Showing papers in "Journal of The European Academy of Dermatology and Venereology in 2013"

European guidelines for topical photodynamic therapy part 1: treatment delivery and current indications - actinic keratoses, Bowen's disease, basal cell carcinoma.

Abstract: Topical photodynamic therapy (PDT) is a widely used non-invasive treatment for certain non-melanoma skin cancers, permitting treatment of large and multiple lesions with excellent cosmesis. High efficacy is demonstrated for PDT using standardized protocols in non-hyperkeratotic actinic keratoses, Bowen’s disease, superficial basal cell carcinomas (BCC) and in certain thin nodular BCC, with superiority of cosmetic outcome over conventional therapies. Recurrence rates following PDT are typically equivalent to existing therapies, although higher than surgery for nodular BCC. PDT is not recommended for invasive squamous cell carcinoma. Treatment is generally well tolerated, but tingling discomfort or pain is common during PDT. New studies identify patients most likely to experience discomfort and permit earlier adoption of pain-minimization strategies. Reduced discomfort has been observed with novel protocols including shorter photosensitizer application times and in daylight PDT for actinic keratoses.

Cardiovascular morbidity and mortality in psoriasis and psoriatic arthritis: a systematic literature review.

Abstract: Previous epidemiological studies have demonstrated a high prevalence of cardiovascular (CV) risk factors in psoriasis patients, including metabolic syndrome, cigarette smoking, obesity, hypertension, diabetes mellitus, insulin resistance and dyslipidaemia. An increase in CV morbidity and mortality attributable to psoriasis is still under question. Primary objective: to assess CV morbidity and mortality in psoriasis and psoriatic arthritis (PsA) including stroke, coronary artery disease, myocardial infarction (MI) and peripheral artery disease. Secondary objectives: to assess if psoriasis per se is an independent CV risk factor and if psoriasis severity is a predictor of CV risk. We also evaluated the effect of conventional systemic treatments for psoriasis on CV mortality. A systematic literature search was carried out from 1980 to December 2011, in the Embase, Medline and Cochrane Library databases, in English and French using a combination of keywords including (Psoriasis) OR (Psoriatic arthritis) AND (Myocardial infarction) OR (Coronaropathy) OR (Stroke) OR (Cardiovascular) AND (Methotrexate) AND (Ciclosporin) AND (Retinoids). Of the 929 identified references, 33 observational studies evaluating the rates of cardiovascular events (CVE) in patients with psoriasis and PsA compared with controls were selected. Meta-analysis of both cohort and cross-sectional studies showed an increased risk of MI with Odds Ratio (OR) of 1.25 (95% CI 1.03–1.52) and 1.57 (95% CI 1.08–2.27) in psoriasis and PsA, respectively, compared with the general population. The risk of MI was more pronounced for patients having severe psoriasis and for patients with psoriasis of early onset. It remained significantly elevated after controlling for major CV risk factors. The meta-analysis identified a small, but significant association between psoriasis, PsA and coronary artery disease with an OR between 1.19 (95% CI 1.14–1.24) for cross-sectional studies, 1.20 (95% CI 1.13–1.27) for cohort studies and 1.84 (95% CI 1.09–3.09) for case–control studies. The risk of coronary artery disease seemed to be more pronounced in patients with severe psoriasis and in patients with psoriasis of early onset. The meta-analysis assessing the risk of stroke gave inconclusive results: analysis of cross-sectional studies suggested that psoriasis patients had a slightly higher risk of stroke with an OR of 1.14 (95% CI 1.08–1.99), whereas the meta-analysis of cohort studies failed to show an association. There was also an increased risk of peripheral artery disease in psoriasis. No significant increased risk of CV mortality could be shown for both psoriasis and PsA patients. The use of methotrexate was associated with a reduced incidence of cardiovascular disease in two studies. The use of etretinate was associated with a reduction of CV mortality in one study. Potential selection bias such as the ‘healthy user effect’ prevents from drawing definite conclusions. There may be a small, but significant increased risk of CVE, but not of CV mortality in psoriasis and PsA patients. The psoriasis attributable risk remains difficult to assess due to confounding factors. The moderate quality of CV risk factors reporting in studies should be acknowledged. In addition, heterogeneity in study design, outcome definition and assessment represent major limitations. Nevertheless, screening and management of CV risk factors are important in psoriasis.

Depression in patients with hidradenitis suppurativa.

Abstract: Background Hidradenitis suppurativa (HS) is a chronic recurrent inflammatory skin disease with abscess formation and scarring predominantly in the inverse areas. The disease is often difficult to treat and patients experience a decreased quality of life (QoL). It is hypothesized that depression is more common in HS patients than among other dermatological patients. Objectives To evaluate the prevalence of depression in patients with HS. Methods In total 211 HS patients were included in the study and 233 were dermatological control patients. Their QoL and depression scores were assessed using the Dermatology Life Quality Index (DLQI) and the Major Depression Inventory (MDI) questionnaires. HS severity was recorded with a questionnaire and Hurley stages were extracted from the case records. Results The DLQI was significantly higher for HS patients than for the control patients, 8.4 +/- 7.5 vs. 4.3 +/- 5.6 (P

Risk of cancer in psoriasis: a systematic review and meta-analysis of epidemiological studies

