Background: The relationship between cutaneous and extracutaneous complications in pediatric patients with type 1 diabetes is unclear. Objective: The objective of the current study is to investigate the relationship between skin disorders and diabetic microangiopathic changes in pediatric and adolescent patients with type 1 diabetes. Patients and methods: Eighty patients with type 1 diabetes and 50 healthy controls were enrolled in the study. All recruited patients were followed up monthly for a total period of 12 month. Monthly visit included thorough clinical examination with system review, as well as whole-body cutaneous examination. HbA1c was assessed every 3 month. Twenty-four hours urine was collected for measurement of urinary albumin. Results: Fifty percent of the screened diabetic cohort had diabetic nephropathy (DN). The overall prevalence of cutaneous lesion among the studied diabetic cohort was high (72.5%), with cutaneous infections (40%) and xerosis (30%) being the most prevalent. The frequency of cutaneous infections, xerosis and rubeosis faciei was higher in patients with nephropathy than in those without nephropathy. Conclusion: cutaneous affection in patients with diabetes may be a clue to the presence of associated microangioapthic complications. The significant association between diabetic nephropathy and cutaneous lesions support the concept that cutaneous lesion in diabetes is a reflection of diabetic angiopathy, highlighting the importance of identifying patients at risk of other microvascular complications.
The sebaceous gland, long considered an evolutionary relic with little-to-no physiological relevance in humans, has emerged in recent decades as a key orchestrator and contributor to many cutaneous functions. In addition to the classical physico-chemical barrier function of the skin against constant environmental challenges, a more novel, neuro-immune modulatory role has also emerged. As part of the complex intercellular communication network of the integumentary system, the sebaceous gland acts as a "relay station" in the skin for many endocrine factors. This review aims to offer a comprehensive overview of endocrine effects and subsequent interactions on this much maligned mini-organ.
Atopic dermatitis is a chronic inflammatory skin disease that arises because of complex environmental, immunological, and genetic interactions. Adipokines are bioactive mediators secreted from adipocytes of white adipose tissue and are known to have a role in body metabolism and regulation of immune responses. Leptin is a proinflammatory adipokine that functions mainly to regulate food intake and energy expenditure. Few studies have implicated adipokines in the pathogenesis of atopic dermatitis. In this study, we investigated the association of three leptin gene polymorphisms: -2548G>A (rs7799039), -188 C/A (rs791620), and A19G (rs2167270), with the incidence of atopic dermatitis. One hundred and sixty-four patients and one hundred and sixty-seven age- and gender-matched controls were genotyped using the polymerase chain reaction-restriction fragment length polymorphism procedure. A significant association was found between rs2167270 and the incidence of atopic dermatitis (P < 0.05). The GG allele was more prevalent in the patients' group with genotype frequency of 38.7%, compared to 26.1% for the control group. No significant differences were found in the genotype distribution or allelic frequency of the other two examined polymorphisms, rs7799039 and rs791620, between atopic dermatitis patients and controls (P > 0.05). The results suggest that rs2167270 might play a role in the pathogenesis of atopic dermatitis.
Background: Acne vulgaris is an inflammatory skin disorder with not as yet fully understood pathogenesis. In this controlled study, we assessed acne vulgaris patients for several possible pathogenic factors such as vitamin D deficiency, vegan diet, increased body mass index (BMI) and positive anti-transglutaminase antibody. Methods: We screened 10 years of records at a family medicine clinic for patients diagnosed with acne vulgaris. In eligible subjects, we collected data regarding 25-hydroxylvitamin D levels, BMI, dietary preference and serum IgA tissue transglutaminase levels. Controls were age- (+/- 12 months) and sex-matched patients seen during the study period without a diagnosis of acne vulgaris. Results: 453 patients were given a diagnosis of acne vulgaris during the study period. Compared with controls, we found significant associations between vitamin D deficiency (<50nmol/L), and/or positive transglutaminase antibody level (>4.0U/mL) and a diagnosis of acne vulgaris. Conclusions: Our study adds important information to the current body of literature in pursuit of elucidating the pathogenesis of this complex multifactorial disease.
