A randomized, single-blind, placebo-controlled, split-face study with pimecrolimus cream 1% for papulopustular rosacea

Background Rosacea is a common inflammatory skin disorder for which the pathogenesis is unclear. Currently, there is no cure for rosacea, and it seems that standard therapies have focused mainly on minimizing inflammation. Objectives The aim of this study is to investigate the potential efficacy, tolerability and safety profile of 1% pimecrolimus cream for the treatment of rosacea. Methods Twenty‐five patients with papulopustular rosacea were enrolled to a randomized, single‐blinded, placebo‐controlled, split‐face trial of pimecrolimus cream 1% consisting 4 week treatment and 2 week follow‐up period. The patients were instructed to apply first the ‘left side cream’ labelled placebo cream (Ultrabase cream, Intendis GmbH, Berlin, Germany) to the left hemi‐face then the ‘right side cream’ labelled 1% pimecrolimus cream (Elidel; Novartis Pharma, Nuremberg, Germany) to the right hemi‐face, twice daily. They were informed to apply a standard amount of each cream with the fingertip‐unit and not allowed to use any other agent concomittantly other than sunblock. Clinical evaluation and subjective severity assessment were obtained along with photographic documentation at baseline, first, second, and fourth weeks of the therapy and at the follow‐up visit. Rosacea severity score for each sign of erythema, papules, pustules, oedema, and telengiectesia were graded from 0 to 3. Patients were questioned for the subjective symptoms, overall improvement on appearance and side‐effects. Results Twenty‐four patients completed the study with an exceptional compliance and tolerable safety profile. One patient withdrew from the study due to severe flare‐up reaction affecting both hemi‐faces. The mean baseline total rosacea severity scores were 5.06 + 1.29 for both sides and reduced to 2.5 ± 1.06 vs. 3.25 ± 1.24 on pimecrolimus vs. placebo applied sides without the significance (P = 0.06). There was not any significant difference concerning each rosacea sign scores and total rosacea severity scores except for the significant improvement in erythema score and total rosacea severity score obtained on the pimecrolimus‐applied hemi‐face at 2nd week of therapy (P =0.01 and P = 0.03, respectively). The reduction rates of the mean subjective severity scores at 4th week were 49.77% vs. 38.89% for pimecrolimus vs. placebo, respectively, without a statistical significance (P = 0.15). Subjective symptoms responded well in 54.16% of patients concerning pimecrolimus application compared with 12.50% for the placebo application. The side‐effects were mostly transient local irritations. Conclusion Our data implicated that pimecrolimus cream is not superior to placebo except for its efficacy on erythema. We believe that pimecrolimus cream can be a treatment option for rosacea patients with high erythema score for whom an initial accelerated improvement is needed. We believe further studies with topical pimecrolimus cream on larger study groups with different subtypes and severity of rosacea will clarify the potential effect of pimecrolimus cream for the treatment of rosacea.     

Pimecrolimus 1% cream for the treatment of rosacea

Rosacea is a common inflammatory skin disorder; the pathogenesis is unclear. Various treatment options for rosacea are available, but most have limited effectiveness. The aim of this study was to investigate the efficacy and safety of 1% pimecrolimus cream for the treatment of rosacea. Thirty patients with rosacea were enrolled in this 4-week, single-center, open-label study of 1% pimecrolimus cream. Patients were instructed to apply the cream to their faces twice daily and were not permitted to use any other agents. Clinical efficacy was evaluated by a rosacea grading system using photographic documentation and a mexameter. The 26 patients who completed the study experienced significantly reduced rosacea clinical scores from 9.65 ± 1.79 at baseline to 7.27 ± 2.11 at the end of treatment (P < 0.05). The mexameter-measured erythema index decreased significantly from 418.54 ± 89.56 at baseline to 382.23 ± 80.04 at week 4 (P < 0.05). The side-effects were mostly transient local irritations. The results of this study suggest that 1% pimecrolimus cream is an effective and well-tolerated treatment for patients with mild to moderate inflammatory rosacea.     

