Exploring the relationship between morphea and malignancy: a decade-long single-center study of 204 patients.

The association between systemic scleroderma and malignancy is well-documented, but there is limited data on the relationship between morphea and malignancy. This study aims to assess the incidence and types of malignancies in morphea patients, comparing demographics, clinical characteristics, treatments, and outcomes between those with and without malignancy. We conducted a retrospective study of 204 morphea patients treated at Rabin Medical Center between 2012 and 2023. Data on demographics, clinical subtypes, comorbidities, treatments, and outcomes were collected. Patients were categorized based on malignancy status and the timing of malignancy relative to their morphea diagnosis. Among the 204 patients (154 women and 50 men, mean age 53.7 ± 20 years), 47 (23%) developed malignancies. In 29 patients (61.7%), malignancy occurred before the onset of morphea; in 23 patients (48.9%), it occurred after morphea. Five patients (10.6%) had malignancies both before and after the diagnosis of morphea. Patients with malignancy were significantly older than those without (64.7 ± 15.1 years vs. 50.3 ± 20 years, p < 0.0001). The all-cause mortality rate was higher in the malignancy group compared to those without malignancy (23.4% vs. 3.8%, p = 0.00002). Moreover, mortality was higher in patients whose malignancy occurred after morphea than in those whose malignancy preceded morphea (26% vs. 17.2%). The most common post-morphea malignancies in our cohort included non-melanoma skin cancer, cervical cancer, breast cancer, stomach cancer, and lung cancer. The most common pre-morphea malignancies included breast cancer, non-melanoma skin cancer, colon cancer, prostate cancer, and testicular cancer. This study suggests potential associations between morphea and malignancies, influenced by patient age, sequence of diagnosis, and treatment regimens. Further control studies are needed to explore these relationships more definitively.

Endpoints and outcomes for localized scleroderma/morphea: a scoping literature review.

BACKGROUND: Current treatment for localized scleroderma (LS) has been shown to halt disease activity, but little is still known about patient experiences with these treatments, nor is there consensus about optimal measurement strategies for future clinical trials. OBJECTIVE: Conduct a scoping review of the literature for the types of outcomes and measures (i.e. clinician-, patient-, and caregiver-reported) utilized in published treatment studies of LS. METHODS: Online databases were searched for articles related to the evaluation of treatment efficacy in LS with a special focus on pediatrics. RESULTS: Of the 168 studies, the most common outcomes used were cutaneous disease activity and damage measured via clinician-reported assessments. The most frequently cited measure was the Localized Scleroderma Cutaneous Assessment Tool (LoSCAT). Few patient-reported outcome measures (PROMs) were used. LIMITATIONS: Some studies only vaguely reported the measures utilized, and the review yielded a low number of clinical trials. CONCLUSION: In addition to evaluating disease activity with clinician-reported measures, the field could obtain critical knowledge on the patient experience by including high-quality PROMs of symptoms and functioning. More clinical trials using a variety of outcomes and measures are necessary to determine the most suitable course of treatment for LS patients.

Extragenital lichen sclerosus et atrophicus-morphea overlap as an initial presentation of genital lichen sclerosus.

Lichen sclerosus et atrophicus (LSA) is a chronic inflammatory disorder, most often characterized by atrophic skin plaques located on female genitalia. Infrequently, LSA may present extragenitally; however, much is unknown about the temporal relationship between genital and extragenital LSA. Morphea, also known as localized scleroderma, is a rare inflammatory skin condition characterized by sclerotic plaques. Investigators debate whether LSA and morphea exist on the same spectrum of disease, with LSA representing a superficial variant of morphea involving genitalia, or if they are distinct but coincidental entities. Although researchers have described LSA and morphea occurring in different locations on the same patient, few reports describe LSA and morphea occurring in the same lesion and in the inguinal folds. Herein, we report a case of a 62-year-old woman with extragenital LSA-morphea overlap in the inguinal folds, who three months later developed genital LSA. Extragenital LSA-morphea in the same plaque, with no signs of genital lesions on initial exam, with later development of genital LSA, is especially uncommon. The temporal progression of extragenital LSA-morphea overlap to genital LSA over a three-month period is an important contribution to the literature, as the temporal relationship between extragenital and genital LSA is not previously discussed.

Morphoea presenting histopathologically as mycosis fungoides: an illustrative series of four cases.

