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BACKGROUND: Prurigo nodularis (PN) is a chronic neuroimmune skin disease characterized by bilaterally distributed pruritic hyperkeratotic nodules on extremities and trunk. Neuroimmune dysregulation and chronic scratching are believed to both induce and maintain the characteristic lesions. OBJECTIVES: This study sought to provide a comprehensive view of the molecular pathogenesis of PN at the single-cell level to identify and outline key pathologic processes and the cell types involved. Features that distinguish PN skin from the skin of patients with atopic dermatitis were of particular interest. We further aimed to determine the impact of the IL31RA antagonist, nemolizumab, and its specificity at the single-cell level. METHODS: Single-cell RNA-sequencing of skin from 15 healthy donors and nonlesional and lesional skin from 6 patients each with PN and atopic dermatitis, combined with spatial-sequencing using the 10x Visium platform. Integration with bulk RNA-sequencing data from patients treated with nemolizumab. RESULTS: This study demonstrates that PN is an inflammatory skin disease characterized by both keratinocyte proliferation and activation of profibrotic responses. This study also demonstrates that the COL11A1+ fibroblast subset is a major contributor to fibrosis and is predominantly found in the papillary dermis of PN skin. Activation of fibrotic responses is the main distinguishing feature between PN and atopic dermatitis skin. This study further shows the broad effect of nemolizumab on PN cell types, with a prominent effect driving COL11A1+ fibroblast and keratinocyte responses toward normal. CONCLUSIONS: This study provides a high-resolution characterization of the cell types and cellular processes activated in PN skin, establishing PN as a chronic fibrotic inflammatory skin disease. It further demonstrates the broad effect of nemolizumab on pathological processes in PN skin.

Patients with chronic prurigo (CPG) experience intense itching leading to constant scratching, resultant lesions and, often, poor sleep and life quality. First-line therapies include emollients, topical corticosteroids and calcineurin inhibitors and ultraviolet therapies, with systemic agents including immunomodulators and neurological agents also suggested. In randomized controlled trials, dupilumab and nemolizumab both improved CPG itch and lesions and have subsequently become the first treatments to receive approval for prurigo nodularis (the most common subtype of CPG). Other emerging treatments, including vixarelimab, and Janus kinase inhibitors (abrocitinib and povorcitinib), show early promise in CPG. [ABSTRACT FROM AUTHOR]

Background: Itch terminology is ambiguous. How itch was described in online materials and how terminology influenced the readability of these materials was previously unknown. Materials and methods: Two groups of search terms, itch and prurigo, were translated into five of the most prevalent European Union (EU) languages. The itch group consisted of "itch" and "pruritus." The prurigo group consisted of "prurigo," "prurigo nodularis," and "chronic prurigo". Then, a search of the terms in each language was queried in the Google search engine in the private mode of the Internet browser. The first 50 results generated were assessed for suitability. Patient education was the primary objective of the materials provided, with no barriers or advertisements included. In cases where the terms yielded identical outcomes, any duplicated materials were omitted from the analysis. When translating search terms within a group led to just one shared transcription, the results were attributed to the search term with the most similar syntax. The Lix score was utilized to assess readability. Results: 314 articles in English, German, Italian, French, and Spanish were evaluated. The term "pruritus" was the most commonly used description for the sensation of itching, with 142 (45%) articles included. Overall, the mean Lix score was 54 ± 9, classifying all articles as hard to comprehend. Articles in the itch group had significantly (P < 0.001) lower mean Lix score (52 ± 9) than materials in the prurigo group (56 ± 10). Conclusions: Despite being more accessible to conceptualize, skin conditions such as prurigo had lower readability compared to information about the itch itself. The distinction between "itch" and "pruritus" was unclear. [ABSTRACT FROM AUTHOR]

