Treatment Of Atopic Dermatitis Research Articles

Interleukin-1α inhibitor bermekimab in patients with atopic dermatitis: randomized and nonrandomized studies

Bermekimab is a human-derived recombinant monoclonal antibody that exhibits immunoregulatory activity by specifically blocking interleukin-1α activity. Four phase 2 studies evaluated efficacy and safety of bermekimab in patients with moderate-to-severe atopic dermatitis (AD). In addition, a novel human skin explant model was developed to assess bermekimab pharmacokinetics/pharmacodynamics and proteomic/transcriptomic effects. Study 1 (NCT03496974, N = 38) was an open-label, dose escalation study of subcutaneous bermekimab (200 mg or 400 mg). Study 2 (NCT04021862, N = 87) was a double-blind, placebo-controlled, randomized (1:1:1) study of subcutaneous bermekimab (400 mg every week (qw) or every 2 weeks) or placebo. GENESIS (NCT04791319, N = 198) was a double-blind, placebo- and active-comparator-controlled, randomized (1:1:2:2) study of placebo, subcutaneous bermekimab (350 mg or 700 mg qw), or dupilumab. LUNA (NCT04990440, N = 6) was a double-blind, placebo-controlled, randomized (4:1) study of intravenous bermekimab 800 mg qw or placebo. A novel human ex vivo skin pharmacodynamic assay supported phase 0 (NCT03953196) and phase 1 (NCT04544813) studies. In Study 1, 400 mg subcutaneous bermekimab showed improvement in efficacy assessments (e.g., ≥ 75% improvement of EASI over baseline, IGA 0/1, and worst itch); however, efficacy was not confirmed in Study 2 or GENESIS. Consequently, GENESIS and LUNA were terminated early. The novel human ex vivo skin pharmacodynamic assay demonstrated that bermekimab reduced downstream skin injury responses. Although bermekimab showed potential as an AD treatment in preclinical and early open-label trials, larger controlled studies (Study 2 and GENESIS) did not confirm those initial results.

Meta-Analysis of Noncompartmental Pharmacokinetic Parameters to Evaluate the Impact of CYP2C19 and CYP2C9 Genetic Polymorphisms on Abrocitinib Exposure.

Abrocitinib is a selective Janus kinase 1 inhibitor approved for the treatment of atopic dermatitis. It is metabolized primarily by cytochrome P450 (CYP) 2C19 (approximately 53%) and CYP2C9 (approximately 30%), which form 2 active metabolites. The pharmacologic activity of abrocitinib is attributable to the unbound exposures of abrocitinib and those metabolites with active moiety area under the plasma concentration-time curve (AUC) considered the best measure of the total pharmacological effect. The effect of CYP2C19 and/or CYP2C9 genotypes on abrocitinib and active moiety exposures were evaluated using a meta-analysis of the noncompartmental estimates of exposure pooled from 10 clinical studies. A linear mixed-effects model was developed on the basis of the power model to evaluate the effect of CYP2C19 and/or CYP2C9 genotypes on exposure (i.e., abrocitinib AUC and peak plasma concentration, active moiety AUC and peak plasma concentration). The genotypes were evaluated individually and as a combined phenotype effect. When evaluating the poor metabolizers of CYP2C19 or CYP2C9 individually, the estimated increases were 44.9% and 42.0% in active moiety AUC, respectively. The combined phenotype models showed a 0.6% decrease, and 25.1% and 10.5% increases in the active moiety AUC for "elevated," "mixed," and "reduced" metabolizers, respectively. Overall, the active moiety exposures did not appear to be affected to a clinically meaningful extent by different genotypes of CYP2C19 and/or CYP2C9.

