Is benzoyl peroxide 3% topical gel effective and safe in the treatment of acne vulgaris in Japanese patients? A multicenter,randomized, double‐blind,vehicle‐controlled,parallel‐group study

Benzoyl peroxide (BPO) as an anti‐acne medication is not yet approved in Japan. This study evaluated the efficacy and safety of a once‐daily topical application of BPO 3% gel versus an inert vehicle gel in Japanese acne patients. Three hundred and sixty patients were randomized to receive BPO 3% or vehicle for 12 weeks. The primary efficacy end‐point was absolute change in number of total lesions (TL) from baseline to week 12 to demonstrate the superiority of BPO 3% versus vehicle. Secondary efficacy end‐points were absolute and percent change in TL, inflammatory lesions (IL), non‐inflammatory lesions (non‐IL) and Investigator's Static Global Assessment (ISGA). Change in TL counts from baseline to week 12 for BPO 3% was superior to vehicle (difference, ?21.0; P < 0.001). Absolute and percent reductions in TL, IL and non‐IL counts were greater for BPO 3% at all study visits. The proportion of patients with improvement in ISGA scores was significantly higher with BPO 3% than with vehicle from week 2. All adverse events were mild or moderate. Adverse drug‐related reactions were higher for BPO 3% (30%) than with vehicle (5%). Local tolerability scores of grade 1 or more (slight to moderate) were more frequent with BPO 3% than vehicle with the most significant differences observed in dryness (56% vs 27% at week 1–4), peeling (19% vs 9% at week 1–2) and burning/stinging (58% vs 15% at week 1–12). These results indicate that BPO 3% is effective while maintaining a favorable safety and tolerability profile in Japanese acne patients.     

Is the step‐up therapy of topical 5‐aminolevulinic acid photodynamic therapy effective and safe for the patients with recalcitrant facial flat wart?

Facial flat wart, caused by human papilloma virus type 3 and less often, type 10, 27, and 41, often brings many cosmetic problems to children and young adults. Considering the disturbing cosmetic problem, the treatment of facial flat wart is always frustrating and often unsuccessful, although there are many treatment modalities. Considering the possible serious side effects of 5‐aminolevulinic acid photodynamic therapy (ALA‐PDT), we designed step‐up therapy of ALA‐PDT on different clinical phases of facial flat wart. As a new protocol of ALA‐PDT, we found the step‐up therapy of ALA‐PDT could also receive excellent effects with the lower side effects. Meanwhile, the tolerance of patients to ALA‐PDT could improve with subsequent treatment sessions and escalating doses of ALA‐PDT.     

Are placebo‐controlled trials of creams for athlete’s foot still justified?

Background Placebo‐controlled trials are useful in identifying effective treatments where none has existed, but their continued use once efficacy is established arguably contravenes ethical standards for medical research. Objectives To consider whether sufficient evidence exists to recommend the abandonment of vehicle‐controlled studies in trials of topical treatments for athlete’s foot. Methods We searched nine electronic databases and bibliographies of review articles as part of an ongoing Cochrane systematic review from 1966 to 2007. Randomized controlled trials (RCTs) using a vehicle control design involving participants with a mycological diagnosis of a dermatophyte infection of the skin of the foot were included. Results Allylamines, azoles, ciclopiroxolamine, tolnaftate, butenafine and undecanoates were all more effective than vehicle controls. Evidence of the superiority of azole creams over vehicle controls was fairly consistent from 1975 onwards. Data from patients treated with allylamines have shown their superior effects relative to vehicle controls since 1991 for even short‐term outcomes. Conclusions The superiority of allylamines and azoles over vehicle in vehicle‐controlled trials has been well established, and data demonstrating this fact have been available since the completion of early RCTs. These preparations are effective and safe, and investigators of RCTs evaluating topical treatments for athlete’s foot need to choose potential comparators as control interventions in the light of this knowledge and to consider the ethics of withholding effective treatment from patients who seek treatment for this common foot infection.     

