Maintenance of remission following successful treatment of papulopustular rosacea with ivermectin 1% cream vs. metronidazole 0.75% cream: 36-week extension of the ATTRACT randomized study.

BACKGROUND: There are a limited number of approved treatments for papulopustular rosacea (PPR) and remission is difficult to maintain after successful treatment. OBJECTIVES: To investigate remission over a 36-week extension period in patients with moderate to severe PPR successfully treated with 16 weeks' treatment with ivermectin 1% cream once daily (QD) or metronidazole 0.75% cream twice daily (BID) in a randomized, parallel-group Phase III study. METHODS: Treatment was discontinued in patients initially successfully treated [Investigator's Global Assessment (IGA) score of 0 or 1] with ivermectin 1% cream QD (n = 399) or metronidazole 0.75% cream BID (n = 365; Part A) and patients were followed every 4 weeks for up to 36 weeks (Part B). Treatment with the same study treatment as used in Part A was only re-initiated if patients relapsed (IGA ≥ 2). Efficacy assessments were: time to first relapse; relapse rate; and number of days free of treatment. Safety assessments included incidence of adverse events and local cutaneous signs and symptoms. RESULTS: The median time to first relapse was significantly longer (115 days vs. 85 days) and relapse rates at the end of the study period significantly lower (62.7% vs. 68.4%) for patients initially successfully treated with ivermectin 1% compared with metronidazole 0.75%; Kaplan-Meier plot demonstrated a statistically significant difference between the two arms (P = 0.0365). The median number of days free of treatment was higher for ivermectin compared with metronidazole (196 days vs. 169.5 days; P = 0.026). The percentage of patients who experienced a related adverse event was equally low in both groups. CONCLUSION: The results of this relapse study showed that an initial successful treatment with ivermectin 1% cream QD significantly extended remission of rosacea compared with initial treatment with metronidazole 0.75% cream BID following treatment cessation.

Superiority of ivermectin 1% cream over metronidazole 0·75% cream in treating inflammatory lesions of rosacea: a randomized, investigator-blinded trial.

BACKGROUND: Few therapeutic alternatives currently exist in the treatment of papulopustular rosacea (PPR). OBJECTIVES: To demonstrate superiority of once-daily ivermectin 1% cream (IVM 1%) once daily vs. twice-daily metronidazole (MTZ 0·75%) cream, regarding percentage reduction of inflammatory lesions in subjects with moderate to severe PPR. METHODS: In this Phase 3, investigator-blinded, randomized, parallel-group study, subjects received IVM 1% once daily, or MTZ 0·75% twice daily over 16 weeks. Efficacy assessments were inflammatory lesion counts and Investigator's Global Assessment (IGA). Safety assessments included incidence of adverse events (AEs) and local tolerance parameters. Subjects evaluated their disease following a 5-grade scale and completed questionnaires. RESULTS: A total of 962 subjects were randomized to receive IVM 1% (n = 478) or MTZ 0·75% (n = 484). At week 16, IVM 1% was significantly superior to MTZ 0·75% in terms of reduction from baseline in inflammatory lesions (83·0% vs. 73·7%; P < 0.001), observed as early as week 3 (Last Observation Carried Forward, LOCF). IGA results (subjects 'clear' or 'almost clear') also favoured IVM 1%: 84·9% vs. 75·4%, respectively (P < 0.001). Incidence of AEs was comparable between groups and local tolerability was better for IVM 1%. More subjects receiving IVM rated their global improvement as 'excellent' or 'good.' CONCLUSIONS: Ivermectin 1% cream was significantly superior to MTZ 0·75% cream and achieved high patient satisfaction.

Human papillomavirus typing of warts and response to cryotherapy.

BACKGROUND: Cutaneous warts are common and caused by a number of different types of human papillomaviruses (HPVs). OBJECTIVE: The aim of this study was to investigate the HPV types causing common warts and to determine any association between the HPV type and the duration of warts and response to cryotherapy. METHODS: Eighty wart samples from 76 immunocompetent patients were taken from warts by paring prior to cryotherapy and analysed by in situ hybridization (ISH) with HPV probes specific to HPV 1, 2, 3, 4, 7, 10 and 57 and PCR analysis using degenerate cutaneous HPV primers with subsequent DNA sequencing. Each patient's details, including site, duration and response of the wart to cryotherapy were recorded. Cryotherapy was performed at 2 week intervals for a maximum of 12 weeks. RESULTS: An HPV type was identified in 65 samples. The majority of warts (58 samples) were typed as HPV 2/27/57 by ISH and/or PCR. Three of the 18 samples that were HPV negative with ISH were HPV positive by PCR. Response to treatment did not correlate with HPV type, duration or location. In the 21 wart parings taken from patients aged 16 and under, response to treatment did not correlate with HPV type but warts of shorter duration were more likely to resolve with cryotherapy treatment than longer standing lesions. CONCLUSION: This study demonstrates that HPV type can be determined from wart parings. HPV-2 related viruses are the prevalent HPV types causing common warts on the hands and feet in this population.

