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The Unique Molecular Signatures of Contact Dermatitis and Implications for Treatment
Irritant contact dermatitis (ICD) and allergic contact dermatitis (ACD) are common skin disorders that are characterized by inflammation, oozing, crusting, and pruritus. Atopic dermatitis (AD) is an inflammatory skin disease characterized by immune and barrier abnormalities and is additionally a risk factor for acquiring ICD and ACD. New work on allergic sensitization to common allergens (e.g., nickel and fragrance) in human skin has shown that different allergens have distinct molecular fingerprinting. For example, nickel promotes strong Th1/Th17 polarization, whereas fragrance allergy causes Th2/Th22 skewing, which is similar to the phenotype of AD. While ACD has previously been considered to be constant across all allergens, largely based on mouse models involving strong sensitizers, these new data suggest that ACD differs mechanistically according to allergen. Further, ACD in the setting of concurrent AD shows a different and attenuated phenotype as compared to healthy individuals with ACD, which influences the way AD patients respond to vaccination and other treatment modalities. As in contact sensitization, skin challenged by food patch testing shows that common food allergens (e.g., peanut and barley) also cause distinct immune polarizations in the skin. Additionally, house dust mite reactions in human skin have been profiled to show unique Th2, Th9, and Th17/22 activation as compared to controls, which are similar to the phenotype of psoriasis and contact responses to nickel. Given this information, ACD patients should be treated based on their unique allergen polarity. Refined understanding of the molecular behavior of contact dermatitis and related diseases translates to improved methods of inducing tolerance in sensitized allergic patients, such as with targeted drug therapy and epicutaneous immunotherapy.
Journal Article
Occupational Hand Dermatitis
AbstractPurpose of ReviewOccupational hand dermatitis is a common work-related disorder of the skin. Prevention and management of this disease is critical to improving workers’ quality of life and for occupation-specific retention.Recent FindingsThis is a critical review of the current literature on occupational hand dermatitis. Occupational dermatitis continues to have a high prevalence among workers although the overall incidence may be slowly decreasing. Irritant contact dermatitis due to wet work exposure is the most common cause of occupational hand dermatitis. Healthcare workers, hairdressers, and metal workers are at particularly high risk for this disease. While some prevention programs have been ineffective in mitigating occupational hand dermatitis, other more resource-intensive initiatives may have benefit.SummaryContinued research is needed on ways to manage wet work exposures and on scalable, effective prevention programs for occupational hand dermatitis. The spectrum of culprit contact allergens continues to evolve, and vigilance for potential occupation-specific allergens remains important.
Journal Article
Two Phase 3 Trials of Lebrikizumab for Moderate-to-Severe Atopic Dermatitis
Lebrikizumab, a high-affinity IgG4 monoclonal antibody targeting interleukin-13, prevents the formation of the interleukin-4Rα-interleukin-13Rα1 heterodimer receptor signaling complex.
We conducted two identically designed, 52-week, randomized, double-blind, placebo-controlled, phase 3 trials; both trials included a 16-week induction period and a 36-week maintenance period. Eligible patients with moderate-to-severe atopic dermatitis (adults [≥18 years of age] and adolescents [12 to <18 years of age, weighing ≥40 kg]) were randomly assigned in a 2:1 ratio to receive either lebrikizumab at a dose of 250 mg (loading dose of 500 mg at baseline and week 2) or placebo, administered subcutaneously every 2 weeks. Outcomes for the induction period were assessed up to 16 weeks and are included in this report. The primary outcome was an Investigator's Global Assessment (IGA) score of 0 or 1 (indicating clear or almost clear skin; range, 0 to 4 [severe disease]) with a reduction (indicating improvement) of at least 2 points from baseline at week 16. Secondary outcomes included a 75% improvement in the Eczema Area and Severity Index score (EASI-75 response) and assessments of itch and of itch interference with sleep. Safety was also assessed.
