Patient preferences for treatment attributes in moderate-to-severe atopic dermatitis: a discrete choice experiment.

Purpose: Evidence on treatment preferences of patients with moderate-to-severe atopic dermatitis (AD) in the United States (US) is limited and an assessment of treatment preferences in this group is warranted.Materials and methods: An online discrete choice experiment survey was conducted (June 2023) among US adults with self-reported moderate-to-severe AD or experience with systemic therapy who had inadequate response to topical treatments. Preference weights estimated from conditional logistic regression models were used to calculate willingness to trade off and attributes' relative importance (RI).Results: Participants (N = 300; mean age: 45 years; 70% females; 52% systemic therapy experienced) preferred treatments with higher efficacy, lower risk of adverse events (AEs), and less frequent blood tests (p < .05). Treatment attributes, from high to low RI, were itch control (38%), risk of cancer (23%), risk of respiratory infections (18%), risk of heart problems (11%), sustained improvement in skin appearance (5%), blood test frequency (3%), and frequency and mode of administration (2%); together, AE attributes accounted for more than half of the RI.Conclusions: Participants preferred AD treatments that maximize itch control while minimizing AE risks, whereas mode of administration had little impact on preferences. Understanding patients' preferences may help improve shared decision-making, potentially leading to enhanced patient satisfaction with treatment, increased engagement, and better clinical outcomes.

Evaluation of linear dermatoses by reflectance confocal microscopy in children.

Lichen striatus (LS), linear psoriasis (LPs), linear cutaneous lupus erythematosus (LCLE) and linear lichen planus (LLP) often have similar clinical manifestations, which makes clinical diagnosis with the naked eye difficult; therefore, they are easily misdiagnosed. The purpose of this study was to determine whether reflectance confocal microscopy (RCM) is helpful in differentiating between these four linear dermatoses in children. This retrospective study included 14 patients with LS, nine with LPs, eight with LCLE and 12 with LLP. All patients were analysed using RCM, and biopsies were collected from lesions previously imaged by RCM. For LS, the dermal papillary rings were partially absent, but when present, manifested with small, homogeneously round, bright cells and occasionally highly refractive plump cellular structures, aggregated in clusters. LPs exhibited dark cyst-like structures with small, bright, round cells aggregated at the epidermal level; at the dermal-epidermal junction, homogeneously distributed, enlarged, faint dermal papillary rings and numerous enlarged low-refractive canalicular structures were observed in the superficial dermis. LCLE and LLP exhibited similar manifestations, including epidermal disarray, almost total absence of dermal papillary rings, and various sized refractive structures densely distributed in the dermis. The key distinguishing features of LCLE were the different sized structures mainly clustered around hair follicles, while LLP demonstrated dense structures with a scattered distribution. RCM may be used to distinguish between the key features of LS, LPs, LCLE and LLP in children.

Comparison of the efficacy among different interventions for radiodermatitis: A Bayesian network meta­analysis of randomized controlled trials.

BACKGROUND: Radiation dermatitis (RD) is a prevalent and difficult-to-manage consequence of radiation therapy (RT). A variety of interventions have been proven effective in preventing and treating RD. However, the optimal approach remains unclear. This network meta-analysis (NMA) conducted a comparison and ranking of the effectiveness and patient-reported outcomes (PROs) of the interventions currently utilized in RD. METHODS: PubMed, Web of Science, Embase, and Cochrane Library were searched to identify pertinent randomized controlled trials (RCTs) focused on the prevention and treatment of RD. The primary outcome measures included the incidence of grade≥2 RD (i.e., percentage of moist desquamation) and RD score. The secondary outcome measures encompassed patients' subjective assessment scores of pains, itching and burning sensations. RESULTS: Our meta-analysis encompassed 42 studies and 4884 participants. Regarding the primary outcomes, photobiomodulation treatment (PBMT) ranked first in surface under curve cumulative ranking area (SUCRA:0.92) for reducing the incidence of grade≥2 RD. It demonstrated a significant difference when compared to Trolamine (OR 0.18,95%CrI 0.09-0.33) and Xonrid® (OR 0.28,95%CrI 0.12-0.66). Mepitelfilm (SUCRA: 0.98) achieved the highest rank in reducing the RD score, demonstrating superiority over StrataXRT® (MD -0.89, 95% CrI -1.49, -0.29). Henna (SUCRA: 0.89) demonstrated the highest effectiveness in providing pain relief, with a significant difference compared to Hydrofilm (MD -0.44, 95% CrI -0.84, -0.04) and Mepitelfilm (MD -0.55, 95% CrI -0.91, -0.19). Hydrofilm (SUCRA: 0.84) exhibited the fewest itching sensations, demonstrating superiority over Mepitelfilm (MD -0.50, 95% CrI -0.84, -0.17). No statistically significant difference was observed among various interventions in the assessment of burning sensations. CONCLUSION: PBMT and Mepitelfilm demonstrated better efficacy in reducing the incidence of grade≥2 RD and RD score, respectively. In terms of PROs, Henna and Hydrofilm had fewer complaints in pain and itching sensations, respectively. However, studies with larger sample size on different interventions are warranted in the future. TRIAL REGISTRATION: PROSPERO registration number CRD42023428598.

