Chronic Dermatitis Research Articles

The Histopathology of Chronic "Radiation Conjunctivitis" Shows Diagnostic Features Similar to Those Seen in Radiation Dermatitis, Including Radiation Fibroblasts.

Radiation therapy is a treatment modality for various ocular and ocular adnexal tumors. The histopathology of chronic radiation dermatitis has been well-described. The authors present two cases demonstrating and characterizing "chronic radiation conjunctivitis" which has not been histopathologically illustrated in detail. Retrospective case review of two patients who received proton beam irradiation for an anterior uveal melanoma and external beam radiation for conjunctival lymphoma, and developed leukoplakia and/or thickening of the eyelid margin and symblepharon. Hematoxylin and eosin-stained sections of eyelid margin and conjunctival biopsies as well as clinical histories were reviewed. Conjunctival biopsies in both cases revealed squamous epithelial metaplasia, chronic inflammation and bizarre-appearing stromal cells with hyperchromatic nuclei in a fibrotic/sclerotic stroma, consistent with chronic radiation conjunctivitis. These stromal cells are believed to be the same "radiation fibroblasts" described in chronic radiation dermatitis. The radiation fibroblast is characteristic for the diagnosis of chronic radiation conjunctivitis, as it is in radiation dermatitis. Features of squamous metaplasia of conjunctival epithelium, keratinization, subepithelial fibrosis/sclerosis and chronic inflammation are frequently found but not specific. A detailed history and other ancillary tests help differentiate cicatrizing conjunctival conditions, and biopsy should be performed in the setting of suspicion for a secondary malignancy.

CREB Is Critically Implicated in Skin Mast Cell Degranulation Elicited via FcεRI and MRGPRX2.

Skin mast cells (MCs) mediate acute allergic reactions in the cutaneous environment and contribute to chronic dermatoses, including urticaria, and atopic or contact dermatitis. The cAMP response element binding protein (CREB), an evolutionarily well conserved transcription factor (TF) with over 4,000 binding sites in the genome, was recently found to form a feedforward loop with KIT, maintaining MC survival. The most selective MC function is degranulation with its acute release of prestored mediators. Herein, we asked whether CREB contributes to the expression and function of the degranulation-competent receptors FcεRI and MRGPRX2. Interference with CREB by pharmacological inhibition (CREBi, 666-15) or RNA interference only slightly affected the expression of these receptors, while KIT was strongly attenuated. Interestingly, MRGPRX2 surface expression moderately increased following CREB-knockdown, whereas MRGPRX2-dependent exocytosis simultaneously decreased. FcεRI expression and function were regulated consistently, although the effect was stronger at the functional level. Preformed MC mediators (tryptase, histamine, β-hexosaminidase) remained comparable following CREB attenuation, suggesting that granule synthesis did not rely on CREB function. Collectively, in contrast to KIT, FcεRI and MRGPRX2 moderately depend on unperturbed CREB function. Nevertheless, CREB is required to maintain MC releasability irrespective of stimulus, insinuating that CREB may operate by safeguarding the degranulation machinery. To our knowledge, CREB is the first factor identified to regulate MRGPRX2 expression and function in opposite direction. Overall, the ancient TF is an indispensable component of skin MCs, orchestrating not only survival and proliferation but also their secretory competence.

Diagnostic Challenge of Lupus with Overlap Syndrome in an Adolescent: A Case Report

Lupus with overlap syndrome is an uncommon autoimmune disease that typically affects teenage females. It can present as various symptoms affecting multiple organs. Delay in the diagnosis of lupus will lead to deleterious effects on the implicated adolescents’ health. The case report aims to describe the diagnostic challenge of a refractory skin disease leading to a delay in diagnosis and highlight its psychosocial impact. Here, we describe a case of a teenager who presented with poorly controlled chronic dermatitis. The chronic dermatitis was refractory to the first-line therapy of topical steroids and emollients. She was finally diagnosed with lupus and overlap syndrome, confirmed by a skin biopsy. In conclusion, any chronic refractory skin diseases warrant further referral and investigation at the tertiary centre. Assessment of psychosocial in managing chronic skin disease in adolescent is essential as it could implicate their mental health further.