Background: Prurigo nodularis (PN) is an intensely pruritic disease characterized by itchy nodules on the trunk/extremities; it is often accompanied by skin pain and sleep disruption with negative impacts on the quality of life (QoL). The patient‐reported outcome (PRO) instruments, Worst Itch‐Numeric Rating Scale (WI‐NRS), Skin Pain‐NRS, Sleep‐NRS and Dermatology Life Quality Index (DLQI) have been psychometrically validated and the clinically meaningful within‐patient improvement thresholds (responder definition) have been established through data pooled from the two Phase‐3 trials (PRIME, NCT04183335 and PRIME2, NCT04202679) of dupilumab in adults with PN uncontrolled on topical therapies. Objectives: To estimate the proportion of dupilumab‐treated patients (vs. placebo) achieving clinically meaningful improvement in itch, skin pain, sleep and QoL, either alone or in combination, from the data pooled from PRIME and PRIME2 trials. Methods: The patient‐level data pooled from the two Phase‐3 trials (N = 311) were used for this post hoc analysis. Thresholds of clinically meaningful within‐patient improvement in PRO instrument scores from baseline at Week 24 used for defining responders were 4 (WI‐NRS and Skin Pain‐NRS), 2 (Sleep‐NRS) and 9 points (DLQI). The proportion of dupilumab‐treated patients, versus placebo, achieving the thresholds, and the time taken to achieve the thresholds were evaluated for the individual and combination of PROs. Results: Responder rates were significantly higher with dupilumab, versus placebo at Week 24 for WI‐NRS (58.8% vs. 19.0%, p < 0.0001), Skin Pain‐NRS (49.7% vs. 20.9%, p < 0.0001), Sleep‐NRS (42.5% vs. 23.4%, p < 0.0001) and DLQI (64.7% vs. 22.8%, p < 0.0001). Proportion of patients achieving simultaneous improvement in symptoms and QoL (24.8% vs. 6.3%, p < 0.0001) were significantly higher in dupilumab‐treated patients versus placebo. The time needed for achieving clinically meaningful improvement in symptoms were significantly lower in dupilumab‐treated patients, versus placebo. Conclusions: Significantly greater proportion of dupilumab‐treated patients with PN, versus placebo, demonstrated clinically meaningful improvements in PRO measures of symptoms and QoL. [ABSTRACT FROM AUTHOR]

Background: Prurigo nodularis (PN) also known as chronic prurigo, is a chronic inflammatory skin disease characterized by intensely itchy nodules/lesions which occur due to intensive scratching. PN management is, in part, based on clinician evaluations of PN lesions, which can be supported by clinician‐reported outcomes (ClinRO) such as the Prurigo Activity and Severity (PAS) instrument. A 5‐item version of PAS was included in recent phase‐3 dupilumab PN trials (PRIME [NCT04183335]/PRIME2 [NCT04202679]). The PAS score was derived using the unweighted sum of 3‐items of the 5‐item PAS (range, 0–11; higher score indicates worse activity and severity): Item 2 (number of lesions), Item 5a (percentage of lesions with excoriations/crusts) and Item 5b (percentage of healed lesions) for use in clinical practice and for communication of treatment benefit to physicians. Objectives: To evaluate the measurement properties of PAS score and derive within‐patient (responder definition) and between‐group improvement thresholds for interpreting changes in PAS score in patients with PN. Methods: The data source was the pooled treatment group, intention‐to‐treat (ITT) data from the phase‐3 PRIME (NCT04183335) and PRIME2 (NCT04202679) studies evaluating the efficacy of dupilumab in adult patients with PN with ≥20 nodules and severe itch uncontrolled with topical therapies. PAS score reliability, validity and sensitivity to change were evaluated, and anchor‐ and distribution‐based methods were applied to derive meaningful change thresholds. Results: The pooled ITT population included 311 patients (mean age 49.5 years, 65.3% female). Adequate to good psychometric properties were demonstrated for PAS score. The within‐patient meaningful improvement threshold was estimated as 3.0 points (absolute change) and 37% (per cent change). A 1.7‐point (absolute change) and 20% (per cent change) improvement were estimated to reflect a between‐group meaningful change in PAS score. Conclusions: PAS score is a simple, clinically relevant indicator of PN lesion activity and severity supported by suitable psychometric performance. [ABSTRACT FROM AUTHOR]

Abstract Prurigo is a reactive, hyperplastic skin condition characterized by pruritic papules, plaques, and/or nodules. The temporal classification includes acute/subacute and chronic disease (≥ 6 weeks), with different clinical variants, synonymies, and underlying etiological factors. The immunology of chronic prurigo shows similarities with atopic dermatitis due to the involvement of IL-4 and IL-13, IL-22, and IL-31. Treatment includes antihistamines, topical steroids, dupilumab, and JAK inhibitors. Several conditions manifest clinically as prurigo-like lesions, and the correct clinical diagnosis must precede correct treatment. Furthermore, chronic prurigos represent a recalcitrant and distressing dermatosis, and at least 50% of these patients have atopic diathesis, the treatment of which may induce adverse effects, especially in the elderly. The quality of life is significantly compromised, and topical treatments are often unable to control symptoms and skin lesions. Systemic immunosuppressants, immunobiologicals, and JAK inhibitors, despite the cost and potential adverse effects, may be necessary to achieve clinical improvement and quality of life. This manuscript reviews the main types of prurigo, associated diseases, their immunological bases, diagnosis, and treatment.

