BACKGROUND:

Vitiligo is a common pigmentation disorder affecting approximately 1% of the world population. Nonetheless, its distribution pattern is not well investigated.

OBJECTIVE:

The aim of this study was to investigate whether the distribution pattern of vitiligo is dependent on the clinical characteristics.

METHODS:

A total of 700 generalized vitiligo patients were included in this retrospective observational cohort study.

RESULTS:

The most important predilection areas were the face (87%), followed by acral areas (76.3%) and extremities (59.7%). In women, joints (P = 0.002) (especially elbows), hips (P < 0.001), trunk (P < 0.001) and body folds (P < 0.001) (especially axillas) were more frequently affected compared to men. In contrast, in men more depigmentations in the beard area and genital area were observed (P < 0.001). Vitiligo at a young age is more prone to be localized at the lower extremities whereas the upper extremities are more susceptible at an older age. In the face, the periocular area is linked to a younger age, in contrast to the perioral area. Acral areas were more frequently affected in patients with autoimmune disorders (in particular thyroid disease) (P = 0.001).

CONCLUSION:

These results point to important differences in the distribution pattern according to the clinical characteristics. Although in some of these areas Koebner's phenomenon probably plays a role, other differences may represent a specific characteristic vulnerability related to the age, gender or typical association with autoimmune disease.

BACKGROUND:

Subjects with atopic dermatitis (AD) have defects in antimicrobial peptide (AMP) production possibly contributing to an increased risk of infections. In laboratory models, vitamin D can alter innate immunity by increasing AMP production.

OBJECTIVE:

To determine if AD severity correlates with baseline vitamin D levels, and to test whether supplementation with oral vitamin D alters AMP production in AD skin.

METHODS:

This was a multi-centre, placebo-controlled, double-blind study in 30 subjects with AD, 30 non-atopic subjects, and 16 subjects with psoriasis. Subjects were randomized to receive either 4000 IU of cholecalciferol or placebo for 21 days. At baseline and day 21, levels of 25-hydroxyvitamin D (25OHD), cathelicidin, HBD-3, IL-13, and Eczema Area and Severity Index (EASI) and Rajka-Langeland scores were obtained.

RESULTS:

At baseline, 20% of AD subjects had serum 25OHD below 20 ng/mL. Low serum 25OHD correlated with increased Fitzpatrick Skin Type and elevated BMI, but not AD severity. After 21 days of oral cholecalciferol, mean serum 25OHD increased, but there was no significant change in skin cathelicidin, HBD-3, IL-13 or EASI scores.

CONCLUSIONS:

This study illustrated that darker skin types and elevated BMI are important risk factors for vitamin D deficiency in subjects with AD, and highlighted the possibility that seasonality and locale may be potent contributors to cathelicidin induction through their effect on steady state 25OHD levels. Given the molecular links between vitamin D and immune function, further study of vitamin D supplementation in subjects with AD is warranted.

BACKGROUND:

Psoriasis has been linked with cardiovascular risk factors (CVRFs), including the metabolic syndrome, yet many patients with psoriasis remain unscreened.

OBJECTIVE:

To assess the reasons for lack of screening for CVRFs in psoriasis patients, and the impact of an education programme targeting these deficiencies.

METHODS:

All patients with psoriasis, regardless of severity, and all dermatologists working at the National Skin Centre (NSC) in Singapore were surveyed over a 2-month period on their attitudes and knowledge regarding psoriasis and cardiovascular risk. This was followed by a targeted programme which was implemented over 2 months to address these identified deficiencies. Patients and doctors were surveyed a second time to assess the effects of the intervention.

RESULTS:

Obstacles to screening included lack of patient knowledge, patients not considering screening important, and lack of time during the clinic consultation. After the intervention, there was a significant increase in the proportion of patients who were aware of increased cardiovascular risk in psoriasis (33.0% to 62%), with more patients attending screening (39.1% to 63.2%). While the level of doctors' knowledge did not significantly increase, there was an increase in the proportion of patients who were screened post-intervention (37.1% to 66.2%), and more doctors reported that they were more likely to screen psoriatic patients from an earlier age (30.2% to 58.1%).

CONCLUSIONS:

The obstacles in implementing universal screening for CVRFs in psoriasis patients stem from patient, doctor and system factors. A comprehensive programme targeting all aspects of this ecosystem helps to achieve holistic care for patients with psoriasis.

BACKGROUND:

Guidelines for the management of genital Lichen sclerosus (LS) have recently been updated.

OBJECTIVE:

To look at the audit points suggested by the updated guidelines: performance of biopsies in active LS not responding to treatment; clear follow-up arrangements for patients with active disease; patient awareness of need to report suspicious lesions; and use of an appropriate topical steroid regieme.

