Extent Of Skin Involvement Research Articles

A large-scale retrospective study in China explores risk factors for disease severity in plaque psoriasis

Severe psoriasis has a long course and poor outcome, and it has long been a problem for patients. Understanding the independent risk factors that contribute to patients with severe psoriasis is critical for the development of effective treatment strategies. This large, multicenter study recruited 2,109 plaque psoriasis patients from 12 hospitals across China (October 31, 2019 – May 31, 2022). The logistic regression model underwent internal validation and external validation using two independent cohorts over future time periods (June 1, 2022 – January 31, 2023). The discriminative power of our model was substantiated by a C-index of 0.863 (95% CI: 0.848–0.879) in internal validation, further affirmed through 1,000 bootstrap validation (C-index: 0.860, 95% CI: 0.836–0.885) and external validation cohorts, where the C-index reached up to 0.910 (95% CI: 0.868–0.953) and 0.951 (95% CI: 0.924–0.977) in 2 external validation cohorts. To enhance accessibility for clinicians, the model has been made available as a dynamic nomogram and QR code. Our study identified 10 risk factors (the “DELPHI” consensus dichotomy, the DLQI index, the extent of skin involvement as measured by body surface area, the age of the patient at the time of clinical visit, sex, body weight in kilograms, career, the presence of scalp involvement, facial involvement, and arthropathy) for the overall severity of psoriasis (PASI ≥ 10). “Nomogram-10” provides clinicians with a practical tool to develop personalized intervention strategies based on an individual’s risk profile.Trial registration: Chinese Clinical Trial Registry: ChiCTR1900024852.

REAÇÕES CUTÂNEAS GRAVES: UMA VISÃO ABRANGENTE SOBRE A SÍNDROME DE STEVENS-JOHNSON, SUA ETIOLOGIA, FISIOPATOLOGIA E ABORDAGENS TERAPÊUTICAS

Stevens-Johnson Syndrome (SJS) is a rare and severe condition characterized by epidermal detachment and mucosal lesions, primarily affecting the mouth, eyes, and genitals. Often triggered by adverse drug reactions, such as antibiotics and anticonvulsants, SJS can also be caused by viral infections and, rarely, neoplasms. SJS forms a spectrum with Toxic Epidermal Necrolysis (TEN), differing in the extent of skin involvement: in SJS, less than 10% of the body surface is affected, while in TEN, the involvement exceeds 30%. Although rare, with an incidence of 1.2 to 6 cases per million people, SJS carries high morbidity and mortality, leading to complications such as severe infections and permanent damage to the skin and mucous membranes. Early diagnosis is crucial, based on characteristic lesions and a recent history of medication use. In some cases, a biopsy is necessary to confirm the diagnosis. Treatment involves a multidisciplinary approach, including intensive care, immediate discontinuation of the causative drug, and immune modulation with corticosteroids or intravenous immunoglobulin. While new therapies, such as cyclosporine and special wound dressings, are being explored, there is still a need for consensus on the ideal treatment protocol, as well as advances in personalized diagnosis and treatment.

Assessment of Skin by High Frequency Musculoskeletal Ultrasound in Egyptian Patients with Systemic Sclerosis