Use of pimecrolimus cream 1% (Elidel) in the treatment of atopic dermatitis in infants and children: the effects of ethnic origin and baseline disease severity on treatment outcome

BACKGROUND: Pimecrolimus cream 1%, a cell-selective inhibitor of inflammatory cytokines, has been shown to be effective in treating atopic dermatitis (AD). This report examines the effect of ethnic origin and baseline disease severity on treatment outcomes in pediatric patients with AD treated with pimecrolimus cream 1%. METHODS: The analysis included 589 patients aged 3 months to 17 years from three 6-week, randomized, multicenter studies of similar design. Patients were treated with pimecrolimus cream 1% or vehicle twice daily. Efficacy, safety and tolerability in Caucasian and non-Caucasian groups were compared. In addition, the effect of baseline disease severity on treatment outcome was investigated. RESULTS: A total of 321 Caucasian and 268 non-Caucasian patients [Blacks, Asians and others (including Hispanics)] with mild, moderate or severe disease at baseline were included. Baseline characteristics were comparable between the pimecrolimus and vehicle control groups and between Caucasian and non-Caucasian groups. Significantly higher efficacy [measured by Investigators' Global Assessment and Eczema Area and Severity Index (EASI) scores] was achieved in the pimecrolimus-treated group, compared with the vehicle group, irrespective of ethnic origin. Baseline disease severity had no effect on treatment outcome: patients with both mild and moderate AD responded well to pimecrolimus (absolute change from baseline in EASI score -2.60 and -5.48, respectively; both P < 0.001). Pimecrolimus cream 1% was safe and well tolerated in all ethnic groups and at all levels of disease severity. CONCLUSIONS: Ethnic origin and baseline disease severity had no effect on treatment outcome with pimecrolimus cream 1% in patients with AD.     

An open-label pilot study to evaluate the safety and efficacy of topically applied pimecrolimus cream for the treatment of steroid-induced rosacea-like eruption

BACKGROUND: Steroid-induced rosacea-like eruption is characterized by facial rosacea-like dermatitis in patients that have been treated with topical steroids for relatively long periods. OBJECTIVE: To evaluate the efficacy and tolerability of 1% pimecrolimus topical cream for steroid-induced rosacea-like eruption. METHODS: In an open-label pilot study, 40 patients were enrolled and instructed to apply 1% pimecrolimus cream twice daily for 6 weeks. Patients were evaluated by a rosacea clinical score, investigator's global assessment, overall erythema severity, and tolerability at weeks 0, 2, and 6. RESULTS: In 35 patients, the rosacea clinical score decreased significantly from 16.0+/-4.3 at baseline to 8.1+/-3.3 at week 2 and 4.2+/-2.5 at week 6 (P<0.0001). Investigator's global assessment was 4.1+/-1.1 (baseline), then decreased to 1.4+/-0.8 (week 2) and 0.5+/-0.6 (week 6) (P<0.0001). By week 6, 48.6% of the patients were clear. Overall erythema severity was 2.4+/-0.7 (baseline), 0.9+/-0.4 (week 2), and 0.3+/-0.4 (week 6) (P<0.0001). Cutaneous adverse events (local burning, stinging, and itching) occurred in 17.5%. CONCLUSION: Pimecrolimus cream might be efficacious, safe, and well tolerated for steroid-induced rosacea-like eruption. The small sample size and open label nature of this study is its limitation. Further double-blind, vehicle-controlled studies are needed.     

A comparison of metronidazole 1% cream and pimecrolimus 1% cream in the treatment of patients with papulopustular rosacea: a randomized open‐label clinical trial