The current study examined the effect of single nucleotide (SNPs) polymorphisms in the ADIPOQ gene (I146T and G276T) on body mass index (BMI) of young adult women. The women were divided into underweight, normal, overweight and obese according to BMI. The circulating levels of adiponectin were measured using commercially available ELISA kits. Genetic polymorphisms were genotyped using the PCR-RFLP method. G276T and I164T SNPs are common in the examined population as the frequency of G allele of 276 SNP was 54.8% and for the T allele of 164 SNP it was 41.7%. Circulating adiponectin levels were related to BMI and were lowest in the obese versus overweight, normal weight and underweight groups (p<0.01). However, ADIPOQ gene SNPs (I146T and G276T) showed no association with BMI groups. In conclusion, the results may suggest that adiponectin level, but not ADIPOQ gene SNPs, is a good indicator to BMI in young adult women.
Any clinical/biochemical marker revealing obesity or diabetes before their appearance is valuable. Insulin resistance (IR) is present in both disorders many years before occurrence. Accordingly, we determined whether acanthosis nigricans (AN) in the knuckles is associated to higher insulin and homeostasis model assessment for estimated insulin resistance (HOMA-IR) index values, and assessed the influence of body-mass index (BMI) and the diagnostic performance of AN in the knuckles to detect IR. In this cross-sectional controlled study, we included men or women, 18 to 23 years old, with or without AN in the knuckles. In 149 cases with AN in the knuckles and 145 controls, fasting insulin was higher in cases (13.45 mu U/mL +/- 7.8 vs. 8.59 mu U/mL +/- 3.63, P < .001, respectively). Mean HOMA-IR index was also higher (2.86 +/- 1.68 vs. 1.78 +/- 0.77, P < .001). A significant increase in fasting insulin and HOMA-IR values between and within BMI groups from normal through obese category was identified in controls and cases. By multivariate regression analysis, cases with normal BMI were significantly associated to a HOMA-IR >= 2.5 (OR = 3.09, CI95% = 1.75-5.48, P = .001). A model of AN in the knuckles, normal BMI, and increased waist circumference allowed identifying 2 out of 3 cases with HOMA-IR index >= 2.5. AN in the knuckles could be addressed with two aims: as an easy, accessible, and costless diagnostic tool suggesting hyperinsulinemia secondary to IR, and, an early marker of IR even in the absence of overweight or obesity.
The pathogenetic role of vitamin D as well as its clinical correlation in inflammatory skin diseases is still uncertain. This study aimed to compare serum levels of 25(OH) vitamin D (calcidiol) in outpatients suffering from different skin diseases using the same laboratory method in one study. In routine serum samples of 1,532 patients from the previous 12 months we identified retrospectively 180 (mean age 49.4 years, 80 female, 100 male) and 205 (mean age 36.3 years, 116 female, 89 male) patients with psoriasis (PSO) and atopic dermatitis (AD), respectively. Clinical disease activity and quality of life was evaluated using Physicians Global Assessment Scores (PGA), Dermatology Life Quality Index (DLQI), and a Visual Analog Scale for pruritus in AD, respectively. The median 25(OH)D serum level of all patients (22.97 ng/mL, range 2.61-96.0, n = 1,461) was significantly lower in comparison to healthy controls (41.6 ng/mL, range 16.9-77.57, p < 0.0001, n = 71). In PSO and AD we measured 21.05 ng/mL (44% < 20 ng/mL) and 22.7 ng/mL (39% < 20 ng/mL), respectively (p = 0.152). Among all subgroups, patients with severe acute or chronic infectious skin diseases had the lowest median 25(OH)D serum levels (17.11 ng/mL, n = 94, 66% < 20 ng/mL, p < 0,001 vs. AD, p = 0,007 vs. PSO). For PSO and AD there was no significant correlation between 25(OH)D levels and PGA scores and DLQI values, respectively, or the extent of pruritus in AD. 25(OH)D serum levels in inflammatory skin diseases might correlate more with the type of disease and the degree of inflammation than with clinical activity itself.