Is ultraviolet exposure acquired at work the most important risk factor for cutaneous squamous cell carcinoma? Results of the population‐based case–control study FB‐181

Squamous cell carcinoma (SCC) is a specific type of skin cancer. It is one of the most common cancers in Europe. SCC therefore causes a significant burden, both for the people affected and also in terms of costs to society. One main cause of SCC is exposure to natural sunlight. SCC can be prevented by avoiding sun exposure. When people go outside, they can protect themselves through clothes (e.g. long sleeves, hat) and using sunscreens. Until now, prevention programs for SCC and other skin cancers have mainly tried to reduce sun exposure during leisure time. However, there are many people working outdoors, e.g. farmers, construction workers and roofers. The role of occupational (work‐related) and leisure‐time sun exposure in causing SCC is still unclear. Our team of physicians and scientists from Germany investigated the association between occupational and leisure‐time sun exposure and the risk of SCC. More than 600 people with SCC were compared to the same number of healthy people without SCC, taking into account their sun exposure in the past. All study participants were medically examined by trained physicians. Lifetime sun exposure in occupation and leisure time was assessed by interviews. The interviews were tested before starting the study to ensure correct results. The study found that people with high levels of sun exposure at work have a 2‐fold risk of SCC. The more sun exposure people had at work, the more likely was the development of SCC. This result is important, as it indicates that sun protection is not only necessary in leisure‐time, but also at work to prevent skin cancer such as SCC.     

Does smoking influence the efficacy of bath‐PUVA therapy in chronic palmoplantar eczema?

Bath-PUVA therapy has been described as successful treatment for palmoplantar eczema. However, our own observations showed that patients with palmoplantar eczema of the dyshidrotic or hyperkeratotic type responded only partially to bath-PUVA therapy. In order to evaluate environmental influences possibly having an impact on the efficacy of this therapy, smokers and non-smokers suffering from palmoplantar eczema treated with bath-PUVA therapy were compared. A retrospective study was conducted involving 62 patients, 39 non-smokers and 23 smokers, with palmar and/or plantar eczema resistant to local corticosteroids. Bath-PUVA therapy was performed according to the European standard regimen for oral PUVA therapy. The total number of treatments and the cumulative UVA-dose were similar in smokers and non-smokers (smokers 24+/-17.7 (mean+/-SD) and 67.6+/-51.3 J/cm2 vs. non-smokers 25.7+/-16.3 and 68.5+/-49.3 J/cm2). In the group of non-smokers, 31% showed complete remission (CR; 100% clearance), 33% partial remission (PR; more than 50% clearance) and 36% no change after treatment (NC; less than 50% clearance). In contrast, the group of smokers showed only 13% CR and 22% PR, whereas 65% exhibited NC. The differences regarding complete or partial remission between the groups were statistically significant (Student t-test for paired samples; P<0.05). Regarding the different type of eczema, bath-PUVA proved to be more successful in the dyshidrotic type of eczema as compared to the hyperkeratotic type in non-smokers (P<0.05). In the group of smokers no CR was achieved in patients suffering from the dyshidrotic form of eczema. Smoking is likely to be a reason for the failure of bath-PUVA therapy in the treatment of chronic palmoplantar eczema, in particular regarding smokers with eczema of the dyshidrotic type where no complete remission was achieved.     

Is the pain of topical photodynamic therapy with methyl aminolevulinate any different from that with 5‐aminolaevulinic acid?

Topical photodynamic therapy (PDT) using 5‐aminolaevulinic acid (ALA) or methyl aminolevulinate (MAL) is widely used in dermatology. It is commonly stated that MAL PDT is less painful than ALA PDT, although published data are conflicting. We report our experience of the use of ALA (4–6 h) (n = 20) and MAL (3 h) (n = 20) in 40 consecutive patients with Bowen's disease or superficial basal cell carcinoma, treated with PDT using an identical irradiation regime. Although there was a trend to higher pain scores with ALA PDT [visual analogue scale (VAS)score, median 4.50], this was not significantly different from that of MAL PDT (VAS score, median 3.55; P = 0.98), nor considered to be clinically important. Importantly, both ALA and MAL PDT regimes were fairly well tolerated in this patient cohort, supporting the use of these prodrugs in dermatological PDT.     