A Refined Comparative Mouse Model of Acute and Chronic Atopic Dermatitis

A Refined Comparative Mouse Model of Acute and Chronic Atopic Dermatitis

Surcharges cutanées endogènes

As in other organs, the diagnosis of endogenous cutaneous overload diseases is based on histopathological analysis of the lesions using special stainings, even if the clinical appearance is sometimes very suggestive. The lesions are sometimes very subtle and can be included in the group of "invisible" dermatoses, such as primary macular cutaneous amyloidosis or calciphylaxis. Superficial dermal melanosis or pigmentary incontinence generally reflects the post-inflammatory stage of a chronic or recurrent interface dermatitis. Section levels should be systematically performed to look for active lesions of diagnostic interest: Alcian blue staining to identify dermal mucinosis (connectivitis) and pan-T markers (fixed pigmented erythema, lichenoid mycosis fungoides, and vitiligo). Some pathologies have a prognostic impact, either because they reflect an underlying disease, monoclonal gammopathies, in particular myeloma, being one of the most common conditions in this context (AL amyloidosis, xanthoma and xanthogranuloma, scleromyxedema), or because they can be associated with visceral damage (AL amyloidosis, scleromyxedema). The clinical-pathological comparison is mandatory to rule out differential diagnoses, especially for life-threatening diseases: nodular amyloidosis and primary cutaneous amyloidosis versus systemic AL amyloidosis, papular mucinosis versus scleromyxedema and calcific panniculitis versus calciphylaxis.

Clinical Characteristics and Therapeutic Management of Atopic Dermatitis in Elderly Patients Compared with Young Adult Patients: A Prospective Multicentre Study.

Atopic dermatitis (AD) is the most common chronic inflammatory dermatitis in developed countries, and has a major impact on those affected. Little is known about AD in elderly patients. This prospective multicentre observational study described the clinical characteristics and burden of AD in elderly subjects ≥ 65 years, as well as the therapeutic options chosen for this population in routine care, and compared findings with those in young adults with AD < 30 years. Cohort data from adult patients with moderate-to-severe AD enrolled in a French national prospective registry (December 2020 to May 2023) were analysed. Patients ≥ 65 years made up 12.5% of the total adult cohort and presented less head-and-neck and extremity involvement, and were less affected by generalized forms than young adult patients. Elderly patients predominantly had late-onset AD and had similar disease severity to younger adults. Although the overall impact of AD appeared to be lower in elderly patients and treatment was initially less used in this age group, the substantial impact on sleep and psychiatric comorbidities was similar in older and younger adult patients. Better understanding of AD in elderly patients and the establishment of age-specific treatment guidelines may help dermatologists manage the disease in older people.

Predictors and mechanisms of self-stigma in five chronic skin diseases: A systematic review.

People with skin disease suffer due to disease-related physical symptoms, as well as due to significant psychosocial burden. A major contributor of this burden is the experience of stigmatization. Research indicates that people with visible skin diseases deal with both social stigma and self-stigma. This systematic literature review aimed to aggregate existing research on correlates and mechanisms that contribute to self-stigmatization among people with atopic dermatitis, psoriasis, vitiligo, alopecia areata or hidradenitis suppurativa and to, ultimately, identify targets for psychosocial interventions. The review followed PRISMA guidelines. Four databases, PubMed, OVID, Web of Science and PsycINFO were searched for peer-reviewed articles. Studies were identified by two independent researchers and were eligible if they (1) assessed adults with one of five chronic skin diseases-atopic dermatitis, psoriasis, vitiligo, alopecia areata or hidradenitis suppurativa, (2) measured self-stigma or relevant synonyms, (3) evaluated psychosocial correlates, predictors or explanatory mechanisms of self-stigma and (4) were published in German or English in a peer-reviewed journal. The Johanna Briggs Institute Checklist for Analytical Cross Sectional Studies was used to evaluate the quality of studies. Twenty-seven studies were included with a mean quality rating of 7.04 (outof 8). Social stigma, coping strategies (such as lack of acceptance) and lack of social support were identified as main predictors of self-stigma. Although study quality was good, all but one study had a cross-sectional design that does not allow examining causal relationships among the determinants of self-stigma. Findings from the present review revealed several psychosocial variables that are malleable and potentially suitable as intervention targets. Those variables such as acceptance should be targeted in evidence-based interventions specifically developed to reduce self-stigma to, ultimately, improve mental health of people affected.