Most keloids are clinically observed as solid nodules or claw-like extensions. However, they appear hypoechoic on ultrasound images and are therefore easily confused with liquid features such as blood or vessels. The pathological manifestations of typical keloids also include prominent, thick blood vessels. The existing classification of scars fails to reflect the natural history of keloids. The outer characteristics of a typical keloid include bright red hyperplasia with abundant vessels, suggesting the importance of vascular components in the process of scar formation and prompting consideration of the role of inflammation in the development of granular hyperplasia. Additionally, we further considered the potential effectiveness of oral isotretinoin for severe keloids secondary to severe acne. We also explored different principles and applications related to 5-fluorouracil (5-FU), pulsed dye laser (PDL), and CO2 laser treatments for scars.
Supplementation by the general public with vitamin D at doses above the Tolerable Upper Level of Intake (UL) is becoming quite common. The objective of the current analysis was to characterize the effect of vitamin D supplementation at doses up to 15,000 IU/d in a community-based program on vitamin D status, calcium homeostasis as well as on kidney, liver and immune function. We evaluated data collected for 3,882 participants in a community program for whom there were blood measurements at program entry and at follow-up within 6-18 months between 2013 and 2015. Participants were supplemented with a wide range of vitamin D doses (1,000 - 15,000 IU/d) aimed at achieving serum 25-hydroxyvitamin D [25(OH)D] levels of at least 100 nmol/L. Serum 25(OH)D concentrations up to 300 nmol/L were achieved without perturbation of calcium homeostasis or incidence of toxicity. Hypercalcemia and hypercalciuria were not related to an increase in 25(OH)D concentrations nor vitamin D dose. To achieve serum 25(OH)D levels >100 nmol/L on average, required vitamin D intakes of 6,000 IU/d for normal Body Mass Index (BMI), 7,000 IU/d for overweight and 8,000 IU/d for obese. Doses of vitamin D in excess of 6,000 IU/d were required to achieve serum 25(OH)D concentrations above 100 nmol/L, especially in individuals who were overweight or obese without any evidence of toxicity. Serum 25(OH)D concentrations up to 300 nmol/L were found to be safe.
Objective: This study was to verify if the skin cleanser could help decrease the infection ratio of Demodex Folliculorum in acne patients. Methods: 132 participants with mild to moderate vulgaris acne participated in this monocentric, prospective, double-blind study. Dermatologists grading and Standardized Skin Surface Biopsy were performed in baseline and after using cleanser only 7 d later. Results: There was no significant difference between the 2 times for each type of acne, but the number of Demodex Folliculorum was significantly decreased compared with baseline. There was no relationship between the number of Demodex Folliculorum and the total number of acne lesions. Limitations: Short follow-up time in 7 d. Conclusion: Using the cleanser could decrease the average number of Demodex Folliculorum in only 7 d in mild to moderate acne patients. There is no relationship between Demodex and acne lesions number.
Recent studies indicate an important role for vitamin D3 in autism spectrum disorder (ASD), although its mechanism is not completely understood. The most puzzling aspect of ASD is that identical twins, who share identical DNA, do not have 100% concordance rates (∼88% for identical and ∼31% for fraternal twins). These findings provide major clues into the etiology: ASD must involve an environmental factor present in the prenatal milieu that both identical twins are not always exposed to because they do not always share it (i.e., placentas). Combined with the exponential increasing rates of ASD around the world, these observations suggest a contagious disease is probably transferred to the fetus via the placenta becoming infected by a cervical virus. Vitamin D3 boosts immune responses clearing viral infections and increases serotonin and estrogen brain levels. Here we review the different roles and untangle the most probable one vitamin D3 plays in ASD.
