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BACKGROUND: Eczema and psoriasis are common diseases. Despite both showing active epidermal contribution to the inflammatory process, their molecular aetiology and pathological mechanisms are different. OBJECTIVE: Further molecular insight into these differences is therefore needed to enable effective future diagnostic and treatment strategies. The majority of our mechanistic and clinical understanding of psoriasis and eczema is derived from RNA, immunohistology and whole skin biopsy data. METHODS: In this study, non-invasive epidermal sampling of lesional, perilesional and non-lesional skin from diseased and healthy skin was used to perform an in depth proteomic analysis of epidermal proteins. RESULTS: Our findings confirmed the psoriasis-associated cytokine IL-36γ as an excellent protein biomarker for lesional psoriasis. However, ELISA and ROC curve analysis of 53 psoriasis and 42 eczema derived samples showed that the sensitivity and specificity were outperformed by elastase-specific protease inhibitor, elafin. Of note, elafin was also found upregulated in non-lesional psoriatic skin at non-predilection sites demonstrating inherent differences between the non-involved skin of healthy and psoriatic individuals. Mass spectrometry and ELISA analysis also demonstrated the upregulation of the anti-inflammatory molecule IL-37 in psoriatic perilesional but not lesional skin. The high expression of IL-37 surrounding psoriatic plaque may contribute to the sharp demarcation of inflammatory morphology changes observed in psoriasis. This finding was also specific for psoriasis and not seen in atopic dermatitis or autoimmune blistering perilesional skin. Our results confirm IL-36γ and add elafin as robust, hallmark molecules distinguishing psoriasis and eczema-associated inflammation even in patients under systemic treatment. CONCLUSIONS: Overall, these findings highlight the potential of epidermal non-invasive sampling and proteomic analysis to increase our diagnostic and pathophysiologic understanding of skin diseases. Moreover, the identification of molecular differences in healthy-looking skin between patients and healthy controls highlights potential disease susceptibility markers and proteins involved in the initial stages of disease.
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Pruritus is defined as a symptom that leads to scratching. Clinically, a heterogeneous group of clinical pictures of different etiology must be considered. Pruritus is characterized by varying intensity and duration. Many patients and/or their social environment, which is influenced by this, cite the impact on sleep quality as an accompanying main symptom. The patient's quality of life is affected depending on the severity of the pruritus and often leads to comorbidity such as depressive disorders or sleep disorders as well as to an impact on psychosocial well-being if it becomes chronic. To date, in addition to the medical history, the established examination methods have been the determination of the disease burden by assessing disease activity, e.g., with validated disease-specific scores, plus the assessment of quality of life using a dermatological quality of life index (DLQI). The latest studies show that this is by no means sufficient to determine the severity of disease and, as a result, to identify adequate treatment options.
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Prurido , Qualidade de Vida , Qualidade do Sono , Transtornos do Sono-Vigília , Qualidade de Vida/psicologia , Humanos , Prurido/psicologia , Prurido/fisiopatologia , Doença Crônica , Transtornos do Sono-Vigília/psicologia , Transtornos do Sono-Vigília/epidemiologiaRESUMO
The scalp is the most common site affected in patients with psoriasis with up to 80% of these patients having some degree of scalp involvement. In this narrative review, we evaluate available data on the use of an innovative aerosol foam formulation of calcipotriol plus betamethasone dipropionate (Cal/BD) to treat patients with psoriasis and scalp involvement. The full PubMed database was searched using the terms "calcipotriol", "betamethasone dipropionate" and "aerosol foam", and all articles relating to "psoriasis with scalp involvement" were retrieved and used in the preparation of this review. The evidence supporting the clinical effectiveness, tolerability and impact on health outcomes of Cal/BD aerosol foam in patients with scalp psoriasis was obtained from a phase II clinical trial and real-world evidence data from a non-interventional study as well as from two case series. The findings from these studies show that Cal/BD aerosol foam is rapidly effective, improves skin condition, alleviates symptoms such as itch, and has a positive impact on patient quality of life. These attributes address several unmet needs for patients with psoriasis with scalp involvement and have the potential to improve individual adherence to treatment.