Exploratory pharmacodynamics and efficacy of PF-06817024 in a Phase 1 study of patients with chronic rhinosinusitis and atopic dermatitis

PF-06817024 is a humanized antibody against interleukin-33 that has the potential to inhibit type 2 inflammation. An exploratory analysis of the pharmacodynamics and clinical effects of single and repeat doses of PF-06817024 was assessed in patients with chronic rhinosinusitis with nasal polyps (CRSwNP) and patients with moderate-to-severe atopic dermatitis (AD), respectively, as part of a Phase 1, first-in-human study. Rhinosinusitis symptoms were improved, and nasal polyps were decreased in size following treatment with PF-06817024 in patients with CRSwNP. In patients with AD, PF-06817024, in aggregate, reduced disease severity and improved symptoms, as demonstrated by greater percentage decrease from baseline in Eczema Area and Severity Index (EASI) scores and reduced pruritus numerical rating scores, compared with placebo. The efficacy in AD appeared to be bimodal with a sub-group of participants exhibiting high levels of improvement (EASI75 and EASI90) for a sustained period of time after dosing. In patients with CRSwNP, a consistent trend of decrease in eosinophil levels was observed in the PF-06817024 group, compared with placebo. Further research would be needed to confirm the clinical benefit and safety of PF-06817024 as a treatment for allergic diseases.Trial registration ClinicalTrials.gov, NCT02743871. Registered 15 April 2016, https://clinicaltrials.gov/study/NCT02743871?term=NCT02743871&rank=1.

Photopatch testing: Clinical characteristics, test results, and final diagnoses from the North American Contact Dermatitis Group, 2009-2020.

Photoallergic contact dermatitis (PACD) is a delayed hypersensitivity reaction to allergens only in the presence of ultraviolet radiation in sunlight. Photopatch testing (PhotoPT) is necessary to confirm the diagnosis of PACD. There are few published studies of PhotoPT in North America. To summarise the results of patients photopatch tested by members of the North American Contact Dermatitis Group (NACDG), 2009-2020. Retrospective analysis of patient characteristics and PhotoPT results to 32 allergens on the NACDG Photopatch Test Series. Most of the 454 tested patients were female (70.3%), 21-60 years old (66.7%) and White (66.7%). There were a total of 119 positive photopatch tests. Sunscreen agents comprised 88.2% of those, with benzophenones responsible for over half of them. Final diagnoses included PACD in 17.2%, allergic contact dermatitis (ACD) in 44.5%, polymorphous light eruption (PMLE) in 18.9% and chronic actinic dermatitis (CAD) in 9.0% of patients. In 454 patients with suspected photosensitivity referred for photopatch testing in North America, approximately one-fifth had PACD. Sunscreen agents, especially benzophenones, were the most common photoallergens. Other common diagnoses included ACD, PMLE and CAD. Photopatch testing is an important tool for differentiating these conditions.

Patch testing with Indian standard series of 20 allergens in 125 patients of chronic dermatitis and dermatoses

