Interrater agreement of classification of photoparoxysmal electroencephalographic response.

Our goal was to assess the interrater agreement (IRA) of photoparoxysmal response (PPR) using the classification proposed by a task force of the International League Against Epilepsy (ILAE), and a simplified classification system proposed by our group. In addition, we evaluated IRA of epileptiform discharges (EDs) and the diagnostic significance of the electroencephalographic (EEG) abnormalities. We used EEG recordings from the European Reference Network (EpiCARE) and Standardized Computer-based Organized Reporting of EEG (SCORE). Six raters independently scored EEG recordings from 30 patients. We calculated the agreement coefficient (AC) for each feature. IRA of PPR using the classification proposed by the ILAE task force was only fair (AC = 0.38). This improved to a moderate agreement by using the simplified classification (AC = 0.56; P = .004). IRA of EDs was almost perfect (AC = 0.98), and IRA of scoring the diagnostic significance was moderate (AC = 0.51). Our results suggest that the simplified classification of the PPR is suitable for implementation in clinical practice.

Assessment of Predictors of Sun Sensitivity as Defined by Fitzpatrick Skin Phototype in an Ecuadorian Population and Its Correlation with Skin Damage.

BACKGROUND: The Fitzpatrick skin phototype scale (FSPTS) is a widely used instrument to assess skin type. METHODS: A cross-sectional survey collected responses from 254 subjects from Quito regarding self-reported FSPTS, gender, age, education, and tobacco and alcohol consumption. Univariate and multivariate logistic regression analyses were performed to determine if ethnicity, hair color, and eye color significantly predict FSPTS. In addition, we studied the correlation between FSPTS and the SCINEXA scale with Pearson's correlation coefficient. RESULTS: Ethnicity, eye color, and hair color are significant independent predictors of FSPTS (p < 0.0001). CONCLUSIONS: Patient self-reported race and pigmentary phenotypes are inaccurate predictors of sun sensitivity as defined by Fitzpatrick skin phototype. Our study does not fully represent the population of the country. There are limitations to using patient-reported race and appearance in predicting individual sunburn risk.

Unusual photodermatosis with lichenoid eruption and apoptosis in a 33-year-old female.

We describe the clinical and dermoscopic features and histopathological findings in a case of a 33-year-old female patient with an adult-onset photodermatosis. This eruption was not typical of well-established photodermatoses due to its apoptotic keratinocytes. To our knowledge, this is the first report of these combined clinical and pathologic features.

Risk factors associated with actinic prurigo: a case control study

Abstract: Background: Actinic prurigo (AP) is an idiopathic photodermatosis. Although its initial manifestations can appear in 6 to 8-year-old children, cases are diagnosed later, between the second and fourth decades of life, when the injuries are exacerbated. Objective: To identify risk factors associated with clinical manifestations of AP such as skin and mucosal lesions. Methods: Thirty patients with AP and 60 controls were included in the study, the dependent variable was the presence of skin or labial mucosal lesions, the independent variables were age, sex, solar exposure, living with pets or farm animals, exposure to wood smoke, smoking habit, years smoking, and hours spent per day and per week in contact with people who smoke. Results: Of the 30 diagnosed AP patients, 66.7% were female. Patients age ranged from 7 to 71 years and the mean age was 35.77 ± 14.55 years. We found significant differences with the age and cohabitation with farm animals. Those who lived with farm animals presented 14.31 times higher probability of developing AP (95% CI 3-78.06). Study limitations: This is a case-control study; therefore, a causal relationship cannot be proven, and these results cannot be generalized to every population. Conclusions: The identification of factors related to the development of AP increases our knowledge of its physiopathology. Moreover, identifying antigens that possibly trigger the allergic reaction will have preventive and therapeutic applications in populations at risk of AP.

Risk factors associated with actinic prurigo: a case control study.

BACKGROUND: Actinic prurigo (AP) is an idiopathic photodermatosis. Although its initial manifestations can appear in 6 to 8-year-old children, cases are diagnosed later, between the second and fourth decades of life, when the injuries are exacerbated. OBJECTIVE: To identify risk factors associated with clinical manifestations of AP such as skin and mucosal lesions. METHODS: Thirty patients with AP and 60 controls were included in the study, the dependent variable was the presence of skin or labial mucosal lesions, the independent variables were age, sex, solar exposure, living with pets or farm animals, exposure to wood smoke, smoking habit, years smoking, and hours spent per day and per week in contact with people who smoke. RESULTS: Of the 30 diagnosed AP patients, 66.7% were female. Patients age ranged from 7 to 71 years and the mean age was 35.77 ± 14.55 years. We found significant differences with the age and cohabitation with farm animals. Those who lived with farm animals presented 14.31 times higher probability of developing AP (95% CI 3-78.06). STUDY LIMITATIONS: This is a case-control study; therefore, a causal relationship cannot be proven, and these results cannot be generalized to every population. CONCLUSIONS: The identification of factors related to the development of AP increases our knowledge of its physiopathology. Moreover, identifying antigens that possibly trigger the allergic reaction will have preventive and therapeutic applications in populations at risk of AP.