Abstract Background Fibrotic involvement of the skin is a cardinal feature of systemic sclerosis (SSc). The extent of skin involvement is associated with internal organ involvement with severe disease course and poor prognosis. SSc skin involvement is characterized by three phases in temporal sequence: edematous, fibrotic, and atrophic. A palpation-based semi- quantitative score, the modified Rodnan skin score (mRSS) is widely used for the assessment of skin involvement. It is a quick, noninvasive clinical assessment that correlates with histological grading of skin fibrosis. However, it lacks the sensitivity to differentiate between clinically indistinguishable pathological phases such as inflammatory edema vs. established fibrosis. More objective approaches to measure skin involvement imaging have been developed in the past decades.In our study, we review the use of ultrasound for the assessment of early changes in skin thickness and echogenicity in patients with SSc, focusing. mainly on high frequency ultrasound. Aim of the Work to evaluate the role of high frequency ultrasound (HFUS) of skin in assessment of early changes in skin thickness and echogenicity in patients with SSc. Patients and Methods Our study is a cross-sectional, observational study involving homogenous groups consisting of 23 SSc patients and 21 healthy age and sex matched controls. Patients who fulfilled the 2013 ACR/EULAR Classification Criteria for SSc. Results DT was evaluated by both mRSS and HFUS at 5 skin areas in both patients and control. We found statistically significant difference between the two studied groups as regards in area 1 longitudinal (P = 0.017) and area 1 in transverse (P = 0.038), tendency to significance in area 2 (P = 0.054). Subclinical dermal involvement was detected by HFUS even in the skin areas in patients who had a normal local MRSS ( These areas were not planned to be assessed by high frequency ultrasound but added to the five areas to be assessed to evaluate for ultrasound detected subclinical involvement of skin in SSc patients ). In particular, DT was highly significantly greater in patients with area with Rodnan zero score at dorsum of hand than in healthy subjects (longitudinal and transverse) (P < 0.001, 0.005 ) respectively. Similar changes at the level of echogenicity occurred in determination of the stage of the disease, with increased skin thickness and decreased echogenicity occurring early and during skin disease activity due to edema; and decrease skin thickness and increased echogenicity occurring late with skin atrophy Conclusion that high frequency ultrasound is a useful tool in assessment of skin pathologic changes (even subclinical changes) in terms of thickness and echogenicity in patients with SSc both at disease onset and during follow up of response to therapy and disease stage. Moreover, it could be a useful screening tool with definite cutoff values at certain areas that differentiate normal from pathologic skin thickness.

Clinical analysis of patients with skin metastasis of cervical squamous cell carcinoma.

Cancers that metastasize to the skin are rare, especially cervical squamous cell carcinoma to the skin. Here, we have reported clinical analysis of patients with cervical squamous cell carcinoma metastasize to skin, to obtain a general understanding of this malignancy for clinicians. A retrospective analysis of patients with skin metastasis from cervical squamous cell carcinoma was conducted, focusing on clinical manifestations, histopathology, diagnosis, treatment, and prognosis. The average age of onset for the six patients with skin metastasis from cervical squamous cell carcinoma was 55.17±17.08 years, with four cases presenting as solitary lesions and two cases as multiple lesions. Treatment strategies included local excision for isolated lesions, chemotherapy, radiotherapy, or targeted therapy based on the extent of skin involvement, and immunotherapy was proved to have promising results in our cases. Among the six patients, three have passed away with a diagnosis-to-death time of approximately 5-6 months, while three patients are alive, with survival times ranging from 30 to 72 months. Skin metastasis from cervical squamous cell carcinoma is rare and often accompanies recurrent metastases to other visceral sites, necessitating early and accurate diagnosis. For isolated metastatic lesions, early detection followed by wide excision surgery and adjuvant radiotherapy can yield favorable outcomes. However, in cases of multiple skin metastases or concurrent metastases to multiple organs, treatment is challenging with a poor prognosis. Nevertheless, with advancements in medicine, combination chemotherapy, immunotherapy, and targeted therapy can effectively prolong survival, offering new hope for patients with skin metastasis from cervical cancer.

Phenotypes of patients with systemic sclerosis in the Chinese Han population: a cluster analysis.