Atopic dermatitis (AD) and prurigo nodularis (PN) are chronic dermatological conditions marked by severe itching and the presence of eczematous lesions such as papules and nodules. Both diseases can pose significant physical and psychological harm, leading to poor quality of life. Notably, AD and PN were clinically linked in the past, with suggestions by researchers that PN might be a distinct clinical phenotype of AD. However, the extent of their relationship had not been fully quantified until our recent investigations. Through a meticulous systematic review and meta‐analysis adhering to the PRISMA guidelines, we extensively searched databases, including PubMed, EMBASE, Scopus, and the Cochrane Library, up to February 18, 2024. Our random effects meta‐analysis presented a strikingly increased risk of AD in patients suffering from PN as opposed to control groups (pooled unadjusted odds ratio [OR], 16.85; 95% confidence interval [CI], 6.13–46.31; I2 = 100%). Correspondingly, an elevated prevalence of PN was identified in subjects with AD (2.00%; 95% CI, 1.62–2.37%). These findings underscore the close association between AD and PN, suggesting a multifaceted overlap and potential bi‐directionality in developing these skin conditions. However, further comprehensive studies are essential to validate these associations and understand their precise clinical implications, with the ultimate goal of refining patient management strategies. [ABSTRACT FROM AUTHOR]

Abrocitinib, an oral small-molecule Janus Kinase 1 (JAK1) inhibitor, is primarily approved for treating moderate-to-severe atopic dermatitis (AD) in adults and adolescents aged 12 and older. This review examines the emerging off-label uses of Abrocitinib. We identified 37 papers reporting on the use of Abrocitinib in various conditions other than AD. The most commonly reported uses were for vitiligo, prurigo nodularis, and hand eczema, with 12 cases each. There were also 10 cases of lichen sclerosus and chronic pruritus of unknown origin and 5 cases each of pityriasis rubra pilaris alopecia areata. Additionally, erythematotelangiectatic rosacea and steroid-induced rosacea were reported in four cases each. Other conditions treated with Abrocitinib were noted, but these mostly had only one or two reported cases. Interestingly, out of the 103 patients reviewed, all studies reported favorable clinical outcomes and satisfactory results, with the exception of one isolated case where Abrocitinib was used to treat erythematotelangiectatic rosacea. [ABSTRACT FROM AUTHOR]

The complex hormonal and immunological changes that occur during pregnancy can lead to the development of specific skin conditions, of which atopic dermatitis, now referred to as atopic eruption of pregnancy (AEP), is the most common. AEP typically presents before the third trimester and is characterized by eczematous or prurigo skin lesions that predominantly involve the flexures, extremities and/or trunk. Management options for AEP include topical treatments, phototherapy and systemic therapies. Novel therapies have been developed for the treatment of atopic dermatitis and further studies of their use in pregnant people will be useful. [ABSTRACT FROM AUTHOR]