Background. There are various treatment options available for rosacea, depending on the subtype, but treatment is still generally unsatisfactory. Some reports have indicated beneficial effects of topical pimecrolimus. Aim. To compare the efficacy and safety of pimecrolimus 1% cream and metronidazole 1% cream in the treatment of patients with papulopustular rosacea (PR). Methods. A group of 49 patients with PR was investigated in this single‐centre, randomized, open‐label study. Patients were randomly assigned treatment with either pimecrolimus 1% cream or metronidazole 1% cream for 12 weeks. Response was evaluated by the inflammatory lesion count, the severity of facial erythema and telangiectasia, Physician’s Global Assessment (PGA), and safety and tolerability at baseline and at weeks 3, 6, 9 and 12. Results. In total, 48 patients completed the study. Both treatments were very effective in the treatment of PR. There were no significant differences between the treatments in inflammatory lesion counts, overall erythema severity scores and PGA evaluated from baseline to week 12 (P > 0.05). Neither treatment produced any clinically relevant improvement in telangiectasia. Conclusion. Pimecrolimus cream is no more efficacious than metronidazole cream in the treatment of PR.     

Pimecrolimus cream 1% is effective in asteatotic eczema: results of a randomized, double-blind, vehicle-controlled study in 40 patients

BACKGROUND AND OBJECTIVE: Pimecrolimus cream 1% is an effective treatment for atopic eczema. The aim was to investigate its efficacy in asteatotic eczema, a skin disease similar to atopic eczema and its associated dry skin and itching. METHODS: Single-centre, randomized, double-blind, vehicle controlled study in 40 patients with asteatotic eczema. Efficacy was assessed by eczema area and severity index (EASI), investigators global assessment (IGA), patient's self-assessment, and pruritus severity. RESULTS: After 4 weeks of treatment, EASI, the primary efficacy variable, was reduced by 62+/-7% from baseline in patients on pimecrolimus, compared to 21+/-14% in patients on vehicle (P=0.013). With pimecrolimus there was also a better control of pruritus (P=0.042) at week 4 whereas a better control of disease according to self-assessment could only be observed at weeks 2 (P=0.01) and week 3 (P=0.08). CONCLUSION: Pimecrolimus cream 1% is effective in patients with asteatotic eczema.     

Treatment of oral erosive lichen planus with 1% pimecrolimus cream: a double-blind, randomized, prospective trial with measurement of pimecrolimus levels in the blood

OBJECTIVES: To evaluate the efficacy of 1% pimecrolimus cream in treating oral erosive lichen planus and to assess its tolerance. DESIGN: Double-blind randomized trial with placebo control. SETTING: Outpatients of the Department of Dermatology, University Hospital of Nice, from December 21, 2004, to April 19, 2005. PATIENTS: Fourteen consecutive patients with oral erosive lichen planus confirmed by histological examination and with a clinical score superior to 3. Of the 14 patients, 2 did not meet the inclusion criteria and 12 were enrolled in the trial. INTERVENTION: The intervention was 1% pimecrolimus cream or its vehicle, which was applied on ulcerated lesions twice a day for 4 weeks. MAIN OUTCOME MEASURES: The efficacy of the treatment was quantified using a 12-point clinical score. The blood level of pimecrolimus was analyzed on days 0 (baseline), 14, and 28. RESULTS: In the placebo group, the mean score was 4.67 on day 0 vs 3.33 on day 28 (P = .22). In the pimecrolimus group, the mean score was 6.83 on day 0 vs 3.33 on day 28 (P = .04). In the pimecrolimus group, blood concentrations of pimecrolimus were always above the threshold (mean value, 2.84 ng/mL; extreme values, 0-6.19 ng/mL). Pimecrolimus cream was well tolerated, and only transient burning sensations were reported by some subjects. Each of the patients in the pimecrolimus group whose condition improved subsequently relapsed when assessed 1 month after treatment. CONCLUSIONS: The 1% pimecrolimus cream seems to be an effective and well-tolerated treatment for oral erosive lichen planus. The finding of systemic levels of pimecrolimus after mucosal applications necessitates long-term study because it seems that long-term application is required to maintain clinical improvement.     