[The disease under chronic urticaria: beyond itching]. / La enfermedad crónica bajo la urticaria: más allá del prurito.

BACKGROUND: Brief erythematous-papular skin rashes suggest the diagnosis of urticaria; However, it may be another type of dermatitis, and complementary examinations must be carried out to establish its diagnosis. CASE REPORT: 53-year-old female patient, diagnosed in 2016 with diffuse large B cell lymphoma, in complete remission. Since 2010, he has had episodes of erythematous-papular lesions lasting 24-36 hours. He received antihistamines, corticosteroids and omalizumab without clinical improvement. The ANA determination was positive (1/320), nuclear mitotic pattern. The skin biopsy was compatible with dermatitis herpetiformis. The study of celiac and locus antibodies showed positivity for HLA-DQ2 and DQ2.5 in heterozygosity. The diagnosis of dermatitis herpetiformis was established. Treatment consisted of a gluten-free diet and prescription of dapsone, with satisfactory results. CONCLUSION: It is important to establish the differential diagnosis of patients with chronic urticaria who do not respond to the reference treatment, in addition to carrying out a thorough clinical examination and physical examination before starting treatment and relying on a multidisciplinary team to establish an accurate diagnosis and treatment. appropriate. Due to the side effects of dapsone, subsequent follow-up of patients is essential.

ANTECEDENTES: Los exantemas cutáneos eritemato-papulares de breve duración sugieren el diagnóstico clínico de urticaria; no obstante, puede tratarse de otro tipo de dermatitis, y para establecer el diagnóstico deben llevarse a cabo exploraciones complementarias. REPORTE DE CASO: Paciente femenina de 53 años, diagnosticada en 2016 con linfoma difuso de células B grandes, en remisión completa. Desde el 2010 manifestó episodios de lesiones eritemato-papulosas, de 24-36 horas de duración. Recibió antihistamínicos, corticoides y omalizumab sin mejoría clínica. La determinación de ANA resultó positiva (1/320), con patrón mitótico nuclear. La biopsia cutánea fue compatible con dermatitis herpetiforme. El estudio de anticuerpos de celiaquía y locus mostró positividad para HLA-DQ2 y DQ2.5 con heterocigosis. Se estableció el diagnosticó de dermatitis herpetiforme. El tratamiento consistió en dieta exenta de gluten y prescripción de dapsona, con resultados satisfactorios. CONCLUSIÓN: Es importante establecer el diagnóstico diferencial de pacientes con urticaria crónica que no responden al tratamiento de referencia, además de efectuar el examen clínico y la exploración física exhaustivos antes de iniciar el protocolo, y apoyarse de un equipo multidisciplinario para establecer el diagnóstico certero y tratamiento adecuado. Debido a los efectos secundarios de la dapsona, es imprescindible el seguimiento posterior de los pacientes.

The relationship and clinical significance of serum cytokine expression level and skin pruritus in patients with Hodgkin lymphoma and angioimmunoblastic T-cell lymphoma.