Background Prurigo nodularis (PN), a chronic inflammatory skin condition, adversely affects the quality of life of affected individuals. Current treatment options for PN in Japan are limited. Objectives To evaluate the optimal dose, efficacy and safety of long-term treatment with nemolizumab in patients with PN in Japan. Methods In a 16-week double-blind phase II/III study, patients aged ≥ 13 years with PN were randomly assigned (1 : 1 : 1) to nemolizumab 30-mg, 60-mg or placebo groups, with concomitant topical corticosteroids, every 4 weeks. The primary efficacy endpoint was the percentage change in the weekly mean Peak Pruritus Numerical Rating Scale (PP-NRS) score (range 0–10, with higher scores indicating worse itching) from baseline to week 16. Secondary efficacy endpoints assessed the impact of treatment on pruritus, PN severity, sleep and quality of life. Results At week 16, the least-squares mean percentage change from baseline in the PP-NRS score was −61.1% in the nemolizumab 30-mg group (n = 77), −56.0% in the 60-mg group (n = 76), and −18.6% in the placebo group (n = 76). Differences between both nemolizumab groups and placebo were significant; the difference between the 30-mg and placebo groups was −42.5% [95% confidence interval (CI) −51.9 to −33.1; P < 0.0001], and between the 60-mg and placebo groups was −37.4% (95% CI −46.7 to −28.1; P < 0.0001). Patients treated with nemolizumab also had greater improvements in the number and severity of prurigo nodules, and in sleep and quality of life compared with the placebo group. Both nemolizumab doses were well tolerated. Conclusions Improvements in PN were greater following nemolizumab treatment, despite continuation of topical corticosteroids in both groups. [ABSTRACT FROM AUTHOR]

Prurigo nodularis (PN) manifests with highly pruritic lesions that negatively impact patient quality of life. Due to the variability in manifestation, hypertrophic lichen planus, pemphigoid nodularis, and neurotic excoriations tend to mimic PN. The pathophysiology of PN is believed to be due to interactions in the neural and immune pathways causing the release of proinflammatory and pruritogenic cytokines. Dermatologic and systemic conditions, including atopic dermatitis and chronic kidney disease, accompany PN diagnoses. Patients with moderate to severe or recalcitrant PN may benefit from dupilumab, the first medication approved by the US Food and Drug Administration (FDA) to treat PN. Here, we provide an updated review of PN with a focus on its pathophysiology, histologic findings, and current treatment options. [ABSTRACT FROM AUTHOR]

Prurigo nodularis (PN) is a debilitating chronic neuroimmunologic skin condition due to the intense pruritus and difficult to treat. The pruritogenic cytokines, particularly IL-4, IL-13, IL-22, IL-31, and oncostatin M (OSM), play a crucial role in the pathogenesis of PN, potentially involving the JAK1-STAT pathway. An oral JAK1 inhibitor, abrocitinib, is presently undergoing Phase 2 trials for the treatment of PN. We evaluated the efficacy of abrocitinib at a daily dosage of 100 mg in treating two patients with PN affecting both lower limbs: a 50-year-old male with a 16-year disease history and a 38-year-old female with over three years of disease history, both of whom had failed to respond to multiple conventional treatments. Both patients responded rapidly after one week of treatment and exhibited a marked improvement. Following eight weeks of therapy, near-complete resolution of both pruritus and lesions was achieved, and no adverse effects were reported. Additionally, there were no reported side effects during the initial four months of continued treatment. Abrocitinib is an effective targeted therapy for PN, offering a promising new option for refractory patients. [ABSTRACT FROM AUTHOR]

Background: Prurigo nodularis (PN) is characterized by intensely itchy nodules/lesions and skin pain, which can have a substantial impact on health‐related quality of life (HRQoL). Treatment benefits on such symptoms and impacts are best assessed in trials using patient‐reported outcome (PROs) instruments such as Skin Pain Numerical Rating Scale (NRS), Sleep‐NRS and Dermatology Life Quality Index (DLQI). However, no guidance exists for interpreting meaningful changes in scores using these PROs in patients with PN. Objectives: The main objective was to derive within‐patient (responder definition) and between‐group improvement thresholds for interpreting Skin Pain‐NRS, Sleep‐NRS and DLQI total scores in patients with PN. The measurement properties of the three PROs were also evaluated. Methods: Intention‐to‐treat (ITT), blinded and pooled data were used from the Phase 3 PRIME (NCT04183335) and PRIME2 (NCT04202679) studies evaluating the efficacy of dupilumab in adult patients with PN. Anchor‐ and distribution‐based methods were applied to derive responder definition and between‐group thresholds for Skin Pain‐NRS, Sleep‐NRS and DLQI. Data were additionally used to examine the instrument measurement properties, including reliability, validity and responsiveness. Results: A total of 311 patients (mean age 49.5 years, 65.3% female) were included in the pooled ITT population. The within‐patient improvement threshold for Skin Pain‐NRS was estimated as 4.0 points, 2.0 points for Sleep‐NRS and 9.0 points for DLQI total score. A 1.5‐point improvement in Skin Pain‐NRS scores, 1.0‐point in Sleep‐NRS and 4.0‐point in DLQI indicated a between‐group meaningful change. Adequate to good psychometric properties were demonstrated for all three instruments. Conclusions: The results of this study can aid interpretation of Skin Pain‐NRS, Sleep‐NRS and DLQI scores in patients with PN in both clinical trials and clinical practice to better understand and treat PN‐related skin pain and the impact of PN on sleep quality and HRQoL. [ABSTRACT FROM AUTHOR]

