Pierre-André Bécherel

Extracorporeal photochemotherapy for chronic erosive lichen planus

Topical steroids and retinoic acid are usually ineffective in the treatment of chronic erosive lichen planus (CELP). Improvement with griseofulvin and dapsone has been reported; topical cyclosporin may also help, but only 30% of patients remain improved after 1 year. We noticed that extracorporeal photochemotherapy (ECP) improved the generalised lichen planus of a patient treated for a cutaneous T-cell lymphoma, and so studied ECP in the treatment of multiresistant CELP. Seven patients (six women; mean age age 61·4 years [range 41–75]) were included with their informed consent in an open prospective study from May, 1994, to August, 1997. All had multiresistant histologically proven CELP, for a mean of 6 years (range 2–15). Lesions were on the tongue, cheeks, lips, gums, and palate; three women also had vulval erosions. Previous treatments were stopped before ECP was done twice a week for 3 weeks and then tapered according to the patients’ needs. Mononuclear cells were extracted from two blood masses (80 mL/kg) with a Code Spectra separator; soluble methoxypsoralen (8-MOP) was added to the cytapheresis product (200 ng/mL); cells were irradiated with UVA at 3 J/cm (Vilbert-Lourmat, Marne la Vallee, France), and reinfused into the patient. The same investigator evaluated the erosive surface every 3 months and the blood count and lymphocyte phenotype were assessed. All patients had complete remission (figure). Improvement began after an average 1·5 months with a mean number of 12 sessions (10–18) to reach remission and a total of 24 sessions (19–27). The longest follow-up after discontinuation of ECP is 24 months. ECP was well tolerated. Haemoglobin and platelets remained unchanged. There was a progressive decrease in lymphocytes in all patients, involving all T-cell subsets. B lymphocytes and NK cells did not decrease. In the seven patients in our series follow-up is short but no patient got worse during this time. The beneficial effects of ECP seem similar to those recently reported in post-graftversus-hose disease lichen. ECP might constitute an alternative therapeutic approach for multiresistant CELP; and a controlled study should be done.

Involvement of cyclic AMP and nitric oxide in immunoglobulin E-dependent activation of Fc epsilon RII/CD23+ normal human keratinocytes.

Epidermal keratinocytes (EK) are exposed to multiple inflammatory stimuli and paracrine factors secreted by various dermal cells (lymphocytes, mast cells, macrophages, fibroblasts) during wounding, cutaneous allergy, and infections. We have previously demonstrated that after stimulation with interleukin 4 or interferon-gamma, human EK express the low-affinity receptor for IgE (Fc epsilon RII/CD23) on their surface. In the present study, we showed that the ligation of CD23 by IgE/anti-IgE immune complexes or specific monoclonal antibody induces a dose-dependent release of interleukin 6 and tumor necrosis factor-alpha from EK. CD23-ligation activates the nitric oxide-dependent pathway, as demonstrated by the high levels of nitrites released in cell supernatants, and the accumulation of intracellular cyclic nucleotides in EK. These second messengers are required for IgE-dependent stimulation of cytokine production by these cells, inasmuch as this is completely abolished by the use of cAMP or nitric oxide synthase antagonists. Human epithelial keratinocytes may thus participate in IgE-mediated immune responses, through their ability to express functional CD23 antigen.