Spotlight on topical pimecrolimus in atopic dermatitis

Pimecrolimus (SDZ ASM 981), an ascomycin derivative, is a nonsteroid, has anti-inflammatory activity, and has demonstrated efficacy in reducing symptoms of atopic dermatitis in adult and pediatric patients when applied topically. Compared with vehicle, topical pimecrolimus 1.0% cream was significantly more effective at reducing symptoms of atopic dermatitis, as measured by the Eczema Area and Severity Index (EASI), in infants aged 3 to 23 months, children aged 2 to 17 years, and adults. The median reductions from baseline in the total EASI score in adults after treatment with pimecrolimus 1.0% or corresponding vehicle twice daily for 3 weeks were 47 and 0%, respectively. In infants and children, treatment with pimecrolimus 1.0% twice daily for 6 weeks resulted in significant decreases in mean EASI scores compared with vehicle. The severity of pruritus was significantly reduced in patients of all age groups after topical treatment with pimecrolimus 1.0% cream. Compared with vehicle, the incidence of eczematous flares was also reduced by intermittent long-term use of topical pimecrolimus 1.0% in adults, children and infants. Sixty-one percent of children treated with pimecrolimus for 1 year completed the first 6 months of treatment without experiencing a flare, compared with 35% of patients who received vehicle. Furthermore, the use of topical corticosteroids for the treatment of uncontrolled flares in adults, children and infants was lower in the pimecrolimus groups than in the vehicle groups. Topical pimecrolimus 1.0% cream is well tolerated in atopic dermatitis patients of all age groups. There were no clinically relevant systemic adverse events reported from any of the studies in patients with atopic dermatitis. The most frequently reported adverse events pertained to application site reactions, such as burning and a feeling of warmth. In conclusion, topical pimecrolimus 1.0% cream has shown efficacy in the treatment of mild to moderate atopic dermatitis in infants, children and adults. Although tolerability data concerning infants and children have not yet been published in full, the drug appears to be well tolerated in all age groups, and there have been no reports of clinically relevant systemic adverse events. Furthermore, pimecrolimus has shown no potential for skin atrophy, a problem commonly associated with treatment with topical corticosteroids. Topical pimecrolimus 1.0% provides a promising and well tolerated treatment option in the management of infants, children and adults with mild to moderate atopic dermatitis.     

Randomized placebo-controlled trial of metronidazole 1% cream with sunscreen SPF 15 in treatment of rosacea

Background: Rosacea is a photoaggravated dermatosis responsive to treatment with topical and oral antibiotics. A formulation combining metronidazole 1% cream with sunscreen SPF 15 was developed for the treatment of rosacea. Objective: The objective of this study was to determine the safety and efficacy of a formulation combining metronidazole 1% cream with sunscreen SPF 15 in the treatment of moderate to severe rosacea. Methods: One hundred and twenty patients with moderate to severe rosacea were enrolled for a randomized, placebo-controlled (vehicle containing sunscreen with SPF 15), double-blind study. Study cream was applied twice daily to the entire face over a 12-week period. Results: Treatment with metronidazole 1% cream with sunscreen SPF 15 resulted in significant improvement (p <0.05) in inflammatory lesion count, erythema and telangiectasiae scores, and investigator and patient global assessment scores compared with baseline and placebo. Adverse reactions related to study medication were typically mild, occurred at the site of application, and were reversible. There was no difference between the safety profiles of metronidazole 1% cream with sunscreen SPF 15 and placebo. Conclusions: The combined topical formulation of metronidazole 1% cream with sunscreen SPF 15 was an effective, well-tolerated topical agent for the treatment of moderate to severe rosacea.     

Pimecrolimus 1% cream for oral erosive lichen planus: a 6‐week randomized,double‐blind,vehicle‐controlled study with a 6‐week open‐label extension to assess efficacy and safety