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This study analyzed data from hospitals located in three regions of Ethiopia: Addis Ababa, Northeastern Ethiopia, and Southern Ethiopia. The research aims to investigate the prevalence and contributing factors associated with skin diseases in these regions. Skin disorders represent a significant health concern in these areas, though their epidemiology differs markedly from that observed in Western countries. We collected data from 6,449 patients, considering factors like education, income, cultural habits, and access to healthcare. Patients in Southern Ethiopia generally had higher Body mass indexes and incomes and were closer to dermatology centers. The findings indicate that infectious diseases and pruritic dermatoses are the most prevalent skin conditions in all regions. The study highlights the significant impact of socio-economic status on skin health, with higher education correlating with a lower incidence of infectious diseases and sebaceous gland disorders. Overcrowding was associated with a higher occurrence of infectious diseases, emphasizing the importance of hygiene and sanitary conditions. Additionally, the distance from a patient’s residence to the hospital influenced the duration of the disease, stressing the need for better accessibility to healthcare services. In conclusion, this research offers important insights into the spectrum of skin diseases in Ethiopia, emphasizing the role of socio-economic factors and the critical need for improved healthcare access and education.

The article explores racial and geographic disparities in global clinical trials for prurigo nodularis (PN), a chronic skin condition. Studies indicate that PN is more prevalent among skin of color (SOC) and atopic dermatitis (AD) patients, with Black patients in the United States being disproportionately affected. The analysis of phase II/III PN clinical trials reveals a lack of diversity in participant representation, with the majority being White. The study emphasizes the need to diversify clinical trials to better reflect the affected patient population and improve outcomes for those disproportionately affected by PN. [Extracted from the article]

Prurigo nodularis (PN) is an inflammatory skin condition characterized by intensely pruritic nodules on the skin. Patients with PN suffer from an intractable itch–scratch cycle leading to impaired sleep, psychosocial distress and a significant disruption in quality of life. The pathogenesis of PN is associated with immune and neural dysregulation, mediated by inflammatory cytokines [such as interleukin (IL)-4, -13, -17, -22 and -31] and neuropeptides (such as substance P and calcitonin gene-related peptide). There is a role for type 2 inflammation in PN in addition to T-helper (Th)17 and Th22-mediated inflammation. The neuroimmune feedback loop in PN involves neuropeptides released from nerve fibres that cause vasodilation and further recruitment of inflammatory cells. Inflammatory cells, particularly mast cells and eosinophils, degranulate and release neurotoxins, as well as nerve growth factor, which may contribute to the neuronal hyperplasia seen in the dermis of patients with PN and neural sensitization. Recent studies have also indicated underlying genetic susceptibility to PN in addition to environmental factors, the existence of various disease endotypes centred around degrees of type 2 inflammation or underlying myelopathy or spinal disc disease, and significant race and ethnicity-based differences, with African Americans having densely fibrotic skin lesions. Dupilumab became the first US Food and Drug Administration-approved therapeutic for PN, and there are several other agents currently in development. The anti-IL-31 receptor A inhibitor nemolizumab is in late-stage development with positive phase III data reported. In addition, the oral Janus kinase (JAK) 1 inhibitors, abrocitinib and povorcitinib, are in phase II trials while a topical JAK1/2 inhibitor, ruxolitinib, is in phase III studies. [ABSTRACT FROM AUTHOR]