Is minocycline therapy in acne associated with antineutrophil cytoplasmic antibody positivity? A cross‐sectional study

BACKGROUND: Minocycline (MN), one of the commonly prescribed therapies for acne, is known to be associated with autoimmune disorders including drug-induced lupus. However, data are sparse regarding the prevalence of autoimmune disease in acne or in patients with acne treated with MN. OBJECTIVES: To establish the prevalence of antinuclear antibodies (ANA), antineutrophil cytoplasmic antibodies (ANCA) and new autoimmune syndromes in an MN-exposed and unexposed population with acne. METHODS: In a cross-sectional study, 252 patients with acne vulgaris were assessed. Sixty-nine per cent had been exposed to MN at some point or were taking the drug at the time of the interview. Data recorded included duration of disease (acne) and drug history as well as possible side-effects of drugs, in particular joint symptoms (pain and swelling). In addition, blood was taken for ANA, ANCA, liver function tests and HLA analysis. RESULTS: There was no statistical difference in the prevalence of ANA positivity between patients exposed (13%) or not exposed (11%) to MN. However, higher titres of ANA (1/160 or higher) were found in the MN-exposed group (45% compared with 12% in the unexposed group). ANCA positivity was found in 7% of the MN-exposed group but no positivity was found in the unexposed cohort (P = 0.022). In 58% of cases, the ANCA detected were of the perinuclear pattern (p-ANCA) with myeloperoxidase specificity, and this finding was associated with clinical symptoms in the majority of cases. Two p-ANCA-positive patients were thought in retrospect to have developed a drug-induced lupus syndrome. CONCLUSIONS: ANA positivity is seen in patients with acne irrespective of exposure to MN; however, p-ANCA appear to be a serological marker for developing autoimmune disease in patients receiving MN.     

Is occupational solar ultraviolet irradiation a relevant risk factor for basal cell carcinoma? A systematic review and meta‐analysis of the epidemiological literature

Summary Background The most important risk factor for basal cell carcinoma (BCC) is ultraviolet (UV) radiation. It is reasonable to assume that outdoor workers with a long history of work‐related UV exposure are at increased risk of developing BCC. Objectives To analyse systematically the epidemiological literature concerning the evidence of an association between occupational UV exposure and BCC risk in outdoor workers. Methods Systematic literature review of cohort studies and case–control studies providing data on occupational UV exposure and BCC occurrence. PubMed (up to 28 January 2011) was searched, supplemented by hand searching and consultation of experts in the field. The association between occupational UV exposure and BCC risk is presented as odds ratios (ORs). A random‐effects meta‐analysis and sensitivity analysis including meta‐regression on study‐specific covariates were performed. Results Twenty‐four relevant epidemiological studies (five cohort studies, 19 case–control studies) were identified. Twenty‐three studies reported sufficient data to be included in the meta‐analysis. The pooled OR for the association between outdoor work and BCC risk was 1·43 (95% confidence interval 1·23–1·66; P = 0·0001). Studies adjusting for sex (P < 0·0001) and individual nonoccupational UV exposure (P = 0·014) showed a significantly stronger association of occupational UV exposure and BCC risk. Meta‐regression revealed a significant inverse relationship between occupational UV radiation exposure and BCC risk with latitude (P = 0·015). Conclusions Published epidemiological literature indicates that outdoor workers are at significantly increased risk for BCC. This finding is highly relevant for health policy to stimulate the implementation of effective prevention strategies.     

Is it possible to improve the patch‐test diagnostics for isocyanates? A stability study of petrolatum preparations of diphenylmethane‐4,4′‐diisocyanate and polymeric diphenylmethane diisocyanate