Objectives: Patch testing is generally done in cases of allergic contact dermatitis to find the offending allergen/s. It has been less reported in patients clinically presenting as non-eczematous contact reactions such as lichen planus, lichenoid eruption, lichen planus pigmentosus and facial melanosis overlap. In addition, it may give clues to the sensitizers leading to chronic, recurring dermatitis and overlap of dermatoses in the form of systemic contact dermatitis. The aim of the present study was to identify the sensitizer/s with patch testing in patients presenting with non-eczematous contact reactions as well as chronic, relapsing dermatitis and overlap of dermatoses. Material and Methods: In the present study, patch testing was done using the Indian standard series in 125 cases presenting clinically as lichen planus, lichen planus pigmentosus, facial melanosis, cheilitis, mucosal lichen planus and vulvar dermatitis, in addition to cases of chronic and recurrent dermatitis such as nummular eczema, lichenoid eruption, pompholyx, photo aggravated dermatitis, air borne contact and hand and feet dermatitis. Results: The tests were positive in 102 (81.6%) patients, negative in 16, doubtful in 3 and invalid in 4 patients. Positive results were found in 100% cases of photo aggravated dermatitis and chronic dermatitis of hands/feet dermatitis and 76% cases of facial melanosis and lichen planus pigmentosus overlap, 88.9% cases of nummular eczema, 81.8% cases of lichenoid eruption, 75% cases of lichen planus, 57% cases of atopic eczema, 66.6% cases of pompholyx, and 100% of mucosal lichen planus. Test for nickel was positive in 40 (32%) cases, parthenium in 37 (29.6%), cobalt in 23 (18.4%), fragrance in 19 (15.2%), paraphenylenediamine in 17 (13.6%), paraben in 9 (7.2%) and neomycin in 5 (4%) cases, either alone or in combination. In the present study, in addition to eczematous dermatoses, non-eczematous conditions such as lichen planus, lichenoid eruption, lichen planus pigmentosus and facial melanosis also showed positive results on patch testing. Conclusion: Patch testing should be considered in patients presenting with chronic and recurrent dermatitis and overlap of more than one type of dermatoses. Identification and elimination of culprit allergens can help in achieving long term remission in these chronic conditions.

Efficacy and safety of azathioprine versus mycophenolate mofetil in chronic actinic dermatitis in skin of color: results of a randomized controlled trial.

Chronic actinic dermatitis (CAD) is an immunologically mediated photodermatosis that has been effectively treated with azathioprine and mycophenolate mofetil (MMF) in uncontrolled studies. We conducted a prospective randomized controlled trial to compare the efficacy and safety of azathioprine and MMF in CAD treatment, aiming to address existing evidence gaps. Consecutive CAD patients were randomized into two groups: azathioprine (Group A) or MMF (Group B) for 12 weeks. Primary outcomes included Eczema Area and Severity Index (EASI) and Dermatology Life Quality Index (DLQI) at baseline and Week 12. Secondary outcomes included various clinicodemographic factors predictive of treatment response, defined at least a 75% reduction in EASI score (EASI75) by Week 12. The median (IQR) percentage reduction in EASI at 12 weeks was higher in Group B than in Group A [78.3% (75.0-83.30%) vs. 68.3% (31.2-80.10%), P = 0.034]. Baseline DLQI scores indicated a moderate impact on quality of life, with significant reductions by Week 12 in both groups and no intergroup differences at baseline (P = 0.291) or Week 12 (P = 0.599). Overall, 23 patients were classified as non-responders, with more extended illness duration (P = 0.026) and outdoor occupations (P = 0.042) associated with poorer responses. Adverse effects were consistent with known profiles, with one patient discontinuing azathioprine due to hypersensitivity. Our study highlights the efficacy and safety of azathioprine and MMF in CAD treatment, with MMF showing superior outcomes. However, further research is warranted to explore emerging therapies and prognostic factors in CAD management.

Patient-Reported Outcome Measures in Chronic Spontaneous Urticaria, Angioedema, and Atopic Dermatitis

Reducing the burden of disease for patients and families requires being able to measure health status changes related to disease severity, control, and response to treatment over time. Patient-reported outcomes are patient perceptions of their health status. Such perceptions are critical to decision making. Some patient-reported outcome measures (PROMs) are extensive and often intended to be used only for detailed research assessments. Many PROMs, however, form critical components of valid, reliable, and responsive assessments in clinical research and routine clinical practice. The smallest score change in a PROM that would lead to different decision making by patients is called the minimally important difference. Using PROMs may also offer advantages over general questions or unvalidated tools. With the innovation of technology, the ability to chronicle disease symptoms using communication technology (mobile phone applications) has become increasingly available. Collection of real-world data in this capacity will be very useful for identifying more precise phenotypes/endotypes necessary for investigation of tailored therapies for chronic spontaneous and inducible urticaria, angioedema, and atopic dermatitis. Here, we provide an overview of PROMs that have been developed for the assessment of disease severity, control, and quality of life and that have been validated for the use of adults and children with these skin disorders.