Single Amino Acid Deletion in Kindlin-1 Results in Partial Protein Degradation Which Can Be Rescued by Chaperone Treatment.

Kindler syndrome, a distinct type of epidermolysis bullosa, is a rare disorder caused by mutations in FERMT1, encoding kindlin-1. Most FERMT1 mutations lead to premature termination codons and absence of kindlin-1. Here we investigated the molecular and cellular consequences of a naturally occurring FERMT1 mutation, c.299_301del resulting in a single amino acid deletion, p.R100del. The mutation led to a 50% reduction of FERMT1 mRNA and 90% reduction of kindlin-1 protein in keratinocytes derived from the patient, as compared with control cells. The misfolded p.R100del kindlin-1 mutant was lysosomally degraded and launched a homeostatic unfolded protein response. Sodium-phenylbutyrate significantly increased kindlin-1 mRNA and protein levels and the area of mutant cells, acting as a chemical chaperone and probably also as a histone deacetylase inhibitor. In a recombinant system, low levels of wild-type or p.R100del mutant kindlin-1 were sufficient to improve the cellular phenotype in respect of spreading and proliferation as compared with kindlin-1 negative keratinocytes. The study of this hypomorphic mutation provides evidence that low amounts of kindlin-1 are sufficient to improve the epidermal architecture and Kindler syndrome cellular phenotype and proposes a personalized chaperone therapy for the patient.

Correlation of serum IgE levels and clinical manifestations in patients with actinic prurigo

Abstract BACKGROUND: Actinic prurigo is an idiopathic photodermatosis, the pathophysiology of which has been hypothesized to involve subtype IV type b (Th2) hypersensitive response, whereby IL4, IL5, and IL13 are secreted and mediate the production of B cells, IgE, and IgG4. OBJECTIVES: To examine the association of serum IgE levels and the clinical severity of injuries. METHODS: This case-control study comprised patients with a clinical and histopathological diagnosis of actinic prurigo, as well as clinically healthy subjects, from whom 3cc of peripheral blood was taken for immunoassay. Cases were classified by lesion severity as mild, moderate, and severe. Descriptive statistics were analyzed, and chi-square test was performed. RESULTS: We included 21 actinic prurigo patients and 21 subjects without disease; 11 patients with actinic prurigo had elevated serum IgE levels, and 10 had low serum levels. Six actinic prurigo (AP) patients with elevated serum levels of IgE had moderate injuries, 4 had severe injuries, and 1 had minor injuries. Eight out of 10 patients with normal IgE levels presented with minor injuries in the clinical evaluation. The 21 controls did not have increased serum IgE levels. CONCLUSIONS: Elevated IgE levels are associated with moderate to severe clinical lesions, suggesting that actinic prurigo entails a type IV subtype b hypersensitivity response in which Th2 cells predominate.

Oxidative Damage to RPA Limits the Nucleotide Excision Repair Capacity of Human Cells.

Nucleotide excision repair (NER) protects against sunlight-induced skin cancer. Defective NER is associated with photosensitivity and a high skin cancer incidence. Some clinical treatments that cause photosensitivity can also increase skin cancer risk. Among these, the immunosuppressant azathioprine and the fluoroquinolone antibiotics ciprofloxacin and ofloxacin interact with UVA radiation to generate reactive oxygen species that diminish NER capacity by causing protein damage. The replication protein A (RPA) DNA-binding protein has a pivotal role in DNA metabolism and is an essential component of NER. The relationship between protein oxidation and NER inhibition was investigated in cultured human cells expressing different levels of RPA. We show here that RPA is limiting for NER and that oxidative damage to RPA compromises NER capability. Our findings reveal that cellular RPA is surprisingly vulnerable to oxidation, and we identify oxidized forms of RPA that are associated with impaired NER. The vulnerability of NER to inhibition by oxidation provides a connection between cutaneous photosensitivity, protein damage, and increased skin cancer risk. Our findings emphasize that damage to DNA repair proteins, as well as to DNA itself, is likely to be an important contributor to skin cancer risk.

