Is it Useful to Calculate Minimal Erythema Dose Before Narrowband UV-B Phototherapy? / ¿Es útil la determinación de la dosis eritematógena mínima previa a la fototerapia ultravioleta B de banda estrecha?

INTRODUCTION AND OBJECTIVES: The starting dose for narrowband UV-B phototherapy is determined by a patient's skin phototype or minimal erythema dose (MED). Calculation of MED identifies patients with unsuspected photosensitivity. The aim of this study was to investigate the influence of factors such as concomitant use of photosensitizing agents, diagnosis, and combination with acitretin in patients with psoriasis on the frequency and severity of adverse effects in patients with a low MED to narrowband UV-B phototherapy. MATERIAL AND METHODS: We undertook a retrospective observational cohort study between February 1, 2009 and March 31, 2015. MED values were classified as normal or low. RESULTS: In total, 302 patients with different skin conditions started narrowband UV-B phototherapy at a dose determined by their MED. No differences were found between patients with a low MED and those with a normal MED for number of drugs taken (P=.071) or use of photosensitizing agents (P=0.806). Following adjustment for age, sex, and phototype, the multivariate analysis showed that psoriasis exerted a protective effect against a low MED (OR=0.31 [95% CI, 0.16-0.58]). No significant risk of erythema or pruritus was detected in patients with a low MED (OR=1.68; 95% CI, 0.91-3.29 and OR=2.04; 95% CI, 0.99-4.22, respectively). CONCLUSIONS: Psoriasis protects against a low MED. Although erythema and pruritus were more common in patients with a low MED, the differences were not significant.

[Prevalence and clinical features of congenital melanocytic nevi in 1,000 Spanish newborns]. / Prevalencia y características clínicas de los nevos melanocíticos congénitos en 1.000 recién nacidos españoles.

BACKGROUND: Congenital melanocytic nevus is a benign proliferation of melanocytes that is present at birth or develops in the first months of life. Although such lesions are common, few studies have analyzed their prevalence in Spain. OBJECTIVES: The aim of this study was to define the prevalence and most frequent anatomical areas affected by congenital melanocytic nevi in our health service area. We also analyzed the influence of maternal and neonatal factors in the development of these lesions. PATIENTS AND METHODS: We performed a prospective study of 1000 consecutive neonates seen in the first 72hours of life in the perinatology clinic of the Pediatrics Department of Hospital Arquitecto Marcide in Ferrol, Spain, recording specific maternal and neonatal variables and the size and site of congenital melanocytic nevi if present. RESULTS: Fourteen infants (10 girls and 4 boys; 12 white European, 2 North African; 1.4% of the study population) presented at least 1 melanocytic nevus. None had more than 1 lesion. Eight of the nevi were located on the trunk, 2 on the face, 2 on the upper limbs, and 2 on the lower limbs. The diameter of the lesions was less than 1.5 cm in half of cases and between 1.5 and 3.5 cm in the remainder. CONCLUSIONS: There was a higher prevalence of congenital melanocytic nevi in preterm infants, females, and nonwhite infants. Maternal age, number of previous pregnancies, and birth weight do not appear to influence the prevalence of these lesions.

[Prevalence of birthmarks and transient skin lesions in 1,000 Spanish newborns]. / Prevalencia de marcas de nacimiento y lesiones cutáneas transitorias en 1.000 recién nacidos españoles.

BACKGROUND AND OBJECTIVES: Almost all newborn children have some sort of birthmark or transient benign skin lesion. Few studies, however, have analyzed their frequency, particularly in Spain. The aims of this study were to determine their prevalence in 1000 newborn children in the health care area of Ferrol in northwest Spain and to compare the results with those of 9 other studies with similar characteristics. PATIENTS AND METHODS: We undertook a descriptive study of 1000 newborn infants seen in the first 3 days of life at the neonatal clinic in the Department of Pediatrics, Hospital Arquitecto Marcide, Ferrol, Spain. Each infant was examined for the presence of 19 different transient benign skin lesions and 11 birthmarks. RESULTS: Birthmarks or benign skin lesions were present in 994 neonates (99.4%). Transient skin lesions were present in 99.2% and birthmarks in 72%. The 5 most prevalent lesions were sebaceous hyperplasia (75%), salmon patch (64.2%), hypertrichosis (59%), sucking calluses (54%), and palatine cysts (53.7%). CONCLUSIONS: The results of this study show that most neonates have benign skin lesions. The findings of studies to assess their frequency are influenced not only by geographic location (affecting variables such as climate, social and health care conditions, and ethnic group) but also by the timing of examination, the inclusion criteria applied, and the terminology used.

