Examining the Role of Estheticians in Skin Cancer Surveillance.

BACKGROUND: Melanoma and non-melanoma skin cancer are significant causes of mortality. Previous studies regarding skin cancer education in nonmedical professionals have shown increases in favorable attitudes and likelihood of approaching clients about concerning lesions with training. However, few studies have investigated the use of estheticians in skin cancer screening. OBJECTIVES: The objective of this study was to develop an education course to train estheticians to recognize concerning lesions, to assess the baseline knowledge of estheticians toward skin cancer detection, and to determine the effect that our curriculum has on lesion detection. METHODS: We administered an education course and corresponding cross-sectional surveys to estheticians to evaluate current knowledge and assess for improvements in attitudes and behaviors regarding skin cancer detection. RESULTS: Of 504 estheticians, most estheticians (85-98%) indicated the correct level of concern for "extremely concerning" lesions on pre- and post-training surveys. Estheticians were more likely to recommend that their client see a medical professional if they previously attended a course on skin cancer (p = 0.012) or had greater than 1 year of work experience (p < 0.001). After completion of the training module, most participants felt "very comfortable," suggesting that clients see a doctor for a suspicious lesion. CONCLUSION: Our findings suggest that estheticians are capable of indicating the appropriate level of concern for abnormal lesions. Estheticians may serve as a valuable screening partner for dermatologists in the detection of skin cancer.

Characterization of Endothelial Cell Subclusters in Localized Scleroderma Skin with Single-Cell RNA Sequencing Identifies NOTCH Signaling Pathway.

Localized scleroderma (LS) is an autoimmune disease characterized by inflammation and fibrosis, leading to severe cutaneous manifestations such as skin hardening, tightness, discoloration, and other textural changes that may result in disability. While LS shares similar histopathologic features and immune-fibroblast interactions with systemic sclerosis (SSc), its molecular mechanisms remain understudied. Endothelial cells (EC) are known to play a crucial role in SSc but have not been investigated in LS. Single-cell RNA sequencing (scRNA-seq) now allows for detailed examination of this cell type in the primary organ of interest for scleroderma, the skin. In this study, we analyzed skin-isolated cells from 27 LS patients (pediatric and adult) and 17 healthy controls using scRNA-seq. Given the known role of EC damage as an initial event in SSc and the histologic and clinical skin similarities to LS, we focused primarily on endothelial cells. Our analysis identified eight endothelial subclusters within the dataset, encompassing both disease and healthy samples. Interaction analysis revealed that signaling from diseased endothelial cells was predicted to promote fibrosis through SELE interaction with FGFBP1 and other target genes. We also observed high levels of JAG in arterial endothelial cells and NOTCH in capillary endothelial cells, indicating the activation of a signaling pathway potentially responsible for epidermal abnormalities and contributing to LS pathogenesis. In summary, our scRNA-seq analysis identified potential disease-propagating endothelial cell clusters with upregulated pathways in LS skin, highlighting their importance in disease progression.

Measuring asymmetry in facial morphea via 3-dimensional stereophotogrammetry.

BACKGROUND: Objectively determining tissue loss in craniofacial morphea is challenging. However, 3-dimensional (3D) stereophotogrammetry is a noninvasive modality that may be a useful adjunct. OBJECTIVE: To prospectively evaluate 3D stereophotogrammetry in the assessment of craniofacial linear morphea. METHODS: Participants underwent clinical, quality-of-life, and 3D-stereophotogrammetry assessments. Traditional photographs and 3D-stereophotogrammetry images were rated as mild, moderate, or severe by 2 experts and 2 nonexperts. In addition, interrater and intrarater reliability (on delayed rescoring) were calculated. RESULTS: Of 23 patients with craniofacial morphea, 3D stereophotogrammetry detected pathologic asymmetry in 14 (20.6%) patients. Providers rated patients as more severely affected when using 3D stereophotogrammetry versus when using traditional photographs (19% severe on 3D stereophotogrammetry vs 0% severe on traditional photographs, P = .004). Qualitative ratings of both traditional and 3D images showed high inter- and intrarater reliability between experts and nonexperts alike. Physicians' Global Assessment of Damage scores correlated with mouth asymmetry (P = .0021), cheek asymmetry (P = .04), and 3D-stereophotogrammetry ratings (median, mild: 27.5 vs moderate: 46.5 vs severe: 64, P = .0152). Lower face asymmetry correlated with worse quality-of-life scores (P = .013). LIMITATIONS: Small sample size and cross-sectional design. CONCLUSION: 3D stereophotogrammetry can reliably detect and quantify asymmetry in craniofacial morphea with greater sensitivity than that observed with traditional assessment alone. 3D stereophotogrammetry may be a useful adjunct to clinical examination.