Objective To assess the efficacy and safety of topical pimecrolimus 1% cream in the treatment of oral erosive lichen planus. Design A 6‐week randomized, double‐blind, vehicle‐controlled phase followed by a 6‐week open‐label phase. Setting Outpatients of the Department of Dermatology, University of Utah. Patients Twenty‐one patients with oral erosive lichen planus were randomized and treated with either pimecrolimus 1% cream or vehicle cream. Intervention Pimecrolimus 1% cream, or its vehicle, were applied twice daily for 6 weeks to each side of the mouth with a 2 × 2 inch gauze pad folded in half and placed directly on the erosive lesion. Main Outcome Measures Efficacy was based on clinical evaluation of Investigator’s Global Assessment (IGA) of the overall severity of the disease, erythema, measurement of the size of any target erosion in millimetres, and assessment of spontaneous pain. Blood levels of pimecrolimus were monitored in all subjects on day 0 and repeated on day 7. Results Pimecrolimus 1% cream was superior to vehicle cream in reducing mean IGA, pain, and erosion size. For the vehicle group that entered the open‐label phase, pimecrolimus 1% cream improved the mean IGA, pain, erosion size, and erythema. Pimecrolimus levels were detected in nine out of 10 of the pimecrolimus‐treated subjects. These levels were consistently low. The pimecrolimus cream was well‐tolerated. No clinically relevant, drug‐related adverse events were reported. Conclusion Pimecrolimus 1% cream was superior to vehicle in reducing pain, erythema, decreasing erosion size, and improving overall severity of disease when compared with vehicle treatment.     

Effects of pimecrolimus cream 1% in the treatment of patients with atopic dermatitis who demonstrate a clinical insensitivity to topical corticosteroids: a randomized, multicentre vehicle-controlled trial

Background  Colonization with Staphylococcus aureus in atopic dermatitis (AD) is often associated with worsening of clinical symptoms. Staphylococcus aureus produces superantigens that contribute to cutaneous inflammation and corticosteroid (CS) resistance.
Objectives  To investigate the relationship between CS insensitivity, S. aureus colonization and superantigen production in AD, and to explore the efficacy of pimecrolimus cream in CS-insensitive AD.
Methods  This was a randomized, double-blind, vehicle-controlled, multicentre, parallel-group study. Seventy-three patients with AD, aged 2–49 years, who had a documented clinical insensitivity to topical CS, were recruited. The primary efficacy parameters combined laboratory (including S. aureus colonization, superantigens) and clinical assessments [including Eczema Area and Severity Index (EASI), whole body Investigator's Global Assessment (IGA), pruritus assessment score, patient's assessment score of disease control].
Results  An increase in S. aureus counts correlated with worsening of clinical score (week 6 vs. baseline) when assessed by IGA, pruritus severity and patient assessment. The presence of superantigens correlated with this worsening. During the 6-week double-blind phase, disease improvement in the pimecrolimus cream group was demonstrated by decreasing EASI scores compared with vehicle. Mean EASI scores for the head and neck showed greater improvement in the pimecrolimus cream group than in the vehicle group at all observed time points.
Conclusions  In a cohort of patients with clinical insensitivity to CS there was a significant positive correlation between S. aureus and disease severity. Results suggest that for some of these patients, treatment with pimecrolimus cream 1% is useful, especially in the head/neck area.     

Pimecrolimus 1% cream for the treatment of steroid-induced rosacea: an 8-week split-face clinical trial

BACKGROUND: Steroid-induced rosacea is a relatively common dermatosis that is caused by the prolonged application of topical steroid to the face. OBJECTIVES: The purpose of this investigator-blind, split-face study was to evaluate the efficacy and safety of pimecrolimus 1% cream for the treatment of steroid-induced rosacea. PATIENTS/METHODS: Patients were instructed to apply pimecrolimus 1% cream twice daily to the involved areas of a randomly allocated half side for the first 2 weeks, and to follow this by applying pimecrolimus 1% cream to both sides for a further 6 weeks. RESULTS: Fifteen of the 18 patients completed the 8-week study. After 1 week of application, a statistically significant improvement was observed for investigator's global assessments of erythema and papules on prior-treated sides (P-side). Later-treated sides (L-side) showed subsequent improvement after use of pimecrolimus on the L-side. Likewise, a statistically significant improvement was also observed for numbers of papules/pustules on P-sides after 1 week, and L-sides showed a significant improvement after application of pimecrolimus on the L-side. Comparative reflectance colorimetric assessments revealed that DeltaL*, Deltaa* and Deltab* tended to converge to zero during the first 4 weeks. A statistically significant improvement was observed for percentage area affected on P-sides after 1 week of application. The L-side showed a significant improvement after use of pimecrolimus cream on that side. The visual analogue scale of P-sides decreased more rapidly than those of L-sides. Cutaneous side-effects were mild and transient. CONCLUSIONS: This study suggests that pimecrolimus 1% cream is an effective and well-tolerated treatment for steroid-induced rosacea.     