We have previously shown that the concentration of diphenylmethane-4,4'-diisocyanate (4,4'-MDI) in commercial test preparations was so low that patch testing with the same was not reliable. The stability of 4,4'-MDI in petrolatum (pet.) was compared with pet. preparations of polymeric diphenylmethane diisocyanate (PMDI), which consists of a complex mixture of monomeric isomers and oligomers of MDI. Preparations of 4,4'-MDI and PMDI were stored under 3 different conditions, i.e. at room temperature, refrigerated and frozen. They were analysed continuously during 1 year with regard to the content of 4,4'-MDI, 3-ring oligomers and 4-ring oligomers using liquid chromatography-mass spectrometry. PMDI preparations kept frozen were stable for a year. All other preparations failed to fulfil the requirements of stability, i.e. +/-20% of the initial concentration. Storage in a freezer prolonged the lifetime for 4,4'-MDI. The decrease in concentration for preparations kept at room temperature and refrigerated was less rapid in PMDI preparations than in 4,4'-MDI preparations. PMDI preparations are better suited for patch testing patients exposed to MDI because they are more stable and homogeneous than 4,4'-MDI preparations. They better reflect possible allergens that workers are exposed to because products used in industry contain both monomers and oligomers.     

Is metronidazole 0.75% gel effective in the treatment of seborrhoeic dermatitis? A double-blind, placebo controlled study

The study aimed to evaluate the effectiveness of metronidazole 0.75% gel in patients with mild and moderate seborrhoeic dermatitis. Sixty-seven patients with seborrhoeic dermatitis were enrolled. Cases were randomly treated with metronidazole 0.75% gel or placebo for four weeks and were additionally followed up for another four weeks. Patients were evaluated by scoring before the treatment, once a week during the treatment and twice after the cessation of the treatment within a 15-day interval. Furthermore, patient satisfaction and doctor global evaluation were done at the end of the treatment and of the study as well. In the metronidazole group 33 patients (median age: 26, total severity score: 15.0 +/- 11.0 (median +/- interquartile range) and in the placebo group 34 patients (median age: 26, total severity score: 13.0 +/- 7.5) were enrolled in the study. Three patients from the metronidazole group and four patients from the placebo group did not attend to follow-up visits. Erythema, scales, papule, pruritus and the total severity scores in both group decreased significantly during the treatment when compared with the basal levels (p < 0.05). There was no difference between the two groups in terms of efficacy (p > 0.05). Total severity scores were found as 7.33 +/- 1.08 and 6.43 +/- 0.93 in the metronidazole and placebo groups at the end of the treatment, respectively. After the cessation of the treatment, all scores had increased rapidly. Total severity scores were 10.40 +/- 1.54 and 11.20 +/- 1.53 in the metronidazole and placebo groups one month after the cessation of the treatment, respectively. Both metronidazole 0.75% gel and the placebo were well tolerated by the patients. In conclusion, in the treatment of seborrhoeic dermatitis, administration of metronidazole 0.75% gel is well tolerated but it is only as effective as placebo and the disease severity quickly returns to the basal levels after the cessation of treatment.     

Can St John's wort (hypericin) ingestion enhance the erythemal response during high‐dose ultraviolet A1 therapy?

Background St John's wort (SJW) is widely used as a treatment for depression. A phototoxic reaction, due to its content of hypericin, can occur in animals and in cell culture, and has been reported in humans. Hypericin displays absorption within the ultraviolet (UV) A1 spectrum and there may therefore be a potential for phototoxicity if taken during high‐dose UVA1 therapy. Objectives To assess the phototoxicity risk of SJW ingestion. Methods Eleven adult volunteers of skin types I and II were exposed to a geometric dose series of UVA1 irradiation from a high‐output source (Dermalight Ultra 1; Dr Hönle, Martinsreid, Germany; irradiance 70–77 mW cm^?2) on the photoprotected lower back skin at eight 1·5‐cm² test areas. Irradiation was carried out at baseline and after 10 days of SJW extract 1020 mg (equivalent to 3000 µg of hypericin) daily. Four, 8, 24 and 48 h after each exposure, the minimal erythema dose (MED) and the presence or absence of pigmentation were recorded visually and erythema was assessed objectively with an erythema meter. Results The median MED and D_0·025, an objective measure of MED, were lower at all time‐points after SJW ingestion. The visual erythemal peak (lowest median MED), which was seen at 8 h postirradiation, was lower after SJW (median 14 J cm^?2, range 10–56) than at baseline (median 20 J cm^?2, range 14–56) (P = 0·047). Similarly, the median D_0·025 at 8 h postirradiation was lower after SJW (median 22·0 J cm^?2, range 15·2–53·9) than at baseline (median 33·7 J cm^?2, range 22·9–136·0) (P = 0·014). The MED and D_0·025 were also significantly different at the 48‐h and 4‐h time‐points, respectively. Significance was not reached at the 24‐h time‐point. Median intensity of postirradiation erythema increased at all time‐points after ingestion of SJW. Despite these differences, the maximum slope of the dose–response curve was not increased after SJW ingestion. Conclusions These data suggest that SJW extract has the potential to lower the erythemal threshold to UVA1 irradiation in a significant proportion of individuals and highlight the importance of ascertaining a full drug history, including herbal remedies, before initiating UVA1 phototherapy.     