Treatment of disseminated superficial actinic porokeratosis with topical diclofenac gel: a case series.

Disseminated superficial actinic porokeratosis (DSAP) is the most common of the of five clinical variants of porokeratosis. These are disorders of keratinization and the distinctive pathological feature is the cornoid lamella at the margin. DSAP usually manifests in the third or fourth decades of life with a female preponderance and with multiple lesions over sun-exposed areas. A diverse range of treatments is employed though evidence of efficacy remains largely anecdotal. We report a series of eight patients with DSAP treated with 3% diclofenac gel (Solaraze gel).

Scalp psoriasis: a review of current topical treatment options.

The scalp is the most common site of disease involvement at the onset and throughout the course of psoriasis. For many patients, psoriasis of the scalp is the most difficult aspect of their disease; yet, despite a wide range of therapy options and an extensive literature base, scalp psoriasis remains difficult to treat, highlighting a long-standing unmet need for the effective treatment of scalp psoriasis. A review of past and current medical literature reveals that a number of interesting therapeutic approaches have been used in the treatment of scalp psoriasis. The diverse and sometimes extreme therapeutic approaches, the marginal benefit of many topical agents, the paucity of controlled studies evaluating the efficacy of topical agents in the treatment of scalp psoriasis and the high level of patient dissatisfaction with currently available treatments for psoriasis all support the need for new, effective and well-tolerated treatment options for scalp psoriasis.

Double-blind, randomised, multicentre, parallel group study comparing a 1% coal tar preparation (Exorex) with a 5% coal tar preparation (Alphosyl) in chronic plaque psoriasis.

BACKGROUND: Exorex lotion is a novel formulation of prepared coal tar indicated for the treatment of psoriasis. OBJECTIVES: To compare the efficacy and tolerability of 1% prepared coal tar lotion versus 5% coal tar extract in patients with mild to moderate plaque psoriasis. PATIENTS AND METHODS: This was a double-blind, randomised controlled study. Patients initially entered a 7-day washout period, during which they applied a yellow soft paraffin plus emulsifying wax ointment used as an emollient three times a day to their plaques. They were then randomised to receive treatment with 1% coal tar (Exorex) lotion or 5% conventional coal tar lotion (Alphosyl), three times a day for 12 weeks. Both treatment groups continued to apply the emollient throughout the duration of the study. Two target plaques were selected at entry for assessment. The clinical measures used were: 1) Total Sign Score (TSS), the sum of 5-point rating scores for erythema, induration and scaling averaged for the two target plaques (range 0-12), 2) the Psoriasis Area and Severity Index (PASI), and 3) patient and investigator 7-point global assessments of improvement at 12 weeks. Patients were assessed at 0, 4, 8 and 12 weeks during the treatment period or at the point of withdrawal. Spontaneously reported and observed adverse events were noted. RESULTS: Three hundred and twenty four of 338 randomised patients were evaluable (ITT analysis): 158 patients received 1% coal tar lotion and 166 patients received conventional coal tar. Both groups showed decreases from baseline to end of treatment in mean TSS (decrease of 2.4 points from 5.6 to 3.2 with 1% coal tar lotion and 1.8 points from 5.5 to 3.7 with conventional coal tar), and mean PASI (decrease of 2.4 points with 1% coal tar lotion and 1.5 points with conventional coal tar). Two hundred and twenty eight patients completed the full course of treatment. There was a statistically significant treatment difference in the percentage change in mean TSS at week 12, in favour of 1% coal tar lotion (-10.6%, 95% CI -20.6% to -0.5%, p=0.04). There was also a difference between treatments in the change in mean PASI in favour of 1% coal tar that was of borderline statistical significance (-11.7%, 95% CI -23.8% to 0.4%, p=0.06). Investigator global assessments also favoured 1% coal tar lotion (38% vs. 27% of patients showed clearance or marked improvement). The 1% coal tar lotion had a similar safety profile to 5% conventional coal tar lotion with the majority of treatment-related events being mild to moderate in severity. CONCLUSIONS: 1% coal tar lotion is more effective than a conventional coal tar lotion in mild to moderate psoriasis and may be preferred for first-line topical treatment.

Successful treatment of recalcitrant psoriasis with a combination of infliximab and hydroxyurea.

