trial of a consensus regimen of pulse cyclophosphamide suggested that it was as effective as a daily oral (DO) cyclophosphamide for remission induction of antineutrophil cytoplasm autoantibodies-associated systemic vasculitis when both were combined with the same glucocorticoid protocol (CYCLOPS study (Randomised trial of daily oral versus pulse Cyclophosphamide as therapy for ANCA-associated Systemic Vasculitis published de groot K, harper L et al Ann Int Med 2009)). The study had limited power to detect a difference in relapse. This study describes the long-term outcomes of patients in the CYCLOPS study. Long-term outcomes were ascertained retrospectively from 148 patients previously recruited to the CYCLOPS Trial. Data on survival, relapse, immunosuppressive treatment, cancer incidence, bone fractures, thromboembolic disease and cardiovascular morbidity were collected from physician records retrospectively. All patients were analysed according to the group to which they were randomised. Median duration of follow-up was 4.3 years (IQR, 2.95-5.44 years). There was no difference in survival between the two limbs (p=0.92). Fifteen (20.8%) DO and 30 (39.5%) pulse patients had at least one relapse. The risk of relapse was significantly lower in the DO limb than the pulse limb (HR=0.50, 95% CI 0.26 to 0.93; p=0.029). Despite the increased risk of relapse in pulse-treated patients, there was no difference in renal function at study end (p=0.82). There were no differences in adverse events between the treatment limbs. Pulse cyclophosphamide is associated with a higher relapse risk than DO cyclophosphamide. However, this is not associated with increased mortality or long-term morbidity. Although the study was retrospective, data was returned in 90% of patients from the original trial.
    Full-text · Article · Nov 2011 · Annals of the rheumatic diseases
  • U. Erdbrügger · K. de Groot

    No preview · Article · Sep 2011 · Zeitschrift für Rheumatologie
  • U Erdbrügger · K de Groot
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    ABSTRACT: Methotrexate (MTX) in low-doses is an important component of anti-inflammatory therapy of rheumatoid arthritis and other inflammatory joint diseases. In contrast to high-dose administration of MTX in oncology, which can lead to direct tubulus toxicity and subsequent renal failure, renal side-effects are a rare exception for low-dose MTX. The biggest problem under low-dose MTX is that an already limited renal function due to comorbidities or an increasing, sometimes clinically insufficiently monitored renal insufficiency due to comedications, such as non-steroidal antirheumatics (NSAR) and antibiotics, leads to a reduced excretion of MTX and therefore to an accumulation in serum. This is primarily accompanied by gastrointestinal mucositis and bone marrow depression. For this reason low-dose MTX should never be administered once the glomerular filtration rate (GFR) is less than <30 ml/min and only 50% of the original dosage should be administered if the GFR is between 30 and 60 ml/min.
    No preview · Article · Jul 2011 · Zeitschrift für Rheumatologie
  • K de Groot · E Märker-Hermann
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    ABSTRACT: Patients with inflammatory rheumatic diseases often suffer from considerable comorbidities that can arise due to the chronic systemic inflammatory activity of the rheumatic disease itself, disorders of immune defense, or as a result of antirheumatic treatment; they can also occur independently. For example, almost 50% of patients with rheumatoid arthritis already exhibit two further chronic diseases at the time of initial manifestation. With regard to the elevated mortality observed in patients with rheumatism, particularly cardiovascular morbidity and increased predisposition to infections are of note. In addition, this article addresses further important possible concomitant diseases, i.e., osteoporosis and tumor diseases. A ground rule is to identify comorbidities and treat them just as diligently as the underlying rheumatic disease so that the patient with rheumatism should be accompanied by an interdisciplinary team of internists during each phase of the disease. Effective control of the systemic inflammatory activity may serve to reduce the risk of certain cardiovascular and neoplastic comorbidities.