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BACKGROUND AND OBJECTIVES: Hidradenitis suppurativa (HS)/Acne inversa (Ai) is a chronic debilitating disease with limited therapy options. The device-based LAight therapy was approved in Europe in 2017. The aim of this study was to evaluate the effect of real-world care with at least one treatment with LAight therapy on disease activity and burden in 3,437 patients. PATIENTS AND METHODS: Patients were included in the analysis if they had a diagnosis of HS and received at least one treatment. The endpoints Hidradenitis Suppurativa Severity Score System (IHS4), pain on the numeric rating scale (pain-NRS) and Dermatology Life Quality Index (DLQI) were analyzed using a linear mixed model for repeated measures (MMRM) over 26 weeks of care with LAight therapy. Furthermore, responder rates were calculated for all endpoints, and the therapy's safety profile and patient satisfaction were thoroughly examined. RESULTS: A significant decrease in IHS4, pain-NRS, and DLQI was achieved during 26 weeks of care with LAight. The BMI at baseline had a significant negative effect on therapy response for pain-NRS and DLQI. CONCLUSIONS: This study confirms that LAight therapy leads to satisfactory disease control in all stages of severity and is a valuable addition to the therapeutic repertoire of HS.
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Hidradenite Supurativa , Qualidade de Vida , Hidradenite Supurativa/terapia , Humanos , Masculino , Feminino , Adulto , Resultado do Tratamento , Satisfação do Paciente , Índice de Gravidade de Doença , Pessoa de Meia-Idade , Medição da DorRESUMO
BACKGROUND: Data on the course of urticaria in children exist, but there is a lack of sound data on patient management to ensure high-quality care. METHODS: Retrospective secondary data analysis in the field of health care and epidemiology in children with urticaria based on routine data from a German health insurance company (DAK-Gesundheit). Data from insured persons under 18 years of age who were treated as outpatients or inpatients with a diagnosis of urticaria (according to ICD-10 classification) in 2010-2015 were included. The control group consisted of children without a corresponding diagnosis, in order to clarify health economic and care-related differences after adjusting for age and gender. RESULTS: In 2015, 1904 (1.3%) of 151,248 insured minors had a diagnosis of urticaria. Of the children with urticaria, 70.9% visited at least one physician on an outpatient basis. Of these visits, 70.9% were made to a pediatrician, 52.5% to a general practitioner and 33.0% to a dermatologist; 11% were treated as inpatients. With a total of 151,248 insured persons, 1904 of whom were diagnosed with urticaria, 72.9% of children and adolescents with versus 28.9% without urticaria were treated topically or systemically in 2015, including 10.5% of children with urticaria vs. 2.6% without urticaria received topical therapy and 70.0% with urticaria received systemic therapy vs. 27.5% without urticaria with systemic therapy. The most commonly used oral medications for urticaria were cetirizine (44.2%), prednisolone (9.8%), and dimetindene (2.0%) . Topical methylprednisolone aceponate (49.8%) was prescribed most frequently. The therapy costs for systemic drugs was â¯24.00 per patient, while topical drugs cost â¯1.58 per patient. CONCLUSION: The lack of guidelines for the standardization of treatment in children still leads to ambiguities and different treatment concepts among the specialist groups, which must be eliminated in order to enable more efficient therapies. The treatment of chronic urticaria in children and adolescents is mainly carried out by pediatricians, general practitioners and dermatologists. Systemic and topical medications as well as inpatient services are the most important cost factors.
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Custos de Cuidados de Saúde , Hospitalização , Urticária , Humanos , Criança , Alemanha , Feminino , Masculino , Adolescente , Pré-Escolar , Estudos Retrospectivos , Urticária/tratamento farmacológico , Urticária/economia , Lactente , Custos de Cuidados de Saúde/estatística & dados numéricos , Hospitalização/economia , Recém-NascidoRESUMO
Atopic dermatitis (AD) is a chronic recurrent inflammatory skin disease with a bipolar age distribution in childhood, adolescence and middle adulthood. Up to 50% of AD patients show ocular involvement, which can be potentially sight threatening. Clinically, the majority of cases present with atopic blepharo(kerato)conjunctivitis or atopic keratoconjunctivitis (AKC); other clinical variants from this group of inflammatory ocular surface diseases are keratoconjunctivitis vernalis in childhood and adolescence and allergic conjunctivitis. In addition to the aforementioned blepharitis, keratitis and conjunctivitis, AD is also associated with eyelid involvement with subsequent eyelid malposition, limbal insufficiency with the development of pseudopterygia, (chronic) cicatrizing conjunctivitis with symblephara formation and fornix shortening, as well as ocular surface malignancies such as conjunctival intraepithelial neoplasia (CIN) and squamous cell carcinoma. In addition, an association with AD or AKC has been described for keratoconus. Whereas the therapy of AD in dermatology has made revolutionary advances in recent years through the use of biologicals, the primary use of these biologicals in ophthalmological complications is still very hesitant. Treatment here is often provided using topical steroids and calcineurin inhibitors. The following article summarises recent developments in basic and clinical dermatological research and discusses them in the context of current concepts for ophthalmological therapy.