Adult female acne is a chronic inflammatory, immune-mediated disease that affects the pilosebaceous unit in women in their 20s to 40s, and is considered different from acne vulgaris. Propionibacterium acnes is recognized by TLR-2, resulting in activation of this receptor and an inflammatory response through the NFκ B pathway. This therapeutic, interventional, open, randomized, evaluator-blinded and comparative trial included 38 adult women with moderate facial acne and 10 age-matched controls, all aged between 26 and 44 years. Two treatments were performed over six months: 15% azelaic acid gel (AA) bid (n = 18) and oral contraceptive (COC) drospirenone 3 mg/ethinylestradiol .02 mg (n = 20). Biopsies were taken at baseline (control, lesion, perilesional) and at the conclusion (lesion and perilesional) of the study to evaluate TLR-2 expression by immunohistochemistry. Lesion count and blind photographic evaluation were used for efficacy. The groups were homogeneous: 70% of lesions were located in the submandibular area, 95% of participants had inflammatory lesions; of these, 50% had persistent and 50% had late-onset acne. The mean ages were 33.7 ± 5.5 and 33.1 ± 5.3 years (COC and AA group, respectively). A moderate clinical improvement was observed in both groups. No difference in TLR-2 expression in the lesion or perilesional areas was observed; however, reduced TLR-2 expression was seen in the control group. A significant reduction in expression was observed after both treatments, with no difference between the groups. This finding suggests an anti-inflammatory effect of COCs and AA in adult female acne, via modulation of the TLR-2 receptor.
ABSTRACT Acne vulgaris is a chronic inflammatory disease that affects the pilosebaceous unit. Recent studies have shown an increasing number of cases of acne in adult women. These cases are predominantly normoandrogenic and have show some clinical differences compared to adolescent acne. In addition to the physical aspects, acne has a strong psychosocial impact and can lead to the onset of signs and symptoms of depression, such as anger. Our objective was to evaluate the effect on acne-specific quality of life in adult women treated with topical azelaic acid versus a combined oral contraceptive. The study population consisted of 38 adult women with acne and without any features of hyperandrogenism recruited from the clinic of Dermatology Hospital Division of São Paulo, Federal University of São Paulo from January 2012 to September 2014. Patients were randomized into two different groups: one receiving containing 20 ug of ethinylestradiol and 3 mg drospirenone in a regimen of 24 days of medication, a combined oral contraceptive (COC), and the other group topical 15% azelaic acid (AA) gel, twice daily, both for six months. The quality of life was evaluated at baseline and end of treatment with an acne specific measure (Acne-QoL). Before treatment, our data revealed a significant impact of the presence of acne on quality of life. Both treatments resulted in improvement with significant statistical values in quality of life scores. Comparing the four domains of Acne-QoL, patients treated with an oral contraceptive showed greater improvement in two domains (self-perception and acne symptoms) than those treated with azelaic acid.
ABSTRACT The major effects of the epidermal growth factor receptor (EGFR) signalling pathway on keratinocytes are cell proliferation, cell differentiation, and wound healing. In addition to these effects, an immunosuppressive effect of EGFR signalling has been reported. However, the precise mechanism of immunosuppression by EGFR signalling is not well understood. In this study, we clarified the involvement of increased local cortisol activation in EGFR signalling-induced immunosuppression in keratinocytes. EGF treatment up-regulated the expression of 11β-hydroxysteroid dehydrogenase 1 (11β-HSD1) and supernatant cortisol levels in a dose-dependent manner in keratinocytes. 11β-HSD1 is an enzyme that catalyses the conversion of cellular hormonally inactive cortisone into active cortisol. qRT-PCR and ELISA assays indicated that EGF significantly decreased tumour necrosis factor α (TNF- α)-induced interleukin-6 (IL-6) expression in keratinocytes. Similarly, 11β-HSD1 overexpression significantly decreased TNF-α-induced IL-6 expression. We evaluated the role of 11β-HSD1 in immunosuppression through EGFR signalling. Blockade of 11β-HSD1 via 11β-HSD1 inhibitor reversed both the expression and production of TNF-α-induced IL-6, which was decreased by EGF in keratinocytes. Therefore, increased local cortisol activation by 11β-HSD1 is involved in EGFR signalling-induced immunosuppression in keratinocytes. Finally, we evaluated whether EGFR inhibition by cetuximab affects the expression of 11β-HSD1. We found that 0.1 µg cetuximab decreased 11β-HSD1 transcript levels in keratinocytes. The changes in 11β-HSD1 were more apparent in TNF-α-treated cells. As 11β-HSD1 expression in keratinocytes is associated with inflammation and cell proliferation, this mechanism may be associated with adverse skin reactions observed in patients treated with EGFR inhibitors.