Itchy skin or pruritus is a common cutaneous symptom that causes an urge to scratch, and the role of interleukins (IL) in itchy skin has been widely studied. IL‐4 and IL‐13 are known to induce chronic itch. Similarly, the direct role of IL‐31 in inducing itch has been demonstrated in clinical situations such as atopic dermatitis and prurigo nodularis. Moreover, IL‐4 receptor α antibodies (dupilumab) and IL‐31 receptor A antibodies (nemolizumab) inhibit pruritus. However, the interplay between these ILs in pruritus remains unclear. Therefore, we investigated the reciprocal effects of these cytokines on pruritus in mice. The intradermal administration of IL‐31 induced itch‐associated scratching behaviour in a dose‐dependent manner. Interestingly, the amount of IL‐31 and IL‐4/IL‐13, co‐administration or 30 min pre‐administration of IL‐4/IL‐13 and intradermal or intravenous pre‐administration of IL‐4 did not affect IL‐31‐induced itch‐associated scratching behaviour when it was observed for 30 min, 2 h, 24 h or 48 h. Pre‐administration of neutralising antibodies against IL‐4 and IL‐13 also did not affect IL‐31‐induced itch‐associated scratching behaviour. These results suggest that IL‐31 can induce itching independently of IL‐4 and IL‐13 in vivo. [ABSTRACT FROM AUTHOR]

Prurigo nodularis (PN) is a chronic inflammatory skin condition that presents with intensely pruritic, hyperkeratotic nodules. The pathophysiology underlying PN is not entirely clear, making treatment challenging. Patients often require a multimodal approach, although many of the available therapies have low efficacy or adverse effects. In this review, we discuss the use of nemolizumab for the treatment of PN in adults. Nemolizumab is a biological therapy that reduces type 2 cytokines and the neuroimmune response implicated in the pathophysiology of PN. It also helps maintain skin barrier integrity, which may be damaged during the vicious itch-scratch cycle. Nemolizumab has demonstrated great efficacy in improving itch and clearing lesions in recent clinical trials with respectable tolerance. Nemolizumab is a promising drug for PN that seems comparable to the recently approved dupilumab in terms of its therapeutic effect and excellent safety profile, although nemolizumab may work more rapidly on itch. JAK inhibitors are also emerging as competitors of biologics for PN, however, their safety profile in this population may differ. Trials evaluating these drugs are needed to assess which is preferable. Additional data on the durability and longevity of nemolizumab for PN treatment is highly anticipated. [ABSTRACT FROM AUTHOR]

Chronic pruritus that lasts for over 6 weeks can present in various forms, like papules, nodules, and plaque types, with prurigo nodularis (PN) being the most prevalent. The pathogenesis of PN involves the dysregulation of immune cell–neural circuits and is associated with peripheral neuropathies, possibly due to chronic scratching. PN is a persistent and challenging condition, involving complex interactions among the skin, immune system, and nervous system. Lesional skin in PN exhibits the infiltration of diverse immune cells like T cells, eosinophils, macrophages, and mast cells, leading to the release of inflammatory cytokines and itch-inducing substances. Activated sensory nerve fibers aggravate pruritus by releasing neurotransmitters, perpetuating a vicious cycle of itching and scratching. Traditional treatments often fail, but recent advancements in understanding the inflammatory and itch transmission mechanisms of PN have paved the way for innovative therapeutic approaches, which are explored in this review. [ABSTRACT FROM AUTHOR]

Background. Breaking the itch-scratch cycle and facilitating lesion healing are pivotal in managing prurigo nodularis (PN). This study seeks to assess the efficacy of baricitinib, an oral JAK1/2 inhibitor, for treating PN. Methods. In this prospective pilot study, 12 patients with moderate to severe PN were administered oral baricitinib at a dosage of 4 mg/day for 12 weeks. The primary objective was to assess the efficacy of baricitinib in PN patients using the numeric rating scale (NRS) for pruritus, NRS sleep score, a 5-point investigator's global assessment (IGA) scale, dermatology life quality index (DLQI), and nodular lesion count at weeks 0, 1, 2, 4, 8 and 12. In addition, the NRS pruritus and sleep scores were assessed via phone on days 2 and 4 after baricitinib treatment. Results. Baricitinib treatment led to a statistically significant improvement in the mean NRS pruritus and sleep scores, evident as early as day 2 (57.7% change from baseline; P < 0.001 , and 34.7% change from baseline, P = 0.029 , respectively) and consistently declining thereafter. Evaluation of nodular lesions revealed a significant reduction starting from week 2 (mean difference of 37.08 from baseline; P < 0.001). Analysis of other endpoints, including mean DLQI and IGA scores, also demonstrated substantial improvement at all time points (week 1, 2, 4, 8, and 12) compared to baseline. However, it is important to acknowledge the limitation of a small sample size. This constraint warrants consideration when interpreting the results and generalizing the findings. Conclusion. This preliminary study underscores baricitinib's potential for PN treatment by providing a rapid clinical response. The larger and longer randomized controlled trials are essential to determine the effectiveness, longevity, and safety of baricitinib in managing PN. This trial is registered with TCTR20230227002. [ABSTRACT FROM AUTHOR]