A randomized controlled trial of pimecrolimus cream 1% in adolescents and adults with head and neck atopic dermatitis and intolerant of, or dependent on, topical corticosteroids

BACKGROUND: There is a need for alternative treatments for atopic dermatitis (AD) of the face and neck as long-term use of topical corticosteroids (TCS) is associated with skin atrophy and telangiectasia and some patients develop allergy, intolerance or other side-effects. OBJECTIVES: This study was designed to assess the efficacy and safety of pimecrolimus cream 1% in patients with AD of the face and neck who are either dependent on, or intolerant of, TCS. METHODS: A 12-week study comprising a 6-week, double-blind, randomized, vehicle-controlled phase was conducted, followed by a 6-week, open-label phase. Two hundred patients aged 12 years or over with mild to moderate head and neck AD, intolerant of, or dependent on, TCS were randomized to either pimecrolimus cream or vehicle cream. The primary efficacy criterion was the facial investigator's global assessment score at 6 weeks. Secondary efficacy criteria were head and neck Eczema Area and Severity Index (EASI), pruritus score and eyelid dermatitis. Facial skin atrophy and telangiectasia were assessed with dermatoscopy. RESULTS: A significantly higher percentage of patients treated with pimecrolimus was cleared or almost cleared of facial AD compared with vehicle (47% vs. 16%, respectively). A statistically significant difference was also seen on head and neck EASI and pruritus score. Significantly more pimecrolimus-treated patients than vehicle-treated patients achieved clearance of eyelid dermatitis (45% vs. 19%, respectively). Among the 77 patients with skin atrophy at baseline, treatment with pimecrolimus was associated with a reversal in skin thinning. Of the 112 patients with telangiectasia at baseline, no statistically significant difference was seen between treatment groups. Adverse events occurred with similar frequency in both groups. CONCLUSION: Pimecrolimus cream 1% is effective in patients with head and neck dermatitis intolerant of, or dependent on, TCS. Reversion of skin atrophy may occur during TCS-free intervals.     

Double-blind comparison of azelaic acid 20% cream and its vehicle in treatment of papulo-pustular rosacea

Previous investigations have indicated that topical azelaic acid has beneficial effects in rosacea. This 3-month randomized, double-blind, multicentre study compared the efficacy and safety of azelaic acid 20% cream with its vehicle, in the treatment of papulo-pustular rosacea. A total of 116 patients were enrolled in the study and medication was applied twice daily. Azelaic acid cream produced significantly greater mean reductions in total inflammatory lesions than did vehicle (azelaic acid: 73.4%; vehicle: 50.6%; (p = 0.011), and erythema severity score (azelaic acid: 47.9%; vehicle: 37.9%; (p = 0.031). Azelaic acid cream treatment also resulted in significantly more favourable overall improvements than vehicle in both physician (p = 0.020) and patient ratings (p = 0.042). Neither azelaic acid cream nor vehicle produced any clinically relevant improvement in telangiectasia. Local adverse events were transient and mainly mild or moderate, and rates were similar for azelaic acid cream (39.5%) and vehicle (38.5%). Burning was the symptom most frequently reported. More than 90% of patients rated the overall local tolerability of their treatment as good or acceptable. In conclusion, azelaic acid 20% cream is effective and well tolerated in the treatment of papulo-pustular rosacea.     