In trial 1, the primary outcome was met in 43.1% of 283 patients in the lebrikizumab group and in 12.7% of 141 patients in the placebo group (P<0.001); an EASI-75 response occurred in 58.8% and 16.2%, respectively (P<0.001). In trial 2, the primary outcome was met in 33.2% of 281 patients in the lebrikizumab group and in 10.8% of 146 patients in the placebo group (P<0.001); an EASI-75 response occurred in 52.1% and 18.1%, respectively (P<0.001). Measures of itch and itch interference with sleep indicated improvement with lebrikizumab therapy. The incidence of conjunctivitis was higher among patients who received lebrikizumab than among those who received placebo. Most adverse events during the induction period were mild or moderate in severity and did not lead to trial discontinuation.
In the induction period of two phase 3 trials, 16 weeks of treatment with lebrikizumab was effective in adolescents and adults with moderate-to-severe atopic dermatitis. (Funded by Dermira; ADvocate1 and ADvocate2 ClinicalTrials.gov numbers, NCT04146363 and NCT04178967, respectively.).
Journal Article
Dupilumab Treatment in Adults with Moderate-to-Severe Atopic Dermatitis
Dupilumab, a monoclonal antibody that inhibits signal transduction by interleukin-4 and interleukin-13, showed unexpected clinical efficacy in this group of small, randomized, controlled trials involving patients with atopic dermatitis, which were designed predominantly for safety.
Atopic dermatitis, which is characterized by a disturbed skin barrier, robust type 2 helper T-cell (Th2)–mediated immune responses to numerous environmental antigens, susceptibility to cutaneous infections, and intractable pruritus, is a common chronic skin condition with a worldwide prevalence of 1 to 20%.
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Approximately 20% of patients with atopic dermatitis have moderate-to-severe disease,
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and treatments approved by the Food and Drug Administration for atopic dermatitis, which include emollients, topical glucocorticoids, and calcineurin inhibitors,
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,
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have limited efficacy in moderate-to-severe disease.
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,
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The Th2 cytokines interleukin-4 and interleukin-13 are believed to play roles in the pathogenesis of atopic dermatitis,
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,
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but . . .
Journal Article
Nutritional adequacy of goat milk infant formulas for term infants: a double-blind randomised controlled trial
The safety and nutritional adequacy of goat milk infant formulas have been questioned. The primary aim of the present study was to compare the growth and nutritional status of infants fed a goat milk infant formula with those of infants fed a typical whey-based cow milk infant formula. The secondary aim was to examine a range of health- and allergy-related outcomes. A double-blind, randomised controlled trial with 200 formula-fed term infants randomly assigned to receive either goat or cow milk formula from 2 weeks to at least 4 months of age was conducted. A cohort of 101 breast-fed infants was included for comparison. Weight, length and head circumference were measured at 2 weeks and 1, 2, 3, 4, 6 and 12 months of age. Nutritional status was assessed from serum albumin, urea, creatinine, Hb, ferritin, and folate and plasma amino acid concentrations at 4 months. Z-scores for weight, length, head circumference and weight for length were not different between the two formula-fed groups. There were differences in the values of some amino acids and blood biomarkers between the formula-fed groups, but the mean values for biomarkers were within the normal reference range. There were no differences in the occurrence of serious adverse events, general health, and incidence of dermatitis or medically diagnosed food allergy. The incidence of parentally reported blood-stained stools was higher in the goat milk formula-fed group, although this was a secondary outcome and its importance is unclear. Goat milk formula provided growth and nutritional outcomes in infants that did not differ from those provided by a standard whey-based cow milk formula.
