P Lamprecht

Lack of efficacy of rituximab in Wegener's granulomatosis with refractory granulomatous manifestations.

Objective: To investigate the safety and efficacy of rituximab (RTX) in patients with refractory Wegener’s granulomatosis (WG). Patients and methods: Eight consecutive patients with active refractory WG were included. In all patients disease activity had persisted despite standard treatment with cyclophosphamide and prednisolone, as well as tumour necrosis factor α blockade 3 months before inclusion in the study. Patients had particular granulomatous manifestations like retro-orbital granulomata (n = 5), nodules of the lungs (n = 1), and subglottic stenosis (n = 2). RTX was given intravenously every 4th week in combination with the standard treatment in five patients and with methotrexate in two others. Disease extent and activity were monitored clinically by interdisciplinary care, immunodiagnostics (ANCA serology, B cells by flow cytometry), and magnetic resonance imaging. Results: Beneficial response and a reduction in disease activity were seen in three patients, two of whom went into complete remission. In three other patients, disease activity remained unchanged while the disease progressed in the remaining two patients. In all patients peripheral blood B cells fell to zero during treatment with RTX. cANCA titres remained unchanged in all except one patient. Conclusion: In this pilot study, B lymphocyte depletion was not associated with a change of the ANCA titres or obvious clinical improvement of refractory granulomatous disease in patients with WG. Further studies are needed to evaluate the role of RTX in WG.

Serum HMGB1 levels are increased in active Wegener's granulomatosis and differentiate between active forms of ANCA-associated vasculitis

High mobility group box 1 (HMGB1) is a non-histone nuclear protein released during cell necrosis and late apoptosis. It contributes to the activation of monocytes/macrophages and induces the secretion of proinflammatory cytokines.1,–,4 HMGB1 serum concentrations are increased in conditions associated with severe tissue damage such as haemorrhagic shock.5 The hypothesis behind this study was that HMGB1 may be released from damaged tissue in antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) and serum levels may correlate with disease activity. Furthermore, with respect to the known sources of HMGB1, high levels were expected in particular in Wegeners granulomatosis (WG) which is characterised by granulomatous inflammation. Serum samples were obtained from 46 patients with WG, 44 with …

The low-penetrance R92Q mutation of the tumour necrosis factor superfamily 1A gene is neither a major risk factor for Wegener’s granulomatosis nor multiple sclerosis

Inherited autosomal-dominant mutations in the tumour necrosis factor receptor superfamily 1A ( TNFRSF1A ) gene encoding the tumour necrosis factor receptor p55 (TNF-R1) are the cause of an auto-inflammatory syndrome that is characterized by periodic fever attacks, aseptic peritonitis, arthritis, meningitis, conjunctivitis, pleuritis and skin rash (OMIM #142680). The most common TNFR-associated periodic syndrome (TRAPS)-like disease that is associated with a R92Q mutation, however, occurs sporadically, with later onset (median 23 years vs 7 years with other mutations) and a milder and often oligosymptomatic course.1,2 Intriguingly, carriers of the R92Q allele bear a slightly increased risk for some other diseases, such as myocardial infarction,3 increased carotid intima-media thickness,3 thrombotic complications in Behcet’s disease4 and early synovitis.1 Due to the low …

Pachymeningitis in mixed connective tissue disease.

Pachymeningitis is a rare illness which can be shown by magnetic resonance imaging (MRI) to be a thickening of the intracranial dura mater, when associated with an infectious, malignant, or rheumatic systematic disease.1–6 “Idiopathic hypertrophic cranial pachymeningitis” is also noticeable, and is based on a process of chronic inflammation whose cause is unclear.4 Typical symptoms are chronic headaches, facial pain, cerebella ataxia, …