Abstract: The relationship between psoriasis and increased cancer risk is debated. The aim of this study was to evaluate if there is an increase in the background risk of cancer in psoriasis patients compared with the general population. A systematic literature search was performed on PubMed, Embase and Cochrane databases, using the keywords ‘Psoriasis [Majr] AND Neoplasms’, from 1980 to January 2012. Meta-analysis was performed based on observational studies showing consistency in cancer risk assessment methods. Of the 1080 articles retrieved, 37 references were selected. There may be an increased risk of some solid cancers in psoriasis: respiratory tract cancer [standardized incidence ratio (SIR) = 1.52, 95% confidence interval (CI) 1.35–1.71], upper aerodigestive tract cancer (SIR = 3.05, 95% CI 1.74–5.32), urinary tract cancer (SIR = 1.31, 95% CI 1.11–1.55) and liver cancer (SIR = 1.90, 95% CI 1.48–2.44). The risk of non-Hodgkin lymphoma appears slightly increased in psoriasis (SIR = 1.40, 95% CI 1.06–1.86). Psoriasis patients have an increased risk of squamous cell carcinoma (SIR = 5.3, 95% CI 2.63–10.71) and basal cell carcinoma (SIR = 2.00, 95% CI 1.83–2.20), whereas the risk of melanoma is not increased. There was a large heterogeneity in studies assessing cancer risk in psoriasis preventing from including all studies in meta-analysis. This systematic literature review shows a small increased risk of some solid cancers in psoriasis, especially those linked to alcohol drinking and cigarette smoking. A higher risk of non-melanoma skin cancers, especially squamous cell carcinoma, is shown, mainly due to previous exposure to 8-methoxypsoralen-ultraviolet-A (PUVA), ciclosporin and possibly methotrexate.

Effect of tranexamic acid on melasma: a clinical trial with histological evaluation.

Abstract: Background Melasma is associated with epidermal hyperpigmentation, weak basement membrane, vascular proliferation and increased numbers of mast cell. Tranexamic acid (TXA), a plasmin inhibitor, is reported to improve melasma when injected locally. However, the effects of oral and topical TXA on melasma have not been well studied and the underlying mechanism remains unclear. Objectives To elucidate the effects of oral and topical TXA on melasma. Methods A clinical study was conducted with 25 women for 8 weeks from March to July 2010. Volunteers were instructed to take two TXA tablets three times a day and apply a TXA topical agent twice a day for 8 weeks. Skin pigmentation and erythema was measured using a Mexameter® during each visit and skin biopsies were collected from eight subjects before and 8 weeks after treatment. Fontana-Masson, anti-CD31, antitryptase and antitype IV collagen staining was performed. Results Twenty-two subjects completed the study and no serious adverse events occurred during the study period. The mean lesional melanin index (MI) scores decreased significantly. Interestingly, the MI scores for the perilesional skin increased. The erythema index scores of lesional and perilesional skin also showed a similar pattern. Histological analysis showed significant reduction of epidermal pigmentation, vessel numbers and mast cell counts. Type IV collagen staining was not observed in all specimens. Conclusion TXA decreased epidermal pigmentation associated with melasma and also reversed melasma-related dermal changes, such as vessel number and increased numbers of mast cells.

Long-term efficacy of ustekinumab in patients with moderate-to-severe psoriasis treated for up to 5 years in the PHOENIX 1 study

Abstract: Background Ongoing evaluation of biological agents in patients with moderate-to-severe psoriasis is needed to support their long-term use. Objective To evaluate long-term efficacy and safety of ustekinumab through 5 years in the PHOENIX 1 study. Methods Patients were randomized to placebo or ustekinumab (45 mg or 90 mg) at Weeks 0, 4 and every-12-weeks thereafter; placebo patients crossed-over to ustekinumab at Week 12. Clinical response through Week 244 was evaluated using the Psoriasis Area and Severity Index (PASI) in the Overall Population (i.e. patients receiving ≥ 1 dose of ustekinumab), Initial Responders (i.e. PASI 75 responders [Weeks 28/40] re-randomized at Week 40 to continue every-12-week maintenance) and Partial Responders (i.e. Results Overall, 68.7% (517/753) of ustekinumab-treated patients completed treatment through Week 244. Initial clinical responses were generally maintained through Week 244 (PASI 75: 63.4% and 72.0%; PASI 90: 39.7% and 49.0%; PASI 100: 21.6% and 26.4%) for patients receiving 45 mg and 90 mg, respectively. Similarly, PASI 75 responses were generally maintained among Initial Responders [79.1% (45 mg) and 80.8% (90 mg)] and Partial Responders [57.6% (45 mg) and 55.1% (90 mg)]. With 3104 patient-years of follow-up, rates of overall adverse events (AEs), serious AEs, serious infections, malignancies and major adverse cardiovascular events were generally consistent over time and comparable between doses. Conclusions Through 5 years of continuous treatment, ustekinumab demonstrated stable clinical response and a safety profile consistent with previous reports.

Relationship between itch and psychological status of patients with atopic dermatitis

Abstract: Background Itching is a cardinal symptom of atopic dermatitis (AD). Objective The study aim was to evaluate the relationships between pruritus and stress, health-related quality of life (HRQoL) and depression in adult patients with AD. Methods Eight-nine patients (30 men and 59 women) with AD were included. Demographic and clinical data were collected. The intensity of pruritus was assessed according to the 10-point Visual Analogue Scale (VAS) and the 4-Item Itch Questionnaire, HRQoL according to Dermatology Life Quality Index, and depression symptoms with Beck’s Depression Inventory (BDI). Stress experienced by patients was evaluated with Social Readjustment Rating Scale and Stress Self-assessment Scale. Results The mean intensity of pruritus according to VAS was 7.9 ± 2.2 points, and according to 4-Item Itch Questionnaire 14.0 ± 4.4 points. The intensity of pruritus was related to the stress experienced by the patients prior to disease exacerbation (ρ = 0.37, P < 0.001). A significant correlation between pruritus and HRQoL was also found (VAS: ρ = 0.5, P < 0.001, 4-Item Itch Questionnaire: ρ = 0.5, P < 0.001) as well as between pruritus and BDI (VAS: ρ = 0.44, P < 0.001, 4-Item Itch Questionnaire: ρ = 0.51, P < 0.001). Patients with symptoms suggesting depression had more intense pruritus compared with the rest of patients (VAS: 9.1 ± 1.6 vs. 7.6 ± 2.2 points, P = 0.004; 4-Item Itch Questionnaire: 17.3 ± 2.5 vs. 13.1 ± 4.4 points, P < 0.001). Conclusions Itching intensity in AD plays an important role in determining patients’ psychosocial well-being. Patients with atopic dermatitis require an effective, long-term antipruritic therapy to improve their QoL and reduce the potential risk of depression.