Vitamin B6 intoxication after inappropriate supplementation with micronutrients following bariatric surgery.

A 50-year-old Caucasian woman was admitted to our hospital with intermittent diarrhoea, emesis and increasingly brown-coloured skin, mainly the in light-exposed areas, after biliopancreatic diversion for obesity treatment. Differential diagnoses such as adrenal insufficiency were ruled out, but biochemical analysis demonstrated unusual high pyridoxine serum levels (vitamin B6). History revealed the intake of 300 mg of vitamin B6 per day over 6 months as described by her general practitioner. All symptoms disappeared after the discontinuation of vitamin B6 supplementation. Importantly, in contrast to many other vitamins and supplements, there is no evidence in the literature of the occurrence of vitamin B6 deficiency after bariatric surgery. Therefore, supplementation of vitamins and supplements in bariatric patients has to be carefully considered according to the existing clinical guidelines, as uncritical oversupplementation of micronutrients might result in intoxication and serious illness as presented here.

Clinical and laboratory predictors of distinct histopathogical features of lupus nephritis.

The authors aimed to explore whether distinct clinical, serological, and urinalysis findings are associated with specific histological classes of lupus nephritis. Clinical and laboratory features were recorded at the time of clinical diagnosis from 297 consecutive patients with biopsy-confirmed lupus nephritis. Univariate and logistic regression analyses were performed and a risk score was developed to estimate the risk for developing different classes of lupus nephritis. Variables independently associated with class II included absence of malar rash, negative anti-dsDNA, and ≤5 urine leucocytes/high power field (hpf); with III/IV: age at nephritis diagnosis ≤32 years old, presence of musculoskeletal features, new-onset hypertension, positive anti-dsDNA, >5 urine leucocytes/hpf, creatinine >1.2 mg/dL, cellular casts >1/hpf, and absence of nephrotic range proteinuria; with V: age at nephritis diagnosis >32 years, malar rash, absence of musculoskeletal complaints or serum C3 hypocomplementemia, nephrotic range proteinuria, and ≤9 urine erythrocytes/hpf. A risk predictive score of specific histological classes was calculated for each patient. Associations between 2, 3 or more risk factors with specific histological classes were also revealed [Odds ratios (95% confidence interval) (≥2 risk factors) was 6.7 (2.8-17.4) for class II nephritis, 15.6 (5.1-47.8), and 8.2 (3.6-19.0) for classes III/IV and for class V, respectively (≥3 risk factors)]. The identification of independent factors associated with specific classes of lupus nephritis can provide guidance in selecting specific therapeutic modalities, particularly in cases in which renal biopsy is contraindicated.

Intoxicação por Enterolobium contortisiliquum em bovinos na região Nordeste do Brasil / Poisoning by Enterolobium contortisiliquum in cattle in Northeastern Brazil

Descreve-se um surto de fotossensibilização causada por favas de Enterolobium contortisiliquum em bovinos no Estado de Pernambuco, Nordeste do Brasil. Os sinais clínicos observados foram hiporexia, prostração, perda de peso, edema generalizado, dermatite e icterícia. Havia anemia e atividades séricas de AST, LDH e GGT elevadas. A concentração sérica de ureia encontrava-se levemente aumentada e creatinina, proteínas séricas e albumina estavam em níveis normais. Na necropsia, o fígado estava aumentado de tamanho e difusamente alaranjado e os rins estavam aumentados de volume e apresentavam estriações esbranquiçadas irregulares entremeadas por áreas escuras na superfície subcapsular. Histologicamente, observou-se na pele, dermatite ulcerativa. No fígado havia vacuolização e necrose de hepatócitos da região centrolobular e ocasionalmente necrose individual de hepatócitos em outras regiões. O rim apresentava nefrose tubular tóxica. O diagnóstico diferencial da intoxicação por E. contortisiliquum na região semiárida deve incluir as intoxicações por Brachiaria spp, Panicum dichotomiflorum e Froelichia humboldtiana, que também causam fotossensibilização...