Pruritus of lymphoma is commonly associated with both Hodgkin lymphoma (HL) and angioimmunoblastic T cell lymphoma (AITL) and critically affects the life quality of patient. Recent evidence suggests that the pruritogenic cytokines seem to play a significant role in the genesis of chronic. This study aims to investigate the cytokines associated with itching in lymphoma patients and provide the basis for potential therapeutic targets. Serum samples were collected from 60 lymphoma patients, including 47 with Hodgkin lymphoma (HL) and 13 with angioimmunoblastic T-cell lymphoma (AITL), serving as the observation group (lymphoma group, LP group, n = 60). Additionally, serum samples from 8 healthy donors (HD group, n = 8) were collected for comparison. Within the lymphoma group, patients were stratified into those with pruritus (LWP group, n = 30) and those without pruritus (LWOP group, n = 30) based on the presence of skin pruritus symptoms. Elevated levels of multiple cytokines were significantly observed in the LP group in comparison to the HD group (p < 0.01). Patients in LWP group exhibited higher serum levels of IL-31 (p < 0.001), IL-1ß (P = 0.039), and IL-1α (P = 0.037) compared to LWOP group. Notably, serum IL-31 levels were higher in advanced AITL patients (stage IV) than in early AITL patients (stage I-Ⅲ, P < 0.05). In subgroup analysis, patients with pruritus in the AITL group exhibited higher serum levels of MIG and CTACK compared to HL group, whereas PDGF-BB levels were significantly lower (p < 0.05). Elevated serum levels of IL-31, IL-1ß, and IL-1α are linked to lymphoma-associated pruritus. Differences in serum cytokine profiles between HL and AITL subgroups are also highlighted. These findings offer valuable insights for clinical intervention in managing lymphoma-related pruritus.

Urticaria Pigmentosa Without Pruritus.

Mastocytosis is a group of disorders characterized by the pathologic accumulation of mast cells in various tissues. One example of mastocytosis is urticaria pigmentosa, which presents with mastocytomas that can cause hives and, when irritated, pruritus. To our knowledge, we are describing the first case of urticaria pigmentosa without pruritus. The patient had a positive Darier's sign, stated that they never felt itchy, and denied ever using a topical steroid or antihistamine. Although our patient declined additional testing, patients like this may benefit from a detailed evaluation of their sensory system through both quantitative sensory testing and genetic analysis. J Drugs Dermatol. 2024;23(3):     doi:10.36849/JDD.7558e.

Perineural Inflammation as a Novel Feature in Lichen Sclerosus: A Case Series of Histologic and Clinical Features.

ABSTRACT: Lichen sclerosus (LS) is a frequently encountered inflammatory skin disorder characterized by whitened, atrophic patches that can cause pain and pruritus. The underlying cause of this condition remains unknown. Primarily affecting the genital area, this condition carries an increased risk of developing cutaneous cancers and frequently co-occurs with autoimmune disorders. Our retrospective study aimed to explore histologic features of LS, with a particular focus on a newly established finding and its potential implications. We examined 53 histologic cases of LS collected over 2 years. Experienced pathologists evaluated and reached a consensus on the assignment of histologic features. Patient charts were manually reviewed to gather relevant demographic and clinical data. Statistical analysis was performed using IBM SPSS Statistics (2021). Of the 53 total patients identified as meeting criteria for inclusion in this study, only 8 (15%) were male. Eight cases (15%) demonstrated perineural inflammatory infiltrate. Notably, half of all samples from male patients exhibited perineural inflammatory infiltrate. A statistically significant increase ( P < 0.01) in the presence of dermal plasma cells was identified in cases with perineural inflammation versus cases without this feature. The findings of our study highlight the recurrent nature of perineural inflammation in LS, providing valuable insights into this condition. Furthermore, we observed a notable correlation between perineural inflammation, male patients, and the presence of dermal plasma cells. These discoveries contribute to a better understanding of the underlying mechanisms of LS and suggest avenues for future research into the condition.

Lazertinib as a frontline treatment in patients with EGFR-mutated advanced non-small cell lung cancer: Long-term follow-up results from LASER201.