METHOD:

Patients with a diagnosis of genital LS seen over the preceding 12 months were identified from eight hospital Trusts. In this study, 194 patients participated, 178 females and 16 males.

RESULTS:

The diagnosis was purely clinical in 62 patients - the remainder required biopsies. The commonest reason for performing a biopsy was to clarify the diagnosis (116), followed by to rule out malignancy (11). The majority (98%) were offered follow-up after the initial consultation and only 19 patients were discharged to primary care. In this study, 37% patients had documented evidence that a patient information leaflet had been given. 112 were treated with the clobetasol propionate 0.05% regieme quoted in the guideline.

CONCLUSION:

We conclude biopsies should be done as indicated in the guideline and the reason for biopsy documented. Discharge may be possible at 6 months for stable uncomplicated disease, although this may prove difficult if adequate follow-up arrangements are not available in the community. We advocate that all patients should receive a patient information leaflet and must be made aware of the increased risk of SCC. Topical corticosteroid treatment should be simplied to the regieme documented in the guidelines unless contraindicated.

BACKGROUND:

Despite acne persisting into adulthood in up to 50% of the population, very few therapeutic studies have been performed in this age group.

OBJECTIVES:

To assess the efficacy of 5 mg/day isotretinoin in adult acne.

METHODS:

An investigator initiated, industry-sponsored, randomized, double-blind, placebo-controlled, parallel-group clinical study of isotretinoin 5 mg/day in the treatment of low-grade adult acne for 16 weeks followed by an open-label phase of 16 weeks. Group 1 received 32 weeks of 5 mg isotretinoin/day; Group 2 first received 16 weeks of placebo, followed by 16 weeks open-label 5 mg isotretinoin/day. Patients were followed for a further 10 weeks off treatment. The primary end-point was the difference in acne lesion count and disability score after 16 weeks isotretinoin compared to placebo. Secondary end-points included differences in these counts/scores after 32 weeks of isotretinoin compared to baseline, and after 10 weeks off treatment, compared to end of treatment (week 32).

RESULTS:

There were highly significant differences (P < 0.0001) in acne lesion count, Dermatology Life Quality Index and self-assessment after 16 weeks of isotretinoin, compared to placebo (both per protocol and intention to treat). Acne lesions fell significantly, within 4 weeks of 5 mg isotretinoin/day (Group 1) and continued to fall during 32 weeks of treatment [acne lesion count (mean ± SD): 11.3 ± 8.1 (baseline), 3.6 ± 5.5 (week 16), 1.3 ± 3.1 (week 32), P < 0.0001)]. There was a similar significant reduction in acne lesion count in Group 2, but only from week 20, 4 weeks after starting open-label 5 mg isotretinoin. Adverse effects were minimal.

CONCLUSIONS:

Isotretinoin 5 mg/day is effective in reducing the number of acne lesions, and improving patients dermatologic quality of life, with minimal adverse effects.

In the last years, several tyrosine kinase inhibitors (TKIs) have been developed and approved for human cancer treatment. Imatinib mesylate was the first of this novel family of drugs that target cancer-specific molecules and signalling pathways. The appearance of imatinib resistances led to the introduction of second-generation TKIs with higher potency and selectivity, such as dasatinib and nilotinib. However, the range of activity of these agents is not simply directed at tumour cells. Patients and their clinicians are indeed frequently confronted with the cutaneous side-effects associated with the employ of these drugs, which represent the most common non-hematological adverse reactions. For this reason, a systematic dermatological survey of patients receiving these therapies is highly important, and an early and appropriate dermatological treatment is required. In this review, we analyse the clinical and pathological characteristics of the most commonly reported adverse skin events associated with first- and second-generation tyrosine kinase inhibitors, with a particular emphasis on our clinical experience.

BACKGROUND:

The significance of associated autoimmune/autoinflammatory diseases in generalized vitiligo patients with respect to their clinical profile has not yet been completely established.

OBJECTIVE:

The objective of this study was to evaluate the clinical significance of associated autoimmune/autoinflammatory diseases in generalized vitiligo patients with respect to some general clinical variables, distribution pattern, disease activity and treatment response.

METHODS:

Seven hundred generalized vitiligo patients were included in this retrospective observational cohort study.

RESULTS:

Associated autoimmune/autoinflammatory diseases were present in 15.4% of the patient population and were more common in women compared with men, especially concerning thyroid disease. Only vitiligo patients with thyroid disease had clear different clinical characteristics. The percentage of total body surface area involvement was significantly (P = 0.005) higher in the presence of thyroid disease which was more pronounced in women compared with men. Patients with thyroid disease had a particular predisposition to acral and joint depigmentations. No clear differences in disease activity or response to therapy were observed in vitiligo patients with or without autoimmune/autoinflammatory disorders.