Rheumatologie—Teil 2

Due to the partial elucidation of the immunopathogenesis of chronic inflammatory diseases during the last years, clinical rheumatology has made a rapid development, which by the consequent use of immunomodulatory therapies including recombinant proteins (biologicals) led to a significantly ameliorated prognosis of these diseases. On this basis, new research projects are continuously performed in the fields of pathogenesis, new drug development, outcome and therapy studies. New developments of imaging techniques and serologic testing facilitate a better classification and definition of disease activity and remission criteria. The current state of research in the field of collagen vascular diseases with its clinical consequences is reviewed in this article on the basis of the most recent data available.ZusammenfassungDie Rheumatologie hat in den letzten Jahren durch die fortschreitende Aufklärung der Immunpathogenese eine rasante Entwicklung durchgemacht, die durch den zunehmend gezielteren Einsatz immunmodulatorischer Therapien, neuerdings auch mit rekombinanten Proteinen (Biologika), zu einer erheblichen Verbesserung der Prognose der entzündlichen rheumatischen Erkrankungen führte. Auf diesen Grundlagen werden laufend neue Forschungsergebnisse zur Pathogenese erarbeitet, neue Medikamente entwickelt sowie Outcome- und Therapiestudien durchgeführt. Neue Entwicklungen in der Bildgebung und serologischen Diagnostik tragen zu einer verbesserten Klassifizierung und Definition von Krankheitsaktivität und Remissionskriterien bei. Der aktuelle Stand der Forschung auf dem Gebiet der Kollagenosen mit seinen Konsequenzen für die Klinik wird in diesem Artikel aufgrund der neuesten verfügbaren Daten dargestellt.AbstractDue to the partial elucidation of the immunopathogenesis of chronic inflammatory diseases during the last years, clinical rheumatology has made a rapid development, which by the consequent use of immunomodulatory therapies including recombinant proteins (biologicals) led to a significantly ameliorated prognosis of these diseases. On this basis, new research projects are continuously performed in the fields of pathogenesis, new drug development, outcome and therapy studies. New developments of imaging techniques and serologic testing facilitate a better classification and definition of disease activity and remission criteria. The current state of research in the field of collagen vascular diseases with its clinical consequences is reviewed in this article on the basis of the most recent data available.

Periostitis as the initial manifestation of systemic vasculitis

The greatest challenge in diagnosing vasculitis is the diversity of its clinical presentation. Awareness of the heterogeneity of uncommon manifestations can be decisive for the course of the disease. We report on a patient presenting with periostitis as the initial manifestation of systemic vasculitis. A 38 year old female patient complained about progressively painful swelling and reddening of the distal right lower leg for several weeks. The patient had been healthy until then and had no history of arterial or venous insufficiency. She presented at hospital with reduced pulses and a severe compartment syndrome of the tibialis anterior compartment. An x ray examination showed typical signs of periostitis …

Progression of lupus nephritis during treatment with mycophenolate mofetil

Lupus nephritis (LN) determines the prognosis of systemic lupus erythematosus. The standard treatment for the proliferative forms (focal and diffuse proliferative LN, WHO classes III and IV) is intravenous pulse cyclophosphamide in combination with oral prednisone (Austin scheme).1,2 Recently mycophenolate mofetil (MMF) has been shown to be as effective as standard pulse cyclophosphamide for the induction of remission in proliferative LN (n = 21 in each treatment group). Side effects of MMF were fewer than with pulse cyclophosphamide.3 We …

Wegener's Granulomatosis: A Pulmonary Perspective

Publisher Summary This chapter presents an overview on pulmonary perspective. Wegeners granulomatosis is a chronic inflammatory disease that affects the respiratory tract, the kidneys and a multitude of other organ systems. It is one of the first vasculitides to be recognized as a separate entity. Wegeners granulomatosis affects the respiratory tract in the form of granulomatous disease, vasculitis or a combination of the two. A spectrum of clinical manifestations originates from either of the two components. This makes Wegeners granulomatosis one of the most complex but also one of the most fascinating vasculitides encountered in pulmonary medicine. The chapter illustrates that “generalized” Wegeners granulomatosis includes renal involvement and imminent organ failure. Two other subgroups—namely, “severe renal” and “refractory” disease—have been defined to cover the spectrum of Wegeners granulomatosis and microscopic polyangiitis, another ANCA-associated vasculitis.