[Salmon patch: a descriptive study]. / Mancha salmón: estudio descriptivo.

BACKGROUND AND OBJECTIVES: salmon patch is a congenital venous malformation that usually affects the midline. Although it is very common, few studies have analyzed its prevalence or predisposing factors. The aim of this study was to determine the prevalence and clinical characteristics of salmon patch in a group of newborn infants from a health care area in northwest Spain and to assess its association with neonatal and maternal variables. PATIENTS AND METHODS: a descriptive study was undertaken of live newborn children seen in the neonatal unit of the Department of Pediatrics at Hospital Arquitecto Marcide, Ferrol, Spain between May 1, 2008 and January 31, 2009. The study protocol included collection of data on neonatal variables (including gestational age, sex, ethnic origin, weight, and presence and anatomical site of salmon patch) and maternal variables (including age and number of previous pregnancies). RESULTS: of the 600 newborn infants included in the study, 59% had salmon patches. The most commonly affected sites were the nape of the neck (226 infants, 37.6%) and eyelids (211 infants, 35.1%). In a number of cases, more than one part of the body was affected. There was a higher prevalence of salmon patch in full-term or post-term births, in girls, white children, heavier children, and infants born to mothers aged between 30 and 34 years or who had not been pregnant previously. CONCLUSIONS: salmon patch occurred most frequently on the nape of the neck, the eyelids, and the glabella. Its prevalence was associated with certain neonatal and maternal factors.

[Influence of neonatal and maternal factors on the prevalence of vernix caseosa]. / Influencia de los factores neonatales y maternos en la prevalencia de vérnix caseosa.

At birth, vernix caseosa can cover the whole body surface or accumulate only on the back and in the skin folds. Interest in its composition and function and its possible applications in adults has increased in recent years. The objective of this study was to determine the prevalence of vernix caseosa in newborn infants in the health care area of Ferrol, Spain, and to assess its relationship with neonatal and maternal factors. We performed a prospective study of 1000 newborns seen within the first 3 days of life in our hospital. Vernix caseosa was observed in 42.9% of cases. The clinical profile associated with the presence of vernix caseosa was the following: healthy newborn girl with a high birth weight, born at term by normal vaginal delivery to a multiparous mother who had received medication and dietary supplements during pregnancy. The absence of vernix caseosa was associated with the presence of physiological scaling of the newborn and erythema toxicum neonatorum.

Observer agreement in toenail disorders: implications for diagnosis and clinical research.

BACKGROUND: Toenail disorders are frequent, especially onychomycosis. The interobserver variability of nail signs needs to be known before these signs can be confidently applied for diagnosis. OBJECTIVES: To describe observer agreement in toenail findings as described by dermatologists in standard clinical practice, focusing on signs that could be useful for diagnosis of onychomycosis. METHODS: Prospective cross-sectional study in five dermatology departments. Eighty-six patients with abnormal toenails that could have onychomycosis as a differential diagnosis were independently examined by a pair of dermatologists using a predefined questionnaire, to describe the presence of 10 findings on previous history and 14 physical signs. RESULTS: Agreement was fine for previous history findings: it was very good (kappa > 0.81) for previous diagnosis of diabetes, smoking and use of public dressing rooms or swimming pools. Agreement was good (kappa 0.61-0.80) for immune suppression (drugs or cancer), previous diagnosis of fungal disease and worsening in the last year. It was moderate (kappa 0.41-0.60) for previous diagnosis of arterial disease, trauma induced by work or sports, and distal vs. proximal or lateral vs. central start of the lesion. Agreement was worse for physical signs: we found good agreement for the presence of the same disease in fingernails, abnormal plantar desquamation, deformity causing nail trauma, and subungual hyperkeratosis. It was moderate for the presence of nail destruction, tinea interdigitalis, onycholysis, and the type of material obtained by subungual curettage (dust vs. hard). Agreement was fair (kappa 0.21-0.40) for the presence of longitudinal or transverse striae, trachyonychia, pachyonychia, and change in colour of the nail plate. Pitting was too infrequent to allow for kappa calculation. Chance expected agreement was between 51% and 84% for all signs except pitting. CONCLUSIONS: Agreement is adequate for most signs. It is low for the presence of longitudinal or transverse striae, trachyonychia, and change in colour of the nail plate. Pitting is rare in toenails.