Systemic sclerosis (SSc) is a heterogeneous connective tissue disease that is commonly subdivided into limited cutaneous SSc (lcSSc) and diffuse cutaneous SSc (dcSSc) based on the extent of skin involvement. This subclassification may not reflect the full range of clinical phenotypic variation. This study aimed to investigate clinical features and aggregation of patients with SSc in Chinese based on SSc manifestations and organ involvements, in order to achieve precise treatment of SSc early prevention of complications. In total 287 SSc patients were included in this study. A cluster analysis was applied according to 13 clinical and serologic variables to determine subgroups of patients. Survival rates between obtained clusters and risk factors affecting prognosis were also compared. In this study, six clusters were observed: cluster 1 (n = 66) represented the skin type, with all patients showing skin thickening. In cluster 2 (n = 56), most patients had vascular and articular involvement. Cluster 3 (n = 14) individuals mostly had cardiac and pulmonary involvement. In cluster 4 (n = 52), the gastrointestinal type, 50 patients presented with stomach symptoms and 28 patients presented with esophageal symptoms. In cluster 5 (n = 50), patients barely had any major organ involvement. Cluster 6 (n = 49) included 46% of all patients presenting with renal crisis. The results of our cluster analysis study implied that limiting SSc patient subgroups to those based only on skin involvement might not capture the full heterogeneity of the disease. Organ damage and antibody profiles should be considered when identifying homogeneous patient groups with a specific prognosis. Key Points • Provides a new method of categorizing SSc patients. • Can better explain disease progression and guide subsequent treatment.

Clinically Recognized Depression and Mental Health Treatment in a Single Center Cohort of Patients with Systemic Sclerosis.

In this study, we investigated the prevalence of depression, depression treatment, and symptom burden in patients with systemic sclerosis (SSc) and examined their associations with the center for epidemiologic studies depression scale revised (CESD-R) scores. The Prospective Registry in Scleroderma at Massachusetts General Hospital (PRISM) is a longitudinal registry of patients with SSc. Among participants with CESD-R score ≥ 16, indicating possible depression, a chart review was performed for mental health diagnoses and treatments. We examined the relation of demographic and clinical factors to the presence of mental health diagnoses or treatment using logistic regression. We evaluated the association of SSc symptoms and the COVID-19 pandemic with a CESD-R score using quantile regression. Of 214 patients enrolled in PRISM, 129 participants (38% diffuse and 59% limited) completed at least one CESD-R questionnaire. In the first survey, 29% had possible depression (CESD - R ≥ 16) and 16% had probable depression (CESD - R ≥ 23). Of 20 participants with probable depression, 90% received treatment for a mood disorder. In a multivariable logistic regression model among participants with CESD - R ≥ 16, none of the evaluated variables (CESD-R score, age, gender, employment status, race, and ethnicity) was associated with mental health diagnosis or treatment. Higher baseline dyspnea index, modified Rodnan skin score, and the University of California Los Angeles Scleroderma Clinical Trials Consortium Gastrointestinal total score and subscores were associated with higher CESD-R score. In this single-center cross-sectional study, 16% of participants had significant depressive symptoms. Dyspnea, extent of skin involvement, and gastrointestinal symptoms were associated with depression symptoms.

The functional disabilities of the dominant and opposite hands in patients with systemic sclerosis.

Hand involvement in patients with systemic sclerosis (SSc) is responsible for 75% of the overall disability but varies greatly among individuals. No study has yet compared the functionalities between the two hands of SSc patients. We thus evaluated the joint limitations and extent of skin involvement in the dominant and contralateral hands. This prospective, descriptive, comparative single-centre study enrolled SSc patients diagnosed using the ACR/EULAR criteria. We assessed limitations in the joint range of motion during active and passive mobilisation; the first commissure opening angles; the Kapandji scale and Rodnan hand scores; the digital pressures; the finger brachial pressure indices; and the number of telangiectasias, calcinosis, digital ulcerations, and painful joints on each hand. Thirty patients were included. Spontaneous flexion joint limitations were significantly greater in the dominant hand (p<0.0001). The Kapandji score was lower (p<0.001) and the Rodnan hand score significantly higher, for the dominant hand (p<0.001). The digital pressure was similar between the hands. The dominant hand exhibited significantly more skin sclerosis and mean flexion deterioration, a lower Kapandji score, and a tendency toward reduced mean extension, compared with the other hand. No vascular pathology was noted in either hand. Larger studies are needed to confirm these results and to draw therapeutic conclusions.

Nutraceutical combination ameliorates imiquimod-induced psoriasis in mice.