Patients with Limited Life Expectancy Are Biopsied for Keratinocyte Cancers at Similar Frequency to Healthy Patients.

BACKGROUND: In many fields of medicine, guidelines recommend reduced cancer screening in patients of advanced age with limited life expectancy (LLE). In dermatology, there are currently no guidelines for adjusted evaluation and management practices of keratinocyte cancer (KC) in patients with LLE. Little is known regarding evaluation and management patterns and frequency of biopsies in these patients. OBJECTIVE: We sought to determine if dermatology providers biopsy LLE patients with similar frequency to their age-matched peers and quantify frequency of associated complications. METHODS: This was a retrospective cohort study of evaluations for skin cancer quantified by skin biopsy frequency at the North Texas Veterans Affairs Health System dermatology clinic for 3,062 patients between 2005 and 2009, including a 5-year follow-up period. Life expectancy was quantified by the validated Charlson Comorbidity Index (CCI) with a Deyo adaptation. RESULTS: There was no significant difference in biopsy frequency of KC in LLE versus non-LLE patients in most age-controlled groups, with increased biopsy frequency in LLE patients in the 65-74 age category (p = 0.02). There was also an increased risk of complications from biopsy in the 75-84 (many comorbidities subgroup: RR = 3.27, p = 0.002; some comorbidities subgroup: RR = 2.26, p = 0.048) and 65-74 (many comorbidities subgroup: RR = 1.52, p = 0.004) age groups when compared to age-matched healthy controls. CONCLUSION: Biopsy frequency is similar or increased in patients with LLE compared with age-matched controls, with increased frequency of complications. Further studies are needed to understand the underlying factors driving these practice patterns.

Single-Cell Transcriptome Analysis Identifies Subclusters with Inflammatory Fibroblast Responses in Localized Scleroderma.

Localized scleroderma (LS) is an autoimmune disease with both inflammatory and fibrotic components causing an abnormal deposition of collagen in the skin and underlying tissue, often leading to disfigurement and disability. Much of its pathophysiology is extrapolated from systemic sclerosis (SSc) since the histopathology findings in the skin are nearly identical. However, LS is critically understudied. Single-cell RNA sequencing (scRNA seq) technology provides a novel way to obtain detailed information at the individual cellular level, overcoming this barrier. Here, we analyzed the affected skin of 14 patients with LS (pediatric and adult) and 14 healthy controls. Fibroblast populations were the focus, since they are the main drivers of fibrosis in SSc. We identified 12 fibroblast subclusters in LS, which overall had an inflammatory gene expression (IFN and HLA-associated genes). A myofibroblast-like cluster (SFRP4/PRSS23) was more prevalent in LS subjects and shared many upregulated genes expressed in SSc-associated myofibroblasts, though it also had strong expression of CXCL9/10/11, known CXCR3 ligands. A CXCL2/IRF1 cluster identified was unique to LS, with a robust inflammatory gene signature, including IL-6, and according to cell communication analysis are influenced by macrophages. In summary, potential disease-propagating fibroblasts and associated gene signatures were identified in LS skin via scRNA seq.

Autoantigen microarrays reveal myelin basic protein autoantibodies in morphea.