We report the use of a combination of the tumour necrosis factor alpha (TNF alpha) inhibitor infliximab and hydroxyurea to achieve control of disabling psoriasis and psoriatic arthritis. Our patient had psoriasis that proved resistant to conventional therapy including vitamin D analogues, topical steroids, dithranol, crude coal tar, narrow band UVB, bath PUVA and acitretin. She subsequently responded to hydroxyurea 1 g daily combined with infliximab infusions repeated at three monthly intervals which led to satisfactory control of her psoriasis and psoriatic arthritis. She has not reported any side-effects from this treatment regimen and her full blood count has remained normal.

Efficacy and tolerability of borage oil in adults and children with atopic eczema: randomised, double blind, placebo controlled, parallel group trial.

OBJECTIVE: To study the efficacy and tolerability of borage oil, which contains a high concentration of gamma linolenic acid, in children and adults with atopic eczema. DESIGN: Single centre, randomised, double blind, placebo controlled, parallel group trial. SETTING: Acute district general hospital in Nuneaton, England. PARTICIPANTS: 151 patients, of whom 11 failed to return for assessment, leaving an evaluable population of 140 (including 69 children). INTERVENTION: Adults received four capsules of borage oil twice daily (920 mg gamma linolenic acid), and children received two capsules twice daily, for 12 weeks. MAIN OUTCOME MEASURES: Change in total sign score at 12 weeks measured with the six area, six sign, atopic dermatitis (SASSAD) score (primary endpoint); symptom scores, assessed on visual analogue scales; topical corticosteroid requirement, assessed on a five point scale; global assessment of response by participants; adverse events and tolerability. RESULTS: The mean SASSAD score fell from 30 to 27 in the borage oil group and from 28 to 23 in the placebo group. The difference between the mean improvements in the two groups was 1.4 (95% confidence interval -2.2 to 5.0) points in favour of placebo (P = 0.45). No significant differences occurred between treatment groups in the other assessments. Subset analysis of adults and children did not indicate any difference in response. The treatments were well tolerated. CONCLUSION: Gamma linolenic acid is not beneficial in atopic dermatitis.

Liquid nitrogen cryotherapy of common warts: cryo-spray vs. cotton wool bud.

BACKGROUND: Viral warts represent a large workload for dermatology departments. Cryotherapy with liquid nitrogen is the most widely used method of treatment by dermatologists and is increasingly used by general practitioners in the U.K. Existing data relating to the response to cryotherapy are virtually all derived from the use of a cotton wool bud as the applicator. There is an increasing trend to use the cryo-spray to freeze warts and it has been assumed that this is equally effective. In view of the workload involved it is important to test this assumption. OBJECTIVES: This prospective study was undertaken to compare these two methods of liquid nitrogen cryotherapy with regards to cure rate after 3 months of treatment. METHODS: Patients referred to two hospital dermatology departments with hand or foot warts were allocated to have liquid nitrogen applied with either a cryo-spray or with a cotton wool bud. Using either technique, liquid nitrogen was applied until ice-ball formation had spread from the centre to include a margin of 2 mm around each wart. Treatment was done fortnightly for up to 3 months. Plantar warts were pared and treated with a double freeze-thaw cycle. The endpoint of the study was complete clearance of all warts. RESULTS: Three hundred and sixty-three patients were enrolled, mean age 21 years (range 3-75), 188 male and 175 female. The mean duration of the warts was 98 weeks (median 78, range 2-936). The number of warts on the hands and feet varied from one to 80 (mean 5). The treatment groups were comparable with regards to baseline demographics. Two hundred and seven patients were evaluable. Cure rates at 3 months were 47% in the cotton wool bud group and 44% in the cryo-spray group (P = 0.8). Warts that had been present for 6 months or less (n = 31) had a greater chance of clearance (84%) compared with warts that had been present for more than 6 months (39%, n = 176) (P < 0.0005). CONCLUSIONS: Cryotherapy with liquid nitrogen for hand and foot warts in our study was equally effective when applied with a cotton wool bud or by means of a spray.

Comparison of cryotherapy with curettage in the treatment of Bowen's disease: a prospective study.