Does interleukin‐33 level correlate with the activity of Pemphigus vulgaris?: A case‐control study

Pemphigus is a group of immune‐mediated blistering diseases of skin and mucus membrane caused by destruction of the intercellular junction (desmosomes) by autoantibodies. Pemphigus vulgaris (PV) is considered the most common type of all pemphigus family. Various cytokines play a major role in pemphigus pathogenesis. Interleukin‐33 (IL‐33) role has been studied in various autoimmune diseases as; psoriasis and rheumatoid arthritis, yet it has not been studied in Egyptian patients with PV. The study aimed to evaluate the possible role of IL‐33 in PV by assessing its level in the serum using ELISA and to detect its correlation with activity score using Pemphigus Disease Area Index (PDAI). Forty‐four patients with PV and 36 age and sex‐matched healthy controls were enrolled in the study. After full history taking and complete dermatological examination, the severity score was calculated using PDAI, then serum samples were taken from each patient and control subjects and subjected to quantitative measurement of serum IL‐33 using ELISA. Serum level of IL‐33 is significantly raised in PV patients compared to control subjects (P‐value = .007). The level of IL‐33 was found to be strongly correlated with the activity of the disease measured by PDAI. IL‐33 might have a role in PV pathogenesis as shown by its rising level in PV patients. In addition, serum level of IL‐33 is strongly correlated with the activity of PV. Thus, we suspect that IL‐33 can be used as marker for monitoring PV severity and measuring treatment efficacy.     

Long‐term results of acitretin therapy for hidradenitis suppurativa. Is acne inversa also a misnomer?

Background Hidradenitis suppurativa (HS) is a distressing chronic inflammatory skin disorder which affects predominantly the groins and axillae. In analogy to acne, oral isotretinoin has been considered in the treatment of HS, although there are strong indications that this drug has only a very limited therapeutic effect. During the past 25 years scattered case reports have described promising results of treatment with acitretin. Objectives To evaluate the long‐term efficacy of acitretin monotherapy. Methods A retrospective study in 12 patients with severe, recalcitrant HS who were treated with acitretin for 9–12 months at one Dermatology Centre in the Netherlands between 2005 and 2007 and were followed up to 4 years. The patients were men and infertile women. The efficacy of the treatment was rated by the patients on global maximum pain of nodules and abscesses on a visual analogue scale (VAS) as well as by physician global assessment. Results All 12 patients achieved remission and experienced a significant decrease in pain as assessed by VAS. In nine patients long‐lasting improvement was observed, with no recurrence of lesions after 6 months (n = 1), 1 year (n = 3), > 2 years (n = 2), > 3 years (n = 2) and > 4 years (n = 1). Conclusions Acitretin appears to be an effective treatment for refractory HS, leading to reduction of pain from painful nodules and reducing the extent of the disease for a prolonged period.     

