Cyclosporine in lamellar ichthyosis

Area of Science:

• Dermatology
• Immunology
• Pharmacology

Background:

• Lamellar ichthyosis is a rare genetic skin disorder characterized by generalized scaling.
• Cyclosporine A is an immunosuppressive drug effective in psoriasis, another skin condition with some overlapping features.

Purpose of the Study:

• To evaluate the efficacy of oral cyclosporine A in treating lamellar ichthyosis.
• To investigate the immunological and histological characteristics of lamellar ichthyosis.
• To compare the pathogenesis of lamellar ichthyosis and psoriasis.

Main Methods:

• An open-label trial involving five patients with lamellar ichthyosis.
• Patients received oral cyclosporine A (6 mg/kg/d) for four weeks.
• Histological and immunofluorescence studies were performed on skin biopsies before and after treatment.

Main Results:

• No clinical improvement was observed in any of the five patients after four weeks of cyclosporine A treatment.
• Histology showed hyperkeratosis, psoriasiform acanthosis, and prominent dermal capillaries with activated endothelial cells.
• Immunofluorescence revealed normal epidermal Langerhans' cells but absent T cells and intercellular adhesion molecule-1 expression in the epidermis; dermal findings were unchanged by treatment.

Conclusions:

• Lamellar ichthyosis exhibits epidermal hyperproliferation and vascular changes but lacks the significant immune cell activity seen in psoriasis.
• The lack of response to cyclosporine A in lamellar ichthyosis, contrasted with its efficacy in psoriasis, suggests its mechanism of action targets the immune system.
• These findings indicate that the therapeutic target of cyclosporine A is likely immune cells, not keratinocytes or endothelial cells, in inflammatory skin conditions.