Discrete papular lichen myxoedematosus: a rare subtype of cutaneous mucinosis.

Primary cutaneous mucinoses are characterized by abnormal mucin deposits in the skin. Discrete papular lichen myxoedematosus (DPLM) is an unusual subtype. Only 11 of the cases described in the literature to date showed no relation to human immunodeficiency virus (HIV) infection. We report a 21-year-old woman with numerous symmetrical asymptomatic papules on her trunk, arms and thighs. Results of investigations were normal. On histological examination, the upper dermis showed a focal mucin deposit. DPLM can be associated with HIV or C hepatitis virus (HCV) infection and therefore an early diagnosis is very important.

Estradiol sustained release from high affinity cyclodextrin hydrogels.

Hydrogels for loading estradiol and controlling its release were prepared cross-linking various cyclodextrins with ethyleneglycol diglycidylether. To select the more adequate cyclodextrins, estradiol solubility diagrams in water with beta-cyclodextrin (betaCD), methyl-beta-cyclodextrin (MbetaCD), hydroxypropyl-beta-cyclodextrin (HPbetaCD), and sulfobutyl-beta-cyclodextrin (SBbetaCD) were made in absence and presence of hydroxypropyl methylcellulose (HPMC) applying or not autoclaving. Although all cyclodextrins showed enough complexation capability, the low solubility of betaCD and the high anionic character of SBbetaCD hindered the cross-linking process, and these cyclodextrins were discarded for preparing hydrogels. Hydrogels prepared with MbetaCD (20%, 25%) or HPbetaCD (20%, 25%, and 30%), with or without HPMC 0.25%, absorbed 4-10 times their weight in water and loaded up to 24 mg estradiol per gram, which is 500 times greater than the amount of drug that can be dissolved in their aqueous phase. Positive linear correlation was found between the stability constant and the network/water partition coefficients of drug. The hydrogels sustained the release up to one week; the affinity of estradiol for the cyclodextrin units controlling the process, as shown by the negative correlation with the release rate constants. These results highlight the potential of cyclodextrin complexation for the development of hydrogels useful in loading hydrophobic drugs and controlling their release.

Perception of psoriasis treatment in the outpatient setting: survey of patients and their prescribing physicians.

BACKGROUND: Patients' perception of disease management can influence compliance to treatment and thus affect outcome. OBJECTIVE: To survey patients and physicians on their perceptions of biologic therapy for treating psoriasis in an outpatient setting. METHODS: The subjective impact of intravenous treatment of severe psoriasis on patients and physicians in the outpatient setting was determined via two surveys. RESULTS: Between September and November 2014, 24 dermatologists and 90 patients were surveyed. Treatment with biologic agents in the outpatient setting was associated with a high level of patient satisfaction: 93.3% of patients considered their psoriasis well controlled and 46.1% reported complete control. Patients highly valued the feeling of greater disease control (72.2%), regular follow-up (66.7%) and rapid improvement of psoriasis (58.9%) when attending an outpatient setting. Other positive aspects of outpatient treatment were control of other health issues and perceived improvements in quality of life (QoL). Outpatient attendance was high; with 90% of patients keeping scheduled appointments and 79.2% of physicians acknowledged that they were able to monitor their patients' condition more closely. CONCLUSION: Administration of treatment in an outpatient setting may provide a feeling of improved QoL and disease control.

Drug solubilization and delivery from cyclodextrin-Pluronic aggregates.

