Atopic dermatitis and skin disease
Anti-CD20 (rituximab) treatment improves atopic eczema

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Background

Atopic eczema (AE) is a chronic inflammatory skin disorder characterized by eczematous skin lesions, pruritus, and typical histopathologic features.

Objective

We asked whether depletion of B cells by monoclonal anti-CD20 antibody therapy (rituximab) would improve severe AE.

Methods

Six patients (4 women and 2 men) with severe AE received 2 intravenous applications of rituximab, each 1000 mg, 2 weeks apart. To evaluate the efficacy of rituximab, we monitored clinical parameters (eczema area and severity index, pruritus), total and allergen-specific IgE levels, skin histology, and inflammatory cells and cytokine expression in the skin and peripheral blood before and after therapy (ClinicalTrials.gov Identifier: NCT00267826).

Results

All patients showed an improvement of their skin symptoms within 4 to 8 weeks. The eczema area and severity index significantly decreased (before therapy, 29.4 ± 4.3; week 8, 8.4 ± 3.6; P < .001). Histologic alterations such as spongiosis, acanthosis, and dermal infiltrate, including T and B cell numbers, also dramatically improved. However, whereas blood B cells were below detectable levels as a consequence of rituximab administration, skin B cells were reduced by approximately 50% only. Expression of IL-5 and IL-13 was reduced after therapy. Moreover, whereas allergen-specific IgE levels were not altered, we observed a slight reduction in total IgE concentrations in blood.

Conclusions

B cells play a major role in AE pathogenesis. Treatment with an anti-CD20 antibody leads to an impressive improvement of AE in patients with severe disease.

Section snippets

Patients

In this investigator-initiated, open-label pilot study, 6 patients with severe AE according to the criteria of Hanifin and Rajka22 (4 women, 2 men; age, 19-63 years; average, 39 ± 7 years) were enrolled between October 2005 and April 2006. All patients had not adequately responded to topical corticosteroid and/or calcineurin inhibitor therapy and were candidates for, or had previously received, systemic treatment. Patient characteristics are given in Table I. The study was approved by the

Reduction of AE symptoms by rituximab

To evaluate the clinical efficacy of the treatment with rituximab, the EASI was determined. Before treatment, the mean EASI was 29.4 ± 4.3 (Table I). All patients had a significant improvement of their AE lesions within 4 weeks of treatment (Fig 2, A and B). In 2 patients, we observed a rapid improvement within the first week of treatment. All patients further improved between weeks 4 and 8. One patient developed a moderate flare-up at week 12. At weeks 16 and 24, all patients had low EASI

Discussion

The inflammatory reaction in AE is orchestrated by various immune cells. In contrast with T cells, little is known about the role of B cells in AE skin, which are also found among the dermal infiltrating cells, although in smaller numbers compared with T cells.3, 4, 5 Inspired by the excellent clinical effects obtained by selective B-cell depletion in autoimmune diseases,11, 12, 13, 14, 15, 16, 17, 18, 19, 20 we initiated this pilot study to evaluate the clinical and immunopharmacologic effects

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    Supported by grants from the Swiss National Science Foundation (310000-107526) and Roche Pharma AG, Reinach.

    Disclosure of potential conflict of interest: The authors have declared that they have received research support from Roche Pharma AG.

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