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Dermatite Atópica , Ceratoconjuntivite , Humanos , Ceratoconjuntivite/terapia , Ceratoconjuntivite/fisiopatologia , Ceratoconjuntivite/diagnóstico , Dermatite Atópica/terapia , Dermatite Atópica/fisiopatologia , Dermatite Atópica/diagnóstico , Resultado do Tratamento , Medicina Baseada em Evidências , Inibidores de Calcineurina/uso terapêutico , Produtos Biológicos/uso terapêutico , Conjuntivite Alérgica/fisiopatologia , Conjuntivite Alérgica/terapia , Conjuntivite Alérgica/diagnósticoRESUMO
INTRODUCTION: The prevalence of atopic diseases remains high. Initial studies suggest that primary prevention with regular basic care may influence the incidence of atopic dermatitis in infants; however, data are unclear. Midwives play an important role in the care of women in the peripartum period and therefore also in providing advice on topics such as skin care, breastfeeding and nutrition of the newborn and young infant. The aim of this study was to determine the care recommendations for newborns by midwives. METHODS: We conducted a cross-sectional survey among German midwives using questionnaires on the topic of newborn skin care. RESULTS: A total of 128 questionnaires were analyzed. The most common recommendations were oil-based herbal topicals (34.9%) and plain water (34.0%). Approximately 70% of midwives reported recommending various options when there was a known family history of atopic diathesis. It was remarkable that most of the midwives' recommendations were identical regardless of the presence of an atopic diathesis. Essential care products are only used "when necessary". CONCLUSION: Training programs for midwives on the topic of "care and strengthening of the skin barrier", taking into account the current guidelines for allergy prevention, should be implemented.
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Dermatite Atópica , Tocologia , Higiene da Pele , Humanos , Recém-Nascido , Feminino , Dermatite Atópica/epidemiologia , Adulto , Alemanha/epidemiologia , Masculino , Inquéritos e Questionários , Estudos Transversais , Guias de Prática Clínica como Assunto , Pessoa de Meia-IdadeRESUMO
INTRODUCTION: Patients with chronic inflammatory skin diseases often suffer from sleep disturbances. However, objective data on sleep architecture, especially to evaluate potential overall influences under therapy, are lacking. PATIENTS AND METHODS: Pilot study on sleep quality changes including psoriasis and atopic dermatitis patients before and 2 weeks after intensive topical treatment. In addition to disease activity rating, patient-rated outcomes for itch severity and sleep quality and polygraphy was performed before and after topical therapy. RESULTS: 14 psoriasis, eleven atopic dermatitis patients (10 female, 15 male) with a mean age of 49 years were included. Disease activity scores (EASI and PASI) were significantly reduced with topical therapy after 2 weeks (p < 0.001). Pruritus intensity (NRS) showed a significant influence on deep sleep, which resolved after therapy. Insomnia severity significantly decreased (r > 0.50, p < 0.05) and daytime sleepiness showed a significant reduction in 40% of patients. N3 (deep sleep) and REM sleep significantly improved, showing a strong effect (r > 0.50). The apnea-hypopnea index decreased in one of four patients independent of the individual BMI. CONCLUSIONS: Through polygraphy, we demonstrated impaired sleep patterns in psoriasis and atopic dermatitis patients with itch as a relevant factor and beyond that, rapid sleep improvement under 2 weeks of topical treatment.