Colloidal systems based on Pluronic F127 (PF127) and hydroxypropyl-beta-cyclodextrin (HPbetaCD) have been characterized with a view to their potential use as delivery systems of hydrophobic drugs. Complexation of PF127 and HPbetaCD was evaluated by surface tension measurements, 1H-NMR spectroscopy and transmission electron microscopy. The critical micellar concentration, CMC, at 25 degrees C of PF127 (0.39 mM in pH 5.8 and 7.4 phosphate buffers, and 0.59 mM in pH 4.5 acetic/acetate and lactic/lactate buffers) was shifted to higher values by the addition of 38.17 mM HPbetaCD (CMC(app) = 1.18 mM). This is related to the threading of HPbetaCD onto the PF127 chains, as confirmed by 1H NMR experiments. HPbetaCD at this concentration notably raised the sol-gel transition temperature; the minimum PF127 concentration required for providing gelling systems in physiological environments being 13.4 mM. Both HPbetaCD and PF127 by themselves are able to notably increase the solubility of sertaconazole (SN). At HPbetaCD concentrations below 80 mM, an additive effect of both components on SN solubility was observed. At greater HPbetaCD concentrations, a non-additive increase occurred, which is related to the complexation of some PF127 unimers with HPbetaCD molecules, decreasing the total number of micelles and HPbetaCD cavities available for interacting with SN. The 13.4 mM PF127/38.17 mM HPbetaCD system, able to increase up to 100 times the SN solubility in pH5.8 phosphate buffer, showed temperature-dependent drug diffusion coefficients, able to control the release for one week at 37 degrees C.

Metabolic syndrome in Spanish patients with psoriasis needing systemic therapy: Prevalence and association with cardiovascular disease in PSO-RISK, a cross-sectional study.

BACKGROUND: Increasing evidence indicates a relationship between psoriasis and metabolic syndrome (MS). We evaluated the prevalence of MS in patients receiving systemic treatment for psoriasis in Spain, and its relationship to cardiovascular disease (CVD). METHODS: This cross-sectional, multicenter, non-interventional study enrolled 368 patients with moderate-to-severe psoriasis requiring systemic treatment. Clinical parameters for psoriasis, CV risk factors, MS and CVD were assessed. Descriptive and logistic regression analyses were performed. RESULTS: 352 patients were included (median psoriasis duration: 18 years, plaque psoriasis [95.7%], psoriatic arthritis [22.8%]). Overall, 132 patients (37.5%) fulfilled diagnostic criteria for MS; the most prevalent MS components were high blood pressure and increased waist circumference. Patients with MS were older, more likely to be obese and to have a sedentary lifestyle and hypercholesterolemia than those without MS. CVD was more prevalent in patients with MS than in those without (29.5% versus 15.9%, p = 0.002), particularly coronary heart disease (CHD), myocardial infarction and heart failure. MS was independently associated with CVD (OR 1.98, p = 0.018) and CHD (OR 2.02, p = 0.044). CONCLUSION: The prevalence of MS was high among patients with moderate-to-severe psoriasis requiring systemic treatment, and was associated with a higher prevalence of CVD. Dermatologists should consider implementing simple screening protocols.

Oversaturated solutions of drug in hydroxypropylcyclodextrins: parenteral preparation of pancratistatin.

The effect of 15 cyclodextrin derivatives (polar-electroneutral, cationic, anionic, and lipophilic) and of three 2-hydroxypropyldigitonins on the solubility of pancratistatin, an anticancer drug, was evaluated. The direct solubilizations into aqueous solutions were invariably low (0.1-1.2 mg/mL compared with 50 micrograms/mL in water). Complexes of pancratistatin with hydroxypropyl-beta-cyclodextrin were more stable (Kapp 153 M-1) than those with hydroxypropyl-gamma-cyclodextrin (Kapp 108 M-1). Acceptable preparations were made by dissolution of pancratistatin in a large excess (50x) of hydroxypropylcyclodextrin by ammonia and then freeze drying to ammonia-free preparations. In these preparations, both the inclusion and interdispersion phenomena were operative, and the preparations dissolved rapidly forming clear solutions of pancratistatin of concentrations up to 9 mg/mL. These solutions were oversaturated and while those based on hydroxypropyl-beta-cyclodextrin precipitated within 1 h; those based on hydroxypropyl-gamma-cyclodextrin were stable for at least 4 h when kept in a plastic container (i.e., time sufficient for potential use in parenteral preparations).