Psoriasis is a chronic inflammatory skin disease that affects both localized and systemic regions of the body. This condition is characterized by the hyperproliferation of keratinocytes, resulting in skin thickening, scaling, and erythema. The severity of psoriasis depends on the extent of skin involvement, the location of the infection, and the symptoms that the person exhibits. While no cure exists, conventional therapies such as topical and systemic drugs are generally used to manage the exacerbation of symptoms. However, chronic use and overdose can lead to other severe adverse effects. Therefore, scientists and researchers are exploring potential nutraceuticals that can be considered as an alternative source of management for psoriasis. Current research aims to use different combinations of natural compounds like cannabidiol, myo-inositol, eicosapentaenoic acid, and krill oil to study the effect of these compounds in the prevention and treatment of psoriasis in the imiquimod (IMQ)-induced psoriatic mice model. The Psoriasis Area Severity Index (PASI) scoring system is used to analyze skin thickness, scales, and erythema. The results indicate that the krill oil combined with the cannabidiol and myo-inositol shows better results than other nutraceutical combinations. In the future, the natural products of krill oil can be combined with cannabidiol and myo-inositol to create an improved alternative to existing steroidal and nonsteroidal anti-inflammatory drugs for psoriasis treatment.

Treatable Traits in Systemic Sclerosis.

Systemic sclerosis (SSc) is a chronic systemic disease within the spectrum of connective tissue diseases, specifically characterized by vascular abnormalities and inflammatory and fibrotic involvement of the skin and internal organs resulting in high morbidity and mortality. The clinical phenotype of SSc is heterogeneous, and serum autoantibodies together with the extent of skin involvement have a predictive value in the risk stratification. Current recommendations include an organ-based management according to the predominant involvement with only limited individual factors included in the treatment algorithm. Similar to what has been proposed for other chronic diseases, we hypothesize that a "treatable trait" approach based on relevant phenotypes and endotypes could address the unmet needs in SSc stratification and treatment to maximize the outcomes. We provide herein a comprehensive review and a critical discussion of the literature regarding potential treatable traits in SSc, focusing on established and candidate biomarkers, with the purpose of setting the bases for a precision medicine-based approach. The discussion, structured based on the organ involvement, allows to conjugate the pathogenetic mechanisms of tissue injury with the proposed predictors, particularly autoantibodies and other serum biomarkers. Ultimately, we are convinced that precision medicine is the ideal guide to manage a complex condition such as SSc for which available treatments are largely unsatisfactory.

Predicting outcomes in systemic sclerosis by skin involvement and autoantibodies.

The Article by Muriel Elhai and colleagues in The Lancet Rheumatology reports important data from the international European Scleroderma Trials and Research (EUSTAR) database.1 The authors assessed whether stratification by systemic sclerosis-specific autoantibodies could predict poor outcomes in systemic sclerosis compared with stratifying by the extent of skin involvement using LeRoy's subsets of limited cutaneous systemic sclerosis, diffuse cutaneous systemic sclerosis, or sine scleroderma,2 or by using both the extent of skin involvement and autoantibodies.

QUALITY OF LIFE ASSESSMENT IN VITILIGO PATIENTS IN LITHUANIA

Vitiligo is a chronic autoimmune skin disorder that re­sults as depigmented patches of the skin due to loss of melanocytes. Although the disease is often asymptomatic, it impairs patients` quality of life. The aim of this study was to assess factors associated with negative impact on quality of life in terms of disease clinical features, pa­tients` functioning and emotional status in Lithuania. An observational, cross-sectional study consisted of 131 res­pondents. An original three-part survey of 41-questions was developed based on 4 standardized questionnaires. 125 respondents were included: 94 women and 31 men. The mean age was 35 ± 12 years. 14 out of 21 quality of life items affect &gt;25% of respondents, including all 10 emotion-related indicators (100%) and 4 out of 11 functioning-related indicators (36.36%). In conclusion, this research supports the evidence that vitiligo has an influence on patients’ quality of life, mainly affecting emotion-related areas. Quality of life is associated with gender, age, and extent of skin involvement. Psycholo­gical consultation should be recommended to patients with vitiligo.