Meta-analysis of digital dermoscopy follow-up of melanocytic skin lesions: a study on behalf of the International Dermoscopy Society

Abstract: It has been demonstrated that dermoscopic monitoring of melanocytic lesions allows for the recognition of melanoma in early stages while minimizing the excision of benign lesions. However, it is still pending to determine the real impact of digital follow-up in the clinical management of pigmented lesions. To assess the evidence of follow-up of melanocytic skin lesions with digital dermoscopy in the management of individuals at risk for melanoma by performing a meta-analysis. Medline database was screened, no limits in terms of date or language were applied. Original studies were selected when the following criteria were met: performed in clinical setting with clinical and dermoscopic evaluation made by physicians, data regarding population characteristics included, follow-up strategy used described. Fourteen of 145 retrieved references were retained. Included studies account for a total of 5787 patients (mean 445 per study) and 52 739 lesions monitored (mean per study 4057; range 272–11 396) with a mean of 12 lesions monitored per patient; a total of 4388 lesions (8.3%) were excised. The mean length of follow-up was 30 months. A mean of <1 lesion was excised per patient along the surveillance period. The number needed to monitor (NNM) ranged from 31 to 1008 (mean: 348) among eligible studies. For every additional month of monitoring, 1additional melanoma was detected. Using digital dermoscopy follow-up, the proportion of in situ melanoma and thin melanomas are higher than expected in general population. Chances to detect a melanoma during surveillance increase as the length of follow-up extends.

Re-evaluation of the risk for major adverse cardiovascular events in patients treated with anti-IL-12/23 biological agents for chronic plaque psoriasis: a meta-analysis of randomized controlled trials

Abstract: Objective To detect a detrimental or beneficial effect of anti-IL-12/23 biological agents (ustekinumab and briakinumab) for the treatment of chronic plaque psoriasis on major adverse cardiovascular events (MACEs). Design Systematic review and meta-analysis MEDLINE, EMBASE, the Cochrane Skin Group Specialised Register, Cochrane Central Register of Controlled Trials (CENTRAL) in The Cochrane Library, SciVerse Scopus and ongoing trial registries were searched from inception until December 2011. Search strategy, eligibility criteria, data and statistical analysis methods were defined prior to the literature search. Randomized, placebo-controlled, double-blind, monotherapy studies with safety data for MACEs of IL-12/23 antibodies in adults were eligible for inclusion. Studies of psoriatic arthritis were excluded. Information from each study was extracted independently by two reviewers, using a standardized data extraction form. The primary outcome measure was the number of MACEs during the placebo-controlled phase of treatment. Results MACEs include myocardial infarction, cerebrovascular accident or cardiovascular death. No statistical heterogeneity across the studies using the I2 statistic (I2 = 0) was found. We employed Peto one-step method to determine odds ratios and quantify a possible detrimental or beneficial association of IL-12/23 antibodies treatment with MACEs. We found a possible higher risk of MACEs in those patients treated with IL-12/23 antibodies compared with those at placebo (OR = 4.23, 95% CI: 1.07–16.75, P = 0.04). This study is unaffected by non-reporting of outcomes with no events. Conclusion Compared with placebo, there was a significant difference in the rate of MACEs observed in patients receiving anti-IL-12/23 biological agents.

Adult female acne: a new paradigm

Abstract: In the adult female, acne is a chronic condition with a substantial negative psychological, social and emotional impact. Based on time of onset, two subtypes of adult female acne are recognized: 'persistent acne' is a continuation of the disease from adolescence, while 'late-onset acne' first presents in adulthood. The morphological characteristics of adult female acne are often distinct from adolescent acne. In adults, inflammatory lesions (particularly papules, pustules and nodules) are generally more prominent on the lower chin, jawline and neck, and comedones are more often closed comedones (micro cysts). Adult acne is mainly mild-to-moderate in severity and may be refractory to treatment. A holistic approach to acne therapy should be taken in adult females, which combines standard treatments with adjunctive therapy and cosmetic use. A number of factors specific to the adult female influence choice of treatment, including the predisposition of older skin to irritation, a possible slow response to treatment, a high likelihood of good adherence, whether of child-bearing age, and the psychosocial impact of the disease. Adherence to therapy should be encouraged through further patient education and a simplified regimen that is tailored to suit the individual patient's needs and lifestyle. This article reviews the specific characteristics of adult female acne, and provides recommendations for acne therapy in this patient group.

Clinical patterns and epidemiological characteristics of facial melasma in Brazilian women.

Abstract: Background Melasma is a common acquired chronic hypermelanosis of sun-exposed areas which significantly impacts quality of life. There are few epidemiological studies in medical literature concerning these patients. Objective Characterize clinical and epidemiological data on Brazilian female patients with melasma. Methods A semi-structured questionnaire was administered to melasma patients treated at a dermatology clinic between 2005 and 2010. Association between variables was performed by multivariate regression models. Results We assessed 302 patients; intermediate skin phototypes III (34.4%) and IV (38.4%) were prevalent. Mean disease onset age was 27.5 ± 7.8 years and familiar occurrence of melasma was identified in 56.3%. The most commonly reported trigger factors were pregnancy (36.4%), contraceptive pills (16.2%) and intense sun exposure (27.2%). Preferred facial topographies were zygomatic (83.8%), labial superior (51.3%) and frontal (49.7%). Pregnancy induced melasma has been associated to early disease (OR = 0.86) and number of pregnancies (OR = 1.39). Childbearing was correlated to melasma extension. Older disease onset age was associated to darker skin phototypes. Co-occurrence of facial topographies supported clinical classification as centrofacial and peripheral melasma. Conclusion This population was characterized by: a high prevalence in adult females, intermediate skin phototypes, disease precipitation by hormonal stimulus and familiar genetic influence.