OBJECTIVE: This analysis of the first-line cohort of LASER201 study evaluated the efficacy and safety of lazertinib 240 mg as a frontline therapy for epidermal growth factor receptor (EGFR)-mutated locally advanced or metastatic non-small cell lung cancer (NSCLC). METHODS: A total of 43 patients, with EGFR mutation-positive (Exon19Del, n = 24; L858R, n = 18; G719X, n = 1) locally advanced or metastatic NSCLC who had not previously received EGFR tyrosine kinase inhibitor (EGFR TKI) therapy, received once-daily lazertinib 240 mg. EGFR mutation status was confirmed by local or central testing. The primary endpoint was objective response rate (ORR) assessed by blinded independent central review. Secondary efficacy endpoints included duration of response (DoR), disease control rate (DCR), progression-free survival (PFS), tumor shrinkage, and overall survival (OS). RESULTS: At the primary data cut-off (DCO; January 8, 2021), the ORR was 70 % (95 % confidence interval [CI]: 56.0-83.5), DCR was 86 % (95 % CI: 75.7-96.4) and the median DoR was 23.5 (95 % CI: 12.5-not reached) months. The median PFS was 24.6 (95 % CI: 12.2-30.2) months. At the final DCO (March 30, 2023), the median OS was not estimable and the median follow-up duration for OS was 55.2 [95 % CI: 22.8-55.7] months. OS rates at 36 months and 54 months were 66 % (95 % CI: 47.5-79.3 %) and 55 % (95 % CI: 36.6-70.7 %), respectively. The most commonly reported TEAEs were rash (54 %), diarrhea (47 %), pruritus (35 %), and paresthesia (35 %). No drug-related rash or pruritus TEAEs of grade 3 or higher were reported. Diarrhea and paresthesia of grade 3 or higher were reported in 3 (7 %) and 1 (2 %) patients, respectively. CONCLUSION: This analysis demonstrated long-term clinical benefit with lazertinib 240 mg in patients with EGFR-mutated NSCLC who had not previously received EGFR TKIs. The safety profile for lazertinib was tolerable and consistent with that previously reported.

Identification of a novel nonsense ATP2A2 gene variant in a patient with Darier's disease flare following COVID-19 infection: A case report.

RATIONALE: Darier disease (DD) is a rare autosomal dominant disorder that primarily manifests as hyperkeratotic papules and itching. The underlying etiology of DD is pathogenic variation in the ATP2A2 gene. However, this disease has a high penetrance but variable expressivity, indicating that patients inheriting the genotype may have different manifestations due to exogenous factors. Meanwhile, a few reports have documented that COVID-19 may be implicated in the flare of DD. PATIENT CONCERNS: A 51-year-old man presented with keratotic papules and scaly erythematous rash on his trunk with pruritus after being infected with COVID-19. Laboratory test results were normal. Histological analysis revealed epidermal hyperkeratosis and intraepidermal lacunae containing dyskeratinized cells. Genetic analysis revealed a novel variant of ATP2A2 (c.815G>A, p.Trp272*), which was considered pathogenic in this case. DIAGNOSES: The patient was diagnosed as having DD. INTERVENTIONS: Oral acitretin and topical corticosteroid hormone ointments were used. OUTCOMES: The patient achieved complete resolution of symptoms during the 3-month follow-up period. LESSONS: We revealed the first novel ATP2A2 variant (c.815G>A, p.Trp272*) in the flare of DD following COVID-19 infection. Additionally, this pathogenic variant enriches the ATP2A2 gene mutation spectrum.

[MACULOPAPULAR CUTANEOUS MASTOCYTOSIS HARBORING A KIT MUTATION (ASP419DEL): A CASE REPORT].