    No preview · Article · Jun 2011 · Der Internist
  • K. de Groot · E. Märker-Hermann
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    ABSTRACT: Patients with inflammatory rheumatic diseases often suffer from considerable comorbidities that can arise due to the chronic systemic inflammatory activity of the rheumatic disease itself, disorders of immune defense, or as a result of antirheumatic treatment; they can also occur independently. For example, almost 50% of patients with rheumatoid arthritis already exhibit two further chronic diseases at the time of initial manifestation. With regard to the elevated mortality observed in patients with rheumatism, particularly cardiovascular morbidity and increased predisposition to infections are of note. In addition, this article addresses further important possible concomitant diseases, i.e., osteoporosis and tumor diseases. A ground rule is to identify comorbidities and treat them just as diligently as the underlying rheumatic disease so that the patient with rheumatism should be accompanied by an interdisciplinary team of internists during each phase of the disease. Effective control of the systemic inflammatory activity may serve to reduce the risk of certain cardiovascular and neoplastic comorbidities.
    No preview · Article · Jun 2011 · Der Internist
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    ABSTRACT: Atherosclerosis is an inflammatory process mediated by circulating immune cells, including monocytes. There is accumulating evidence for the involvement of Toll-like receptor 4 (TLR-4) as a mediator of atherogenesis. We evaluated the association between CD14+/TLR-4+ monocytes in peripheral blood (flow cytometry) and future cardiovascular events (CVE), e.g. myocardial infarction, percutaneous transluminal coronary angioplasty (including stenting), aortocoronary bypass, stroke and angiographically verified stenosis of peripheral arteries and cardiovascular (CV) death, in 191 patients with chronic kidney disease Stage V receiving hemodialysis therapy. At baseline, CD14+/TLR-4+ monocytes correlated significantly with age (r = 0.2; P = 0.007), high-sensitivity C-reactive protein (r = 0.2; P = 0.008) and mean arterial pressure (r = -0.2; P = 0.02), but not with gender (P = 0.5), smoking (P = 0.6) and the presence of diabetes (P = 0.5). During a median follow-up period of 36 [1-54] months, 79 (41%) patients experienced a CVE. A total of 55 patients died during the follow-up period, 25 of those due to a confirmed CV cause. Log-rank test did not reveal statistical significance for TLR-4+ monocytes concerning incident CVE (P = 0.3), CV death (P = 0.85) and overall death (P = 0.8). In a multiple Cox-regression analysis, we identified age (P = 0.003) and smoking (P = 0.001) as the only independent variables associated with incident CVE. Unexpectedly, we could not detect an association between CD14+/TLR-4+ monocytes and incident CVE as well as CV death in stable hemodialysis patients. Further studies have to clarify the potential role of this cell population for CV outcome in this population.
    Full-text · Article · Apr 2011 · Nephrology Dialysis Transplantation
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    ABSTRACT: Wegener's granulomatosis and microscopic polyangiitis are antineutrophil cytoplasm antibodies (ANCA)-associated vasculitides with significant morbidity and mortality. The long-term survival of patients with ANCA associated vasculitis treated with current regimens is uncertain. To describe the long-term patient survival and possible prognostic factors at presentation in an international, multicentre, prospectively recruited representative patient cohort who were treated according to strictly defined protocols at presentation and included the full spectrum of ANCA-associated vasculitis disease. Outcome data were collected for 535 patients who had been recruited at the time of diagnosis to four randomised controlled trials between 1995 and 2002. Trial eligibility was defined by disease severity and extent, covered the spectrum of severity of ANCA-associated vasculitis and used consistent diagnostic criteria. Demographic, clinical and laboratory parameters at trial entry were tested as potential prognostic factors in multivariable models. The median duration of follow-up was 5.2 years and 133 (25%) deaths were recorded. Compared with an age- and sex-matched general population there was a mortality ratio of 2.6 (95% CI 2.2 to 3.1). Main causes of death within the first year were infection (48%) and active vasculitis (19%). After the first year the major causes of death were cardiovascular disease (26%), malignancy (22%) and infection (20%). Multivariable analysis showed an estimated glomerular filtration rate <15 ml/min, advancing age, higher Birmingham Vasculitis Activity Score, lower haemoglobin and higher white cell count were significant negative prognostic factors for patient survival. Patients with ANCA-associated vasculitis treated with conventional regimens are at increased risk of death compared with an age- and sex-matched population.
