Clinical and immunological follow-up of pemphigus patients on adjuvant treatment with immunoadsorption or rituximab.

BACKGROUND: Pemphigus vulgaris (PV) is a life-threatening autoimmune blistering skin disease which is associated with pathogenic IgG autoantibodies against desmogleins (Dsg) 1 and 3. Novel therapeutic strategies such as immunoadsorption (IA) or the anti-CD20 antibody rituximab (Rtx) hold promise to be effective in severe or recalcitrant PV. PATIENTS AND METHODS: In the present retrospective study, 6 patients with extensive cutaneous PV were subjected to adjuvant IA treatment while 5 patients with severe mucosal PV received adjuvant Rtx treatment. RESULTS: Within 6 months, IA and Rtx induced excellent clinical responses which were associated with a significant reduction of prednisolone doses and a decrease in anti-Dsg-specific IgG. Over a 12-month period, 3 IA-treated patients required additional adjuvant drugs while all of the PV patients on Rtx had no or only minimal residual symptoms. CONCLUSION: The relative therapeutic (long-term) efficacy of IA and Rtx in cutaneous versus mucosal PV needs to be evaluated in a prospective study.

Recommendations for the use of rituximab (anti-CD20 antibody) in the treatment of autoimmune bullous skin diseases.

Autoimmune bullous skin disorders are induced by autoantibodies against distinct adhesion complexes of the epidermal and dermal-epidermal junction. Since most of these disorders are characterized by a severe, potentially lethal course,they require long-term immunosuppressive treatment to reduce the de novo synthesis of pathogenic autoantibodies by B lymphocytes. Rituximab, a chimeric monoclonal antibody against CD20 on B lymphocytes, has shown promise in several case reports or cohort studies in the treatment of paraneo-plastic pemphigus,refractory cases of pemphigus vulgaris and foliaceus and in other autoimmune bullous disorders. Treatment with rituximab leads to depletion of pathogenic B-cells which may last up to 12 months resulting in a reduction of plasma cells secreting pathogenic autoantibodies. Rituximab is usually administered in an adjuvant setting at a dose of 375 mg/m(2) i.v.in weekly intervals for four consecutive weeks in addition to the standard immunosuppressive treatment. The present consensus statement of German-speaking dermatologists, rheumatologists and oncologists summarizes and evaluates the current evidence for the use and mode of application of rituximab in autoimmune bullous skin disorders.

Lack of differences of motorcortical excitability in the morning as compared to the evening in juvenile myoclonic epilepsy--a study using transcranial magnetic stimulation.

We used transcranial magnetic stimulation (TMS) in patients with juvenile myoclonic epilepsy (JME) and healthy controls to characterise motorcortical excitability in the morning as compared to the evening. Intra- and interindividual comparisons in JME-patients and controls showed no significant differences of any TMS parameter. The expected rise of the resting motor thresholds (RMT) in JME-patients taking anticonvulsants could not be detected which may indicate a decreased RMT in JME-patients.

Clinical response of severe mechanobullous epidermolysis bullosa acquisita to combined treatment with immunoadsorption and rituximab (anti-CD20 monoclonal antibodies).

BACKGROUND: Epidermolysis bullosa acquisita (EBA) is an autoimmune bullous disorder with mucocutaneous involvement, skin fragility, and tendency to scarring. The mechanobullous form of EBA has a chronic relapsing course and is difficult to treat. We describe herein the therapeutic response of 2 patients with recalcitrant mechanobullous EBA to combined treatment with immunoadsorption and rituximab, an anti-CD20 monoclonal antibody that induces depletion of B cells in vivo. OBSERVATIONS: Two patients with mechanobullous EBA received combined treatment with immunoadsorption and rituximab, resulting in an almost complete clinical remission in one patient and stable disease in the other patient. In the patient with complete remission, prolonged B-cell depletion and clinical improvement with disappearance of mucocutaneous erosions paralleled the decline in titers of circulating anti-basement membrane zone autoantibodies. In the other patient, combined treatment with immunoadsorption and rituximab reduced the de novo appearance of blisters but did not lead to significant improvement of gingivitis, despite depleted B cells for 6 months that remained at 5% 12 months after the last administration of rituximab, as well as a reduction in autoantibody titers. CONCLUSION: The patients' response suggests that combined treatment with immunoadsorption and rituximab may be a valuable adjuvant treatment regimen for severe mechanobullous EBA, which is in line with recently observed beneficial effects in inflammatory EBA.

Introducing a novel Autoimmune Bullous Skin Disorder Intensity Score (ABSIS) in pemphigus.

At present, there is no consensus about the clinical criteria that define disease severity of pemphigus. During recent years several scoring systems have been introduced which mainly compare inter-individual differences in disease activity. It thus remains a challenge to reflect the disease activity of individual patients by a standardised scoring system. Due to the remarkable clinical variability of pemphigus, several parameters are needed to reflect phenotypical varieties of this severe autoimmune bullous skin disorder. In view of the evaluation of different therapeutic options a scoring system sensitive enough to reflect gradual changes in disease activity seems more appropriate than a grading system for inter-individual comparison of disease severity. Taking this challenge into account we introduce and discuss a newly developed autoimmune bullous skin disorder intensity score (ABSIS).