A 2-year-old, male patient presented with an 18-month history of scattered, brown macules and nodules up to 2 cm in size on his trunk and extremities. These macules were accompanied by pruritus and were positive for Darier's sign. A skin biopsy of a brown macule on the left thigh revealed a dense accumulation of CD117-positive, round or oval cells with amphophilic cytoplasm within the upper to middle dermis. The patient was otherwise healthy and had normal laboratory and imaging test results. Sequence analysis of genomic DNA from a skin biopsy demonstrated the presence of an Asp419del mutation in exon 8 of the KIT gene. Based on these findings, maculopapular cutaneous mastocytosis (MPCM) was diagnosed. The patient received H 1-antihistamine. Although the pruritus resolved, the brown macules remained for one year after the initial treatment. To the best of our knowledge, only three cases of cutaneous mastocytosis (CM) with an Asp419del mutation, including the present case, have been reported in the Japanese literature to date; moreover, while the previous two cases were of DCM, the present case was the first instance of MPCM. Normally, the symptoms of childhood-onset MPCM are dormant until puberty. However, a recent study reported that many MPCM patients may experience persistent or exacerbated symptoms. The present study therefore evaluated 53 Japanese cases of childhood onset MPCM with a KIT gene mutation and discussed the patients' clinical outcomes.

Resolution of painful trichodysplasia spinulosa with topical cidofovir: case report.

Purpose: Trichodysplasia spinulosa (TS) is a rare, disfiguring skin condition which presents with widespread asymptomatic or pruritic, skin-colored papules with white protruding keratin spiculations in immunocompromised individuals. Due to its rarity, there is little data to guide treatment decisions. The purpose of this article is to report a case of TS that completely resolved after treatment with topical cidofovir.Materials and methods: A 19-year-old immunosuppressed female presented with widespread painful, itchy bumps on the nose and face. Upon examination, there were erythematous papules with hyperkeratinized spicules affecting the central face. Biopsy of the lesions was consistent with TS which was confirmed via PCR analysis. The tenderness of this patient's eruption was highly atypical for TS. Once daily topical application of compounded 1% cidofovir cream was prescribed.Results: The patient's symptoms resolved completely after 4 weeks of therapy with topical cidofovir 1% cream, without reduction of immunosuppression.Conclusions: Topical cidofovir 1% cream may be a valuable treatment for this rare disease.

Real-world experience of maralixibat in Alagille syndrome: Novel findings outside of clinical trials.

OBJECTIVE: Maralixibat, an ileal bile acid transporter inhibitor, is the first drug approved by the U.S. Food and Drug Administration for the treatment of cholestatic pruritus in patients aged ≥3 months with Alagille syndrome (ALGS). Approval was based on reductions in pruritus from the pivotal ICONIC trial, information from two additional trials (ITCH and IMAGO), and long-term extension studies. Although participants in these trials met strict inclusion and exclusion criteria, patients have received maralixibat under broader circumstances as part of an expanded access program or commercially. The expanded access and postapproval settings inform a real-world understanding of effectiveness and safety. The objective was to report on the use of maralixibat in the real-world setting in eight patients who otherwise would not have met entrance criteria for the clinical trials, providing unique insights into its effectiveness in the management of ALGS. METHODS: We reviewed records of patients with ALGS who received maralixibat but would have been excluded from trials due to surgical biliary diversion, reduction of antipruritic/cholestatic concomitant medications, administration of medication through a gastrostomy or nasogastric tube, or use in patients under consideration for transplantation. RESULTS: Maralixibat appeared to be effective with reductions in pruritus compared to baseline. Consistent with clinical trials, maralixibat was well tolerated without appreciable gastrointestinal complications. Liver enzyme elevations were observed but were interpreted as consistent with normal fluctuations observed in ALGS, with no increases in bilirubin. CONCLUSION: Maralixibat may be effective and well tolerated in patients with ALGS in broader clinical contexts than previously reported.

Acute liver injury in pregnancy.

A woman in her fifth month of pregnancy presented to the outpatient department with vomiting, generalised itching and yellowish discolouration of the skin for 1 week. No history of rashes, fever, pain abdomen or altered stools. In view of four pregnancy losses previously, she was evaluated to have antiphospholipid antibody syndrome and was advised low molecular weight heparin. She was a known type-II diabetic on insulin. Prophylactic oral dydrogesterone and natural micronised progesterone were started at a local hospital 2 months prior, in view of threatened abortion. Investigations revealed grossly elevated serum bilirubin and liver enzymes. Other blood investigations were unremarkable and abdominal ultrasonography was normal. The most likely diagnosis in this case, is drug-induced liver injury due to oral progestin consumption. Causality assessment by Roussel Uclaf Causality Assessment Model was used to establish the diagnosis. High doses of progestin over a prolonged period resulted in acute hepatic toxicity causing itching, jaundice and transaminitis. Cautious use of progestins in appropriate dosage is recommended during pregnancy.