Metformin for the treatment of hidradenitis suppurativa: a little help along the way

Abstract: Background Despite recent insights into its aetiology, hidradenitis suppurativa (HS) remains an intractable and debilitating condition for its sufferers, affecting an estimated 2% of the population. It is characterized by chronic, relapsing abscesses, with accompanying fistula formation within the apocrine glandbearing skin, such as the axillae, ano-genital areas and breasts. Standard treatments remain ineffectual and the disease often runs a chronic relapsing course associated with significant psychosocial trauma for its sufferers. Objective To evaluate the clinical efficacy of Metformin in treating cases of HS which have not responded to standard therapies. Methods Twenty-five patients were treated with Metformin over a period of 24 weeks. Clinical severity of the disease was assessed at time 0, then after 12 weeks and finally after 24 weeks. Results were evaluated using Sartorius and DLQI scores. Results Eighteen patients clinically improved with a significant average reduction in their Sartorius score of 12.7 and number of monthly work days lost reduced from 1.5 to 0.4. Dermatology life quality index (DLQI) also showed a significant improvement in 16 cases, with a drop in DLQI score of 7.6. Conclusion Metformin helps control HS with minimal side effects and good patient compliance and can represent a further agent in the spectrum of treatments available in the treatment of this disease.

Scleromyxedema: A multicenter study of characteristics, comorbidities, course, and therapy in 30 patients

Abstract: Background Scleromyxedema is associated with a monoclonal gammopathy and other comorbidities. Its prognostic and therapeutic features are poorly documented because most reports deal with single cases or small series. Objective We sought to describe the characteristics of patients with scleromyxedema regarding demographics, clinical characteristics, comorbidities, therapeutic interventions, and course. Methods We conducted a retrospective and prospective multicenter study. Results We identified 30 patients with scleromyxedema (17 men and 13 women). The mean age at diagnosis was 59 years. The mean delay between disease onset and diagnosis was 9 months. Monoclonal gammopathy was detected in 27 patients. Extracutaneous manifestations were present in 19 patients including neurologic (30%), rheumatologic (23.3%), and cardiac (20%) manifestations. Two patients developed hematologic malignancies. The most common therapies included oral steroids and intravenous immunoglobulins. Although corticosteroids were ineffective, intravenous immunoglobulins (alone or in combination with other drugs) induced complete remission in 4 and partial remission in 9 patients with a mean treatment duration of 2 years. In all, 21 patients were followed up for a mean period of 33.5 months, at which time 16 patients were alive, 12 with and 4 without skin disease. Five patients died: 2 with dermatoneuro syndrome and 1 each with myeloid leukemia, Hodgkin lymphoma, and myocardial insufficiency. Limitations This is mainly a retrospective study. Conclusions Our study confirms that scleromyxedema is a chronic and unpredictable disease with severe systemic manifestations leading to a guarded prognosis. There is no specific definitive treatment. Our data support the contention that intravenous immunoglobulin is a relatively effective and safe treatment. The response is not permanent and maintenance infusions are required.

Prurigo as a symptom of atopic and non-atopic diseases: aetiological survey in a consecutive cohort of 108 patients.

Abstract: Background Prurigo nodularis Hyde (PN) is a highly pruritic condition due to a vicious circle of repeated itching and scratching. There are no representative clinical studies investigating comorbidities in a large collective of PN patients. Objective This pilot study aimed to investigate the exact distribution of the coexisting diseases in a large representative consecutive cohort of PN patients. Methods A total of 108 PN patients (36.1% male; mean age of 61.5 ± 16.7 years) were enrolled in the study. Results In 87.0% of patients, diseases underlying PN could be established (18.5% skin disease, 7.4% systemic origin, 1.8% neurological diseases, 59.3% mixed origin). Due to several possible causative co-factors, the majority of patients were classified in the group of mixed origin (59.3%). In 53.1% of these patients, at least one dermatological factor was involved in the induction of PN. Interestingly, nearly half (46.3%) of all PN patients had either an atopic predisposition or atopic dermatitis as a single cause of PN (18.5%) or as one co-factor of PN of mixed origin (27.8%). Considering the different underlying diseases, there was no significant age or gender difference. Conclusion PN does not seem to represent a characteristic symptom of one disease only. Multiple pruritogenic diseases are linked to evolution and improvement of PN upon treatment. Atopic predisposition is a major factor in nearly half of PN patients. The large collective of the present study helped detect a broad range of underlying diseases and thus to provide recommendations for rational diagnostics.

2012 European guideline for the management of anogenital warts

Abstract: Background Although new HPV vaccines have been developed and are in the process of implementation, anogenital warts remain a very frequent problem in clinical practice. Objective We wished to update previously published European guidelines for the management of anogenital warts. Methods We performed a systematic review of randomized controlled trials for anogenital warts. The primary data were analyzed and collated, and the findings were formulated within the structure of a clinical guideline. The IUSTI Europe Editorial Board reviewed the draft guideline which was also posted on the web for comments which we incorporated into the final version of the guideline. Results The data confirm that only surgical therapies have primary clearance rates approaching 100%. Recurrences, including new lesions at previously treated or new sites, occur after all therapies, and rates are often 20–30% or more. All therapies are associated with local skin reactions including itching, burning, erosions and pain. Conclusions Physicians treating patients with genital warts should develop their own treatment algorithms which include local practice and recommendations. Such patient level management protocols should incorporate medical review of cases at least every 4 weeks, with switching of treatments if an inadequate response is observed. First episode patients should be offered sexually transmitted disease screening. Management should include partner notification and health promotion.

