Pimecrolimus 1% cream in the Pimecrolimus 1% cream in the treatment of facial psoriasis: A treatment of facial psoriasis: A

16-week open label study16-week open label studyJacobi A et al. Jacobi A et al.

One of authors Braeutigam M belongs to clinical Research and Development, Novartis Pharma GmBH, One of authors Braeutigam M belongs to clinical Research and Development, Novartis Pharma GmBH, Nuernberg.Nuernberg.

  Dermatology 2008; 216: 133-136Dermatology 2008; 216: 133-136

IntroductionIntroduction

Psoriasis affects 2-3% of the western population Psoriasis affects 2-3% of the western population more frequent in the Northern Caucasian more frequent in the Northern Caucasian population.population.

It is characterized by accelerated proliferation and It is characterized by accelerated proliferation and abnormal differentiation of epidermal abnormal differentiation of epidermal keratinocytes.keratinocytes.

Psoriasis has an immunological origin, caused by Psoriasis has an immunological origin, caused by inappropriate activation of the cellular immune inappropriate activation of the cellular immune system with inflammatory infiltration of the system with inflammatory infiltration of the affected epidermis and dermis with leucocytes affected epidermis and dermis with leucocytes macrophages and activated T-cells.macrophages and activated T-cells.

In a subset of psoriasis lesions extend beyond the In a subset of psoriasis lesions extend beyond the hairline involving the forehead, neck ears and hairline involving the forehead, neck ears and facial skin.facial skin.

Patients with these lesions complain of intense Patients with these lesions complain of intense itching and suffer from psychosocial problems.itching and suffer from psychosocial problems.

Long term treatment with topical corticosteroids Long term treatment with topical corticosteroids [hydrocortisone not mentioned] is associated with [hydrocortisone not mentioned] is associated with telangiectasia, easy bruising, purpura, perioral telangiectasia, easy bruising, purpura, perioral dermatitis and atrophy. Usage on the face of dermatitis and atrophy. Usage on the face of topical steroids is therefore avoided.topical steroids is therefore avoided.

Topical pimecrolimus (Elidel), a Topical pimecrolimus (Elidel), a macrolactam ascomycin derivative works macrolactam ascomycin derivative works via calcineurin inhibition. It is effective in via calcineurin inhibition. It is effective in treating inflammatory disease and has treating inflammatory disease and has gained approval for topical therapy of gained approval for topical therapy of atopic dermatitis.atopic dermatitis.

Also effective in the treatment of plaque-Also effective in the treatment of plaque-type psoriasis under occlusion.type psoriasis under occlusion.

MethodsMethods

20 Patients (7female, 13 male) aged 19-65 20 Patients (7female, 13 male) aged 19-65 years old with plaque type psoriasis years old with plaque type psoriasis enrolled.enrolled.

Pimecrolimus 1% cream applied twice daily Pimecrolimus 1% cream applied twice daily on the face for 8 weeks. Bland emollients on the face for 8 weeks. Bland emollients were also allowed.were also allowed.

Assesment:Assesment:-total symtom score(erythema and induration): 0 to 4 (4= very -total symtom score(erythema and induration): 0 to 4 (4= very

severe erythema and induration) severe erythema and induration) -investigator’s total assessment (IGA): 0 to 5 (= very severe)-investigator’s total assessment (IGA): 0 to 5 (= very severe)-pruritus severity assessment: 0 to 3 (3= severe itching)-pruritus severity assessment: 0 to 3 (3= severe itching)-patient’s assessment score: 0 to 3 (3=uncontrolled disease)-patient’s assessment score: 0 to 3 (3=uncontrolled disease)-DLQI (Dermatology Life quality index) : 0 to 30 : 0 to 1 =no, -DLQI (Dermatology Life quality index) : 0 to 30 : 0 to 1 =no,

over 10=severe disturbance due to psoriasis or its treatment. over 10=severe disturbance due to psoriasis or its treatment. Based on 10 questions: symptoms and impressions, Based on 10 questions: symptoms and impressions, disabilities in various daily activities, recreation, work, disabilities in various daily activities, recreation, work, school and relationships, difficulties with treatment.school and relationships, difficulties with treatment.

Patients were:Patients were: -not allowed to have had systemic treatment for -not allowed to have had systemic treatment for

psoriasis 4 weeks prior to the study (Phtotherapy)psoriasis 4 weeks prior to the study (Phtotherapy) -allowed to have emollients (5% urea in -allowed to have emollients (5% urea in

unguentum leniens) only the week priori to study.unguentum leniens) only the week priori to study.

Patients with an IGA above one were allowed low Patients with an IGA above one were allowed low potency topical steroids, calcipotriol cream and potency topical steroids, calcipotriol cream and salicylic acid cream except for the face.salicylic acid cream except for the face.

ResultsResults

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

Week 8:Week 8:-74.3% improvement of the total symptom score-74.3% improvement of the total symptom score

-65.5% of IGA-65.5% of IGA-70.6% of pruritus severity-70.6% of pruritus severity-68.3% of patient’s assessment score-68.3% of patient’s assessment score-63.5% of DLQI-63.5% of DLQI

Week 16 (8 weeks after stopping treatment):Week 16 (8 weeks after stopping treatment):-48.5% of total symptom score-48.5% of total symptom score-39.7% of IGA-39.7% of IGA-38.2% of pruritus severity-38.2% of pruritus severity-37.2% of patient’s assessment score-37.2% of patient’s assessment score-41.7% of DLQI-41.7% of DLQI

DiscussionDiscussion

Pimecrolimus useful in atopic dermatitisPimecrolimus useful in atopic dermatitis Not useful in plaque psoriasis because of thick Not useful in plaque psoriasis because of thick

scalesscales Useful in psoriasis of the face which psoriasis Useful in psoriasis of the face which psoriasis

lesions are not covered with thick scales.lesions are not covered with thick scales. The authors hypothesizee that the effectiveness of The authors hypothesizee that the effectiveness of

pimecroliumus is due to better penetration in pimecroliumus is due to better penetration in atopic skin.atopic skin.

New galenical formulations are suggested by other New galenical formulations are suggested by other studies with 10%urea as penetration enhancing.studies with 10%urea as penetration enhancing.

Mechanism of action:Mechanism of action: psoriasis is considered to be a disorder of keratinocyte psoriasis is considered to be a disorder of keratinocyte

hyperproliferation in the epidermis, secondary to influx of hyperproliferation in the epidermis, secondary to influx of activated T lymphocytes into the dermis.activated T lymphocytes into the dermis.

As a result of the inhibition of the calcineurin pathway, there is As a result of the inhibition of the calcineurin pathway, there is selective inhibition of transcription and production of early Th1 selective inhibition of transcription and production of early Th1 cytokines such as Interleukin 2 or gamma-interferon in T cytokines such as Interleukin 2 or gamma-interferon in T lymphocytes as well as of the Th2 cytokines interleukin 4, 5 lymphocytes as well as of the Th2 cytokines interleukin 4, 5 and 10.and 10.

This mode of action together with the low penetration through This mode of action together with the low penetration through the skin could explain the specific anti-inflammatory activity of the skin could explain the specific anti-inflammatory activity of topically applied pimecrolimu in psoriatic skin with low topically applied pimecrolimu in psoriatic skin with low potential for affecting the systemic immune response and no potential for affecting the systemic immune response and no signe of inducing skin atrophy.signe of inducing skin atrophy.