Increased tissue expression of IL-31 in patients with psoriasis.

Psoriasis is a chronic inflammatory skin disease, and its pathogenesis remains unclear. Although many studies have demonstrated the role of serum interleukin-31 (IL-31) in psoriasis, only one study has examined histopathological expression in lesional skin. This study aimed to investigate the expression of IL-31 in skin biopsy specimens of psoriasis patients compared to healthy subjects and identify its possible correlation to disease severity and itch intensity. Psoriasis patients and healthy volunteers were recruited. Four-millimeter punch biopsy was performed at the lesional skin of psoriasis patients and normal skin of healthy subjects. Expression of IL-31 was measured by immunohistochemistry. Baseline characteristics, disease activity, itch intensity, and related laboratory results were collected. Twenty-six biopsy specimens of psoriasis patients and 10 tissue samples of healthy subjects were evaluated. Epidermal and dermal psoriasis lesions had significantly higher IL-31 expression compared to the healthy skin (P < 0.001). However, there was no significant difference in lesional expression of IL-31 by disease severity or itch intensity. Increased IL-31 expression in the lesions of psoriasis patients suggests the involvement of IL-31 in the pathogenesis of psoriasis.

Impact of neurofibromatosis type 1 on quality of life using the Skindex-29 questionnaire quality of life in NF1.

BACKGROUND: Neurofibromatosis type 1 (NF1) is one of the most common RASopathies predisposing affected patients to melanic lesions and benign tumors. NF1 is associated with considerable esthetic and functional burden negatively affecting the patient's quality of life (QoL). This study aims to assess the clinical features of NF1 patients and evaluate their impact on QoL. We identified NF1 patients from a public health database of a region in Spain. All patients underwent clinical and ophthalmological evaluation for NF1 features. We measured QoL using the Spanish version of the Skindex-29. RESULTS: Forty patients fulfilled the NF1 National Institute of Health criteria when we recruited patients. The median age was 42.00 years (IQR 26.5 -53.75). The median total Skindex-29 score was 12.3 (IQR 5.9-22.4); (emotion: 15.0, IQR 5.0-37.5; symptoms 8.9, IQR 0.0-17.9 and functioning 8.3; IQR 0.5-18.3). Women and NF1 patients with lower educational levels were associated with poorer QoL scores. We identified itching and sleep troubles to influence NF1 patients' QoL negatively. CONCLUSION: NF1 considerably influences the psychological well-being of NF1 patients. We observed that female and low-educated patients scored higher on the emotional dimension of the Skindex-29 and could, therefore, be more at risk of depression. We also pointed out some "minor symptoms" that negatively impact NF1 patients' QoL such, as itching and sleep troubles which doctors could treat if sought by doctors.

Factors associated with the quality of life of women undergoing radiotherapy.

OBJECTIVE: To evaluate the skin characteristics and quality of life of patients with breast cancer undergoing radiotherapy. METHOD: Cross-sectional study conducted with 60 women. The classification scales of skin changes resulting from exposure to ionizing radiation (RTOG) and the validated versions in Portuguese of those that classified skin types (Fitzpatrick), symptoms (RISRAS) and quality of life (DLQI) were applied. in the period between December 2021 and October 2022. For data analysis, Fisher's Exact Test, Chi-Square and Asymptotic General Independence Test were used. RESULTS: 100% of patients had skin irritation. As the treatment progressed and the radiodermatitis appeared or worsened, there was a tendency for the intensity of signs and symptoms to increase, such as: sensitivity, discomfort or pain, itching, burning and heat, dry and wet desquamation, which may have impacted the quality of life and reflected in other aspects, such as: shopping activities or outings (p=0.0020), social activities or leisure activities (p=0.0420). CONCLUSION: Radiodermatitis is a common condition that affects women with breast cancer undergoing radiotherapy, skin characteristics and quality of life of patients affected during this treatment.

20-HETE mediated TRPV1 activation drives allokinesis via MrgprA3+ neurons in chronic dermatitis.