Epidermolysis Bullosa Simplex

ABSTRACT Epidermolysis bullosa simplex (EBS) is a rare autosomal dominant, genetic condition where bullous lesions, larger than 0.5 cm, affect an area of the skin that is exposed to mechanical friction or minor trauma. Prevention of the bullous lesions starts with family and patient education, with infants requiring greater care and control of their environment. Every individual with EBS will have a treatment plan specifically tailored to the severity and extent of skin involvement. This article provides a comprehensive overview of EBS, including diagnostic approach, preventative considerations, and current treatments.

Therapeutic Approaches to Systemic Sclerosis: Recent Approvals and Future Candidate Therapies.

Systemic sclerosis is the rheumatic disease with the highest individual mortality. The severity of the disease is determined by the extent of fibrotic changes to cutaneous and internal organ tissues, the most life-threatening visceral manifestations being interstitial lung disease, SSc-associated-pulmonary arterial hypertension and myocardial involvement. The heterogeneity of the disease has initially hindered the design of successful clinical trials, but considerations on classification criteria have improved patient selection in trials, allowing the identification of more homogeneous groups of patients based on progressive visceral manifestations or the extent of skin involvement with a focus of patients with early disease. Two major subsets of systemic sclerosis are classically described: limited cutaneous systemic sclerosis characterized by distal skin fibrosis and the diffuse subset with distal and proximal skin thickening. Beyond this dichotomic subgrouping of systemic sclerosis, new phenotypic considerations based on antibody subtypes have provided a better understanding of the heterogeneity of the disease, anti-Scl70 antibodies being associated with progressive interstitial lung disease regardless of cutaneous involvement. Two targeted therapies, tocilizumab (a monoclonal antibody targeting interleukin-6 receptors (IL-6R)) and nintedanib (a tyrosine kinase inhibitor), have recently been approved by the American Food & Drug Administration to limit the decline of lung function in patients with SSc-associated interstitial lung disease, demonstrating that such better understanding of the disease pathogenesis with the identification of key targets can lead to therapeutic advances in the management of some visceral manifestations of the disease. This review will provide a brief overview of the pathogenesis of SSc and will present a selection of therapies recently approved or evaluated in this context. Therapies evaluated and approved in SSc-ILD will be emphasized and a review of recent phase II trials in diffuse cutaneous systemic sclerosis will be proposed. We will also discuss selected therapeutic pathways currently under investigation in systemic sclerosis that still lack clinical data in this context but that may show promising results in the future based on preclinical data.

Vascular endothelial growth factor profile and Vitamin D level in Systemic Sclerosis Egyptian patients

Vascular endothelial growth factor (VEGF) was described as a potentially important driver of systemic sclerosis (SSc) pathogenesis. Additionally, recent literature elucidated that vitamin D serum level was found to be significantly lower in SSc patients in comparison to healthy individuals. The aim of the current study was to evaluate serum level of VEGF and its correlation with clinical features and vitamin D level in systemic sclerosis (SSc) Egyptian patients. This current case control study included 30 female SSc patients and 20 healthy controls. VEGF level was measured by ELISA. Serum level of 25-OH vitamin D was measured by electrochemiluminescence. Nailfold video capillaroscopy and modified Rodnan skin score (mRSS) were assessed. Thirty SSc female patients were included in the study, 13 patients had diffuse cutaneous SSc. The mean age of the patients' group was 49.3±4.3years, and the mean serum VEGF level was 3445.9±1183 ng/dl. The mean serum level of vitamin D was 15.57±9.9ng/ml in SSc patients and 30.6±2.26 in the controls. There was a significant association between high level of VEGF and hypovitaminosis D. Serum level of VEGF positively correlated with nailfold capillaroscopy changes and mRSS. In conclusion, high level of VEGF is associated with hypovitaminosis D, suggesting a role of vitamin D in SSc pathogenesis. VEGF levels correlate positively with nailfold capillaroscopy changes and extent of skin involvement.