AIMS: There have been exceptional reports of morphoea presenting with epidermal changes overlapping histopathologically with cutaneous T cell lymphoma of the mycosis fungoides type (MF). This phenomenon gives rise to an ambiguous clinicopathological scenario in which distinguishing these conditions may be challenging. The aim of this study is to characterise the clinical, histopathological and molecular findings of this phenomenon through a case series. METHODS AND RESULTS: Four patients with classical clinical presentation of morphoea but unusual histopathology displaying typical findings of morphoea, together with intra-epidermal CD8 positive lymphocytes indistinguishable from MF, were identified. The clinical phenotypes of morphoea were varied, and they all presented early in the active phase of the disease. They all exhibited intra-epidermal lymphocytes with tagging and cytological atypia. Pautrier-like microabscesses were also seen. Using molecular analysis, two cases showed clonal TCR gene rearrangement. Follow-up of all cases has been consistent with classical morphoea. CONCLUSION: Early morphoea can seldom present with atypical clonal intra-epidermal lymphocytes indistinguishable from MF. The fact that these changes can occur in several different clinical subtypes of morphoea raises the possibility that this could be a pattern of inflammation in early disease more common than currently appreciated.

Responsiveness to Change of the Morphea Activity Measure in Pediatric Patients.

Importance: Detecting activity of morphea can be complex but is crucial for adequate treatment and outcome assessment. The Morphea Activity Measure (MAM) was recently validated, but its responsiveness to change in disease activity has not been studied. Objective: To evaluate the internal and external responsiveness of MAM to changes in disease activity in pediatric patients. Design, Setting, and Participants: This multicenter prospective, longitudinal prognostic study was performed from October 2021 to January 2023 at 4 pediatric referral centers in North America. Consecutive pediatric patients with morphea who were available for data collection at baseline and at a follow-up visit at least 3 months later were studied. Exposure: Patient demographics, clinical characteristics, and measurements of disease activity collected at baseline and the subsequent visit. Main Outcome and Measures: Responsiveness of MAM to disease activity according to the modified Localized Scleroderma Severity Index (mLoSSI), the Physician Global Assessment (PGA), and a patient and parent global assessment (PtGA) was analyzed using mean and percentage change, standardized effect size, and standardized response mean (SRM) from baseline to follow-up 3 or more months later. Differences between patients whose activity improved vs did not improve were evaluated using the Mann-Whitney U test. The correlation between percentage change in MAM score and mLoSSI, the PGA, and the PtGA was calculated using Spearman rank correlation. Results: A total of 43 patients (mean [SD] age at onset, 7.11 [3.18] years; 26 [60.5%] female) were included. The mean change and percentage change in MAM score were significantly larger in those whose disease activity improved by the PGA (mean: -18.75 [95% CI, -31.92 to -5.57] vs 2.73 [95% CI, -1.97 to 7.45]; percentage: -108.08% [95% CI, -155.21% to -60.95%] vs -24.11% [95% CI, -81.22% to 32.99%]) and by mLoSSI (mean: -24.15 [95% CI, -41.89 to -6.41] vs -1.30 [95% CI, -8.50 to 5.70]; percentage: -172.06% [95% CI, -263.68% to -80.45%] vs -21.57% [95% CI, -48.13% to 4.97%]) than in those whose activity did not change. The SRM of MAM was significantly different between groups for both measures; the responsiveness was large in those whose activity decreased by the PGA (-0.75 [95% CI, -1.29 to -0.22]) and mLoSSI (-0.97 [95% CI, -1.69 to -0.25]) and none to small in those whose activity did not change by the PGA (0.11 [95% CI, -0.08 to 0.30]) or mLoSSI (-0.05 [95% CI, -0.34 to 0.23]). Percentage change in MAM score correlated strongly and significantly with change in mLoSSI (ρ = 0.69; P < .001) and PGA (ρ = 0.65; P < .001), but there was no correlation with change in the PtGA (ρ = 0.26; P = .09). Conclusions and Relevance: In this prognostic study, MAM was found to be internally and externally responsive to changes in disease activity. Further evaluation in mixed cohorts of all ages and specialties is needed.

International exchange on the clinical practice and research of rheumatic skin diseases: A report of the 5th International Conference of Cutaneous Lupus Erythematosus.

The 5th International Conference of Cutaneous Lupus Erythematosus was held in Tokyo, Japan on May 9 and 10, 2023. The latest topics on the pathogenesis, diagnosis, assessment, and treatment of cutaneous lupus erythematosus, dermatomyositis, and scleroderma (systemic sclerosis, morphea) were presented by experts in each field and new developments discussed. In these rheumatic skin diseases, many clinical trials of novel therapies targeting cytokines, signaling molecules, plasmacytoid dendritic cells, B cells, and other molecules are currently underway, and standardization of outcome assessment was discussed. In addition, the selection of the therapeutic agents available for the diversity of each case is becoming more important, together with the ongoing pathophysiological analysis of the diseases. The achievements of this conference will further promote the development of clinical practice and research in rheumatic skin diseases through international exchange among researchers. We hope that by reporting a summary of the conference in this manuscript, we can share its contents with readers.