Acne vulgaris is an incompletely understood disorder of poliosebaceous follicles. A scourge of adolescence, it is increasingly persisting into the mid-forties, especially in females. 45% of women aged 21–30 years, 26% aged 31–40 years, and 12% aged 41–50 years, suffer from clinically-visible acne.1 The reasons for this rising prevalence have been unclear. Polycystic ovarian syndrome (PCOS) has been suggested as a possible contributor, however most acne sufferers have normal serum androgen levels.2,3 There has been increasing suspicion of a key autoinflammatory role in pathogenesis of chronic acne vulgaris. Autoinflammatory syndromes associated with acne have been described as possibly sharing common pathogeneses, involving dysregulated immunity with abnormal interleukin-1 signaling, leading to clinically significant inflammation.4,5 Thyroid autoimmunity has been detected in a number of chronic inflammatory skin conditions including acne vulgaris and chronic idiopathic urticaria.6,7 In 2012, Vergou and colleagues were the first to show female post-adolescent acne sufferers had significantly higher rates of thyroid autoimmunity compared with healthy controls.7 The relationship has not been examined since, despite a sound theoretical grounding. We aimed to confirm this association between thyroid autoimmunity and post-adolescent acne in adult women, as well as qualify its practical value with subsequent endocrinologist referral and intervention.
5-Aminolevulinic acid photodynamic therapy (ALA-PDT) has been an effective method for treating acne vulgaris. Red light is the most widely used light source while Intense pulsed lights (IPL) is reported effective and well-tolerated. The purpose of this study was to evaluate the efficacy and adverse reactions of ALA-PDT with red light on acne compared with ALA-PDT with IPL.12 patients were recruited in the randomized, prospective and split-face study. 5% ALA cream were applied on the whole face with 2 hours' incubation before narrow band LED(633 ± 10 nm, 36 ∼ 108J/cm2) on one side of face and IPL(590∼1200 nm, 15∼17J/cm2) on the other side. Three treatment sessions were administered with 2-week interval each time and 8 weeks' follow up. The number of the total acne lesions and inflammatory lesions of the side treated by red light-PDT showed a relatively higher reduction rate that that by IPL-PDT (P < 0.05). Significant PpIX fluorescence decrease was observed only for the group of red light (P < 0.05). Lower pain intensity numeric rating scale values and Investigator's Global Severity Assessment (IGA) grading for erythema of the IPL side were observed (P<0.05).The results suggested that both red light and IPL are effective for ALA-PDT on acne vulgaris. ALA-PDT with red light may achieve better efficacy by more effective photobleaching of protoporphyrin IX (PpIX), whereas IPL may accomplish less adverse reactions and better tolerance.
The major role of sebaceous glands in mammals is to produce sebum, which coats the epidermis and the hair providing waterproofing, thermoregulation and photoprotection. However, as the need for these functions decreased along the evolutionary changes in humans, a relevant question has been raised: are sebaceous glands and sebum the remnants of our mammalian heritage or do they have overtaken a far more complex role in human skin biology? Trying to provide answers to this question, this review introduces the evolving field of sebaceous immunobiology and puts into the focus the pathways that sebum lipids use to influence the immune milieu of the skin. By introducing possible modifiers of sebaceous lipogenesis and discussing the - human-specific - alterations in composition and amount of sebum, the attribute of sebum as a sensitive tool, which is capable of translating multiple signalling pathways into the dermal micro environment is presented. Further their interaction with macrophages and keratinocytes involves sebum lipid fractions into disease pathogenesis, which could lead - on the other side - to the development of novel sebum-based therapeutic strategies.