The impact of rosacea on quality of life: effects of demographic and clinical characteristics and various treatment modalities

Summary Background Rosacea has a major psychosocial impact on a patient’s life. Objectives To determine the impact of rosacea on patient quality of life, the relationship of quality of life scores to clinical and demographic variables, and the change in quality of life following various treatments. Methods Patients’ demographic and clinical characteristics were recorded at their initial examination and their response to treatment and side‐effects were recorded additionally at their follow‐up examination. Rosacea severity was scored for each of four signs from 0 to 3. Patients were requested to complete Dermatology Life Quality Index (DLQI) questionnaires. Results A total of 308 patients took part in this study. Mean ± SD DLQI total score at the initial visit was 6·93 ± 5·18 and was related to patients’ age, sex, age at disease onset, subjective symptoms, triggering factors, previous treatments, rosacea severity scores and patients’ self‐assessment of ease of living with rosacea. Of these 308 patients, 164 completed the DLQI following treatment. Mean ± SD post‐treatment DLQI score was 4·36 ± 4·82. Post‐treatment scores were also related to sex, type of treatment modality, development of side‐effects, improvement of rosacea, rosacea severity scores and patients’ self‐reported ease of living with rosacea. Topical metronidazole, oral tetracycline and oral isotretinoin were observed to reduce signs and symptoms of rosacea and DLQI scores significantly at this repeat examination. Conclusions Rosacea affects patients’ lives to a moderate extent, and this can be assessed by using DLQI. DLQI is also sensitive to quality of life changes brought about by treatment of rosacea. As a preliminary result we can say that topical metronidazole, oral tetracycline and oral isotretinoin seem to improve quality of life of patients by improving lesions of rosacea more efficiently than other therapeutic agents.     

Improvement in pruritus in children with atopic dermatitis using pimecrolimus cream 1%

The objective of this study was to assess time to onset of pruritus improvement in a pediatric population treated with pimecrolimus cream 1%. This 8-day, double-blinded, vehicle-controlled study randomized 174 children and adolescents (aged 2-17 years) with mild to moderate atopic dermatitis (AD) and moderate to severe pruritus to twice-daily applications of pimecrolimus cream 1% or vehicle. There were no significant between-group differences in demographics or baseline disease characteristics. Pruritus was assessed by subjects using a 4-point pruritus severity scale (0-3). The primary efficacy variable was time to a 1 point or more improvement in pruritus score from baseline. The 2 treatment groups were compared using log-rank testing of the time-to-event data. In the per-protocol (PP) population, median times to a 1 point or more improvement in pruritus score were 48 and 72 hours for pimecrolimus and vehicle groups, respectively (P = .038). From day 3 onward, significantly more subjects (P = .023) in the pimecrolimus group versus the vehicle group reported complete pruritus resolution. Pimecrolimus cream 1% improved pruritus within 48 hours in children and adolescents with mild to moderate AD and achieved complete resolution of pruritus in a significantly greater number of subjects in the pimecrolimus group versus the vehicle group by the end of the 7-day treatment period (P = .008).     

A case of granulomatous rosacea successfully treated with pimecrolimus cream

A 43-year-old male attended with lesions on his face that had been present for 3 months. On dermatological examination, multiple papules and pustules were seen on the forehead, nose, bilateral cheeks and lower eyelids. The patient used systemic clindamycin and doxycycline and topical benzoyl peroxide therapies, but the lesions did not regress. Routine laboratory tests were normal. Histopathological examination of the lesions confirmed the diagnosis of granulomatous rosacea. Pimecrolimus cream 1% was applied to the lesions. The regression of lesions began in the first month and complete improvement was observed at the end of the fourth month of therapy. Rosacea is a chronic, inflammatory skin disorder characterized by remissions and relapses. Although it is known that the disease is a treatable disorder, it may be resistant to standard therapies and there is a need for new therapy alternatives in some patients. We present a case of granulomatous rosacea successfully treated with pimecrolimus cream and believe that pimecrolimus may be a good alternative for the treatment of granulomatous rosacea.     