Rationale: Noxious stimuli are often perceived as itchy in patients with chronic dermatitis (CD); however, itch and pain mechanisms of CD are not known. Methods: TRPV1 involvement in CD was analyzed using a SADBE induced CD-like mouse model, and several loss- and gain-of-function mouse models. Trigeminal TRPV1 channel and MrgprA3+ neuron functions were analyzed by calcium imaging and whole-cell patch-clamp recordings. Lesional CD-like skin from mice were analyzed by unbiased metabolomic analysis. 20-HETE availability in human and mouse skin were determined by LC/MS and ELISA. And finally, HET0016, a selective 20-HETE synthase inhibitor, was used to evaluate if blocking skin TRPV1 activation alleviates CD-associated chronic itch or pain. Results: While normally a pain inducing chemical, capsaicin induced both itch and pain in mice with CD condition. DREADD silencing of MrgprA3+ primary sensory neurons in these mice selectively decreased capsaicin induced scratching, but not pain-related wiping behavior. In the mice with CD condition, MrgprA3+ neurons showed elevated ERK phosphorylation. Further experiments showed that MrgprA3+ neurons from MrgprA3;Braf mice, which have constitutively active BRAF in MrgprA3+ neurons, were significantly more excitable and responded more strongly to capsaicin. Importantly, capsaicin induced both itch and pain in MrgprA3;Braf mice in an MrgprA3+ neuron dependent manner. Finally, the arachidonic acid metabolite 20-HETE, which can activate TRPV1, was significantly elevated in the lesional skin of mice and patients with CD. Treatment with the selective 20-HETE synthase inhibitor HET0016 alleviated itch in mice with CD condition. Conclusion: Our results demonstrate that 20-HETE activates TRPV1 channels on sensitized MrgprA3+ neurons, and induces allokinesis in lesional CD skin. Blockade of 20-HETE synthesis or silencing of TRPV1-MrgprA3+ neuron signaling offers promising therapeutic strategies for alleviating CD-associated chronic itch.

Prospective Randomized Double-Blind Vehicle-Controlled Study of Topical Coconut and Sunflower Seed Oil-Derived Isosorbide Diesters on Atopic Dermatitis.

Background: Preliminary studies support the use of topical coconut and sunflower seed oil for atopic dermatitis (AD). However, standardized topical formulations of fatty acids from these sources have not been studied. Objective: This study investigates whether coconut oil- and sunflower seed oil-derived isosorbide diesters can be used in conjunction with colloidal oatmeal to improve itch, AD severity, and the need for topical steroids in adults. Methods: This was a single-center, 4-week, randomized, double-blind, and vehicle-controlled study conducted between 2021 and 2022. Thirty-two male and female adults with mild-to-moderate AD were enrolled and completed the study. Participants were randomized to receive either 0.1% colloidal oatmeal (vehicle) or isosorbide diesters (IDEAS, 4% isosorbide dicaprylate and 4% isosorbide disunflowerseedate) along with 0.1% colloidal oatmeal. The main outcomes of the study were changes in the visual analogue rating of itch and 75% improvement in the Eczema Area and Severity Index score (EASI 75) at 4 weeks. Other measures included the use of topical steroids and the relative abundance of skin Staphylococcus aureus. Results: Participants in the IDEAS group had a 65.6% improvement in itch compared with 43.8% in the vehicle group (P = 0.013). In total, 56.5% and 25% of the those in the IDEAS and vehicle groups, respectively, achieved EASI 75 at 4 weeks (P = 0.07). There was no difference in skin hydration or transepidermal water loss. The relative abundance of S. aureus was decreased in the IDEAS group at week 4 compared with no change in the vehicle group (P = 0.044). Topical corticosteroid use increased in the vehicle group compared with a decrease in the IDEAS group at week 1 (292.5% vs 24.8%; P value = 0.039) and week 2 (220% vs 46%; P value = 0.08). Conclusions: Topical application of emollients containing coconut oil- and sunflower seed oil-derived fatty esters may improve itch, reduce topical steroid use, and reduce the relative abundance of S. aureus in mild-to-moderate AD. CTR number: NCT04831892.