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Article ; Online: Morphea disease activity during pregnancy: A case series.

Walker, Amanda M / Bermas, Bonnie L / Jacobe, Heidi T

2022 Volume 49, Issue 12, Page(s) 1278–1283

Abstract: Little is known about pregnancy in women with morphea. We aimed to describe the clinical presentation, pregnancy outcomes, and medical management of morphea during pregnancy. We conducted a case series of female patients of reproductive age (18-49 years) ...

Abstract	Little is known about pregnancy in women with morphea. We aimed to describe the clinical presentation, pregnancy outcomes, and medical management of morphea during pregnancy. We conducted a case series of female patients of reproductive age (18-49 years) who were part of the longitudinal MAC (Morphea in Adults and Children) cohort seen in the outpatient dermatology clinic at the University of Texas Southwestern from July 2007 to February 2022. Women who were pregnant during research visits and had at least 6 months of follow-up in the MAC cohort were included. Data collected included demographics, morphea characteristics, pregnancy outcomes, and medication history. Median clinical disease activity and damage scores using the Localized Scleroderma Cutaneous Assessment Tool were recorded. Ten patients were pregnant during the study period. Five patients had pediatric-onset morphea and five had adult-onset morphea. Eight patients had linear and two had plaque morphea. Six patients had at least one morphea lesion on their abdomen. Median age at first pregnancy was 31 years (interquartile range [IQR], 26.0-35.8 years) and median duration of morphea was 13.5 years (IQR, 4.8-19.0 years). In seven patients, damage scores were stable with no increased morphea activity. Three patients (30%) experienced reactivation of morphea activity during pregnancy with a median Localized Scleroderma Activity Index of 4 (IQR, 2.5-10). Only one patient required immunosuppressive therapy during pregnancy for her morphea diagnosis. Seven of 10 patients had cesarean deliveries and one adverse fetal outcome was reported. In this small series, most patients maintained stability of their morphea and there were no adverse pregnancy outcomes directly related to morphea.
MeSH term(s)	Humans ; Adult ; Child ; Female ; Pregnancy ; Adolescent ; Young Adult ; Middle Aged ; Scleroderma, Localized/diagnosis ; Scleroderma, Localized/drug therapy ; Cohort Studies ; Immunosuppression Therapy
Language	English
Publishing date	2022-09-12
Publishing country	England
Document type	Journal Article
ZDB-ID	800103-0
ISSN	1346-8138 ; 0385-2407
ISSN (online)	1346-8138
ISSN	0385-2407
DOI	10.1111/1346-8138.16572
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Article ; Online: Patients with autoimmune skin diseases are at increased risk of adverse pregnancy outcomes.

Keum, Heejo / Bermas, Bonnie / Patel, Shivani / Jacobe, Heidi T / Chong, Benjamin F

American journal of obstetrics & gynecology MFM

2023 Volume 6, Issue 1, Page(s) 101226

Abstract: Background: Increased rates of adverse pregnancy outcomes have been reported in association with rheumatologic diseases such as systemic lupus erythematosus, rheumatoid arthritis, dermatomyositis. However, little is known about pregnancy outcomes in ... ...