An outbreak of photosensitization caused by Enterolobium contortisiliquum pods is reported in cattle in the state of Pernambuco, semiarid region of Northeastern Brazil. The clinical signs included decreased appetite, prostration, weight loss, subcutaneous edema, dermatitis and jaundice. The animals presented mild anemia, elevated serum activities of AST, LDH and GGT, and increased serum concentrations of urea. Serum concentrations of creatinine, total proteins and albumin were within normal ranges. At necropsy, the liver was increased in size and diffusely orange. The subcapsular surface of the kidneys showed irregular whitish striations interspersed with dark areas. Histologically, the skin showed dermatitis, and the liver had centrolobular vacuolation and necrosis of hepatocytes and occasionally single cell necrosis. Tubular toxic nephrosis was also observed. The poisoning by E. contortisiliquum should be differentiate from photosensitation caused by other plants including Brachiaria spp., Panicum dichotomiflorum and Froelichia humboldtiana...

[Aged skin and skin care]. / Altershaut und Hautpflege.

BACKGROUND: Aged skin is the sum of chronological und UV-induced aging. Light-exposed skin is unattractive, with irregular pigmentation, roughness und scaliness. The skin is often dry and itches. METHODS: The present paper provides an overview of diseases of aging skin and describes how to prevent or reduce disease by prophylactic and therapeutic skin care. RESULTS: Aged skin can develop into several skin diseases, e.g., different types of eczema and skin cancer. In the body folds we often find an irritant contact eczema caused by friction from skin to skin, sweating, and urinary and fecal incontinence. In the bedridden, bed sores can also develop. Furthermore, there is a delay in wound healing owing to old age. Use of adequate creams and ointments is very helpful in preventing and improving most skin diseases of mature skin. However, the knowledge of aged people and healthcare professionals about the importance of skin care is low. Older people are often unable to care for their skin because they are lacking the physical and mental ability. CONCLUSION: Healthcare professionals are not sufficiently trained about the value of proper skin care. Adequate studies on the role of skin care and selection of the correct preparation in various aged-related diseases are lacking.

Oxidative stress and mitochondrial dysfunction in Kindler syndrome.

BACKGROUND: Kindler Syndrome (KS) is an autosomal recessive skin disorder characterized by skin blistering, photosensitivity, premature aging, and propensity to skin cancer. In spite of the knowledge underlying cause of this disease involving mutations of FERMT1 (fermitin family member 1), and efforts to characterize genotype-phenotype correlations, the clinical variability of this genodermatosis is still poorly understood. In addition, several pathognomonic features of KS, not related to skin fragility such as aging, inflammation and cancer predisposition have been strongly associated with oxidative stress. Alterations of the cellular redox status have not been previously studied in KS. Here we explored the role of oxidative stress in the pathogenesis of this rare cutaneous disease. METHODS: Patient-derived keratinocytes and their respective controls were cultured and classified according to their different mutations by PCR and western blot, the oxidative stress biomarkers were analyzed by spectrophotometry and qPCR and additionally redox biosensors experiments were also performed. The mitochondrial structure and functionality were analyzed by confocal microscopy and electron microscopy. RESULTS: Patient-derived keratinocytes showed altered levels of several oxidative stress biomarkers including MDA (malondialdehyde), GSSG/GSH ratio (oxidized and reduced glutathione) and GCL (gamma-glutamyl cysteine ligase) subunits. Electron microscopy analysis of both, KS skin biopsies and keratinocytes showed marked morphological mitochondrial abnormalities. Consistently, confocal microscopy studies of mitochondrial fluorescent probes confirmed the mitochondrial derangement. Imbalance of oxidative stress biomarkers together with abnormalities in the mitochondrial network and function are consistent with a pro-oxidant state. CONCLUSIONS: This is the first study to describe mitochondrial dysfunction and oxidative stress involvement in KS.

Pain during topical photodynamic therapy of actinic keratoses with 5-aminolevulinic acid and red light source: randomized controlled trial.

BACKGROUND: Pain is the major drawback of photodynamic therapy (PDT), an otherwise effective treatment for actinic keratoses (AKs). OBJECTIVE: To determine pain intensity and its dependence upon various factors during PDT with 5-aminolevulinic acid for face/scalp AKs. METHODS: A prospective, randomized, within-patient comparison study was performed. Thirty-eight patients with at least two clearly definable, mild or moderate AKs were randomized to receive either a red light dose of 70 or 100 J/cm(2) as a first or second split face/scalp treatment. They were blinded to the light dose administered. Pain during treatment was assessed using a visual analog scale (VAS). RESULTS: The mean intensity of pain during the first treatment session was 5.00 (± 1.78), while during the follow-up VAS score was 4.50 (± 1.51). Bigger AKs (> 130 mm(2) ) were more painful than the smaller ones (P = 0.003) and AKs on the face were twice more painful than the ones on the scalp (P = 0.002). Gender and patient age were poor pain predictors. Pain was independent of the patient's Fitzpatrick skin type, AK clinical grade, pretreatment fluorescence intensity, and the light dose during PDT. CONCLUSION: Pain during PDT is associated with AK location and size. Treatment of bigger lesions (> 130 mm(2) ) results in more pain than smaller ones and treatment of the face is more painful than the scalp area.