Topical aminolaevulinic acid‐based photodynamic therapy as a treatment option for psoriasis? Results of a randomized,observer‐blinded study

BACKGROUND: Topical aminolaevulinic acid-based photodynamic therapy (ALA-PDT) has recently been tried in small open studies for several inflammatory dermatoses including psoriasis. OBJECTIVES: The purpose of this randomized, within patient comparison study was to investigate whether topical ALA-based PDT using a range of light doses can induce a satisfactory response in localized psoriasis. PATIENTS AND METHODS: Twenty-nine patients with chronic plaque type psoriasis were enrolled in the study. After keratolytic pretreatment three psoriatic plaques in each patient were randomly allocated to PDT with 1% ALA and a light dose of 5 J cm(-2), 10 J cm(-2) or 20 J cm(-2), respectively. Treatment was performed twice weekly until complete clearance or for a maximum of 12 irradiations. As a measure of clinical response the psoriasis severity index (PSI) of the three target plaques was assessed separately by an observer blinded to the treatment at baseline, before each PDT treatment and 3-4 days after the last irradiation. RESULTS: Eight patients withdrew prematurely from the study. Keratolytic pretreatment alone reduced the baseline PSI in all three dose groups by about 25%. Subsequent PDT with 20 J cm(-2) resulted in a final reduction of PSI by 59%, PDT with the lower doses of 10 J cm(-2) and 5 J cm(-2) decreased the baseline PSI by 46% and 49%, respectively. The difference in clinical efficacy between 20 J cm(-2) and 10 J cm(-2) or 5 J cm(-2) was statistically significant (P = 0.003; P = 0.02), whereas no difference was found between 10 J cm(-2) and 5 J cm(-2) (P = 0.4). All patients reported some degree of PDT-induced stinging or burning during irradiation. CONCLUSIONS: The unsatisfactory clinical response and frequent occurrence of pain during and after irradiation renders topical ALA-based PDT an inadequate treatment option for psoriasis.     

Is there a role for infliximab in the current therapy of hidradenitis suppurativa? A report of three treated cases

BACKGROUND: Hidradenitis suppurativa is one of the follicular occlusion diseases favoring the flexural areas of the body. Because of the past failure of medical therapy, surgery is today the definitive therapeutic approach. There is a need for effective medical anti-inflammatory therapy to control the disease and minimize the pathologic and socioeconomic consequences of the disease process. Generally the patients fail to respond to topical or systemic antibiotics and retinoids. Temporary responses are achieved with intralesional steroids and cyclosporin. METHODS: The association of hidradenitis suppurativa with inflammatory bowel disease permitted the opportunity to utilize infliximab and to observe not only its impact on the bowel, but also skin. RESULTS: Infliximab dramatically and favorably impacted on three cases of hidradenitis, but also in one of the patients who also had pyoderma gangrenosum. CONCLUSIONS: Infliximab appears to be an effective medical approach to the management of hidradenitis suppurativa and also to prepare the patient for "curative" surgery. However, one must be cognizant of the potential of acquired drug resistance or adverse drug reactions, which can be minimized by "no vacations" from this systematic therapy and the use of methotrexate to minimize the above potential problems.     

Hair transplantation for therapy‐resistant alopecia areata of the eyebrows: Is it the right choice?

Alopecia areata is a common skin disorder of presumed autoimmune etiology and it usually shows an unpredictable course. Treatment of alopecia areata is challenging. There is very little information on the use of surgical therapies for the treatment of alopecia areata in the medical published work. A 24-year-old male patient was referred to a private hair transplantation clinic owned by one of the authors for the treatment of therapy-resistant alopecia areata affecting both eyebrows. He had quickly lost all body hair 4 years prior beginning from the scalp. He received psoralen and ultraviolet A (PUVA) therapy for alopecia universalis and all body hair re-grew except his eyebrows. Alopecia areata was stable for the 18 months following the last medical treatment he received. Because there was no response to various medical therapeutic agents, we decided to transplant occipital hairs to the eyebrow area. After the patient understood and accepted all risks, occipital hairs were transplanted to the eyebrows by using the follicular unit extraction technique. Postoperatively, the patient did not receive any topical or systemic therapies for alopecia areata. Although 40% hair re-growth was detected in his eyebrows at 1 year postoperation, this rate was 80% by 2 years postoperation. However, there was resistance to re-growth in the medial eyebrow regions. New eyebrows grew as occipital hairs and required trimming. His satisfaction from the surgical procedure was 90% at the end of the 24th postoperative month. Surgical treatment of diseases like alopecia areata is still controversial. Our case report offers an additional contribution to the published work on the surgical methods used in the treatment of stable alopecia areata.