Abstract	Background: Increased rates of adverse pregnancy outcomes have been reported in association with rheumatologic diseases such as systemic lupus erythematosus, rheumatoid arthritis, dermatomyositis. However, little is known about pregnancy outcomes in patients with autoimmune skin diseases. Objective: This study aimed to determine the frequency of adverse pregnancy outcomes in patients with autoimmune skin diseases. We hypothesized that similar to rheumatic diseases, the rate of adverse pregnancy outcomes in patients with autoimmune skin diseases would be higher than the general population. Study design: This is a case control study using the TriNetX US Collaborative Network, which is a database of electronic medical records of >95 million patients seen at 57 healthcare organizations in the United States. All pregnant women between the ages of 15 and 44 years who were seen at a healthcare organization between January 1, 2016 and December 31, 2021 were included. Participants with autoimmune skin disease were matched to healthy controls and controls with systemic rheumatologic conditions (systemic lupus erythematosus or rheumatoid arthritis). For both the autoimmune skin disease and healthy control groups, those with systemic rheumatologic condition or hidradenitis suppurativa were excluded. The primary outcomes were adverse pregnancy outcomes defined as spontaneous abortion, gestational hypertension, preeclampsia or eclampsia, gestational diabetes mellitus, intrauterine growth restriction, preterm premature rupture of membranes, preterm birth, and stillbirth. Patients with autoimmune skin diseases and controls were 1:1 propensity score-matched by age, race, ethnicity, comorbidities, obesity, and substance use. For each outcome, odds ratio with a 95% confidence interval was calculated. Results: A total of 2788 patients with autoimmune skin diseases were matched to 2788 healthy controls. Patients with autoimmune skin diseases were at a higher risk of spontaneous abortions than controls (odds ratio, 1.54; 95% confidence interval, 1.36-1.75; P<.001). Compared with patients with systemic lupus erythematosus, patients with autoimmune skin diseases were at lower risk of having infants with intrauterine growth restriction (odds ratio, 0.59; 95% confidence interval, 0.4-0.87; P=.01), preterm birth (odds ratio, 0.68; 95% confidence interval, 0.47-0.98; P=.04), and stillbirth (odds ratio, 0.50; 95% confidence interval, 0.25-0.97; P=.04). The differences in adverse pregnancy outcomes between patients with autoimmune skin diseases and those with rheumatoid arthritis were not statistically significant. Conclusion: Patients with autoimmune skin diseases are at a higher risk of spontaneous abortions than patients without autoimmune skin diseases. When analyzed by each autoimmune skin disease, patients with cutaneous lupus erythematosus or vitiligo remained at increased risk of spontaneous abortions compared with patients without autoimmune skin diseases. Patients with autoimmune skin diseases have similar risks of adverse pregnancy outcomes as patients with rheumatoid arthritis, but lower risks than patients with systemic lupus erythematosus.
MeSH term(s)	Humans ; Infant, Newborn ; Pregnancy ; Female ; United States/epidemiology ; Adolescent ; Young Adult ; Adult ; Pregnancy Outcome/epidemiology ; Abortion, Spontaneous/epidemiology ; Abortion, Spontaneous/etiology ; Premature Birth/epidemiology ; Premature Birth/etiology ; Stillbirth/epidemiology ; Case-Control Studies ; Fetal Growth Retardation/diagnosis ; Fetal Growth Retardation/epidemiology ; Fetal Growth Retardation/etiology ; Pregnancy Complications/diagnosis ; Pregnancy Complications/epidemiology ; Pregnancy Complications/etiology ; Lupus Erythematosus, Systemic/complications ; Lupus Erythematosus, Systemic/diagnosis ; Lupus Erythematosus, Systemic/epidemiology ; Arthritis, Rheumatoid/complications ; Arthritis, Rheumatoid/diagnosis ; Arthritis, Rheumatoid/epidemiology ; Skin Diseases/complications
Language	English
Publishing date	2023-11-14
Publishing country	United States
Document type	Journal Article
ISSN	2589-9333
ISSN (online)	2589-9333
DOI	10.1016/j.ajogmf.2023.101226
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Article: Morphea: progress to date and the road ahead.

Abbas, Laila / Joseph, Adrienne / Kunzler, Elaine / Jacobe, Heidi T

Annals of translational medicine

2021 Volume 9, Issue 5, Page(s) 437

Abstract: Morphea is a rare autoimmune condition causing inflammation and sclerosis of the skin and underlying soft tissue. It is characterized by periods of activity (inflammation admixed with fibrosis), ultimately resulting in permanent damage (pigment change ... ...

Abstract	Morphea is a rare autoimmune condition causing inflammation and sclerosis of the skin and underlying soft tissue. It is characterized by periods of activity (inflammation admixed with fibrosis), ultimately resulting in permanent damage (pigment change and tissue loss). Damage resulting from unchecked activity can lead to devastating, permanent cosmetic and functional sequelae including hair loss; cutaneous, soft tissue and bony atrophy; joint contractures; and growth restriction of the affected body site in children. This makes the early identification of activity and initiation of appropriate treatment crucial to limiting damage in morphea. To this end, recent investigative work has focused on validation of clinical, biomarker, imaging, and histologic outcomes aimed at accurately quantifying activity and damage. Despite promising results, further work is needed to better validate these measures before they can be used in the clinic and research settings. Although there has been recent approval of less toxic, targeted therapies for many inflammatory skin conditions, none have been systematically investigated in morphea. The mainstays of treatment for active morphea are corticosteroids and methotrexate. These are often limited by substantial toxicity. The paucity of new treatments for morphea is the result of a lack of studies examining its pathogenesis, with many reviews extrapolating from research in systemic sclerosis. Recent studies have demonstrated the role of dysregulated immune and fibrotic pathways in the pathogenesis of morphea, particularly interferon (IFN) gamma related pathways. Active morphea lesions have been found to display an inflammatory morphea signature with CXCR3 receptor ligands, as well as a distinct fibrotic signature reflecting fibroblast activation and collagen production. CXCL9 and 10 have been associated with increased measures of disease activity. While immune dysfunction is thought to play the primary role in morphea pathogenesis, there are other factors that may also contribute, including genetic predisposition, environmental factors, and vascular dysregulation. There remains an essential need for further research to elucidate the pathogenesis of morphea and the mode of action of dysregulated upstream and downstream immune and fibrotic pathways. These studies will allow for the discovery of novel biomarkers and targets for therapeutic development.
Language	English
Publishing date	2021-04-06
Publishing country	China
Document type	Journal Article ; Review
ZDB-ID	2893931-1
ISSN	2305-5847 ; 2305-5839
ISSN (online)	2305-5847
ISSN	2305-5839
DOI	10.21037/atm-20-6222
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Article ; Online: Emerging treatments for scleroderma/systemic sclerosis.