An open-label efficacy pilot study with pimecrolimus cream 1% in adults with facial seborrhoeic dermatitis infected with HIV

BACKGROUND: Seborrhoeic dermatitis (SD) is a common dermatosis in human immunodeficiency virus (HIV)-positive patients, many of whom do not respond satisfactorily to conventional topical treatments such as corticosteroids and antifungals. OBJECTIVE: A pilot study to investigate the efficacy and tolerability of pimecrolimus cream 1% in HIV-positive patients with facial SD. METHODS: In a single-centre study, 21 HIV-infected patients with mild to severe SD were treated twice daily with pimecrolimus cream 1% for 14 days. Thereafter, treatment was discontinued and patients followed up for 5 weeks. Skin involvement at baseline and on days 7, 14, 21, 35 and 49 was assessed using a four-point clinical score and digital photography. MAIN OUTCOME MEASURES: Efficacy and safety of pimecrolimus cream 1% treatment and incidence of relapse in the follow-up phase. Results Marked improvement was seen in clinical parameters at day 7, with >or= 90% patients clear of symptoms at day 14. Relapse was observed at day 35 but signs were milder than at baseline. All patients responded to therapy, despite their immunological status. Pimecrolimus did not alter CD4(+) and CD8(+) T-cell counts or viral load during the treatment period. CONCLUSION: Pimecrolimus cream represents a new, effective therapeutic option for facial SD in HIV patients.     

Safety and efficacy of pimecrolimus (ASM 981) cream 1% in the treatment of mild and moderate atopic dermatitis in children and adolescents

BACKGROUND: The ascomycin derivative pimecrolimus (ASM 981) is a cell-selective cytokine inhibitor, specifically developed for the treatment of inflammatory skin diseases. OBJECTIVE: When applied topically, pimecrolimus cream 1% has shown promise as a treatment for inflammatory skin conditions, including atopic dermatitis (AD) in children and adults, allergic contact dermatitis, and chronic contact irritant hand dermatitis in adults. METHODS: In two independent 6-week, randomized, multicenter studies of identical design, the efficacy and safety of pimecrolimus cream 1% in children with predominantly moderate AD were compared with vehicle. Pooled data from a total of 403 patients were used in the analysis. The primary efficacy parameter was the Investigator's Global Assessment (IGA) score. Secondary parameters included Eczema Area and Severity Index (EASI) and severity of pruritus scores. Subjects were also asked to assess their disease control as uncontrolled, limited, good, or complete. RESULTS: Significant therapeutic benefits relative to vehicle were observed in the pimecrolimus-treated group at the first efficacy assessment, 8 days after initial application of the study medication (eg, relief of pruritus). At each subsequent postbaseline visit, pimecrolimus-treated patients showed significant improvement relative to controls in all efficacy measures. The medication was well tolerated. CONCLUSION: Pimecrolimus cream 1% appears to be a safe and effective alternative to currently used therapies for AD.     

Azelaic acid in the treatment of papulopustular rosacea: a systematic review of randomized controlled trials

OBJECTIVE: To evaluate the clinical efficacy of topical 20% azelaic acid cream and 15% azelaic acid gel compared with their respective vehicles and metronidazole gel in the treatment of papulopustular rosacea. DATA SOURCES: Electronic searches of MEDLINE, EMBASE, BIOSIS, and SciSearch through July or August 2004 and the Cochrane Central Register of Controlled Trials through 2004 (issue 3). We performed hand searches of reference lists, conference proceedings, and clinical trial databases. Experts in rosacea and azelaic acid were contacted. STUDY SELECTION: Randomized controlled trials involving topical azelaic acid (cream or gel) for the treatment of rosacea compared with placebo or other topical treatments. Two authors independently examined the studies identified by the searches. Ten studies were identified, of which 5 were included (873 patients). DATA EXTRACTION: Two authors independently extracted data from the included studies, then jointly assessed methodological quality using a quality assessment scale. DATA SYNTHESIS: Because standard deviation data were not available for 4 of the 5 studies, a meta-analysis could not be conducted. Four of the 5 studies demonstrated significant decreases in mean inflammatory lesion count and erythema severity after treatment with azelaic acid compared with vehicle. None of the studies showed any significant decrease in telangiectasia severity. CONCLUSIONS: Azelaic acid in 20% cream and 15% gel formulations appears to be effective in the treatment of papulopustular rosacea, particularly in regard to decreases in mean inflammatory lesion count and erythema severity. Compared with metronidazole, azelaic acid appears to be an equally effective, if not better, treatment option.