Crisaborole combined with vitamin D demonstrates superior therapeutic efficacy over either monotherapy in mice with allergic contact dermatitis

This study evaluated the therapeutic efficacy and underlying mechanisms of crisaborole combined with vitamin D in the treatment of allergic contact dermatitis. While crisaborole, a phosphodiesterase 4 inhibitor, and vitamin D analogs are commonly used in the treatment of atopic dermatitis, their combined therapeutic potential in allergic contact dermatitis (ACD) remains unexplored. Given their anti-inflammatory properties, we hypothesized that the combination of crisaborole and vitamin D could offer superior efficacy in mitigating the symptoms and underlying mechanisms of allergic contact dermatitis. In vitro, HaCaT cells stimulated with tumor necrosis factor-α and interferon-γ were treated with a combination of crisaborole and vitamin D, followed by cytokine expression analysis. In vivo, male C57BL/6 mice were divided into five groups and treated accordingly: blank control, dinitrochlorobenzene-induced model, crisaborole alone, vitamin D alone, and a combination of crisaborole and vitamin D. On day 14, dorsal skin and ear thickness were measured, followed by comprehensive pathological evaluations. In vivo and in vitro experiments showed that the expression levels of inflammatory factors were significantly lower in the DNCB + VD + Cri group than in the DNCB group. Histological analyses revealed that, compared with the DNCB group, the combined treatment group significantly reduced epidermal hyperkeratosis, improved epidermal transdermal water loss, decreased dermatitis scores, and diminished mast cell infiltration. Moreover, it lowered the expression levels of IL-6, IL-4, TNF-α, iNOS, IL-17, CC chemokine ligand 2 (CCL2), and CC chemokine receptor 2 (CCR2). CCL2 recognizes CCR2 and stimulates inflammatory cells, enhancing the inflammatory response. Increased CCL2 expression correlates with heightened inflammation and dendritic cell infiltration in ACD, while downregulation of CCL2 attenuates inflammation. Thus, the combined use of crisaborole and vitamin D demonstrates superior therapeutic efficacy over monotherapy in a mouse model of ACD. The combination of vitamin D and crisaborole significantly reduces inflammation and epidermal hyperkeratosis in a mouse model of allergic contact dermatitis, demonstrating superior therapeutic efficacy compared to either treatment alone. This suggests that the combined therapy could be a promising approach for the prevention and treatment of allergic contact dermatitis.

Benvitimod upregulates filaggrin, involucrin and loricrin expressions via aryl hydrocarbon receptor-OVO-like 1 axis

Benvitimod has been successfully used in the treatment of psoriasis and atopic dermatitis (AD). However, the mechanism remains to be clarified. We aim to assess the effects of benvitimod on MC903-induced dermatitis in mice and to investigate the effects of benvitimod on filaggrin (FLG), involucrin (IVL), and loricrin (LOR) expressions and possible mechanism. MC903-induced mouse AD model was used to evaluate the effects of benvitimod. Filaggrin, involucrin, and loricrin protein and mRNA expressions in lesions of mice dermatitis were measured by Western blot and quantitative real-time PCR. In vitro, normal human epidermal keratinocytes (NHEKs) were cultured and benvitimod was used to treat NHEKs primed with IL-4 and IL-13. Then AHR and OVOL1 in NHEKs were knocked down to evaluate the role of AHR and OVOL1 in the effects of benvitimod. Topical treatment of benvitimod repaired skin barrier and alleviated skin inflammation in mouse AD model. This effect was inhibited by pretreatment with an AHR antagonist. Benvitimod upregulated the filaggrin, involucrin, and loricrin expressions in lesions of mouse AD model. In addition, benvitimod upregulated the filaggrin, involucrin, and loricrin expressions in NHEKs. Knockdown of AHR or OVO-like (OVOL)1 abrogated the upregulation of filaggrin, involucrin, and loricrin induced by benvitimod. Benvitimod attenuated MC903-induced mouse dermatitis and upregulated filaggrin, involucrin, and loricrin expressions via AHR-OVOL1 axis.Graphical Possible pathway of benvitimod upregulating FLG, IVL and LOR expression. Benvitimod activates AHR, then AHR translocates into the nucleus and upregulates OVOL1 expression. OVOL1 further translocates into the nucleus and upregulates the FLG, IVL and LOR expression