Zhu, Jane L / Black, Samantha M / Chen, Henry W / Jacobe, Heidi T

Faculty reviews

2021 Volume 10, Page(s) 43

Abstract: Systemic sclerosis (SSc) is a connective tissue disease characterized by progressive fibrosis of the skin and internal organs and has significant clinical sequelae. Management of SSc cutaneous disease remains challenging and often is driven by ... ...

Abstract	Systemic sclerosis (SSc) is a connective tissue disease characterized by progressive fibrosis of the skin and internal organs and has significant clinical sequelae. Management of SSc cutaneous disease remains challenging and often is driven by extracutaneous manifestations. Methotrexate is the typical first-line therapy for patients with early progressive cutaneous disease. However, in patients with diffuse progressive skin disease and inflammatory arthritis, methotrexate or rituximab monotherapy should be considered. First-line therapy for patients with concomitant myositis includes methotrexate or intravenous immunoglobulin (IVIG). For patients with both cutaneous findings and interstitial lung disease, studies have suggested the efficacy of mycophenolate mofetil or rituximab. Second-line therapies, including UVA-1 phototherapy, IVIG, or rituximab, can be considered in patients with disease refractory to first-line treatments. Clinical trials investigating the utility of emerging therapies such as abatacept and tocilizumab in the treatment of SSc are under way, and preliminary results are promising. Nonetheless, all patients with SSc benefit from a gentle skin-care regimen to alleviate pruritis, which is a commonly reported symptom. Additional cutaneous manifestations of SSc include telangiectasias, calcinosis cutis, microstomia, and Raynaud's phenomenon. Telangiectasia may be managed with camouflage techniques, pulse dye laser, and intense pulse light. Calcinosis cutis therapy is guided by the size of the calcium deposits, although treatment options are limited. Mouth augmentation and oral stretching exercises are recommended for patients with reduced oral aperture. Raynaud's phenomenon is treated with a combination of lifestyle modification and calcium channel blockers, such as amlodipine. Overall, SSc is a clinically heterogenous disease that affects multiple organ systems. Providers should assess extracutaneous involvement and use evidence-based recommendations to select the most appropriate therapy for patients with SSc.
Language	English
Publishing date	2021-05-05
Publishing country	England
Document type	Journal Article ; Review
ISSN	2732-432X
ISSN (online)	2732-432X
DOI	10.12703/r/10-43
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Article ; Online: Current Utilization of Qualitative Methodologies in Dermatology: A Scoping Review.

Foster, Jenny / Teske, Noelle M / Zigler, Christina K / Hamilton, Andrew / Jacobe, Heidi

JID innovations : skin science from molecules to population health

2022 Volume 3, Issue 2, Page(s) 100172

Abstract: 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, ... ...

Abstract	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.
Language	English
Publishing date	2022-11-18
Publishing country	Netherlands
Document type	Journal Article ; Review
ISSN	2667-0267
ISSN (online)	2667-0267
DOI	10.1016/j.xjidi.2022.100172
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Article ; Online: Knowledge, attitudes, and behaviors of nail technicians in detecting acral lentiginous melanoma.

Joseph, Adrienne K / Walker, Amanda M / Irek, Melissa / Berry, Emily / Argenbright, Keith / Jacobe, Heidi

Journal of cosmetic dermatology

2022 Volume 21, Issue 11, Page(s) 6449–6452

MeSH term(s)	Humans ; Health Knowledge, Attitudes, Practice ; Skin Neoplasms/diagnosis ; Melanoma/diagnosis ; Melanoma, Cutaneous Malignant
Language	English
Publishing date	2022-05-23
Publishing country	England
Document type	Letter ; Research Support, Non-U.S. Gov't
ZDB-ID	2280551-5
ISSN	1473-2165 ; 1473-2130
ISSN (online)	1473-2165
ISSN	1473-2130
DOI	10.1111/jocd.15068
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Article ; Online: Patients with morphea with neurologic involvement: A cross-sectional study and review from the morphea in adults and children cohort.