BACKGROUND: Morphea is an autoimmune, sclerosing skin disorder. Despite the recent emphasis on immune dysregulation in morphea, the role of autoantibodies in morphea pathogenesis or utility as biomarkers are poorly defined. METHODS: Autoantigen microarray was used to profile autoantibodies from the serum of participants from the Morphea in Adults and Children (MAC) cohort. Clinical and demographic features of morphea patients with myelin basic protein (MBP) autoantibodies were compared to those without. MBP immunohistochemistry staining was subsequently performed in morphea skin to assess for perineural inflammation in areas of staining. Immunofluorescence staining on mouse brain tissue was also performed using patient sera and mouse anti-myelin basic protein antibody to confirm the presence of MBP antibodies in patient sera. RESULTS: Myelin basic protein autoantibodies were found in greater frequency in morphea (n = 50, 71.4%) compared to systemic sclerosis (n = 2, 6.7%) and healthy controls (n = 7, 20%). Patients with MBP antibodies reported pain at higher frequencies. Morphea skin biopsies, highlighted by immunohistochemistry, demonstrated increased perineural inflammation in areas of MBP expression. Immunofluorescence staining revealed an increased fluorescence signal in myelinated areas of mouse brain tissue (i.e. axons) when incubated with sera from MBP antibody-positive morphea patients compared to sera from MBP antibody-negative morphea patients. Epitope mapping revealed target epitopes for MBP autoantibodies in morphea are distinct from those reported in MS, and included fragments 11-30, 41-60, 51-70, and 91-110. CONCLUSIONS: A molecular classification of morphea based on distinct autoantibody biosignatures may be used to differentially classify morphea. We have identified anti-MBP as a potential antibody associated with morphea due to its increased expression in morphea compared to healthy controls and systemic sclerosis patients.

Morphea patients with mucocutaneous involvement: A cross-sectional study from the Morphea in Adults and Children (MAC) cohort.

BACKGROUND: Demographic and clinical findings of patients with mucocutaneous morphea have not been well characterized, to our knowledge. OBJECTIVE: To determine the demographic and clinical characteristics of morphea patients with mucocutaneous lesions who were enrolled in the Morphea in Adults and Children cohort. METHODS: Cross-sectional study of 735 patients in the Morphea in Adults and Children cohort from 2007 to 2018. RESULTS: A total of 4.6% of linear morphea patients had oral involvement versus 2.4% among the entire cohort, whereas 10.3% of generalized morphea patients had genital involvement versus 3.7% among the entire cohort. Patients with genital lesions were older at disease onset than those with oral morphea (57 versus 11.5 years; P < .001) and had more frequent extragenital lichen sclerosus et atrophicus (59.2% versus 5.6%; P = .004). LIMITATIONS: Selection bias and limited number of affected subjects. CONCLUSION: Oral morphea lesions predominate in younger patients with facial linear morphea, whereas genital lesions predominate in postmenopausal women with overlying extragenital lichen sclerosus et atrophicus.

Body site distribution of pediatric-onset morphea and association with extracutaneous manifestations.

BACKGROUND: The distribution of pediatric-onset morphea and site-based likelihood for extracutaneous complications has not been well characterized. OBJECTIVE: To characterize the lesional distribution of pediatric-onset morphea and to determine the sites with the highest association of extracutaneous manifestations. METHODS: A retrospective cross-sectional study was performed. Using clinical photographs, morphea lesions were mapped onto body diagrams using customized software. RESULTS: A total of 823 patients with 2522 lesions were included. Lesions were more frequent on the superior (vs inferior) anterior aspect of the head and extensor (vs flexor) extremities. Linear morphea lesions were more likely on the head and neck, whereas plaque and generalized morphea lesions were more likely on the trunk. Musculoskeletal complications were more likely with lesions on the extensor (vs flexor) extremity (odds ratio [OR], 2.0; 95% confidence interval [CI], 1.2-3.4), whereas neurologic manifestations were more likely with lesions on the anterior (vs posterior) (OR, 2.8; 95% CI, 1.7-4.6) and superior (vs inferior) aspect of the head (OR, 2.3; 95% CI, 1.6-3.4). LIMITATIONS: Retrospective nature and the inclusion of only patients with clinical photographs. CONCLUSION: The distribution of pediatric-onset morphea is not random and varies with body site and within individual body sites. The risk stratification of extracutaneous manifestations by body site may inform decisions about screening for extracutaneous manifestations, although prospective studies are needed.

The importance of development standards for anchoring vignettes: an illustrative example from pediatric localized scleroderma quality of life.