Upadacitinib - New Janus Kinase Inhibitor - Literature Review

Atopic dermatitis (AD) is a chronic, recurrent dermatosis that affects an increasing percentage of the population. It usually affects children and resolves spontaneously, however, symptoms can persist into adulthood and even appear de novo later in life. The skin lesions that appear in this disease significantly reduce patients quality of life. Visual skin symptoms are exacerbated during stress, and pruritus leads to sleep problems. The effect of an inadequately controlled disease can even be a reduction in social activities and a reluctance to leave the house. The basis of treatment is skin care using emollients and avoiding triggers and aggravating factors. In the next stage, the doctor may prescribe topical or systemic treatment for the patient, depending on the severity of the disease. Such measures may not be enough, so more and more new drugs are being registered for the treatment of atopic dermatitis. One of them is upadacitinib, which appears to be extremely effective compared to other medications used to treat moderate to severe ad. It is a selective JAK inhibitor that reduces the inflammatory response by inhibiting migration, proliferation and cytokine secretion by granulocytes. It brings rapid and sustained effects in reducing skin lesions and reducing one of the most bothersome symptoms, pruritus.It may serve as a good alternative to the existing methods for treating moderate to severe atopic dermatitis The purpose of our study is to describe this new drug, its mechanism of action and discuss its possible benefits versus side effects.

A wearable iontophoresis enables dual-responsive transdermal delivery for atopic dermatitis treatment

Atopic dermatitis is a chronic, inflammation skin disease that remains a major public health challenge. The current drug-loading hydrogel dressings offer numerous benefits with enhanced loading capacity and a moist-rich environment. However, their development is still limited by the accessibility of a suitable driven source outside the clinical environment for precise control over transdermal delivery kinetics. Here, we prepare a sulfonated poly(3,4-ethylenedioxythiophene) (PEDOT) polyelectrolyte hydrogel drug reservoir that responds to different stimuli-both endogenous cue (body temperature) and exogenous cue (electrical stimulation), for wearable on-demand transdermal delivery with enhanced efficacy. Functioned as both the drug reservoir and cathode in a Zn battery-powered iontophoresis patch, this dual-responsive hydrogel achieves high drug release efficiency (68.4 %) at 37 °C. Evaluation in hairless mouse skin demonstrates the efficacy of this technology by facilitating transdermal transport of 12.2 μg cm−2 dexamethasone phosphate when discharged with a 103 Ω external resistor for 3 h. The Zn battery-driven iontophoresis results in an effective treatment of atopic dermatitis, displaying reductions in epidermal thickness, mast cell infiltration inhibition, and a decrease in IgE levels. This work provides a new treatment modality for chronic epidermal diseases that require precise drug delivery in a non-invasive way.

Current approach to moisturizer and emollient utilization in atopic dermatitis: a review

Atopic dermatitis (AD) is a chronic inflammatory skin disease that primarily affects the barrier function of the skin in patients. The condition has been documented to cause xerosis in patients from birth onwards. In order to protect the skin barrier in AD, it is of the utmost importance to moisturize the skin. Moisturizers and emollients play a pivotal role in the prevention and treatment of AD. Concordantly, the use of moisturizers and emollients can facilitate the reduction in the necessity for the application of topical treatments such as corticosteroids. An understanding of the use of moisturizers and emollients, in conjunction with an appreciation of the pathophysiology of the skin barrier, will prove invaluable in the treatment of AD.

Qualitative study with mothers of children with atopic dermatitis: emotional and social impacts.

Atopic Dermatitis (AD) is the most common skin disease in childhood and its control requires the support of the family members. This disease significantly interferes with the Quality of Life (QoL) of children and families, however, literature on the social and emotional impact of the disease on the caregivers is lacking. To evaluate the emotional and social impact of AD on mothers of children with the disease. This is a qualitative study of semi-structured interviews with mothers of children diagnosed with AD. The following variables were evaluated: diagnosis and start of treatment, knowledge about the disease, and impact on the mothers' lives. The material was analyzed using Lawrence Bardin's content analysis technique. The AD severity was assessed by SCORAD. A total of 23 interviews were conducted with mothers of children diagnosed with AD. In 82.6% of the cases, the mothers presented conflicts in the face of the first contacts with the disease. In 43.5% of cases, mothers were solely responsible for their children's treatment. About 56.6% defined AD as a cause of suffering and difficulty and 21.7% pointed out the AD experience as a learning experience. The AD is a chronic disease that has a psychological and social impact on the lives of mothers. In the treatment of AD, mothers must be screened and offered psychological support to improve adherence to treatment in the long term.