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Dermatite Atópica , Psoríase , Humanos , Dermatite Atópica/tratamento farmacológico , Dermatite Atópica/complicações , Feminino , Masculino , Psoríase/tratamento farmacológico , Psoríase/complicações , Pessoa de Meia-Idade , Transtornos do Sono-Vigília/tratamento farmacológico , Projetos Piloto , Resultado do Tratamento , Adulto , Prurido/tratamento farmacológico , Prurido/etiologia , Administração Tópica , Fármacos Dermatológicos/administração & dosagem , Fármacos Dermatológicos/uso terapêutico , Efeitos Psicossociais da DoençaRESUMO
BACKGROUND: There is a lack of real-life safety data on treatment options for chronic urticaria in the presence of comedication and comorbidities. METHODS: We present a single-center UCARE pilot study of 212 outpatients with chronic urticaria. Patients were divided into three groups according to different CU therapies according to international guidelines. RESULTS: Of 212 patients, 108 (mean age 48.9 years, 71.3% female) had 59 comorbidities, including cardiovascular, autoimmune and malignant diseases. Patients were followed for a mean of 24.6 months (SD ± 21.3). Urticaria therapies were divided into three groups: A: 105 (97.2%) with omalizumab and 2nd generation antihistamines), B: 16 patients (14.8%): dual therapy with antihistamines and cyclosporine in 10 (9.3%), montelukast in five (4. 6%), dapsone in four (3.7%), hydroxychloroquine in one patient (0.9%), C: 12 (11.1%) patients received a third drug for 4.9 months (SD ± 3.2) and one quadruple therapy (2.1 months). 10 out of 12 (83.3%) patients received montelukast, two (16.7%) cyclosporine, two (16.7%) dapsone and one (8.3%) hydroxychloroquine as a third drug for chronic urticaria. CONCLUSIONS: Combining treatment modalities for chronic urticaria and comorbidities are available and feasible with a good safety profile.
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Acetatos , Antialérgicos , Urticária Crônica , Ciclopropanos , Quinolinas , Sulfetos , Urticária , Humanos , Feminino , Pessoa de Meia-Idade , Masculino , Hidroxicloroquina/uso terapêutico , Projetos Piloto , Doença Crônica , Urticária Crônica/tratamento farmacológico , Urticária/tratamento farmacológico , Omalizumab/uso terapêutico , Antagonistas dos Receptores Histamínicos H1/uso terapêutico , Ciclosporina/uso terapêutico , Dapsona/uso terapêutico , Antialérgicos/uso terapêuticoAssuntos
Alopecia , Líquen Plano , Humanos , Cetrimônio , Testes do Emplastro , Alopecia/diagnósticoRESUMO
Lichen planus (LP) presents with a range of clinical subtypes. It can affect the outer skin, involve the nails and present with alopecia and mucosal symptoms to varying degrees. LP of the outer skin mostly shows a self-limiting course; however, this is not the case for lichen planopilaris and the mucosa-affecting subtypes. The pathogenesis of LP is still incompletely understood. As a result, an effective, targeted therapy is currently lacking and different immunomodulatory approaches are being used in clinical practice. The management of patients with severe oral LP mucosae can be particularly challenging. Although the true risk remains controversial, oral LP is considered a risk factor for the development of squamous cell carcinoma and there is a need for regular screening. The quality of life in patients with LP is significantly impaired because of frequent clinical visits, pain, soreness, inability to eat certain foods, side effects to medication, frustrating therapy attempts and worry regarding cancer risk. We highlight here the advantages of an interdisciplinary dermatology and oral surgery clinic, which can address the domains of tooth status, nutrition, pain and malignant transformation and optimized patient management.
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Dermatologia , Líquen Plano Bucal , Líquen Plano , Procedimentos Cirúrgicos Bucais , Humanos , Qualidade de Vida , Líquen Plano/patologia , Líquen Plano Bucal/diagnóstico , DorRESUMO
Sleep is a normal physiological process that accounts for approximately one third of a person's life. Disruption of the normal sleep cycle, which maintains physiological homeostasis, can lead to pathology. It is not known whether sleep disturbance causes skin disease or skin disease causes sleep impairment, but a bidirectional influence is suspected. We have compiled the data from published articles on "sleep disorders in dermatology" in PubMed Central from July 2010 to July 2022 (with the option "full text available") and provide an overview of sleep disorders associated with dermatological conditions and certain drugs used in dermatology as well as sleep disturbances for which some drugs used can cause itch or dermatological issues. Atopic dermatitis, eczema and psoriasis have been shown to be exacerbated by sleep problems and vice versa. Sleep deprivation, night-time pruritus and disrupted sleep cycles are often used to assess treatment response and quality of life in these conditions. Some medications used primarily for dermatological conditions have also been associated with alterations in the sleep-wake cycle. Addressing patients sleep disorders should be an integral part of the management of dermatological conditions. More studies are needed to further investigate the influence of sleep and skin disorders.