Continuum of light sensitivity in atopic dermatitis: A retrospective analysis of 139 cases in Scotland

BackgroundPrevious reports have characterized photosensitivity in atopic dermatitis (AD), but with differences in terminology and criteria. ObjectiveThis study aims to assess outcomes in 139 AD patients referred for photodiagnostic testing and to establish diagnostic criteria for photosensitivity in AD. MethodsClinical and photodiagnostic data were reviewed, categorizing photosensitivity into Photo-Exacerbated AD (PEAD), Photo-Sensitive AD (PSAD), and Chronic Actinic Dermatitis (CAD). ResultsOf the patient cohort, mean age was 42.6±16.7 years and 61.9% were male. PEAD patients (51.1%) had normal monochromator phototesting. PSAD patients (7.9%) displayed slight-to-moderate UVA sensitivity (≥30% of normal minimal erythema dose [MED]) and mostly normal/slightly reduced UVB MEDs (≥80% of normal MED). Conversely, 41% of patients had CAD and 93% of this group demonstrated significant UVB sensitivity, with very low UVB MEDs (<80% of normal MED) and/or very low UVA MEDs (<30% of normal MED). No significant differences in sex, age, or skin phototype were observed between groups. Serial phototesting revealed changes in photosensitivity status over time in eight patients. LimitationsSmall sample size and retrospective design. ConclusionsThis study highlights the heterogeneity of photosensitivity patterns in AD patients and the importance of follow-up assessments due to potential shifts in disease spectrum over time.

Pharmacologic inhibition of Il6st/gp130 improves dermatological inflammation and pruritus

Chronic dermatitis is a disease with large unmet need for pharmacological improvement. Dermatitis conditions are maintained and exacerbated by various cytokine actions in the context of inflammation. Interleukin 6 signal transducer (Il6st), also known as glycoprotein 130 (Gp130), is a key component for surface reception of a multitude of cytokines and transduction and amplification of their pro-inflammatory signals. We hypothesized accordingly that pharmacological inhibition of Il6st can alter dermatitis pathology. Treatment with SC-144 and bazedoxifene, two representative small molecule Il6st inhibitors with different binding modes led to moderate but significant improvement of skin conditions in a 1-chloro-2,4-dinitrobenzene animal model. Part of cytokine expressions indicating the dermatological index were normalized particularly when treated with SC-144. Pruritic behaviors were blunted, also possibly giving limited contribution to disease improvement. In psoriatic skin and itch of an imiquimod animal model, those two treatments appeared to be relatively moderate. Collectively, pharmacological inhibition of Il6st seems to lessen pathological irritation. Inversely, this experimental attempt newly implies that Il6st participates in pathological mechanisms. In conclusion, we suggest Il6st as a novel target for improving dermatitis, and that agents with suitable efficacy and safety for its modulation are translatable.

Beyond the classic players: Mas-related G protein-coupled receptor member X2 role in pruritus and skin diseases.

Chronic spontaneous urticaria (CSU), atopic dermatitis (AD), psoriasis and rosacea are highly prevalent inflammatory skin conditions which impose a significant burden on patients' quality of life. Their pathophysiology is likely multifactorial, involving genetic, immune and environmental factors. Recent advancements in the field have demonstrated the key role of mast cells (MC) in the pathophysiology of these conditions. The Mas-related G protein-coupled receptor X2 (MRGPRX2) has emerged as a promising non-IgE-mediated MC activation receptor. MRGPRX2 is predominately expressed on MC and activated by endogenous and exogenous ligands, leading to MC degranulation and release of various pro-inflammatory mediators. Mounting evidence on the presence of endogenous MRGPRX2 agonists (substance P, cortistatin-14, LL37, PAMP-12 and VIP) and its high expression among patients with CSU, AD, rosacea, psoriasis and chronic pruritus emphasizes the pathogenic role of MRGPRX2 in these conditions. Despite the currently available treatments, there remains a pressing need for novel drug targets and treatment options for these chronic inflammatory skin conditions. Here, we reviewed the pathogenic role of MRGPRX2 and its potential as a novel therapeutic target and provided an update on future research directions.