[Normal and abnormal skin color]. / La couleur de la peau normale ou anormale.

The varieties of normal skin color in humans range from people of "no color" (pale white) to "people of color" (light brown, dark brown, and black). Skin color is a blend resulting from the skin chromophores red (oxyhaemoglobin), blue (deoxygenated haemoglobin), yellow-orange (carotene, an exogenous pigment), and brown (melanin). Melanin, however, is the major component of skin color ; it is the presence or absence of melanin in the melanosomes in melanocytes and melanin in keratinocytes that is responsible for epidermal pigmentation, and the presence of melanin in macrophages or melanocytes in the dermis that is responsible for dermal pigmentation. Two groups of pigmentary disorders are commonly distinguished: the disorders of the quantitative and qualitative distribution of normal pigment and the abnormal presence of exogenous or endogenous pigments in the skin. The first group includes hyperpigmentations, which clinically manifest by darkening of the skin color, and leukodermia, which is characterized by lightening of the skin. Hypermelanosis corresponds to an overload of melanin or an abnormal distribution of melanin in the skin. Depending on the color, melanodermia (brown/black) and ceruloderma (blue/grey) are distinguished. Melanodermia correspond to epidermal hypermelanocytosis (an increased number of melanocytes) or epidermal hypermelanosis (an increase in the quantity of melanin in the epidermis with no modification of the number of melanocytes). Ceruloderma correspond to dermal hypermelanocytosis (abnormal presence in the dermis of cells synthesizing melanins) ; leakage in the dermis of epidermal melanin also exists, a form of dermal hypermelanosis called pigmentary incontinence. Finally, dyschromia can be related to the abnormal presence in the skin of a pigment of exogenous or endogenous origin.

[Pigmentary lesions in patients with increased DNA damage due to defective DNA repair]. / Lésions pigmentaires et maladies de la réparation de l'ADN.

The occurrence of abnormally pigmented skin lesions is a common phenomenon and often associated with the influence of ultraviolet radiation (UV) and other sources of DNA damage. Pigmentary lesions induced by UV radiation and other sources of DNA damage occur in healthy individuals, but human diseases with defective DNA repair represent important models which allow the investigation of possible underlying molecular mechanisms leading to hypo- and hyperpigmentations. There are several hereditary diseases which are known to go along with genetic defects of DNA repair mechanisms comprising Xeroderma pigmentosum (XP), Cockayne syndrome (CS), Trichothiodystrophy (TTD), Werner syndrome (WS), Bloom syndrome (BS), Fanconi anemia (FA) and Ataxia telangiectasia (AT). These diseases share clinical characteristics including poikilodermatic skin changes such as hypo-and hyperpigmentation. Since UV radiation is the most common source of DNA damage which can cause pigmentary lesions both in healthy individuals and in patients with genetic deficiency in DNA repair, in the present article, we focus on pigmentary lesions in patients with XP as an example of a disease associated with genetic defects in DNA repair.

[Mechanisms underlying post-inflammatory hyperpigmentation: lessons from solar lentigo]. / Mécanismes de l'hyperpigmentation post-inflammatoire: ce que le lentigo actinique nous a appris.

Hyperpigmentation of the skin is a common dermatologic condition in all skin types but most prominent in brown-skinned population. In skin of color any inflammation or injury can be accompanied by alterations in pigmentation (hyper/hypo-pigmentation). Postinflammatory hyperpigmentation (PIH) can be observed in many skin conditions including acne, eczema, and contact dermatitis. In the control of skin pigmentation, parallel to the cross-talk between keratinocytes and melanocytes, increasing evidence has underlined the crucial role exerted by the interactions between mesenchymal and epithelial cells through the release of fibroblast-derived growth factors. Among these factors, the keratinocyte growth factor (KGF), alone or in combination with interleukin-1α, induces melanin deposition in vitro and hyperpigmented lesions in vivo. Furthermore, a moderate increase of KGF and a high induction of its receptor have been shown in solar lentigo lesions, suggesting the involvement of this growth factor in the onset of the hyperpigmented spots. Several studies highlight the possible contribution of the fibroblast-derived melanogenic growth factors to the hyperpigmentated lesions, in the context of the mesenchymal - epithelial interactions modulating melanocyte functions.