Plasma Hsp90 levels in patients with systemic sclerosis and relation to lung and skin involvement: a cross-sectional and longitudinal study

Our previous study demonstrated increased expression of Heat shock protein (Hsp) 90 in the skin of patients with systemic sclerosis (SSc). We aimed to evaluate plasma Hsp90 in SSc and characterize its association with SSc-related features. Ninety-two SSc patients and 92 age-/sex-matched healthy controls were recruited for the cross-sectional analysis. The longitudinal analysis comprised 30 patients with SSc associated interstitial lung disease (ILD) routinely treated with cyclophosphamide. Hsp90 was increased in SSc compared to healthy controls. Hsp90 correlated positively with C-reactive protein and negatively with pulmonary function tests: forced vital capacity and diffusing capacity for carbon monoxide (DLCO). In patients with diffuse cutaneous (dc) SSc, Hsp90 positively correlated with the modified Rodnan skin score. In SSc-ILD patients treated with cyclophosphamide, no differences in Hsp90 were found between baseline and after 1, 6, or 12 months of therapy. However, baseline Hsp90 predicts the 12-month change in DLCO. This study shows that Hsp90 plasma levels are increased in SSc patients compared to age-/sex-matched healthy controls. Elevated Hsp90 in SSc is associated with increased inflammatory activity, worse lung functions, and in dcSSc, with the extent of skin involvement. Baseline plasma Hsp90 predicts the 12-month change in DLCO in SSc-ILD patients treated with cyclophosphamide.

Generalized epidermolytic ichthyosis with palmoplantar hyperkeratosis

Epidermolytic ichthyosis (EI, OMIM 113800) is a rare autosomal dominant keratinization disorder that is caused by keratin 1 or 10 gene mutation. It can be classified clinically based on the presence of palmoplantar hyperkeratosis involvement and extent of skin involvement. The diagnosis is made by clinical and histopathological examinations that can be confirmed by genetic testing. We present a 2-year-old girl who presented with erythematous and thick scaling skin. Her condition began at birth as multiple flaccid blisters that would easily break into erosions. There was no history of similar condition nor consanguinity within her family. Skin examination revealed diffuse erythematous skin covered with thick scales and erosion, predominantly on her face, extremities, palms, and soles. The skin histopathology examination showed diffuse parakeratosis with vacuolar and granular degeneration within granular and spinous layers along the epidermis. She was diagnosed with generalized EI with palmoplantar hyperkeratosis based on the clinical and histopathological examinations. Clinical improvement was observed after a one-month treatment with mupirocin cream, sodium bicarbonate bath, and moisturizer after bathing.

Considerations for a combined index for limited cutaneous systemic sclerosis to support drug development and improve outcomes.

Systemic sclerosis (SSc; systemic scleroderma) is characterized by a heterogeneous range of clinical manifestations. SSc is classified into limited cutaneous SSc (lcSSc) and diffuse cutaneous subgroups (dcSSc) based on the extent of skin involvement. Randomized controlled trials in scleroderma have mainly focused on dcSSc partly because the measurement of skin involvement, critical for evaluating a therapeutic intervention is more dynamic in this subset. Nonetheless, lcSSc, the most common cutaneous subset (about 2/3), is also associated with significant morbidity and detrimental impact on health-related quality of life. The lack of interventional studies in lcSSc is partly due to a lack of relevant outcome measures to evaluate this subgroup. Combining several clinically meaningful outcomes selected specifically for lcSSc may improve representativeness in clinical trials and responsiveness of outcomes measured in randomized controlled trials. A composite index dedicated to lcSSc combining such relevant outcomes could advance clinical trial development for lcSSc by providing the opportunity to test and select among candidate drugs that could act as disease-modifying treatments for this neglected subgroup of SSc. This proposed index would include items selected by expert physicians and patients with lcSSc across domains grounded in the lived experience of lcSSc. This article reviews the reasons behind the relative neglect of lcSSc, discusses the current state of outcome measures for lcSSc, identifies challenges, and proposes a roadmap for a combined lcSSc-specific treatment response index.