Budget impact and cost per responder analysis of upadacitinib for the treatment of moderate to severe atopic dermatitis from the perspective of the social security and the private sector in Argentina

ABSTRACT Objectives Our study assessed the budget impact and cost per responder of upadacitinib15mg and 30 mg for moderate to severe atopic dermatitis (MS-AD) treatment from social security and private health sector perspective in Argentina. Methods A budget impact model was adapted to depict clinical and economic aspects of treatment over a 5-years horizon time. Scenario analyses and deterministic sensitivity analyses were performed. A 16-weeks cost per responder model was adapted based on a network meta-analysis. Primary analyses assessed the cost per Eczema Area and Severity Index 50, 75 and 90 at week 16. Results The inclusion of upadacitinib 15 mg and 30 mg in the biological treatment mix for MS-AD was associated with an average budget saving per-member per-month ofU$S0.062 (social security) and U$S0.064 (private sector). Percentage of patients with access to treatment, acquisition cost of upadacitinib 30 mg and prevalence of MS-AD were the most influential parameters in the budget impact results. At week 16, upadacitinib 30 mg was associated with the lowest number needed to treat and the lowest cost per responder for all outcomes. Conclusion The introduction of upadacitinib in MS-AD treatment was associated with modest savings for the social security and private payer budget in Argentina.

Diterpenoid DGT alleviates atopic dermatitis–like responses in vitro and in vivo via targeting IL-4Rα

BackgroundAtopic dermatitis is a common chronic inflammatory skin disease characterized by relapsing eczema and intense itch. DGT is a novel synthetic heterocyclic diterpenoid derived from plants. Its therapeutic potential and mechanism(s) of action are poorly understood. ObjectivesWe investigated the potent therapeutic effect of DGT on atopic dermatitis, exploring the underlying mechanisms and determining whether DGT is a safe and well-tolerated topical treatment. MethodsWe observed anti-inflammatory effects of DGT on tumor necrosis factor-α/interferon-γ–treated human keratinocytes, and anti-allergic effects on immunoglobulin E–sensitized bone marrow–derived mast cells. In vivo, DGT was topically applied to two experimental mouse models of atopic dermatitis: oxazolone-induced sensitization and topically applied calcipotriol. Then the therapeutic effects of DGT were evaluated physiologically and morphologically. Moreover, we performed nonclinical toxicology and safety pharmacology research, including general toxicity, pharmacokinetics, and safety pharmacology on the cardiovascular, respiratory, and central nervous systems. ResultsIn keratinocytes, DGT reduced the expression of inflammatory factors, promoting the expression of barrier functional proteins and tight junctions and maintaining the steady state of barrier function. DGT also inhibited the activation and degranulation of mast cells induced by immunoglobulin E. Moreover, we found that interleukin-4 receptor-α was the possible target of DGT. Meanwhile, DGT had therapeutic effects on oxazolone/calcipotriol-treated mice. Notably, our pharmacology results demonstrated that DGT was safe and nontoxic in our studies. ConclusionDGT’s potent anti-inflammatory effects and good safety profile suggest that it is a potential candidate for the treatment of atopic dermatitis.

Effect of Omega-3 Polyunsaturated Fatty Acid Supplementation on Clinical Outcome of Atopic Dermatitis in Children.

The use of omega-3 fatty acids (omega-3 FA) in the treatment of atopic dermatitis (AD) is an area of ongoing research. Some studies suggest that dietary supplementation with omega-3 FA can help manage symptoms of AD by reducing lesion severity, skin inflammation, dryness and itching, while others show no significant beneficial effect. The aim of this study was to evaluate the effect of omega-3 FA from fish oil in combination with gamma-linolenic acid (GLA) from blackcurrant seed oil in children with AD. This is a longitudinal, prospective, randomized, triple blind, placebo-controlled parallel clinical trial. The study was conducted during the 2-year period throughout autumn, winter, and spring, avoiding the summer when AD usually improves. Children were randomized to receive the active study product (Mega Kid®) containing a specific blend of omega-3 and omega-6 fatty acids or placebo. The primary outcomes were changes in severity of AD measured using SCORing Atopic Dermatitis (SCORAD), patient-oriented SCORAD (PO-SCORAD) and the difference in topical corticosteroid (TCS) use. The secondary outcomes were changes in itch intensity, sleep quality and Family Dermatology Life Quality Index (FDLQI). Data were analyzed for 52 children (26 in the intervention group and 26 in the placebo group). In children receiving the active product, intention-to-treat analysis showed that after 4 months of treatment, there was a significant decrease in the SCORAD index (from median 42 to 25, p < 0.001) and the use of topical corticosteroids (from median 30 to 10 mg/month, p < 0.001), but also significant improvements in itch, sleep quality, and overall quality of life. Omega-3 fatty acids in combination with GLA and vitamin D may decrease symptoms and were associated with an improvement clinical picture of AD in children. Therefore, we can conclude that supplementation with this specific combination could be considered a safe and effective intervention that may significantly reduce the severity of AD in pediatric patients.