Simple Summary: This study investigated a new imaging technique called ex vivo confocal microscopy to examine rare skin conditions. By analyzing tissue samples from different skin disorders, we found that this technique could accurately identify unique microscopic features of both common and rare skin diseases. Importantly, examiners with more experience in interpreting these images achieved higher accuracy in diagnosis. This suggests that ex vivo confocal microscopy has the potential to be a valuable tool alongside traditional methods for diagnosing rare skin conditions early and accurately, leading to better treatment outcomes for patients. While ex vivo confocal laser scanning microscopy has previously demonstrated its utility in most common skin diseases, its use in the assessment of dermatological entities with lower incidence remains unexplored in most cases. We therefore aimed to evaluate the diagnostic efficacy of some rare skin tumors as well as a few inflammatory skin diseases, that have not yet been studied in ex vivo confocal laser scanning microscopy. A total of 50 tissue samples comprising 10 healthy controls, 10 basal cell carcinoma, 10 squamous cell carcinoma, and 20 rare skin conditions were imaged using the newest generation ex vivo confocal microscopy (Vivascope 2500 M-G4, Vivascope GmbH, Munich, Germany). Three blinded investigators were asked to identify characteristic features of rare skin disorders and distinguish them from more common skin diseases in the ex vivo confocal microscopy images. Our findings present the capability of ex vivo confocal microscopy to display distinctive morphologic patterns in common and rare skin diseases. As might be expected, we found a strong correlation between imaging experience and diagnostic accuracy. While the imaging inexperienced dermatohistopathologist reached 60% concordance, the imaging-trained dermatologist obtained 88% agreement with dermatohistopathology. The imaging-trained dermatohistopathologist achieved concordance up to 92% with gold-standard dermatohistopathology. This study highlights the potential of ex vivo confocal laser scanning microscopy as a promising adjunct to conventional dermatohistopathology for the early and precise identification of rare dermatological disorders. [ABSTRACT FROM AUTHOR]

Background: Prurigo nodularis (PN) is a rare chronic inflammatory skin disease with a high disease burden, but data on clinical and economic burden are still scarce. Objective: To describe the real-world epidemiologic, clinical and therapeutic characteristics and related economic burden of patients with PN compared to a benchmark population in Germany. Methods: This retrospective study was based on an excerpt of German Statutory Health Insurance data of patients with an initial PN diagnosis between 2012 and 2016. PN cohort contained no record of PN in eight quarters before the index quarter and was followed up for eight quarters (unless deceased). Benchmark cohort without PN was calculated using direct standardization and 1:1 matching to PN cohort. Results: Out of 4,536,002 insured patients, 2309 incident patients with PN were identified and matched to the benchmark cohort out of 3,018,382 patients without PN. Patients were mostly between 45 and 80 years when diagnosed with PN. Higher comorbidity rates were reported for PN than benchmark, with a rising disease burden at follow-up. Most patients with PN (91.3%) were diagnosed outpatient and had >50% more outpatient visits than the benchmark cohort. Hospitalization rates were higher in PN (53.9%) versus benchmark (35.1%), yielding twice longer mean hospital stays for PN (12 days) compared to benchmark (6 days) (p < 0.001). The most common initial therapy for patients with PN was topical corticosteroids (47.6%); ≥10% of patients were treated with antidepressants, antihistamines or systemic corticosteroids. Therapy rates were higher for PN compared to benchmark (p < 0.001). Mean initial costs were twofold higher in PN versus benchmark for outpatient, inpatient and drugs. During follow-up, an increase of >70% in mean PN costs compared to benchmark was identified for outpatient, inpatient and concomitant treatments (p < 0.001). Conclusion: This study highlights the significantly higher clinical and economic burden incurred by PN compared to benchmark patients in Germany, reflecting the unmet medical need for PN. [ABSTRACT FROM AUTHOR]