Increased Serum Level and High Tissue Immunoexpression of Interleukin 17 in Cutaneous Lichen Planus: A Novel Therapeutic Target for Recalcitrant Cases?

Background Interleukin-17 is supposed to play an important role in the pathogenesis of oral lichen planus (OLP). However, there is scarce data in the literature on its significance in the cutaneous variant of the disease. Objectives To determine the serum level and tissue immunoexpression of IL-17 in cutaneous lichen planus (CLP). Methods Fifty-two adult patients with CLP, without any significant autoimmune or inflammatory conditions, were included in the first part of the study. The control group consisted of 27 age- and sex-matched healthy volunteers. Serum concentration of IL-17 was quantified using enzyme-linked immunosorbent assay (ELISA) kit. In the second part of the study, the tissue expression of IL-17 was assessed in archival paraffin-embedded biopsy specimens from CLP (n = 14) against normal control tissues (n = 11) using immunohistochemical assays. The expression was evaluated using Zeiss Axio Imager A2 light microscope. Positively stained cells were counted in 10 fields of view for biopsy specimen at 200x magnification, and the mean value was calculated. Results The serum level of IL-17 was significantly elevated in patients with CLP, compared with healthy volunteers (0.218 ± 0.221 ng/ml versus 0.126 ± 0.058 ng/ml, respectively; p = 0.025). No correlation was found between the serum concentration of IL-17 and patient age, gender, disease duration, extent of skin involvement, the presence or intensity of pruritus, and coexistence of mucosal lesions. In tissue samples from CLP lesions, significantly higher numbers of cells expressing IL-17 were found when compared to a healthy skin (p < 0.001). Conclusion Elevated serum concentration of IL-17 and high expression in a lesional skin support the hypothesis that IL-17 is implicated in the immunopathogenesis of CLP. These findings may constitute a premise for the future use of anti-IL-17 monoclonal antibodies in the treatment of severe and recalcitrant forms of CLP.

Clinical and Molecular Phenotyping in Scleromyxedema Pretreatment and Posttreatment With Intravenous Immunoglobulin.

Scleromyxedema (SMX) is a rare systemic sclerosis mimic that often responds to intravenous immunoglobulin (IVIG) therapy, yet the resulting clinical and biochemical changes have not been well characterized. To better understand the pathogenesis of the disease and the efficacy of IVIG, we sought to explore whether IVIG would introduce a measurable biologic effect corresponding with clinical improvement. Fifteen patients with SMX were recruited for the study. Clinical information and peripheral blood mononuclear cells for flow cytometry were obtained immediately before and again 1-2 weeks after patients received IVIG therapy. Ten patients also underwent skin biopsies for gene expression analysis both before and after IVIG therapy. Clinical data included measures of skin involvement (modification of the modified Rodnan skin thickness score [MMRSS] and percentage of body surface area) and several patient-reported outcome measures assessing patients' skin. Posttreatment, the average MMRSS score decreased from mean ± SD 13.6 ± 2.6 to 10.3 ± 1.9; P = 0.003. There were also significant improvements in skin flexibility (mean ± SD 5.4 ± 0.8 to 3.2 ± 0.7; P = 0.003) and softening (mean ± SD 4.9 ± 0.9 to 2.6 ± 0.6; P = 0.022). Baseline levels of Tc17 cells (CD8+CCR6+CXCR3+CCR4-) correlated with the extent of skin involvement as measured by MMRSS pretreatment (r = 0.69, P = 0.012) and decreased after IVIG therapy (mean ± SD 3.4% ± 3.2% to 1.3% ± 1.7%; P = 0.008). Posttreatment analysis of RNA in skin tissue revealed a decrease in gene expression of transforming growth factor β (TGFβ) cytokines as well as several interferon-inducible proteins. This open-label study further supports the evidence that patients with SMX respond both objectively and subjectively to IVIG therapy. Biologic studies suggest a role for T lymphocytes in the pathogenesis of the disease and reveal the potential significance of TGFβ and interferon pathways.