Evaluation of dupilumab on the disease burden in children and adolescents with atopic dermatitis: A population-based cohort study.

Dupilumab is the first and only biologic agent approved for the treatment of atopic dermatitis (AD) in pediatric patients aged from 6 months to 17 years. The study aimed to evaluate the impact of dupilumab on the occurrence of comorbidities in pediatric patients with AD. In this population-based cohort study, we utilized electronic healthrecords from multiple healthcare organizations across the United States. Pediatric patients (<18 years of age) with a diagnosis of AD initiating dupilumab were propensity-score matched 1:1 to those initiating other systemic agents (azathioprine, cyclosporine, methotrexate, mycophenolate mofetil, or systemic corticosteroids). The primary outcomes were new-onset comorbidities emerging during the study period measured by the risk ratio (RR) and its confidence interval (CI). Subgroup analyses were stratified by age (0-5 years, 6-11 years, and 12-17 years), sex, and race. A total of 3575 pediatric patients with AD treated with dupilumab were matched to 3575 patients treated with other systemic agents. The dupilumab cohort was associated with a lowered risk of new-onset atopic comorbidities (including asthma [RR, 0.72; 95% CI, 0.59-0.89] and allergic rhinitis [RR, 0.62; 95% CI, 0.52-0.74]), infections (e.g., skin and soft tissue infection [RR, 0.70; 95% CI, 0.63-0.76] and respiratory tract infection [RR = 0.56; 95% CI, 0.51-0.61]), psychiatric disorders (e.g., mood disorder [RR, 0.52; 95% CI, 0.39-0.70] and anxiety [RR, 0.57; 95% CI, 0.46-0.70], sleep disturbance [RR, 0.60; 95% CI, 0.47-0.77]), neurologic and developmental disorders (e.g., attention deficit hyperactivity disorder [RR, 0.54; 95% CI, 0.38-0.75]). Furthermore, the positive effects are found to be more pronounced in younger children (aged 0-5 years) with AD. Treatment with dupilumab compared to systemic agents resulted in reductions in AD-related comorbidities in pediatric patients.

An Encompassing Review on Therapeutic Targets, Therapies and Nanostructure Based Formulations for Atopic Dermatitis

Atopic dermatitis (AD) is a complex inflammatory skin disease that frequently develops in childhood and can last into adulthood. It can be very painful and harm a person's quality of life. The exact cause of atopic dermatitis is not fully known but is believed to be a combination of genetic disorders and environmental factors. Currently used drugs in the treatment are topical corticosteroids and topical calcineurin inhibitors. This comprehensive review summarizes the pathophysiology of atopic dermatitis, therapeutic targets, current treatment, newer and emerging therapies in AD treatment, and the role of nanoparticles in formulation development for AD treatment.

Acute generalised exanthematous pustulosis associated with upadacitinib treatment.

Acute generalised exanthematous pustulosis (AGEP) is a rare drug-induced pustular eruption characterised by the rapid onset of superficial pinhead pustules. We discuss the case of a 27-year-old man who presented with a generalised pustular eruption on the neck, trunk and limbs. He commenced upadacitinib for the treatment of atopic dermatitis (AD) 6months before developing the rash, and the dose was increased from 15 to 30mg daily, 3months prior. His only other medication was oral terbinafine, for suspected tinea corporis, which was initiated 1month before developing the pustular eruption. Laboratory investigations showed a mildly raised CRP 25mg/L, neutrophilia 8.22 10×9/L, and a mildly raised ALT 46U/L. A skin biopsy showed subcorneal pustules and a few scattered keratinocytes. Upadacitinib and terbinafine were suspended and the pustular eruption resolved. Updacitinib was reintroduced 3weeks later as the rash was thought to be due to terbinafine and the rash recurred. He was diagnosed with AGEP secondary to upadacitinib. Upadacitinib is a selective JAK inhibitor that is increasingly used for the management of AD and clinicians should be aware that AGEP is a rare but severe adverse effect.