Nail digital dermoscopy (Onychoscopy) in the diagnosis of onychomycosis

Abstract: Background Distal subungual onychomycosis and traumatic onycholysis are the most common causes of toenail abnormalities, and differential diagnosis is often impossible without mycology. Objectives To identify and describe dermoscopic signs specific for distal subungual onychomycosis that could facilitate its diagnosis and differentiation from traumatic mycologically negative onycholysis and to determine the sensitivity and specificity of these dermoscopic features. Methods We performed a retrospective study at the Outpatient Consultation for Nail Diseases of the Department of Dermatology of the University of Bologna. Dermoscopic digital images of 57 consecutive patients who underwent global photography, videodermoscopy and mycological examination for onycholysis of a single toenail between 1 December, 2010 and 30 June, 2011, were evaluated and compared. Digital dermoscopic images of onycholysis of the great toenail were evaluated for the presence of peculiar dermoscopic features. The presumptive dermoscopic diagnosis was compared with results of mycology. Results Evaluation of videodermoscopic images allowed us to identify three recurring peculiar dermoscopic features, two of which were present only in distal subungual onychomycosis (jagged proximal edge with spikes of the onycholytic area and longitudinal striae) and one only in traumatic onycholysis (linear edge – without spikes – of the onycholytic area). Conclusions We found distinctive dermoscopic signs that are exclusive to distal subungual onychomycosis and to traumatic onycholysis. Detection of these signs is simple and can, in selected cases, help to avoid mycology.

Alcohol consumption and psoriasis: a systematic literature review.

Abstract: The association between alcohol consumption and psoriasis has been frequently discussed since the 1980s, but no systematic review has been elaborated on the subject so far. The aim of this systematic literature review was to assess whether alcohol consumption is more prevalent in psoriasis patients than in the general population and whether alcohol consumption is a risk factor of psoriasis. A systematic literature search was carried out in the Medline, Embase and Cochrane databases using the keywords 'psoriasis' AND 'alcohol drinking' OR 'alcohol-related disorders'. The search was then enlarged with the keywords 'psoriasis' AND 'risk factor' OR 'comorbidity'. Altogether 911 references in English and French were found. Out of these, 837 articles were excluded by reading the abstract and 46 by reading the article. A total of 28 articles were selected. Alcohol consumption in psoriasis patients versus the general population: 23 studies were selected; 18 concluded that alcohol consumption was more prevalent in psoriasis patients, and 5 did not. Three studies compared the prevalence of excessive drinking using a questionnaire on alcohol dependence (CAGE or Self-administered alcohol screening test (SAAST)) or with quantitative criteria for excessive drinking. In these studies, excessive drinking was more prevalent among psoriasis patients than in the general population. Other articles studied the quantity and type of alcohol consumed. In 11 studies, psoriasis patients consumed more alcohol than the controls. Four other studies showed excessive alcohol consumption in psoriasis patients without control group comparison. Conversely, five studies identified no difference in alcohol consumption between psoriasis patients and the general population. The heterogeneity in the measurement of alcohol consumption did not allow performing meta-analysis. Alcohol as a risk factor for psoriasis: only five studies were selected. In four of these studies alcohol was found to be a risk factor for psoriasis. Alcohol consumption seems to be greater in psoriasis patients than in the general population. However, there is not enough evidence to establish whether alcohol consumption is indeed a risk factor for psoriasis.

4-n-butylresorcinol, a highly effective tyrosinase inhibitor for the topical treatment of hyperpigmentation.

Abstract: Background Hyperpigmentary disorders like melasma, actinic and senile lentigines are a major cosmetic concern. Therefore, many topical products are available, containing various active ingredients aiming to reduce melanin production and distribution. The most prominent target for inhibitors of hyperpigmentation is tyrosinase, the key regulator of melanin production. Many inhibitors of tyrosinase are described in the literature; however, most of them lack clinical efficacy. Methods We were interested in evaluating the inhibition of skin pigmentation by well-known compounds with skin-whitening activity like hydroquinone, arbutin, kojic acid and 4-n-butylresorcinol. We compared the inhibition of human tyrosinase activity in a biochemical assay as well as inhibition of melanin production in MelanoDerm™ skin model culture. For some compounds, the in vivo efficacy was tested in clinical studies. Results Arbutin and hydroquinone only weakly inhibit human tyrosinase with a half maximal inhibitory concentration (IC50) in the millimolar range. Kojic acid is 10 times more potent with an IC50 of approximately 500 μmol/L. However, by far the most potent inhibitor of human tyrosinase is 4-n-butylresorcinol with an IC50 of 21 μmol/L. In artificial skin models, arbutin was least active with an IC50 for inhibition of melanin production > 5000 μmol/L. Kojic acid inhibited with an IC50 > 400 μmol/L. Interestingly, hydroquinone inhibited melanin production in MelanoDerms with an IC50 below 40 μmol/L, probably due to a mechanism different from tyrosinase inhibition. Again, 4-n-butylresorcinol was the most potent inhibitor with an IC50 of 13.5 μmol/L. In vivo efficacy of 4-n-butyl-resorcinol was confirmed in clinical studies. Subjects with age spots on the forearm treated twice daily two age spots with a formula containing 4-n-butylresorcinol and two control age spots with the corresponding vehicle. Within 8 weeks, 4-n-butylresorcinol reduced visibly the appearance of age spots, while the control spots showed no improvement. A second study showed that 4-butylresorcinol was more effective than 4-hexylresorcinol and 4-phenylethylresorcinol. Conclusion The present in vitro and in vivo data prove the high inhibitory capacity of 4-n-butylresorcinol on human tyrosinase activity, exceeding by far the potency of hydroquinone, arbutin and kojic acid. The resulting clinical improvement of skin hyperpigmentations reveals 4-n-butylresorcinol as a very valuable active compound for the management of pigmentation disorders.