Serum Concentration of IL-5 Receptor (IL-5R) and Associations with Disease Severity in Patients with Chronic Spontaneous Urticaria (CSU) and Atopic Dermatitis (AD).

The immunological pathogenesis of atopic dermatitis (AD) and chronic spontaneous urticaria (CSU) has not been fully elucidated yet. The aim of our research was to assess the serum concentration of interleukin-5 receptor (IL-5R) in relation to the disease activity and pruritus intensity in adult patients with AD and CSU. This pilot study included 45 participants (15 patients with AD, 15 patients with CSU, and 15 healthy controls). Blood samples were taken to examine the serum levels of IL-5R using the enzyme-linked immunosorbent assay (ELISA) test. The Scoring Atopic Dermatitis (SCORAD) index, the Urticaria Activity Score (UAS7), and the Visual Analogue Scale (VAS) were used to assess the disease activity and the pruritus intensity, respectively. Obtained results revealed that the IL-5R concentration was significantly higher in patients with CSU than in patients with AD and in the controls (p = 0.038). There was a positive correlation between the IL-5R level and the SCORAD index in patients with AD (r = -0.9, p = 0.047), which was not found for the CSU activity by UAS7 and with the pruritus severity by VAS in both examined groups of patients. Our findings underscore higher serum levels of IL-5R among CSU and AD patients, which may highlight its functional role in the pathogenesis of these diseases. In contrast, IL-5R might not be fully useful in reflecting the severity of symptoms. Although our results are promising, this study should be conducted on a larger cohort of patients.

Inhibition of mast cell degranulation by novel small molecule MRGPRX2 antagonists

BackgroundMas-related G-protein coupled receptor X2 (MRGPRX2) is a promiscuous receptor on mast cells that mediates IgE-independent degranulation and has been implicated in multiple mast cell-mediated disorders, including chronic urticaria, atopic dermatitis, and pain disorders. Although it is a promising therapeutic target, few potent, selective, small molecule antagonists have been identified, and functional effects of human MRGPRX2 inhibition have not been evaluated in vivo. ObjectiveWe identified and characterized novel, potent, and selective orally active small molecule MRGPRX2 antagonists for potential treatment of mast cell-mediated disease. MethodsAntagonists were identified using multiple functional assays in cell lines overexpressing human MRGPRX2, LAD2 mast cells, human peripheral stem cell-derived mast cells, and isolated skin mast cells. Skin mast cell degranulation was evaluated in Mrgprb2em(-/-) knockout (KO) and Mrgprb2em(MRGPRX2) transgenic human MRGPRX2 knock-in (KI) mice by assessment of agonist-induced skin vascular permeability. Ex vivo skin mast cell degranulation and associated histamine release was evaluated by microdialysis of human skin tissue samples. ResultsMRGPRX2 antagonists potently inhibited agonist-induced MRGPRX2 activation and mast cell degranulation in all mast cell types tested, in an IgE-independent manner. Orally administered MRGPRX2 antagonists also inhibited agonist-induced degranulation and resulting vascular permeability in MRGPRX2 KI mice. In addition, antagonist treatment dose dependently inhibited agonist-induced degranulation in ex vivo human skin. ConclusionMRGPRX2 small molecule antagonists potently inhibited agonist-induced mast cell degranulation in vitro and in vivo as well as ex vivo in human skin, supporting potential therapeutic utility as a novel treatment for multiple human diseases involving clinically relevant mast cell activation.

New Applications of the Anterior Intercostal Artery Perforator Flap for Prosthetic Breast Reconstruction in the Setting of Postoperative Radiotherapy.

