Recent Advances in Treatment of Systemic Sclerosis and Morphea.

Systemic sclerosis (SSc) and morphea are autoimmune sclerosing diseases that cause significant morbidity, and in the case of SSc, mortality. The pathogenesis of both SSc and morphea share vascular dysfunction, auto-reactive T cells and Th2-associated cytokines, such as interleukin 4, and overproduction of transforming growth factor beta (TGFß). TGFß stimulates fibroblast collagen and extra-cellular matrix production. Although morphea and SSc have similar pathogenic pathways and histological findings, they are distinct diseases. Recent advances in treatment of morphea, skin sclerosis in SSc, and interstitial lung disease in SSc are focused on targeting known pathogenic pathways.

Current Utilization of Qualitative Methodologies in Dermatology: A Scoping Review.

The focus of this review was to determine how qualitative methods are used in dermatology research and whether published manuscripts meet current standards for qualitative research. A scoping review of manuscripts published in English between January 1, 2016 and September 22, 2021 was conducted. A coding document was developed to collect information on authors, methodology, participants, research theme, and the presence of quality criteria as outlined by the Standards for Reporting Qualitative Research. Manuscripts were included if they described original qualitative research about dermatologic conditions or topics of primary interest to dermatology. An adjacency search yielded 372 manuscripts, and after screening, 134 met the inclusion criteria. Most studies utilized interviews or focus groups, and researchers predominantly selected participants on the basis of disease status, including over 30 common and rare dermatologic conditions. Research themes frequently included patient experience of disease, development of patient-reported outcomes, and descriptions of provider and caregiver experiences. Although most authors explained their analysis and sampling strategy and included empirical data, few referenced qualitative data reporting standards. Missed opportunities for qualitative methods in dermatology include examination of health disparities, exploration of surgical and cosmetic dermatology experiences, and determination of the lived experience of and provider attitudes toward diverse patient populations.

The Keloid Area and Severity Index (KASI): an objective tool for the evaluation of keloids.

To aid in the standardization of evaluating patients with multiple keloids, a Keloid Area and Severity Index (KASI) was developed using patient feedback, previous literature, and clinical expertise. The system was validated using intrarater and interrater reliability assessments. Here, we present a verified, reliable method of assessing keloid area and severity in clinical and research settings.

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.

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.

Natural history of disease activity and damage in patients with cutaneous lupus erythematosus.

BACKGROUND: Long-term studies characterizing disease course of cutaneous lupus erythematosus (CLE) patients on standard-of-care treatments are lacking. OBJECTIVE: We characterized and compared disease course of CLE patients using Cutaneous Lupus Erythematosus Disease Area and Severity Index (CLASI). METHODS: In total, 83 CLE patients with CLASI scores collected from ≥3 study visits within 2 years had disease activity and damage trends calculated by average change scores (ACS). Trends were classified as improved (ACS ≤-3), worsened (ACS ≥3), or stable (-3 < ACS < 3). Linear regression models compared CLASI trends between groups. RESULTS: Most patients (72.73%) with initial CLASI activity (CLASI-A) scores >9 (N = 33) had improved disease activity versus 14.00% of those with initial CLASI-A scores ≤9 (N = 50). Linear regression analyses showed significant improvement in CLASI-A scores in patients of minority races (P < .05), with baseline CLASI-A scores >9 (P < .0001), baseline CLASI damage (CLASI-D) scores ≥10 (P = .0001), and CLE disease duration ≤1 year (P = .01). Of 28 patients with baseline CLASI-D scores ≥10, 35.71% had improvements in damage, while 5.26% of patients with initial CLASI-D scores of 5-9 (N = 19) and 0% with initial CLASI-D scores <5 (N = 36) (P = .0005) had improvements. LIMITATIONS: Limitations include small sample size. CONCLUSION: Baseline CLASI-A score >9, minority race, and short disease duration predict CLE disease activity improvement. A baseline CLASI-D score ≥10 is associated with disease damage improvement.

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.

Phototherapy for sclerosing skin conditions.

Phototherapy is an effective treatment strategy for a variety of sclerosing skin conditions. There are a number of phototherapeutic modalities used for the treatment of sclerosing skin conditions, including ultraviolet (UV)A1, broadband UVA, psoralen plus UVA, and narrowband UVB phototherapy. As controlled trials with validated outcome measures are lacking for these therapies, existing evidence is largely level II for morphea and is even more minimal for scleroderma and other sclerosing disorders (scleroderma, lichen sclerosus, and chronic graft-versus-host disease, among others). Studies do suggest that phototherapy may be effective for many of these disorders, including those that have been unresponsive to other therapies. Phototherapy remains an attractive therapeutic option for patients due to its efficacy and favorable risk-versus-benefit profile. Phototherapy also offers a therapeutic alternative to systemic immunosuppressives for patients who cannot tolerate these medications.

A subset of CD163+ macrophages displays mixed polarizations in discoid lupus skin.

INTRODUCTION: Lesional skin of patients with discoid lupus erythematosus (DLE) contains macrophages, whose polarization has yet to be investigated. To test our hypothesis that M1 macrophages would be increased in DLE skin, we examined transcriptome alterations in immune cell gene expression and macrophage features in DLE and normal skin by using gene expression and histochemical approaches. METHODS: Gene expression of RNA from DLE lesional and normal control skin was compared by microarrays and quantitative real-time polymerase chain reaction (RT-PCR). Both skin groups were analyzed for CD163 expression by immunohistochemistry. Double immunofluorescence studies were performed to characterize protein expression of CD163+ macrophages. RESULTS: DLE skin had twice as many upregulated genes than downregulated genes compared with normal skin. Gene set enrichment analysis comparing differentially expressed genes in DLE and normal skin with previously published gene sets associated with M1 and M2 macrophages showed strong overlap between upregulated genes in DLE skin and M1 macrophages. Quantitative RT-PCR showed that several M1 macrophage-associated genes--e.g., chemokine (C-X-C motif) ligand 10 (CXCL10), chemokine (C-C motif) ligand 5 (CCL5), and signal transducer and activator of transcription 1 (STAT1)-had amplified mRNA levels in DLE skin. CD163+ macrophages were increased near the epidermal-dermal junction and perivascular areas in DLE skin compared with normal skin. However, double immunofluorescence studies of CD163+ macrophages revealed minor co-expression of M1 (CXCL10, tumor necrosis factor-alpha, and CD127) and M2 (CD209 and transforming growth factor-beta) macrophage-related proteins in DLE skin. CONCLUSION: Whereas a subset of CD163+ macrophages displays mixed polarizations in DLE skin, other immune cells such as T cells can contribute to the expression of these macrophage-related genes.

Prospective comparison of subtalar arthroereisis with lateral column lengthening for painful flatfeet.

We prospectively compared subtalar arthroereisis with lateral column calcaneal lengthening for the treatment of painful flatfeet. Twenty-four feet (mean age of patients 12.8 years) were treated. Kinematic motion analysis, pedobarometry, and radiography were performed, and the Oxford Ankle-Foot Questionnaire for Children was administered for each patient before surgery and at the 1-year follow-up. We found statistically significant improvements in both groups, with no difference in their outcomes. Both groups showed significantly improved hindfoot and midfoot motion and positioning. Hindfoot range of motion was preserved. Radiography and pedobarometry also revealed significant improvements. Subtalar arthroereisis is a valid and potentially less-invasive alternative to lateral column lengthening that merits further investigation.