Rosacea is a chronic relapsing inflammatory skin disease with a high prevalence among adults of Northern European heritage with fair skin. Symptoms present in various combinations and severity, often fluctuating between periods of exacerbation and remission. Based on morphological characteristics, rosacea is generally classified into four major subtypes: erythematotelangiectatic, papulopustular, phymatous, and ocular. Diverse environmental and endogenous factors have been shown to stimulate an augmented innate immune response and neurovascular dysregulation; however, rosacea's exact pathogenesis is still unclear. An evidence-based approach is essential in delineating differences between the many available treatments. Because of the diverse presentations of rosacea, approaches to treatment must be individualized based on the disease severity, quality-of-life implications, comorbidities, trigger factors, and the patient's commitment to therapy.
Objective: To increase the level of awareness that Ehlers-Danlos/hypermobility syndrome (EDS) and vitamin D deficiency are associated with infantile fragility fractures and radiologic features that may be mistakenly reported to be caused by non-accidental trauma due to Child Abuse and Neglect (CAN). Patients and Methods: We constructed a case series, the largest to date, of infants with EDS who were vitamin D sufficient, insufficient and deficient and infants without EDS but with documented vitamin D deficiency and radiologic evidence of rickets who presented with multiple fractures originally diagnosed as being non-accidental and caused by child abuse. These infants were referred to the outpatient Bone Health Care Clinic at Boston University Medical Campus over a 6-year (2010-2015) period. We also present 6 index cases in which the court concluded that there was no convincing evidence of child abuse and the infants were returned to their parents. Institutional Review Board (IRB) approval was obtained. Results: We present 72 cases of infants with multiple fractures diagnosed to be caused by non-accidental trauma. All infants were younger than one year of age. Among them, 93%(67) had clinical evidence of EDS and/or a family history with a confirmed clinical diagnosis of at least one parent having EDS and the other 7%(5) without evidence of EDS had vitamin D deficiency/infantile rickets. Three of the EDS infants were diagnosed as osteogenesis imperfecta (OI)/EDS overlap syndrome. The most common fractures noted at diagnosis were ribs and extremity fractures (including classic metaphyseal lesions). Serum levels of 25-hydroxyvitamin D [25(OH)D] were reported in 48 infants (18.0 ± 8.5 ng/ml) and in 30 mothers (21.3 ± 11.7 ng/ml). Sixty-three percent (27) of the EDS infants who had their serum 25(OH)D measured were vitamin D deficient 25(OH)D<20 ng/ml and 5 were vitamin D sufficient 25(OH)D>30 ng/ml. The mean serum level for infants with vitamin D deficiency/rickets was (10.2 ± 3.0 ng/ml) Conclusion: EDS, OI/EDS and vitamin D deficiency/infantile rickets are associated with fragility fractures in infants that can be misinterpreted as caused by non-accidental trauma due to child abuse.
Dehydroepiandrosterone (DHEA) is a weak androgen and had been shown to have anti-cancer, anti-adipogenic and anti-inflammatory effects on mouse and other rodent models, but not on humans, suggesting a systemic level difference between mouse and human. Our previous study on DHEA biological functions involving a variety of cell lines, suggested that the functional differences between mouse and human existed even at the cellular level. Hence, using mouse and human melanoma cell models, in-vitro effects of DHEA on cell growth, mechanism of cell death and mechanism of DHEA action were studied. Results indicated a differential biological effects of DHEA between mouse and human melanoma cell lines. These in-vitro studies also suggested that the differential biological effects observed between these two cell lines could be due to the difference in the way DHEA was processed or metabolized inside the cell.