Diagnostic Potential of Five Different Biomechanical Parameters to Detect Sclerotic Cutaneous Graft-Versus-Host Disease

INTRODUCTION Skin sclerosis is a significant cause of morbidity in chronic graft-versus-host disease (cGVHD). The current accepted standard for response assessment is the NIH skin score (0-3 scale) which is based on extent of skin involvement and clinician assessment of degree of sclerosis (superficial vs. deep; movable vs. hidebound). There is an urgent need to develop objective measures of skin sclerosis to enable accurate monitoring of disease. The Myoton device is able in a single rapid measurement to simultaneously measure five biomechanical parameters in soft tissue: dynamic stiffness, mechanical stress relaxation time, tissue oscillation frequency, logarithmic decrement, and creep. Sclerotic cGVHD patients have been shown to have increased skin stiffness, relative to normal individuals, in a small study that lacked post-transplant controls.1 In a cross-sectional study including both cGVHD patients and post-transplant controls, we report the ability to differentiate sclerotic from unaffected post-transplant skin for all five available biomechanical parameters. METHOD Sclerotic cGVHD patients (NIH skin score 2-3) (n=13), post-BMT controls (n=10), and healthy controls (n=14) were measured with the Myoton device modified for skin biomechanical assessment. Each subject was measured on 10 bilateral sites (shin, dorsal forearm, volar forearm, upper arm, shoulder, chest, abdomen, upper back, lower back, calf) for a total of 20 measurement sites. For each of the five biomechanical parameters, the overall value per subject was calculated as the average over all 20 measurement sites. We performed receiver operating characteristic (ROC) and area under the curve (AUC) analyses to compare the diagnostic sensitivity of these parameters. RESULTS Sclerotic cGVHD patients showed significant increases (p&lt;0.05) in stiffness and frequency and decreases (p&lt;0.05) in relaxation time compared to controls. The ROC and AUC analyses revealed that the overall frequency (sensitivity: 91%; specificity: 93%; AUC: 0.92), stiffness (sensitivity: 91%; specificity: 93%; AUC: 0.92), and relaxation time (sensitivity: 100%; specificity: 82%; AUC: 0.85) allow for high accuracy in the differentiation of sclerotic patients from post-BMT controls. Multivariate analysis suggested that stiffness, frequency, and relaxation time provide more value in combination than any parameters alone in the differentiation of sclerotic patients and post-BMT controls. By contrast, decrement and creep likely do not add significant value beyond the other three parameters. The Pearson correlation for each pair of the 3 key parameters (frequency, stiffness, and relaxation time) in post-BMT patients was lowest (R2 = 0.651) for stiffness versus relaxation time, suggesting that this combination provides the highest diagnostic yield. Further, within cGVHD patients, all parameters except decrement were able in univariate analysis to distinguish between a site of affected and unaffected skin on the shin and dorsal forearm (p&lt;0.05). CONCLUSIONS Frequency, stiffness and relaxation time of skin demonstrated high accuracy in the differentiation of sclerotic GVHD patients from post-BMT controls. Larger study is needed to develop a multivariate predictive model based on the combination of stiffness and relaxation time. Prospective longitudinal study is also warranted to assess the ability of the Myoton to monitor progression and treatment response in cGVHD patients as compared to the NIH skin score. ACKNOWLEDGEMENTS This work is partially supported by Career Development Award Number IK2 CX001785 from the United Sates Department of Veterans Affairs Clinical Science R&amp;D (CSRD) Service. REFERENCES: Chen F, Dellalana LE, Gandelman JS, et al. Non-invasive measurement of sclerosis in cutaneous cGVHD patients with the handheld device Myoton: a cross-sectional study. Bone marrow transplantation. 2019; 54(4):616 Disclosures Jagasia: Janssen: Research Funding; Kadmon: Consultancy; Incyte: Consultancy. Tkaczyk:Incyte: Consultancy.