PURPOSE: Anchoring vignettes (AVs) are a promising measurement technique to reduce bias in patient-reported outcome (PRO) measures by helping researchers understand differences in how individuals and groups interpret response options. However, little attention has been paid to ensure quality development of AVs, and their performance has not been well assessed in pediatric populations. In this study, we explore the application of a rigorous development process for AVs based upon current standards for PROs, as well as feasibility of AVs when administered to children and adolescents. METHODS: We developed AVs using a rigorous, patient-centered mixed methods process including three phases: (1) development, (2) a pilot study, and (3) a field test. Our proposed process included the generation of a conceptual framework based on the PRO, the Localized Scleroderma Quality of Life Instrument, and numerous vignette-specific considerations. We qualitatively explored readability and comprehension of the AVs (pilot study) and then analyzed ranking patterns within vignette sets (field test). RESULTS: Four sets of four vignettes were developed. Revisions were suggested at each phase of development. The pilot study demonstrated that children ≥ 10 years had no trouble indicating understanding of the AVs. In the field test, although appropriate rankings of vignettes were generally demonstrated by participants, the percentage of tied rankings was higher than expected in this pediatric group. CONCLUSIONS: This work supports the need for rigorous developmental standards for AVs, as each stage of development suggested revisions. Additionally, AVs showed initial promise for use with pediatric populations; general feasibility and understanding were supported.

Linear morphea: Clinical characteristics, disease course, and treatment of the Morphea in Adults and Children cohort.

BACKGROUND: Prospective, longitudinal studies examining the features of linear morphea are limited. OBJECTIVE: To utilize the Morphea in Adults and Children cohort to determine clinical characteristics, impact on life quality, and disease course of linear morphea in a prospective, longitudinal manner. METHODS: Characteristics of linear morphea versus other subtypes were compared in a cross-sectional manner. Next, linear morphea participants were examined in depth over a 3-year period. RESULTS: Linear morphea was the most common morphea subtype (50.1%, 291/581) in the cohort. Deep involvement was more common in linear (64.3%, 187/291) than other morphea subtypes. Linear morphea participants with deep involvement were more likely to have a limitation in range of motion (28.6%, 55/192) than those without (11.1%, 11/99, P < .001). Adult-onset disease occurred in 32.6% (95/291) of those with linear morphea. Frequency of deep involvement was similar between pediatric (66.8%, 131/196) and adult-onset linear morphea (58.9%, 56/95, P = .19). Quality of life and disease activity scores improved over time, while damage stabilized with treatment. LIMITATIONS: Results of the study are associative, and the University of Texas Southwestern Medical Center is a tertiary referral center. CONCLUSION: A substantial number of linear morphea patients have adult-onset disease. In all age groups, linear morphea with deep involvement was associated with functional limitations.

Skin mapping for the classification of generalized morphea.

BACKGROUND: Generalized morphea lacks cohesive clinical features, limiting its clinical and investigative utility. OBJECTIVE: We sought to use computerized lesion mapping to objectively subtype morphea. METHODS: We conducted a 2-part cross-sectional study. In part 1, we created a discovery cohort of patients with generalized morphea of whom lesion maps were created to characterize subsets. Clinical and demographic features were compared between proposed subsets to determine if they identified clinically relevant differences. In part 2, we created a validation cohort to determine if proposed criteria were applicable to different individuals. RESULTS: A total of 123 patients with generalized morphea were included. Mapping produced 2 distribution patterns that encompassed the majority in both cohorts: isomorphic (areas of skin friction) and symmetric (symmetrically distributed on trunk/extremities). In the discovery cohort, the isomorphic subset was older (55.6 ± 12.7 vs 42.2 ± 20.1 years, P < .001), all female (30/30 vs 38/43, P = .05), and more often had lichen sclerosus changes (12/43 vs 8/43, P = .02); involvement of the reticular dermis, subcutaneous fat, and/or fascia was more common in symmetric (10/43 vs 1/30) (P = .02). These features persisted in the validation cohort. LIMITATIONS: Single cohort was a limitation. CONCLUSIONS: Symmetric and isomorphic subsets possess distinctive demographic and clinical features, suggesting they more accurately define the phenotype of generalized morphea. Consideration should be given to revising classification.

Histopathological changes in morphea and their clinical correlates: Results from the Morphea in Adults and Children Cohort V.