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Dermatite Atópica , Dermatologia , Transtornos do Sono-Vigília , Humanos , Qualidade de Vida , Prurido/complicações , Dermatite Atópica/diagnóstico , Dermatite Atópica/tratamento farmacológico , Dermatite Atópica/complicações , Transtornos do Sono-Vigília/complicaçõesRESUMO
Background Frontal fibrosing alopecia (FFA) and lichen planopilaris (LPP) is scarring alopecias with limited evidence supporting their treatment options. We investigated the use of low-dose naltrexone (3 mg oral daily) as adjunctive therapy in the treatment of FFA and LPP. Methods A single-center, uncontrolled open-label prospective study was performed, with 26 patients who took low-dose naltrexone for one year included in the per-protocol analysis. Both patient-reported (pruritus and burning/pain) and physician-assessed (erythema, scale, and scalp involvement) outcomes were analyzed. Results There were decreases in erythema and scale for the overall longitudinal outcomes using linear mixed effects model analysis. However, only erythema had a significant decrease at 12 months compared with baseline. Mean erythema decreased by 0.93 at 12 months compared with baseline on a 0-3-point scale (p<0.0001, 95% mean CI [-1.32, -0.53]). There was no statistically significant difference comparing 12 months to baseline for the other outcomes including pruritus, burning/pain, and scalp involvement. Limitations include the possibility of spontaneous stabilization, concurrent medications, a small sample size with limited racial diversity, and mild subjective symptoms at baseline. Conclusion Our study supports further investigation of oral low-dose naltrexone as adjunctive therapy in the treatment of FFA and LPP if there is prominent erythema, and possibly scale.
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The excitatory/inhibitory (E/I) imbalance hypothesis posits that imbalance between excitatory (glutamatergic) and inhibitory (GABAergic) mechanisms underlies the behavioral characteristics of autism. However, how E/I imbalance arises and how it may differ across autism symptomatology and brain regions is not well understood. We used innovative analysis methods-combining competitive gene-set analysis and gene-expression profiles in relation to cortical thickness (CT) to investigate relationships between genetic variance, brain structure and autism symptomatology of participants from the AIMS-2-TRIALS LEAP cohort (autism = 359, male/female = 258/101; neurotypical control participants = 279, male/female = 178/101) aged 6-30 years. Using competitive gene-set analyses, we investigated whether aggregated genetic variation in glutamate and GABA gene-sets could be associated with behavioral measures of autism symptoms and brain structural variation. Further, using the same gene-sets, we corelated expression profiles throughout the cortex with differences in CT between autistic and neurotypical control participants, as well as in separate sensory subgroups. The glutamate gene-set was associated with all autism symptom severity scores on the Autism Diagnostic Observation Schedule-2 (ADOS-2) and the Autism Diagnostic Interview-Revised (ADI-R) within the autistic group. In adolescents and adults, brain regions with greater gene-expression of glutamate and GABA genes showed greater differences in CT between autistic and neurotypical control participants although in opposing directions. Additionally, the gene expression profiles were associated with CT profiles in separate sensory subgroups. Our results suggest complex relationships between E/I related genetics and autism symptom profiles as well as brain structure alterations, where there may be differential roles for glutamate and GABA.