Agrimonia coreana Extract Exerts Its Therapeutic Effect through CRAC Channel Inhibition for Atopic Dermatitis Treatment.

Atopic dermatitis (AD) is a common allergic inflammatory skin condition marked by severe itching, skin lichenification, and chronic inflammation. AD results from a complex immune response, primarily driven by T lymphocytes and environmental triggers, leading to a disrupted epidermal barrier function. Traditional treatments, such as topical corticosteroids, have limitations due to long-term side effects, highlighting the need for safer alternatives. Here, we aimed to show that Agrimonia coreana extract (ACext) can be used in treating AD-related dermatologic symptoms. ACext could inhibit CRAC (Calcium Release-Activated Calcium) channel activity, reducing Orai1/CRAC currents and decreasing intracellular calcium signaling. This inhibition was further confirmed by the reduced IL-2 levels and T cell proliferation upon ACext treatment. In a mouse model of AD, ACext significantly ameliorates symptoms, improves histological parameters, and enhances skin barrier function, demonstrating its potential for treating AD.

Phase 1 Safety and Pharmacokinetics Study of TAVO101, an Anti-Human Thymic Stromal Lymphopoietin Antibody for the Treatment of Allergic Inflammatory Conditions.

TAVO101 is a humanized anti-human thymic stromal lymphopoietin (TSLP) monoclonal antibody under clinical development for the treatment of atopic dermatitis (AD) and other allergic inflammatory conditions. The crystallizable fragment region of the antibody was engineered for half-life extension and attenuated effector functions. This Phase 1, double-blinded, randomized, placebo-controlled study assessed the safety, tolerability, pharmacokinetics, and immunogenicity of TAVO101 in healthy adult subjects in seven ascending dose cohorts. Subjects received a single intravenous administration of TAVO101 or placebo with a 195-day follow-up. TAVO101 was safe and well tolerated. The incidences and severities of treatment-emergent adverse events were mostly mild and comparable between the active and placebo groups, with no trends of dose relationship. There were no severe adverse events, deaths, or treatment-related withdrawals. TAVO101 exhibited a linear pharmacokinetic profile, low clearance, and a median elimination half-life of 67 days in healthy subjects. All TAVO101-treated subjects tested negative for anti-drug antibodies. To support development in AD, TAVO101 was studied in an oxazolone-induced AD model in hTSLP transgenic mice and demonstrated efficacy. This long-acting anti-TSLP antibody has the potential for stronger and sustained allergic inflammatory disease control. The results from this study warranted further clinical development of TAVO101 in patients.

The role of nemolizumab in the treatment of atopic dermatitis for the adult population.

Atopic dermatitis (AD) often requires long-term treatment that may be associated with adverse effects. This review aims to characterize nemolizumab as a treatment for AD in adults. A literature search was performed to assess nemolizumab's role in moderate-to-severe AD in adults. Currently, clinical trials are being conducted to evaluate the clinical efficacy, safety profile and optimal dosing of nemolizumab for adults with moderate-to-severe AD. The most common adverse effects include nasopharyngitis, AD exacerbation and increased blood creatinine phosphokinase. Recent data from clinical trials suggest nemolizumab may be an acceptable treatment in adults with moderate-to-severe AD.