Treatment of frontal fibrosing alopecia and lichen planopilaris: a systematic review

Abstract: Frontal fibrosing alopecia (FFA) is a primary lymphocytic cicatricial alopecia with characteristic clinical pattern of progressive frontotemporal hairline recession, perifollicular erythema and hyperkeratosis and symptoms of itch and burning, occurring mainly in post-menopausal women. FFA is considered a subtype of lichen planopilaris (LPP), based on their identical histopathology. Currently, no evidence-based treatment is available for FFA. Our aim was to determine the effectiveness of available treatment options for FFA, and to identify promising treatment options for future studies. For this, literature search was conducted to find all primary studies on the treatment of FFA and LPP. From the primary studies, data were subtracted and analysed. No randomized controlled trials were found, and one controlled trial. Treatment of 114 patients is described in the literature. They received 10 different regimes, of which oral 5-alpha-reductase inhibitors were provided most often, resulting in good clinical response in 45% of them. Hydroxychloroquine resulted in good clinical response in 30% of the 29 treated patients. Topical corticosteroid preparations are ineffective in FFA. The remaining treatments were all reported in less than 10 patients. For the treatment of LPP, topical corticosteroid preparations are the first line of treatment, followed by oral cyclosporine and systemic corticosteroids, although they are characterized by a high relapse rate. Summarizing, there is currently no effective treatment of FFA, the most effective being oral 5-alpha-reductase inhibitors that possibly affect the accompanying androgenetic alopecia. We argue that oral cyclosporine A might be a good candidate for future studies on the treatment of FFA.

Clinical practice guideline for an integrated approach to comorbidity in patients with psoriasis

Abstract: Background The relationship between psoriasis and associated diseases has drawn particular interest in recent years. To provide appropriate management of psoriasis from an early stage, it is necessary to include prompt diagnosis of concomitant disease and to prevent and treat any comorbidity found. Such an integrated approach also serves to ensure that the drugs used to treat associated diseases do not interfere with the management of psoriasis, and vice versa. Objective To provide the dermatologist a guide focuses specifically on the diagnosis and management of the diseases most often found in patients with psoriasis. Methods The selection of the diseases, and corresponding supporting research, to be included was based on a systematic review of the literature. The recommendations on diagnostic criteria are based on the main clinical practice guidelines for each of the diseases discussed as well as on the recommendations of a clinical expert advisory group. The information regarding the repercussions of psoriasis treatments on associated comorbid diseases was obtained from the summary of product characteristics of each drug. In turn, the statements concerning the impact of the associated diseases, and their treatment, on psoriasis are based on the review of the literature. Results This guide is a precise, easy-to-use tool for systematizing the diagnosis of comorbidity in patients with psoriasis and facilitate decision making regarding referral and treatment of patients diagnosed with an associated disease. Conclusion The application of this guide not only will benefit psoriasis patients’ health and quality of life but it will also optimize available resources.

Obesity, waist circumference, weight change and the risk of psoriasis in US women.

Abstract: Objective To evaluate the associations between body mass index (BMI), weight change, waist circumference, hip circumference and risk of incident psoriasis. Methods A prospective study of female nurses who were followed up over a 12-year period (1996–2008) in Nurses’ Health Study, a cohort of 121 700 US women at the inception in 1976. The study included 67 300 women who responded to a question about a history of physician-diagnosed psoriasis in last 12 years in 2008 (mean age at 1996, 62 years). The primary outcome was self-reported, physician-diagnosed psoriasis. Results During the 12 years of follow-up, there were a total of 809 incident psoriasis cases. There was a graded positive association between BMI (both baseline and updated) and the risk of psoriasis (both P values for trend <0.0001). Compared to women with updated BMI of <25, the multivariate relative risks (RRs) of incident psoriasis were 1.21 (95% CI, 1.03–1.43) for a BMI of 25.0–29.9, 1.63 (95% CI, 1.33–2.00) for a BMI of 30.0–34.9 and 2.03 (95% CI, 1.58–2.61) for a BMI of 35.0 or greater. Higher waist circumference, hip circumference and waist–hip ratio were associated with a higher risk of incident psoriasis, but became non-significant after additionally adjusting for BMI. The BMI at age of 18 years was not associated with the risk of psoriasis. Weight gain since the age of 18 years was associated with an increased risk of psoriasis, and RR of 10 lb gain was 1.08 (95% CI, 1.06–1.11; P < 0.0001). Conclusion This large prospective study indicates that higher BMI and weight gain are risk factors for incident psoriasis in older US women.

European guidelines for topical photodynamic therapy part 2: emerging indications--field cancerization, photorejuvenation and inflammatory/infective dermatoses.

Abstract: In addition to established indications in non-melanoma skin cancer in immunocompetent patients, photodynamic therapy (PDT) has been studied for the treatment, and possible prevention, of superficial skin cancers in immunosuppressed patients. As a topical photosensitizer can be applied over large areas, PDT is also increasingly used for field cancerization in photodamaged skin, with evidence of potential to delay the development of actinic keratoses and basal cell carcinoma, although direct evidence of prevention of invasive squamous cell carcinoma remains limited. PDT has been studied in patch/plaque-stage cutaneous T-cell lymphoma, with efficacy more likely in unilesional disease. Accumulating evidence supports the use of PDT in acne and several other inflammatory/infective dermatoses including cutaneous leishmaniasis, although protocols are still to be refined. Despite proven efficacy, PDT is not widely used in viral/genital warts, where pain during treatment can be intense. PDT is a therapeutic option for photorejuvenation, with improvement in fine wrinkles, mottled hyperpigmentation, roughness and sallowness reported.