Effect of cyclodextrins on the solubility and antimycotic activity of sertaconazole: experimental and computational studies.

This study investigated the effects of the complexation of sertaconazole nitrate with different cyclodextrin (CD) derivatives (alpha-CD, beta-CD, gamma-CD, hydroxypropyl-beta-CD, and hydroxypropyl-gamma-CD) on the aqueous solubility and antimycotic activity of the drug. Phase solubility studies indicated that the solubility of sertaconazole in enzyme-free simulated gastric- and enzyme-free simulated enteric fluids was significantly increased in the presence of cyclodextrins. The observed order of solubility increasing effect was: gamma-CD > HPgamma-CD > HPbeta-CD > beta-CD > alpha-CD. Solid-state sertaconazole-cyclodextrin complexes were prepared by freeze drying, and characterized by X-ray powder difractometry, differential scanning calorimetry (DSC), and infrared spectroscopy (FTIR). Freeze-dried complexes showed markedly higher solubility than both physical mixtures and sertaconazole alone. The antimycotic activities of sertaconazole-cyclodextrin complexes in solution were evaluated by inhibition zone assays with Candida albicans. The activity ranking agrees with the solubility ranking observed for these complexes, with the gamma-CD-sertaconazole complex showing the strongest antimycotic activity. Finally, molecular modeling studies were carried out using the MM2 force field method, for complexes in vacuum and in water. This enable indentification of the preferred orientation of sertaconazole in the gamma-CD cavity and of the main structural features responsible for the enhancement of its solubility and antimycotic activity.

Utility of nuclear magnetic resonance spectroscopy to characterize the structure of dexamethasone sodium phosphate inclusion complexes with cyclodextrins in solution and to analyze potential competitive effects.

The interaction between dexamethasone sodium phosphate (DSP) and four cyclodextrin (CyD) derivatives [2,6-di-O-beta-cyclodextrin (DIMEB), gamma-cyclodextrin (gamma-CyD), and hydroxypropyl-beta-cyclodextrin with either 2.7 or 4.6 degrees of substitution (HPbetaCyD 2.7 and HPbetaCyD 4.6, respectively)] was investigated by proton nuclear magnetic resonance spectroscopy (1H NMR). The data suggested the formation of inclusion complexes in solution in which B and C rings of the molecule are located inside the cavity. Nevertheless, the structure, in terms of depth within CyD, depends on the derivative considered. Molecular mechanics calculations of DSP complexes with DIMEB and gamma-CyD support the NMR results. The potential displacement of DSP from the CyD cavity by usual ophthalmic drugs (e.g., polymyxin B, trimethoprim, and benzalkonium chloride) was determined by NMR. The technique has been found useful to analyze this problem in pharmaceutical preparations.

Complexation of the interferon inducer, bropirimine, with hydroxypropyl-beta-cyclodextrin.

Bropirimine (ABPP) is an orally active immunomodulator that increases endogenous alpha-interferon and other cytokines used clinically against carcinoma in situ of the bladder. The oral absorption of ABPP is poor because its low solubility in water. The purpose of this study is to develop a technological procedure useful to increase the water solubility of ABPP. To this end, the interaction of ABPP with several cyclodextrin derivatives-alpha-, beta-, gamma- and hydroxypropyl-beta-cyclodextrin with a degree of substitution 2.7 (HPbetaCD) was studied and the effect of the complexation process on the water solubility of the drug was evaluated. The best results were obtained with the hydroxypropyl derivative, HPbetaCD, that interacts in a 1:1 drug:cyclodextrin molar ratio. The inclusion complex ABPP-HPbetaCD was characterized in solution by nuclear magnetic resonance (1H-NMR). The solid inclusion complex was obtained by freeze-drying and characterized by differential scanning calorimetry (DSC), X-ray diffractometry and mass spectrometry. The dissolution rate of ABPP from the HPbetaCD solid inclusion complex was increased compared to the powdered drug but not differences were found between the complex and a physical mixture with a similar molar ratio. The increase of the dissolution rate of the drug can be attributed to the breakdown in solution of the drug dimers in the presence of the cyclodextrin and to the complex formation.