Abbas, Laila F / Joseph, Adrienne K / Zhu, Jane L / Okuda, Darin / Jacobe, Heidi T

Journal of the American Academy of Dermatology

2022 Volume 88, Issue 1, Page(s) 172–174

MeSH term(s)	Adult ; Humans ; Child ; Scleroderma, Localized/epidemiology ; Cross-Sectional Studies ; Cohort Studies ; Severity of Illness Index ; Patients
Language	English
Publishing date	2022-01-06
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural
ZDB-ID	603641-7
ISSN	1097-6787 ; 0190-9622
ISSN (online)	1097-6787
ISSN	0190-9622
DOI	10.1016/j.jaad.2021.12.049
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Article ; Online: Single-Cell Transcriptome Analysis Identifies Subclusters with Inflammatory Fibroblast Responses in Localized Scleroderma.

Werner, Giffin / Sanyal, Anwesha / Mirizio, Emily / Hutchins, Theresa / Tabib, Tracy / Lafyatis, Robert / Jacobe, Heidi / Torok, Kathryn S

International journal of molecular sciences

2023 Volume 24, Issue 12

Abstract: 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 ...

Abstract	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.
MeSH term(s)	Adult ; Humans ; Child ; Scleroderma, Localized/metabolism ; Scleroderma, Localized/pathology ; Single-Cell Gene Expression Analysis ; Scleroderma, Systemic/pathology ; Fibrosis ; Fibroblasts/metabolism ; Skin/metabolism ; Transcriptome
Language	English
Publishing date	2023-06-06
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2019364-6
ISSN	1422-0067 ; 1422-0067 ; 1661-6596
ISSN (online)	1422-0067
ISSN	1422-0067 ; 1661-6596
DOI	10.3390/ijms24129796
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Article ; Online: Patients with Limited Life Expectancy Are Biopsied for Keratinocyte Cancers at Similar Frequency to Healthy Patients.

Chen, Henry W / Coias, Jennifer / Walker, Amanda M / Prasad, Smriti / Ma, Liqiao / Hynan, Linda S / Jacobe, Heidi

Dermatology (Basel, Switzerland)

2023 Volume 239, Issue 4, Page(s) 565–571

Abstract: 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 ... ...

Abstract	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.
MeSH term(s)	Humans ; Retrospective Studies ; Skin Neoplasms/pathology ; Biopsy ; Keratinocytes/pathology ; Life Expectancy
Language	English
Publishing date	2023-03-15
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	1099692-8
ISSN	1421-9832 ; 1018-8665
ISSN (online)	1421-9832
ISSN	1018-8665
DOI	10.1159/000530103
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Article ; Online: Clinical Characteristics Associated with Musculoskeletal Extracutaneous Manifestations in Pediatric and Adult Morphea: A Prospective, Cohort Study.

Chen, Henry W / Walker, Amanda M / Stein, Amy Buros / Chen, Sojung L / Schollaert-Fitch, Kaila L / Torok, Kathryn S / Jacobe, Heidi T

The Journal of investigative dermatology

2023 Volume 143, Issue 10, Page(s) 1955–1963.e3

Abstract: Morphea is an autoimmune condition of the skin associated with functional sequelae resulting from musculoskeletal involvement. Systematic investigation of risk for musculoskeletal involvement is limited, particularly in adults. This knowledge gap impairs ...

Abstract	Morphea is an autoimmune condition of the skin associated with functional sequelae resulting from musculoskeletal involvement. Systematic investigation of risk for musculoskeletal involvement is limited, particularly in adults. This knowledge gap impairs patient care because practitioners are unable to risk stratify patients. To address this gap, we determined the frequency, distribution, and type of musculoskeletal (MSK) extracutaneous manifestations affecting joint and bone with overlying morphea lesions using cross-sectional analysis of 1,058 participants enrolled in two prospective cohort registries (Morphea in Children and Adults Cohort [n = 750] and National Registry for Childhood Onset Scleroderma [n = 308]). Additional analysis included the identification of clinical features associated with MSK extracutaneous manifestations. MSK extracutaneous manifestations occurred in 274 of 1,058 participants (26% overall, 32% pediatric, and 21% adults). Children had a limited range of motion of larger joints (i.e., knees/hips/shoulders), whereas the involvement of smaller joints (i.e., toes/temporomandibular joint) was more common in adults. Multivariable logistic regression showed that deep tissue involvement had the strongest association with musculoskeletal features, with a lack of deep tissue involvement having a negative predictive value of 90% for MSK extracutaneous manifestations. Our results underscore the need to evaluate MSK involvement in adult and pediatric patients and the utility of using depth of involvement in addition to anatomic distribution to risk stratify patients.
MeSH term(s)	Humans ; Child ; Adult ; Scleroderma, Localized ; Cohort Studies ; Prospective Studies ; Cross-Sectional Studies ; Autoimmune Diseases
Language	English
Publishing date	2023-05-02
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	80136-7
ISSN	1523-1747 ; 0022-202X
ISSN (online)	1523-1747
ISSN	0022-202X
DOI	10.1016/j.jid.2023.04.010
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