    Full-text · Article · Mar 2011 · Annals of the rheumatic diseases
  • Ulf Schönermarck · Kirsten de Groot
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    ABSTRACT: Available evidence suggests that rituximab may be safe and effective for the treatment of refractory antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis. Two studies now show that rituximab is not less effective than cyclophosphamide for treating ANCA-associated vasculitides. Should rituximab be the new standard of care for patients with ANCA-associated vasculitis?
    No preview · Article · Jan 2011 · Nature Reviews Nephrology
  • U. Erdbrügger · K. Groot
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    ABSTRACT: Methotrexat (MTX) in ,,Low-dose“-Applikation ist eine wichtige Säule der antientzündlichen Therapie der rheumatoiden Arthritis und anderer entzündlicher Gelenkerkrankungen. Im Gegensatz zur ,,High-dose“-Anwendung von MTX in der Onkologie, das zur direkten Tubulustoxizität und zum konsekutiven Nierenversagen führen kann, sind renale Nebenwirkungen bei Low-dose-MTX eine seltene Ausnahme. Das größere Problem unter Low-dose-MTX liegt darin, dass eine a priori eingeschränkte Nierenfunktion durch Komorbiditäten oder eine zunehmende, manchmal klinisch nichtausreichend beachtete Niereninsuffizienz im Rahmen einer Komedikation mit z. B. nichtsteroidalen Antirheumatika (NSAR), Antibiotika etc. zu einer verminderten MTX-Ausscheidung und damit Kumulation der Substanz im Serum führt. Dies geht in erster Linie mit gastrointestinaler Mukositis und Knochenmarkdepression einher. Aus diesem Grund sollte auch Low-dose-MTX bei einer glomerulären Filtrationsrate (GFR) Keywords: Arzneimittelwechselwirkung; Dose-response relationship; Dosis-Wirkung-Verhältnis; Drug interactions; Glomerular filtration rate; Glomeruläre Filtrationsrate; Hematuria; Hämaturie; Proteinuria; Proteinurie Document Type: News DOI: Affiliations: 1: Division of Nephrology, University of Virginia Health System, 800133, 22908, Charlottesville, USA, Email: 2: Medizinische Klinik III (Nephrologie, Hypertensiologie, Rheumatologie), KfH Nierenzentrum Offenbach, Klinikum Offenbach GmbH, Starkenburgring 66–70, 63069, Offenbach, Deutschland, Email: Publication date: September 1, 2011 $(document).ready(function() { var shortdescription = $(".originaldescription").text().replace(/\\&/g, '&').replace(/\\, '<').replace(/\\>/g, '>').replace(/\\t/g, ' ').replace(/\\n/g, ''); if (shortdescription.length > 350){ shortdescription = "" + shortdescription.substring(0,250) + "... more"; } $(".descriptionitem").prepend(shortdescription); $(".shortdescription a").click(function() { $(".shortdescription").hide(); $(".originaldescription").slideDown(); return false; }); }); Related content In this: publication By this: publisher By this author: Erdbrügger, U. ; Groot, K. GA_googleFillSlot("Horizontal_banner_bottom");
    No preview · Article · Jan 2011 · Zeitschrift für Rheumatologie
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    ABSTRACT: Current remission maintenance therapies for antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) are limited by partial efficacy and toxicity. To compare the effects of mycophenolate mofetil with azathioprine on the prevention of relapses in patients with AAV. Open-label randomized controlled trial, International Mycophenolate Mofetil Protocol to Reduce Outbreaks of Vasculitides (IMPROVE), to test the hypothesis that mycophenolate mofetil is more effective than azathioprine for preventing relapses in AAV. The trial was conducted at 42 centers in 11 European countries between April 2002 and January 2009 (42-month study). Eligible patients had newly