Dermoscopy of early stage mycosis fungoides

Abstract: Background Early stage mycosis fungoides (MF) is difficult to be clinically differentiated from chronic dermatitis(CD) in a high proportion of patients. Dermoscopy is a rapid, cheep, non-invasive and widely used method for theevaluation of skin tumours and, recently, of inflammatory skin diseases, as well.Objective To describe the dermoscopic pattern of early stage MF and compare it with the dermoscopic featuresobserved in CD.Methods This was a retrospective study. Dermoscopic images of lesions that were clinically equivocal betweenMF and CD were evaluated for the presence of predefined morphologic criteria. Diagnosis had been histo-pathologically and immunohistochemically confirmed in all cases. Sensitivity, specificity, positive predictive value, andnegative predictive value were calculated for predefined dermoscopic criteria in relation to the diagnosis of mycosisfungoides.Results A total of 67 dermoscopic images were selected for dermoscopic evaluation. Mycosis fungoides lesionsexhibited a characteristic dermoscopic pattern consisting of fine short linear vessels (sensitivity 93.7%, specificity97.1%) and orange-yellowish patchy areas (sensitivity 90.6%, specificity 99.7%). A characteristic vascular structureresembling spermatozoa was also found to be highly specific for the diagnosis of mycosis fungoides. CD wastypified by a different dermoscopic pattern, usually consisting of dotted vessels.Conclusions These observations provide a first indication that early stage MF exhibits a characteristicdermoscopic pattern which is different from CD. Prospective studies with long term follow-up are needed todetermine the value of these dermoscopic criteria in the differentiation between the two entities in the daily routine.Received: 3 January 2012; Accepted: 14 February 2012

Melasma pathogenesis and influencing factors – an overview of the latest research

Abstract: Melasma is an acquired, symmetrical hypermelanosis of the face. The pathogenesis of melasma is complex and the treatment is often challenging with frequent relapses. Genetic background, exposure to ultraviolet radiation, and female sex hormones are classical influencing factors. To the light of the recent literature, other factors could promote melasma lesions. Moreover, there are increasing evidences showing that melanocytes are not the only cells involved, and that other players probably have a key role in the development and the relapses of melasma. Identifying those associated factors should provide new targets for a more efficient treatment of melasma and a better prevention of the relapses.

Perceived relationships between severity of psoriasis symptoms, gender, stigmatization and quality of life.

Abstract: Background Psoriasis is a skin disease with negative physical, psychological and social repercussions for those affected, but we still lack knowledge of how somatic and non-somatic factors directly and indirectly combine to affect patients’ quality of life (QoL). Objectives This study seeks a better understanding of the relations between symptom severity, discomfort, stigmatization, gender and QoL among psoriasis patients. Methods The sample comprised 381 psoriasis patients in inpatient care. Symptom severity and discomfort were measured subjectively with single items. Stigmatization was measured with the Questionnaire on Experience with Skin Complaints. QoL was measured using the Dermatology Life Quality Index (DLQI) and the Short Form-8 Health Survey (SF-8). Results Symptom severity was associated with higher discomfort, stigmatization and lower skin-related QoL. Symptom severity correlated weakly with more general aspects of QoL as measured by the SF-8. Men and women reported different experiences with discomfort, stigmatization and mental aspects of QoL (SF-8 mental component summary score). Some stigmatization parameters function as mediating variables between symptom severity and QoL. Conclusions Our findings suggest that the effect of stigmatization on skin-related QoL is driven by symptom severity and stigmatization combined, whereas its effect on mental health is driven mostly by stigmatization alone. Further, although women and men experience the social impact of psoriasis differently, the effect of stigmatization on QoL is similar for both genders.

Efficacy and safety of apremilast in subjects with moderate to severe plaque psoriasis: results from a phase II, multicenter, randomized, double‐blind, placebo‐controlled, parallel‐group, dose‐comparison study

Abstract: Background Apremilast, a small molecule specific inhibitor of phosphodiesterase 4, works intracellularly to modulate pro-inflammatory and anti-inflammatory mediator production. Objective Assess apremilast efficacy and safety in moderate to severe plaque psoriasis. Methods Phase II, 12-week, multicenter, double-blind, placebo-controlled, parallel-group, dose-comparison study of 259 subjects randomized 1 : 1 : 1 to placebo, apremilast 20 mg QD or apremilast 20 mg BID. Results More subjects receiving apremilast 20 mg BID achieved ≥ 75% reduction in Psoriasis Area and Severity Index (PASI-75) vs. placebo (24.4% vs. 10.3%; P = 0.023). A similar proportion of subjects receiving apremilast 20 mg QD and placebo achieved PASI-75 at week 12 [9/87 (10.3%, each group)]. Mean per cent reduction in PASI from baseline was 17.4% for placebo, 30.3% for apremilast 20 mg QD (P = 0.021 vs. placebo) and 52.1% for apremilast 20 mg BID (P 90%) were mild to moderate and did not lead to study discontinuation. Serious adverse events occurred in four placebo subjects (panic attack, hospitalization for rehabilitation, hospitalization for alcoholism, worsening psoriasis), one receiving apremilast 20 mg QD (knee surgery) and in one receiving apremilast 20 mg BID (worsening psoriasis). The panic attack was considered treatment-related; both cases of worsening psoriasis occurred after medication discontinuation. No deaths or opportunistic infections were reported. Conclusion Apremilast 20 mg BID for 12 weeks was effective and well tolerated in subjects with moderate to severe plaque psoriasis.

Report of 457 sporotrichosis cases from Jilin province, northeast China, a serious endemic region.

Abstract: Background Most reported sporotrichosis cases came from South American countries, the USA, India and Japan. This mycosis is also endemic in Northeast China. However, the situation is not clear for international researchers due to lack of large series reported in English. Objectives To report and analyse 457 sporotrichosis cases. Methods Retrospective study of 457 cases of sporotrichosis diagnosed by fungal culture at the First Hospital of Jilin University from 1 January 2007 to 31 December 2009. Results In this series, the male: female ratio was 1:1.42. Mean age was 41.2 years. Cases from age group 51–60 years accounted for most of the cases (22.54%). A total of 434 patients lived in rural areas (94.97%). The onset of symptoms in 67.61% cases happened in cold seasons (winter and spring). History of trauma presented in 133 cases (29.1%). The mean duration of the symptoms before the presentation was 6.41 months. A total of 190 (41.58%) showed lymphocutaneous form, 252 patients (55.14%) showed fixed form, 8 patients (1.75%) showed disseminated cutaneous sporotrichosis and the clinical form of 7 patients (1.53%) could not be defined. Extremities and nodules were the most frequently involved sites and founded manifestation. Main histopathology findings were suppurative granuloma, tuberculoid granuloma and mixed inflammatory granuloma. A total of 75 cases (19.74%) had fungal elements revealed by Periodic Acid-Schiff staining. Patients responded well to potassium iodide (KI), itraconazole, terbinafine and combinations of these agents with a mean course of 2.17 months to resolve. Conclusion As the first report of a large series of sporotrichosis cases from China to be published in English literature, our study indicated a serious sporotrichosis endemic situation in Jilin province, Northeast China, with epidemiological and clinical characteristics similar to those of previous Chinese reports, but different from those in other countries. KI, itraconazole and terbinafine are effective for the treatment.