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Transtorno do Espectro Autista , Transtorno Autístico , Adulto , Adolescente , Humanos , Masculino , Feminino , Transtorno Autístico/genética , Transtorno Autístico/metabolismo , Ácido Glutâmico/metabolismo , Ácido gama-Aminobutírico/metabolismo , Encéfalo/diagnóstico por imagem , Encéfalo/metabolismo , Transcriptoma , Transtorno do Espectro Autista/diagnóstico por imagem , Transtorno do Espectro Autista/genéticaRESUMO
OBJECTIVE: Autism spectrum disorder (ASD) is a lifelong neurodevelopmental condition that is associated with significant difficulties in adaptive behavior and variation in clinical outcomes across the life span. Some individuals with ASD improve, whereas others may not change significantly, or regress. Hence, the development of "personalized medicine" approaches is essential. However, this requires an understanding of the biological processes underpinning differences in clinical outcome, at both the individual and subgroup levels, across the lifespan. METHODS: The authors conducted a longitudinal follow-up study of 483 individuals (204 with ASD and 279 neurotypical individuals, ages 6-30 years), with assessment time points separated by â¼12-24 months. Data collected included behavioral data (Vineland Adaptive Behavior Scale-II), neuroanatomical data (structural MRI), and genetic data (DNA). Individuals with ASD were grouped into clinically meaningful "increasers," "no-changers," and "decreasers" in adaptive behavior. First, the authors compared neuroanatomy between outcome groups. Next, they examined whether deviations from the neurotypical neuroanatomical profile were associated with outcome at the individual level. Finally, they explored the observed neuroanatomical differences' potential genetic underpinnings. RESULTS: Outcome groups differed in neuroanatomical features (cortical volume and thickness, surface area), including in "social brain" regions previously implicated in ASD. Also, deviations of neuroanatomical features from the neurotypical profile predicted outcome at the individual level. Moreover, neuroanatomical differences were associated with genetic processes relevant to neuroanatomical phenotypes (e.g., synaptic development). CONCLUSIONS: This study demonstrates, for the first time, that variation in clinical (adaptive) outcome is associated with both group- and individual-level variation in anatomy of brain regions enriched for genes relevant to ASD. This may facilitate the move toward better targeted/precision medicine approaches.
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Transtorno do Espectro Autista , Transtorno Autístico , Adaptação Psicológica , Transtorno do Espectro Autista/genética , Seguimentos , Humanos , Imageamento por Ressonância MagnéticaRESUMO
Background: Standard treatment options for urticaria are second-generation antihistamines; however, their effect on sleep is uncertain. This study measures the influence of different antihistamines on the biologic sleep pattern of urticaria patients and the relevance of sleep in urticaria patients. Methods: Ten patients with chronic spontaneous urticaria (CSU) and uncontrolled symptoms under a single dose of second-generation antihistamines were included. Two nights were monitored: the first night after 5 days on single dosage and the second night after 5 days on fourfold dosage. Patient-rated questionnaires were used and sleep was monitored using polygraphy. Results: The patients' rated daytime sleepiness decreased (p = 0.0319), as did their insomnia severity (p = 0.0349). The urticaria control (UCT) improved (p = 0.0007), as did the quality of life (p < 0.0001). There was no significant change of nightly pruritus (p = 0.1173), but there was an improvement of daytime pruritus (p = 0.0120). A significant increase in rapid eye movement (REM) sleep was seen (p = 0.0002) (from a mean of 3.9% to 14.3%). The deep sleep state (N3) also improved (8.7% to 12.3%) (p = 0.1172). Conclusion: This study has demonstrated an improvement of the sleep pattern in CSU patients under up-dosed second-generation antihistamines, without increased daytime sleepiness, alongside an improvement of urticaria symptoms and quality of life.
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This is a retrospective study of 18 children with chronic spontaneous urticaria (CSU), where standard therapies, including up-dosing of antihistamines and omalizumab, were unable to cure the disease and where alternative strategies with experimental and off-label medication had to be used. MATERIALS: Being aware that our questionnaire is validated only for elder children or adults, we utilized the UAS7 to monitor disease control with the help of the parents. RESULTS: The UAS7 score decreased from a mean of 25 to an average of 13 after 8 weeks of therapy in 13 patients. Five patients had no significant reduction of UAS7 by week 8. In two of five patients, where periodic improvement was seen, omalizumab therapy was continued and showed complete response after 1-2 years. In three children, alternative treatments with cyclosporine and dupilumab, approved by the ethics committee, showed symptom improvement from a mean UAS7 of 29 to a mean value of 6. CONCLUSIONS: When omalizumab therapy including up-dosing strategies or shortened interval shows no symptom improvement, alternative therapies, sometimes off-label have to be considered in time.