diagnosed AAV (Wegener granulomatosis or microscopic polyangiitis) and were aged 18 to 75 years at diagnosis. Patients were randomly assigned to azathioprine (starting at 2 mg/kg/d) or mycophenolate mofetil (starting at 2000 mg/d) after induction of remission with cyclophosphamide and prednisolone. The primary end point was relapse-free survival, which was assessed using a Cox proportional hazards model. The secondary end points were Vasculitis Damage Index, estimated glomerular filtration rate, and proteinuria. A total of 156 patients were assigned to azathioprine (n = 80) or mycophenolate mofetil (n = 76) and were followed up for a median of 39 months (interquartile range, 0.66-53.6 months). All patients were retained in the analysis by intention to treat. Relapses were more common in the mycophenolate mofetil group (42/76 patients) compared with the azathioprine group (30/80 patients), with an unadjusted hazard ratio (HR) for mycophenolate mofetil of 1.69 (95% confidence interval [CI], 1.06-2.70; P = .03). Severe adverse events did not differ significantly between groups. There were 22 severe adverse events in 13 patients (16%) in the azathioprine group and there were 8 severe adverse events in 8 patients (7.5%) in the mycophenolate mofetil group (HR, 0.53 [95% CI, 0.23-1.18]; P = .12). The secondary outcomes of Vasculitis Damage Index, estimated glomerular filtration rate, and proteinuria did not differ significantly between groups. Among patients with AAV, mycophenolate mofetil was less effective than azathioprine for maintaining disease remission. Both treatments had similar adverse event rates. Identifier: NCT00307645.
    Full-text · Article · Nov 2010 · JAMA The Journal of the American Medical Association
  • E Reinhold-Keller · K de Groot
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    ABSTRACT: Since the introduction of combined immunosuppressive therapy consisting of oral cyclophosphamide (CYC) and glucocorticosteroids (GC) in the 1970s, the outcome of antineutrophil cystoplasmic antibodies (ANCA)-associated vasculitides has improved dramatically over the last decades. However, the long-term follow-up of patients treated with CYC plus GC has revealed a high treatment-related morbidity and mortality and a high proportion of patients suffering from relapses (up to 50%), requiring CYC and GC again. Methotrexate (MTX) can replace CYC for induction of remission in patients with a non life-threatening disease course of ANCA associated vasculitides ('early systemic'). Furthermore, MTX can be used as a maintenance medication after induction of remission with CYC (plus GC), provided there is a decent renal function with a GFR >50 ml /min. As with any maintenance regimen, we do not know exactly for how long to continue MTX maintenance therapy. When using MTX as remission induction or maintenance regimen a tight control of urinary sediment and kidney function is mandatory in order to detect a potential renal relapse or de novo manifestation.
    No preview · Article · Sep 2010 · Clinical and experimental rheumatology

Publication Stats

6k Citations
603.41 Total Impact Points


  • 2007-2015
    • Klinikum Offenbach GmbH
      Frankfurt, Hesse, Germany
  • 2011
    • University of Virginia
      Charlottesville, Virginia, United States
  • 2001-2011
    • Hannover Medical School
      • Institute for Pathology
      Hanover, Lower Saxony, Germany
  • 2008
    • Universitätsklinikum Münster
      Muenster, North Rhine-Westphalia, Germany
  • 1998-2001
    • Universität zu Lübeck
      • • Poliklinik für Rheumatologie
      • • Abteilung Klinische Rheumatologie
      Lübeck Hansestadt, Schleswig-Holstein, Germany