Morphology of basal cell carcinoma in high definition optical coherence tomography: en-face and slice imaging mode, and comparison with histology

Abstract: Background Optical coherence tomography (OCT) allows real-time, in vivo examination of basal cell carcinoma (BCC). A new high definition OCT with high lateral and axial resolution in a horizontal (en-face) and vertical (slice) imaging mode offers additional information in the diagnosis of BCC and may potentially replace invasive diagnostic biopsies. Objectives To define the characteristic morphologic features of BCC by using high definition optical coherence tomography (HD-OCT) compared to conventional histology. Methods A total of 22 BCCs were examined preoperatively by HD-OCT in the en-face and slice imaging mode and characteristic features were evaluated in comparison to the histopathological findings. Results The following features were found in the en-face mode of HD-OCT: lobulated nodules (20 ⁄ 22), peripheral rimming (17 ⁄ 22), epidermal disarray (21 ⁄ 22), dilated vessels (11 ⁄ 22) and variably refractile stroma (19 ⁄ 22). In the slice imaging mode the following characteristics were found: grey ⁄ dark oval structures (18 ⁄ 22), peripheral rimming (13 ⁄ 22), destruction of layering (22 ⁄ 22), dilated vessels (7 ⁄ 22) and peritumoural bright stroma (11 ⁄ 22). In the en-face mode the lobulated structure of the BCC was more distinct than in the slice mode compared to histology. Conclusion HD-OCT with a horizontal and vertical imaging mode offers additional information in the diagnosis of BCC compared to conventional OCT imaging and enhances the feasibility of non-invasive diagnostics of BCC.

Metabolic abnormalities associated with initiation of systemic treatment for psoriasis: evidence from the Italian Psocare Registry.

Abstract: Objective To evaluate variations in laboratory parameters and diagnoses of selected clinical conditions up to 16 weeks after starting a new systemic psoriasis treatment for Psocare Registry enrollees. Design Prospective cohort study. Setting Italian public referral centres for psoriasis treatment. Patients First-time recipients (n = 10,539) of continuous systemic psoriasis treatment for at least 16 weeks. Main outcome measure Mean variations in (weeks 8 and 16) and proportions of patients reaching a clinically meaningful increase in serum levels (week 16) of total and low-density lipoprotein cholesterol, triglycerides, aspartate amino transferase, alanine amino transferase and creatinine, as well as week-16 cumulative incidences of new diagnoses of diabetes mellitus and arterial hypertension. Results Mean cholesterol and triglyceride levels significantly increased in patients treated with acitretin or cyclosporine. Mean triglyceride levels also increased in efalizumab- and etanercept-treated patients. Mean transaminase values increased in methotrexate-treated patients, and mean aspartate amino transferase levels increased in infliximab-treated patients. The average serum creatinine value increased in cyclosporine-treated patients. Acitretin and cyclosporine were associated with risk of hypercholesterolaemia (odds ratios 1.51 and 1.34) and acitretin with risk of hypertriglyceridaemia (odds ratio 1.43). Methotrexate and infliximab were associated with risk of more than doubling the upper normal aspartate amino transferase (odds ratios 2.06 and 1.87) and alanine amino transferase (odds ratios 2.38 and 1.74) values. The relative risk of developing arterial hypertension and diabetes was increased for patients receiving cyclosporine (odds ratios 3.31 and 2.88). Conclusion Systemic treatments for psoriasis resulted in heterogeneous effects on the parameters analysed.

High discordance between punch biopsy and excision in establishing basal cell carcinoma subtype: analysis of 500 cases.

Abstract: Background Basal cell carcinoma (BCC) is the most frequently occurring cancer in humans. Worldwide incidences rise about 10% each year, increasing the burden on dermatologists, general practitioners and pathologists as well as increasing costs for the health care system. Increasingly non-surgical treatment options are used in the treatment of BCC, without histological confirmation of BCC subtype, potentially resulting in under-treatment. Objective We evaluated the diagnostic accuracy of a punch biopsy for the BCC histological subytpe in a primary BCC and the prevalence of biopsy-based under-diagnosis of aggressive subtypes. Accuracy of a punch biopsy was defined as concordance of the diagnosis of subtype of BCC at punch biopsy and excision. Methods A retrospective chart-review was performed of primary BCC, which were proven by punch biopsy and subsequently treated by excision. The first 100 consecutive BCCs per year during the years 2004-2009 were included, yielding a total of 500 evaluated BCCs. Results The overall accuracy of punch biopsy for BCC subtype at excision was 69%, in single-type BCC 83% (n = 343) and in mixed-type BCC 37% (n = 157). Accuracy varied substantially according to BCC subtype, being highest in the superficial subtype (84%) and subsequently in infiltrative (69%), nodular (63%) and micronodular subtype (38%). In 11% of all cases, an unsuspected more aggressive subtype was present. Conclusion Punch biopsy has a high accuracy in single-type BCCs and a considerably lower accuracy in mixed-type BCCs for establishing BCC subtype compared to excision. The presence of an unsuspected aggressive subtype could explain therapy failure of non-surgical treatments like imiquimod or photodynamic therapy.