Introduction

1. Pimecrolimus 1% cream in the treatment of facial psoriasis: A 16-week open label studyJacobi A et al. One of authors Braeutigam M belongs to clinical Research and Development, Novartis Pharma GmBH, Nuernberg.Dermatology 2008; 216: 133-136

2. Introduction • Psoriasis affects 2-3% of the western population more frequent in the Northern Caucasian population. • It is characterized by accelerated proliferation and abnormal differentiation of epidermal keratinocytes. • Psoriasis has an immunological origin, caused by inappropriate activation of the cellular immune system with inflammatory infiltration of the affected epidermis and dermis with leucocytes macrophages and activated T-cells.

3. In a subset of psoriasis lesions extend beyond the hairline involving the forehead, neck ears and facial skin. • Patients with these lesions complain of intense itching and suffer from psychosocial problems. • Long term treatment with topical corticosteroids [hydrocortisone not mentioned] is associated with telangiectasia, easy bruising, purpura, perioral dermatitis and atrophy. Usage on the face of topical steroids is therefore avoided.

4. Topical pimecrolimus (Elidel), a macrolactam ascomycin derivative works via calcineurin inhibition. It is effective in treating inflammatory disease and has gained approval for topical therapy of atopic dermatitis. • Also effective in the treatment of plaque-type psoriasis under occlusion.

5. Methods • 20 Patients (7female, 13 male) aged 19-65 years old with plaque type psoriasis enrolled. • Pimecrolimus 1% cream applied twice daily on the face for 8 weeks. Bland emollients were also allowed.

6. Assesment: -total symtom score(erythema and induration): 0 to 4 (4= very severe erythema and induration) -investigator’s total assessment (IGA): 0 to 5 (= very severe) -pruritus severity assessment: 0 to 3 (3= severe itching) -patient’s assessment score: 0 to 3 (3=uncontrolled disease) -DLQI (Dermatology Life quality index) : 0 to 30 : 0 to 1 =no, over 10=severe disturbance due to psoriasis or its treatment. Based on 10 questions: symptoms and impressions, disabilities in various daily activities, recreation, work, school and relationships, difficulties with treatment.

7. Patients were: • -not allowed to have had systemic treatment for psoriasis 4 weeks prior to the study (Phtotherapy) • -allowed to have emollients (5% urea in unguentum leniens) only the week priori to study. • Patients with an IGA above one were allowed low potency topical steroids, calcipotriol cream and salicylic acid cream except for the face.

8. Results • All patients showed improvement at 8 weeks following initiation of treatment and 16 weeks (8weeks after stopping the treatment) compared to baseline.

11. Week 8: -74.3% improvement of the total symptom score -65.5% of IGA -70.6% of pruritus severity -68.3% of patient’s assessment score -63.5% of DLQI • Week 16 (8 weeks after stopping treatment): -48.5% of total symptom score -39.7% of IGA -38.2% of pruritus severity -37.2% of patient’s assessment score -41.7% of DLQI

13. Discussion • Pimecrolimus useful in atopic dermatitis • Not useful in plaque psoriasis because of thick scales • Useful in psoriasis of the face which psoriasis lesions are not covered with thick scales. • The authors hypothesizee that the effectiveness of pimecroliumus is due to better penetration in atopic skin. • New galenical formulations are suggested by other studies with 10%urea as penetration enhancing.

14. Mechanism of action: • psoriasis is considered to be a disorder of keratinocyte hyperproliferation in the epidermis, secondary to influx of activated T lymphocytes into the dermis. • As a result of the inhibition of the calcineurin pathway, there is selective inhibition of transcription and production of early Th1 cytokines such as Interleukin 2 or gamma-interferon in T lymphocytes as well as of the Th2 cytokines interleukin 4, 5 and 10. • This mode of action together with the low penetration through the skin could explain the specific anti-inflammatory activity of topically applied pimecrolimu in psoriatic skin with low potential for affecting the systemic immune response and no signe of inducing skin atrophy.