Combined treatment with immunoadsorption and rituximab leads to fast and prolonged clinical remission in difficult-to-treat pemphigus vulgaris.

BACKGROUND: Pemphigus vulgaris (PV) is a potentially life-threatening autoimmune bullous disorder which is characterized by blisters and erosions of the skin and mucous membranes. A frequently applied first-line therapy for PV consists of systemic corticosteroids (CS) combined with immunosuppressive agents. In refractory cases, novel therapeutic strategies such as immunoadsorption (IA) and the anti-CD20 antibody rituximab (Rtx) aim at directly interfering with pathogenic autoantibodies (auto-Abs). OBJECTIVES: To investigate the long-term efficacy of IA in combination with Rtx in patients with difficult-to-treat PV, we assessed the clinical response to treatment by monitoring the Autoimmune Bullous Skin Disorder Intensity Score, IgG auto-Abs against desmoglein 1 and 3 (Dsg1 and Dsg3) and the dose of systemic CS. METHODS: We retrospectively analysed clinical and serological parameters of 10 patients with difficult-to-treat PV who received IA at 4-week intervals, followed by Rtx either twice at 1000 mg or four times at 375mg m(-2) . During a 12-month follow-up period, CS were tapered according to the individual clinical status. RESULTS: Six months after the first IA treatment eight of 10 patients were in complete remission on therapy while one patient showed a partial response and one patient was unresponsive to the treatment. At 12 months, six of eight patients were in complete remission on therapy, one patient showed stable disease and one patient had relapsed. Overall, anti-Dsg3 IgG and anti-Dsg1 IgG auto-Abs correlated well with the clinical activity and systemic CS were tapered gradually. CONCLUSIONS: The present findings show that the combination of IA and Rtx induces rapid clinical remission and long-term control in difficult-to-treat pemphigus.

IgG autoantibody reactivity against bullous pemphigoid (BP) 180 and BP230 in elderly patients with pruritic dermatoses.

BACKGROUND: Pruritic dermatoses of the elderly often pose a diagnostic and therapeutic challenge. Specifically, a prodromal phase of bullous pemphigoid (BP) has to be considered in patients with pruritic lesions of polymorphic appearance. These conditions frequently do not fulfil all the clinical, histological and immunopathological criteria for establishing the diagnosis of BP. OBJECTIVES: To investigate IgG reactivity against the autoantigens of BP, BP180 and BP230, by enzyme-linked immunosorbent assay, in elderly patients affected with various pruritic disorders who had never experienced clinically apparent blisters. METHODS: The sera of 15 elderly patients with pruritic disorders (group I) were tested for IgG reactivity against BP180 and BP230. Also included were 30 patients with full-blown BP (group II) and 25 age-matched patients with immediate-type allergic reactions (group III). RESULTS: Thirty-three per cent of the patients with pruritic disorders (group I) showed IgG against BP230 and/or BP180: four of 15 patients had IgG against BP230 while two of the 15 group I patients were BP180 reactive. All the BP sera (group II) showed IgG reactivity against BP180 and/or BP230. Notably, two of 25 control sera (group III) showed IgG reactivity against either BP180 or BP230. CONCLUSIONS: The present findings suggest that IgG reactivity against BP230 (i.e. the COOH terminus), and to a lesser extent against BP180, is a common finding in pruritic disorders of the elderly with a wide clinical spectrum. IgG-mediated autoimmunity against the intracellular BP230 may facilitate a chronic, inflammatory response eventually leading to full-blown BP which is presumably associated with IgG against BP180.