BACKGROUND: Histopathological features in morphea (localized scleroderma) and their clinical correlates are poorly described. OBJECTIVE: We sought to systematically describe histologic changes of morphea in a large, well-annotated cohort and determine the association between histopathology and clinical features. METHODS: This was a cross-sectional study of 83 patients enrolled in the Morphea in Adults and Children cohort. The main outcome measure was the association of microanatomical location and degree of sclerosis and inflammation seen on histologic samples with patient-reported symptoms and physician-based measures of severity. RESULTS: Pattern of sclerosis was associated with morphea subtype, the presence of patient-reported symptoms, and functional limitation. A bottom-heavy pattern of sclerosis was associated with pain and tightness (P = .0039 and .001, respectively). These symptoms were not associated with a top-heavy pattern. Severe inflammation may be associated with pain and functional limitation (P = .073 for both). LIMITATIONS: Small sample size limits ability to detect associations, particularly in subgroups. CONCLUSIONS: Histopathological examination of morphea may assist in identifying patients who may require additional monitoring and treatment. Features such as patterns of sclerosis and severity of inflammation should be included in pathology reports to help aid in clinical management.

Correspondence: The association between morphea profunda and monoclonal gammopathy: A case series.

It is known that eosinophilic fasciitis can be associated with monoclonal gammopathy. There is clinical similarity between eosinophilic fasciitis and morphea profunda, but it is unclear whether morphea profunda might be associated with monoclonal gammopathy. The temporal quantification of gammopathy in morphea profunda has not been well characterized. We describe four patients with morphea profunda that were associated with monoclonal gammopathy. Three were associated with monoclonal IgG protein and one with IgM. No patients in our series developed myeloma. In conclusion, the association of monoclonal gammopathy is not unique to eosinophilic fasciitis and scleromyxedema. Further studies are necessary to characterize further the relationship between the two conditions.

Correlates of self-reported quality of life in adults and children with morphea.

BACKGROUND: Determining a disease's impact on life quality is important in clinical decision making, research, and resource allocation. Determinants of quality of life (QOL) in morphea are poorly understood. OBJECTIVE: We sought to ascertain demographic and clinical variables correlated with negative impact on self-reported QOL in morphea. METHODS: We conducted a cross-sectional survey of the Morphea in Adults and Children cohort. RESULTS: Symptoms (pruritus and pain) and functional impairment were correlated with decreased QOL in children and adults. This was true in both sexes and was independent of subtype and age. Patient-reported QOL correlated with physician-based measures of disease severity in adults, but not in children. Patients with linear and generalized morphea had the greatest impact on QOL. LIMITATIONS: Small sample size is a limitation. CONCLUSION: Symptoms and functional impairment were determinants of impaired life quality in both children and adults independent of morphea subtype. These results suggest that clinicians should consider suppressing the accumulation of new lesions (when rapidly accumulating) and symptoms (pain and pruritus) in the treatment of patients with morphea.

Recurrence of morphea after successful ultraviolet A1 phototherapy: A cohort study.

BACKGROUND: Studies support efficacy of ultraviolet (UV)A1 phototherapy, but little is known about recurrence after successful UVA1 treatment. OBJECTIVE: We sought to determine the frequency of recurrent activity after UVA1 phototherapy and variables associated with recurrence. METHODS: This was a case series and prospective cohort study of patients treated with UVA1 phototherapy with minimum 6 months of follow-up. Demographics, clinical features, and cumulative UVA1 dose were analyzed for association with recurrence. RESULTS: Of 37 patients, 46% (n = 17) had recurrence of active morphea lesions after successful UVA1 phototherapy. Two-year and 3-year (after the last UVA1 phototherapy treatment) recurrence rates were 44.5% (95% confidence interval 30.1%-62.2%) and 48.4% (95% confidence interval 33.2%-66.1%), respectively. The only variable associated with recurrence was duration of morphea before UVA1 (P value = .02, hazard ratio 1.15, 95% confidence interval 1.06-1.27). LIMITATIONS: The sample size limits conclusions. CONCLUSION: With the exception of increased duration of morphea, risk of recurrence is no different in adults and children, or between morphea subtypes, skin types, and medium- to high-dose regimens. This indicates treatment doses in the medium-high UVA1 range are adequate with respect to frequency of recurrence.