Journal Article
Left atrial volume index in patients with seborrheic dermatitis
Objectives: Seborrheic dermatitis is a chronic inflammatory skin condition that primarily affects the scalp, face, and body folds. Emerging research indicates a potential link between seborrheic dermatitis and cardiac parameters. This study aims to further investigate this relationship. Methods: Fifty individuals diagnosed with seborrheic dermatitis who presented to the dermatology outpatient clinic were included, alongside a control group of healthy participants (n=30) matched by age and sex. Echocardiographic assessments were carried out for both groups, and the data were recorded using standardized forms. Results: The left atrial volume index (LAVI) was recorded as 28.3±1.24 in seborrheic dermatitis patients and 26.2±1.47 in the control group, with this difference reaching statistical significance (P<0.001). Similarly, the E/e' ratio was found to be 8.52±0.777 in the patient group and 7.16±0.706 in the control group, demonstrating a statistically significant difference (P<0.001). Conclusions: The observed increase in LAVI and E/e' ratio among seborrheic dermatitis patients suggests a potential association with an elevated risk of cardiovascular disease and atrial fibrillation. Given these findings, long-term monitoring of individuals with seborrheic dermatitis may be warranted.
Journal Article
Angiogenesis in Chronic Inflammatory Skin Disorders
Angiogenesis, the growth of new blood vessels from preexisting vessels, is associated with inflammation in various pathological conditions. Well-known angiogenetic factors include vascular endothelial growth factor (VEGF), angiopoietins, platelet-derived growth factor, transforming growth factor-β, and basic fibroblast growth factor. Yes-associated protein 1 (YAP) and transcriptional co-activator with PDZ-binding motif (TAZ) have recently been added to an important angiogenic factor. Accumulating evidence indicates associations between angiogenesis and chronic inflammatory skin diseases. Angiogenesis is deeply involved in the pathogenesis of psoriasis. VEGF, angiopoietins, tumor necrosis factor-a, interleukin-8, and interleukin-17 are unregulated in psoriasis and induce angiogenesis. Angiogenesis may be involved in the pathogenesis of atopic dermatitis, and in particular, mast cells are a major source of VEGF expression. Angiogenesis is an essential process in rosacea, which is induced by LL-37 from a signal cascade by microorganisms, VEGF, and MMP-3 from mast cells. In addition, angiogenesis by increased VEGF has been reported in chronic urticaria and hidradenitis suppurativa. The finding that VEGF is expressed in inflammatory skin lesions indicates that inhibition of angiogenesis is a useful strategy for treatment of chronic, inflammatory skin disorders.
Journal Article
Atopic Dermatitis
Atopic dermatitis is a chronic disorder that usually starts in childhood but often persists in adulthood. The appearance and extent of lesions vary with age and race or ethnic group. Topical and systemic treatments targeting the underlying immune condition have been introduced.
Journal Article
Contact Dermatitis: Classifications and Management
Contact dermatitis (CD) is a common inflammatory skin disease caused by exposure to contact allergens and irritants. It is also the most common reason of occupational dermatitis and contributes greatly to hand dermatitis and facial dermatitis. Besides the two major forms of contact dermatitis: allergic contact dermatitis and irritant contact dermatitis, other subtypes of CD have been recognized including immediate skin reactions, photoinduced contact dermatitis, systemic contact dermatitis, and non-eczematous contact dermatitis. CD is a great imitator which can mimic many kinds of skin diseases, such as atopic dermatitis, lichen planus, and angioedema. For the diagnosis of CD, a complete medical history, including occupational history, is very important. It can give a clue of CD and provide a list of suspected substances. Besides the well-known diagnostic test, patch testing, there are many other diagnostic tests can be used to help diagnosis of CD and identify the causative allergens, including photopatch test, skin tests for detecting of immediate contact reactions, serum allergen-specific IgE test, and qualitative and quantitative testing of allergen in the suspected materials patients exposed to and challenge test. Before the treatment, the suspected irritants or allergens should be avoided completely. This includes both the removal of the patient from the environment that contains those substances and the promotion of the metabolism and expulsion of the allergens that have been absorbed by the body. In addition, it is also important to restore the skin barrier and reduce skin inflammation through multiple treatments, such as emollients, topical corticosteroids, and antihistamines, as well as systemic corticosteroids and immunosuppressants. Early and appropriate treatments are important to prevent further deterioration and persistence of the skin condition.
Journal Article