BACKGROUND: In our departments, curettage and cautery (C&C) and liquid nitrogen cryotherapy are the preferred methods of treatment for Bowen's disease (BD). OBJECTIVES: We aimed to compare these two treatments with regard to efficacy, time to heal, morbidity and recurrence rate. METHODS: Cryotherapy was performed using a liquid nitrogen spray giving two freeze-thaw cycles, each freeze cycle being maintained for 5-10 s after the formation of an ice ball to the intended margin. Curettage was performed with a conventional disposable curette under local anaesthesia, and electrocautery was then used for haemostasis. RESULTS: Eighty lesions in 67 patients (55 female) were analysed. The mean age of the patients was 74 years (range 46-89). The most frequent site was the lower leg, below the knee (n = 59, 74%). The average time taken for complete healing after the procedure was 60 days. The mean size of the lesions was 336 mm(2) (range 30-1890). The patients were followed up for a mean of 22 months (range 6-24, median 2 years). In the cryotherapy group (n = 36 lesions), the median time to complete healing was 46 days (range 14-210; mean 69). Twelve lesions took more than 90 days to heal. Infection requiring antibiotics developed in four patients. Thirteen of the treated lesions had recurred by 24 months. In the C&C group (n = 44 lesions), the median time to healing was 35 days (range 14-330; mean 53). Six of the lesions took more than 90 days to heal. Infection developed in two patients. Recurrence occurred in four lesions over the follow-up period. Considering BD on the lower legs separately, lesions took on average 90 days to heal in the cryotherapy group (n = 23), whereas in the C&C group (n = 36) they took 39 days to heal (P < 0.001). During the procedure and the subsequent 24 h, patients were 10.4 times more likely to report pain of any degree for lesions treated by cryotherapy than by C&C (P < 0.001). CONCLUSIONS: This study suggests a superiority of C&C over cryotherapy in the treatment of BD, especially for lesions on the lower leg. Curettage of lesions of BD is associated with a significantly shorter healing time, less pain, fewer complications and a lower recurrence rate when compared with cryotherapy.

Imiquimod: a novel treatment for lentigo maligna.

Lentigo maligna is the in situ phase of lentigo maligna melanoma, and if left untreated it may progress to invasive melanoma. It most commonly occurs on the exposed sites of the face and neck of middle-aged or elderly patients. Conventional surgery using a 5-10 mm margin is the recommended treatment; however, lesions can be quite large and surgical removal may involve extensive plastic repair. We report an elderly patient with a large lentigo maligna on the scalp who was reluctant to have surgery. We tried topical imiquimod 5% cream (Aldara), a local immunomodulator, which has recently become available for the treatment of external genital and perianal warts. Initially used over a test area and then over the whole of the lesion, for a total of 7 months, the imiquimod cream resulted in complete clinical and histological cure. The patient has been followed up for 9 months without evidence of recurrence.

Co-existing actinic granuloma and giant molluscum contagiosum.

Actinic granuloma of O'Brien and giant molluscum contagiosum in immunocompetent adults are rare skin disorders. There have been no previous reports of these two conditions occurring together. We report this occurrence in a 57-year-old Caucasian woman.

Mutations of keratin 9 in two families with palmoplantar epidermolytic hyperkeratosis.

The hereditary palmoplantar keratodermas are a heterogeneous group of diseases unified by thickening of the stratum corneum of the palms and soles with consequent painful fissuring, discomfort on pressure, and resultant disability. One of the histologic patterns underlying palmoplantar hyperkeratosis is that of epidermolytic hyperkeratosis. Because that histologic pattern has been found in its generalized form to be due to keratin gene mutations, we assessed the inheritance of the form localized to the palms and soles. In each of two families studied, the mutant gene causing the disease is linked strongly to the chromosome 17 cluster of genes encoding type I keratins, and mutations are present in the conserved helix initiation region of keratin 9 in affected members of both kindreds. These data, as well as those generated recently by others, indicate that keratin gene mutations may underlie not only the generalized phenotype but also this more localized phenotype of epidermolytic hyperkeratosis and suggest one mechanism by which skin diseases can achieve their characteristic localization.

Diffuse primary cutaneous amyloidosis.

A case of extensive primary cutaneous amyloidosis exhibiting both macular and lichenoid lesions is reported. Lesions were arranged in a distinctive linear pattern covering much of the trunk and limbs, in places following Blaschko's lines. The coexistence of macular and lichenoid lesions suggests that this is an unusual variant of biphasic cutaneous amyloidosis.

Modern treatment of warts: cure rates at 3 and 6 months.

Four-hundred consecutive referrals with viral warts of the hands and/or feet were investigated to determine the cure rate from a combination of cryotherapy, keratolytic wart paint and paring. For treatment failures after 3 months, the value of continuing cryotherapy and of additional treatment with the immunomodulator inosine pranobex were assessed. Subjects were treated for 3 months with wart paint and cryotherapy and were randomized to receive, or not, paring in addition. Those who did not respond by 3 months were randomized to receive, or not, 3 months further cryotherapy, and to receive inosine pranobex 60 mg/kg/day for 1 week each month, or matching placebo. Fifty-two per cent of subjects were cured by 3 months. The chance of cure was inversely related both to the length of history and to the diameter of the largest wart. Paring improved the cure rate for plantar warts but not for hand warts. During the second 3 months the cure rate fell to 41%. Neither cryotherapy nor inosine pranobex significantly improved this response.