Several studies have reported preliminary experiences with the anterior intercostal artery perforator (AICAP) flap for treating partial breast defects or breast implant exposure following reconstruction. As radiotherapy is commonly administered for breast cancer, some patients may present with heavily damaged skin flaps and chronic radiodermatitis. We describe new applications of a de-epithelialized AICAP flap, used in combination with an implant, for breast reconstruction when other treatment options are unavailable. A retrospective study was conducted, including all patients who underwent implant-based breast reconstruction with the aid of an AICAP flap. A literature review was also performed. Between November 2022 and August 2023, four pedicled AICAP flaps were harvested in four patients. The indications were breast implant coverage in cases of chronic dermatitis of the mastectomy skin flaps (two unilateral flaps) and inferolateral coverage of partially submuscular expanders for immediate breast reconstruction (two unilateral flaps). All four flaps were based on one perforator. The mean harvesting time was 40 minutes. Complete flap survival was achieved, with no complications at the donor site. The AICAP flap is a safe and reliable technique for difficult cases of breast reconstruction when no other options are available. Moreover, this technique can easily provide additional coverage for the breast implant when needed.

Exploratory Efficacy Evaluation of Apremilast for the Treatment of Japanese Patients with Palmoplantar Pustulosis: 32-Week Results from a Phase2, Randomized, Placebo-Controlled Study.

Palmoplantar pustulosis (PPP) is a pruritic, painful, chronic dermatitis that greatly impacts functioning and quality of life and can be difficult to treat. Approved treatment options for PPP are limited, and many patients do not fully respond to current treatments. This was a randomized, double-blind, placebo-controlled, phase2 study in Japanese patients with moderate to severe PPP and inadequate response to topical treatment. Patients were randomized 1:1 to receive apremilast 30mg twice daily or placebo for 16weeks followed by an extension phase where all patients received apremilast through week32. PPP Area and Severity Index (PPPASI), modified PPPASI (which evaluates pustules and vesicles separately), and Palmoplantar Severity Index (PPSI) total scores and subscores (erythema, pustules/vesicles, and desquamation/scales) were evaluated over 32weeks of apremilast treatment. Achievement of ≥ 50% improvement in PPPASI (PPPASI-50) was evaluated at week16 among baseline demographic and clinical characteristic subgroups. At week16, improvements in total score and subscores for PPPASI, modified PPASI, and PPSI, as well as rates of PPPASI-50 were at least moderately greater with apremilast than placebo. Mean PPPASI total score decreased by - 68.3% from baseline to week32 with continued apremilast treatment. At week32, mean change from baseline in PPPASI/modified PPPASI subscores ranged from - 58.5% to - 77.0% with apremilast. At week32, PPSI total score for physician and patient assessments decreased by - 51.3% and - 40.0%, respectively, with continued apremilast treatment. PPPASI-50 response at week16 was greater with apremilast versus placebo in most demographic and baseline characteristic subgroups. Improvements in all PPPASI and PPSI total scores and subscores observed with apremilast over 16weeks were maintained through 32weeks in patients with moderate to severe PPP and inadequate response to topical treatment. Rates of PPPASI-50 response at week16 were mostly consistent across patient subgroups. GOV: NCT04057937.

Differential diagnosis of erythemato-squamous diseases using a hybrid ensemble machine learning technique

Erythemato-squamous Diseases (ESD) encompass a group of common skin conditions, including psoriasis, seborrheic dermatitis, lichen planus, pityriasis rosea, chronic dermatitis, and pityriasis rubra pilaris. These dermatological conditions affect a significant portion of the population and present a current challenge for accurate diagnosis and classification. Traditional classification methods struggle due to shared characteristics among these diseases. Machine Learning offers a valuable tool for aiding clinical decision-making in ESD classification. In this study, we leverage the UC Irvine (UCI) dermatology dataset by applying necessary preprocessing steps to handle missing data. We conduct a comparative analysis of two feature selection methods: One-way ANOVA and Chi-square test. To enhance the model’s performance, we employ hyper-parameter tuning through GridSearchCV. The training process encompasses various algorithms, including Support Vector Machine (SVM), Logistic Regression, k-Nearest Neighbors (kNN), and Decision Trees. The culmination of our work is a hybrid ensemble machine learning model that combines the strengths of the trained classifiers. This ensemble classifier achieves an impressive accuracy of 98.9% when validated using a 10-fold cross-validation approach.