CONCLUSION:

The presence of associated autoimmune/autoinflammatory diseases seems to influence the clinical profile of generalized vitiligo patients. Our results support the hypothesis that in the presence of a thyroid disorder, the disease activity of vitiligo is more extensive, in particular on areas prone to friction.

BACKGROUND:

Patients with in situ extramammary Paget's disease (EMPD) tend to have a good prognosis, although dermal invasion and metastasis are associated with significantly increased morbidity and mortality. Previous studies have addressed mechanisms underlying the EMPD pathogenesis; however, no molecular markers that reflect invasiveness or progression have been established.

OBJECTIVE:

This study aims to identify a reliable marker for predicting the risk of invasion and metastasis in EMPD.

METHODS:

We performed an initial microarray screening for in situ, invasive or metastatic lymph node lesions of EMPD. We analysed 44 specimens from 38 primary EMPD cases by immunohistochemical staining.

RESULTS:

We found that expressions of MUC5AC directly correlate with invasion and prognosis. Labelling rates of tumour cells were scored by staining intensity on a four-tiered scale (- to 3+) to investigate the correlation between the expression score of these molecular markers and the type of EMPD lesion. All the specimens scored positive (3+) for MUC1 and negative (-) for MUC6. MUC5AC expression was detected in 19 of 44 (43.2%) specimens. Invasive lesions and metastatic lymph nodes tended to express MUC5AC significantly higher than in situ lesions (P < 0.01). MUC2 was positive in 10 specimens (22.7%). There was no significant difference between the degree of MUC2 expression and invasiveness.

CONCLUSION:

The degree of MUC5AC expression may correlate with the invasiveness and progression of EMPD, and may be a useful marker for identifying high-risk EMPD cases.

BACKGROUND:

Cyclophosphamide has been commonly used for the treatment of pemphigus vulgaris and mucous membrane pemphigoid with satisfactory results. Published data of this therapeutic approach for bullous pemphigoid are scant and showed significant morbidity and mortality.

OBJECTIVE:

To assess the clinical efficacy and safety of low-dose oral cyclophosphamide (CFM) (50-100 mg/day) in patients with refractory bullous pemphigoid.

METHODS:

We conducted a retrospective study including patients with bullous pemphigoid treated with CFM in the department of Dermatology in the Hospital Clínic of Barcelona, Spain.

RESULTS:

Complete response was observed in 11 (58%) over 19 evaluable patients. Cyclophosphamide at 50 mg/day was enough to achieve clinical remission in eight of these patients. Partial response was observed in four (21%) more patients. Bone marrow suppression appeared in 12 (60%) patients, but treatment discontinuation was only required in three (15%) cases. Gastrointestinal intolerance occurred in one (5%) patient. One patient died during therapy from heart failure (not attributed to CFM) and another patient developed acute myeloid leukaemia 1.5 years after CFM therapy.

CONCLUSIONS:

In our series, CFM had a marked therapeutic effect in bullous pemphigoid. These results of efficacy are similar to those described in other autoimmune blistering skin diseases. Only a few patients had to discontinue their treatment due to adverse effects. Therefore, we consider that low-dose oral CFM can be valuable therapeutic alternative in elderly patients with moderate-to-severe bullous pemphigoid.

BACKGROUND:

Patients with Gorlin syndrome develop multiple basal cell carcinomas (BCC), for which treatment is often difficult. Methylaminolevulinate-photodynamic therapy (MAL-PDT) is approved for the treatment of superficial and nodular BCCs in Canada and several European countries.

OBJECTIVES:

To establish consensus recommendations for the use of MAL-PDT in patients with Gorlin syndrome.

METHODS:

The Gorlin consensus panel was comprised of 7 dermatologists who had treated a total of 83 patients with Gorlin syndrome using MAL-PDT. Consensus was developed based on the personal experience of the expert and results of literature review (on PUBMED using the keywords 'MAL' and 'PDT' and 'Gorlin' or 'naevoid basal cell carcinoma syndrome').

RESULTS:

Consensus was reached among the experts and the literature review identified 9 relevant reports. The experts considered MAL-PDT a generally effective and safe therapy for treatment of BCC in Gorlin syndrome. For superficial BCC (sBCC), all sizes can be treated, and in nodular BCC (nBCC), better efficacy can be achieved in thinner lesions (<2 mm in thickness). MAL-PDT treatment schedule should be performed according to labelling although in individual cases, it may be adapted and performed on a monthly basis based on clinical assessment. Follow-up should be related to frequency of recurrence, and severity, number and location of lesions. Multiple lesions and large areas may be treated during the same session; however, adequate pain management should be considered.

CONCLUSIONS:

MAL-PDT is safe and effective in patients with Gorlin syndrome. Utilization of these recommendations may improve efficacy and clearance rates in this population.