Evaluation of Scoring Atopic Dermatitis (SCORAD) and scratching behavior in BALB/c mice treated with house dust mite immunotherapy

Allergen specific immunotherapy controls the reaction and builds immunological tolerance by giving an allergen in escalating doses. Research on immunotherapy in atopic dermatitis (AD) mouse model offers a new perspective on the approach of treatment in AD. This was an experimental study of 33 male BALB/c mice, 6-8 weeks old, divided into 3 groups (control, AD model, and house dust mite/HDM immunotherapy). The mice received spray and patch containing allergen extract of Dermatophagoides pteronyssinus. Immunotherapy was injected subcutaneously in increasing doses. The evaluation of SCORAD and scratching behavior were observed at the end of the treatment on day 93. The SCORAD of the model group that received HDM allergen had a mean of 1.27 ± 0.467 and the immunotherapy group had a mean of 0.36 ± 0.505. There were significant differences between the groups. The model group had a mean of 5.18 ± 4.119 and the immunotherapy group had mean of 1.55 ± 1.293. The statistical analysis showed that there were significant differences between control group and model group, as well as model group and immunotherapy group. Interobserver agreement was assessed and showed substantial agreement for SCORAD (ĸ = 0.613 and p &lt; 0.001) and scratching evaluation (ĸ = 0.714 and p &lt; 0.001). House dust mite immunotherapy significantly reduced SCORAD and scratching behavior in BALB/c mice compared to placebo groups.

Unravelling the Complexities and Recent Advances in the Management of Atopic Dermatitis

Abstract: Atopic dermatitis (AD) is a non-fatal, non-communicable, chronic skin inflammatory condition marked by itching, lesions, and skin barrier dysfunction. As per the International Eczema Council, as of 2022, more than 200 million people were suffering from AD, with the disease burden reported highest in children. Environmental factors, genetic predisposition, and lifestyle have been found to be essential factors in triggering the adverse skin response. In this review, we provide a detailed overview of the pathophysiology of AD, how the skin barrier gets altered from normal condition to AD, and the role of genetic defects in Filaggrin protein, affecting the skin barrier function by altering the skin pH and hydration. Also, we highlight the role of toll-like receptors (TLRs) and the altered skin and gut microbiota in inducing chronic inflammatory responses and playing a significant role in the pathogenesis of the disease. Further, we discuss the role of several chemokines and cytokines, which could serve as important prognosis markers for early detection, monitoring the disease progression, and assessing the response to the treatment. We also report the current treatment regime of multimodal therapeutics ranging from topical emollients to topical, oral, and injectable immune modulatory agents. Besides, we discuss the importance of the gut-skin microbiome axis and the increasingly important role of prebiotics in AD treatment.

The Effect of Phototherapy on Systemic Inflammation Measured with Serum Vitamin D-Binding Protein and hsCRP in Patients with Inflammatory Skin Disease.

Vitamin D plays a role in inflammatory skin disease, but the exact mechanisms and the clinical significance remain unclear. According to the free hormone hypothesis, it is the free concentration of 25-hydroxy vitamin D (25(OH)D) that is biologically active. Vitamin D-binding protein (DBP) acts as the major transporter of vitamin D in the circulation, and DBP concentration defines the free 25(OH)D levels. DBP levels are elevated in various inflammatory conditions, including psoriasis. Narrowband-ultraviolet B (NB-UVB) is the most widely used phototherapy and is an established first-line treatment for psoriasis and atopic dermatitis (AD), often used before proceeding to systemic treatment. The aim of this study was to investigate the influence of NB-UVB phototherapy on DBP and high-sensitivity C-reactive protein (hsCRP) levels, as markers of systemic inflammation, in inflammatory skin disease. Thirty adults (psoriasis (n = 20) and AD (n = 10)) were treated with NB-UVB. Serum DBP, hsCRP, total and free 25(OH)D, and 1,25-dihydroxy vitamin D (1,25(OH)2D) were measured before and after NB-UVB. Disease severity was assessed with Psoriasis Area and Severity Index (PASI), SCORing Atopic Dermatitis (SCORAD), and Visual Analogue Scale (VAS). DBP decreased in psoriasis patients and varied with no clear trend in AD patients. HsCRP decreased in both groups, but this did not reach statistical significance. PASI, SCORAD, and VAS improved, and vitamin D levels increased after NB-UVB. Sub-analysis indicated a better response to NB-UVB for patients with vitamin D deficiency and insufficiency compared to vitamin D-sufficient patients. The decrease in DBP after NB-UVB in psoriasis patients suggests a potential systemic anti-inflammatory effect of phototherapy. Measurement of vitamin D levels may potentially serve as a tool to identify patients who would derive the greatest benefit from NB-UVB phototherapy.