Consensus statement on the diagnosis and treatment of sclerosing diseases of the skin, Part 1: Localized scleroderma, systemic sclerosis and overlap syndromes.

The term 'sclerosing diseases of the skin' comprises specific dermatological entities, which have fibrotic changes of the skin in common. These diseases mostly manifest in different clinical subtypes according to cutaneous and extracutaneous involvement and can sometimes be difficult to distinguish from each other. The present consensus provides an update to the 2017 European Dermatology Forum Guidelines, focusing on characteristic clinical and histopathological features, diagnostic scores and the serum autoantibodies most useful for differential diagnosis. In addition, updated strategies for the first- and advanced-line therapy of sclerosing skin diseases are addressed in detail. Part 1 of this consensus provides clinicians with an overview of the diagnosis and treatment of localized scleroderma (morphea), and systemic sclerosis including overlap syndromes.

S2k guideline: Diagnosis and therapy of localized scleroderma.

The updated S2k guideline deals with the diagnosis and therapy of localized scleroderma (LoS). LoS represents a spectrum of sclerotic skin diseases in which, depending on the subtype and localisation, structures such as adipose tissue, muscles, joints, and bones may also be affected. Involvement of internal organs or progression to systemic sclerosis does not occur. LoS can be classified into four main forms: limited, generalized, linear, and mixed forms, with some additional subtypes. For cases of limited skin involvement, the guideline primarily recommends therapy with topical corticosteroids. UV therapy can also be recommended. In subtypes with severe skin or musculoskeletal involvement, systemic therapy with methotrexate is recommended. During the active phase of the disease, systemic glucocorticosteroids can be used additionally. In cases of methotrexate and steroid refractory courses, contraindications, or intolerance, mycophenolate mofetil, mycophenolic acid, or abatacept can be considered as second-line systemic therapies. In the case of linear LoS, autologous adipose-derived stem cell transplantation can also be performed for correcting soft tissue defects.

[Localized scleroderma]. / Lokalisierte Sklerodermie.

Localized scleroderma (LS), also called circumscribed scleroderma or morphea, comprises a heterogeneous group of diseases that can be classified into four subtypes: limited, linear, generalized, and mixed LS. All manifestations are primarily due to chronic progressive fibrosis of the skin or structures close to the skin. Involvement of internal organs or the transition to systemic sclerosis is excluded by definition. A distinction is made between forms that primarily affect the skin (up to the dermis) or that severely involve subcutaneous fat tissue, muscle fascia or muscles. A detailed examination is required for clinical diagnosis. In order to improve comparability of findings, photo documentation and the use of clinical scores should be carried out. For superficial subtypes the use of topical glucocorticosteroids, calcineurin inhibitors or phototherapy is initially recommended, whereas for severe forms with deep involvement or overall therapy refractoriness, the diagnosis should first be expanded and systemic therapy initiated at an early stage. Especially, in cross joint or extremity-dominant forms of linear LS or in cases with head and neck involvement, such as en coup de sabre, Parry-Romberg syndrome and other subtypes with a prominent musculoskeletal affection, an MRI examination should be arranged. Depending on location, an ophthalmological, neurological, orthodontic, rheumatological or orthopedic consultation may be necessary. For systemic therapy, methotrexate alone or in combination with systemic glucocorticosteroids as pulse therapy is recommended as first-line treatment.

Morphea-like discoid lupus erythematosus in a patient with a history of polyacrylamide gel injection: A case report.

BACKGROUND: Discoid lupus erythematosus (DLE) is an autoimmune disease with multifactor etiology which develops in genetically susceptible patients. Rarely, DLE lesions can mimic other connective tissue disorders such as morphea. The growing application of soft tissue fillers is associated with increasing complications. Some substances used for soft tissue augmentation such as silicon implants may trigger lupus erythematosus diseases. CASE REPORT: Here we report a case of morphea-like discoid lupus erythematosus developed several years after polyacrylamide dermal filler (PAAG) injection for facial rejuvenation. CONCLUSION: As noninvasive procedures like dermal filler injections are increasing worldwide, physicians may consider the long-term probable side effects of these compounds.

[Juvenile localized scleroderma]. / Zirkumskripte Sklerodermie im Kindesalter.

Juvenile scleroderma, often referred to as juvenile localized scleroderma or "morphea", is a rare inflammatory disease of the skin and skin-related structures, accompanied by local sclerosis and tissue fibrosis. Depending on the clinical manifestation, four different subtypes can be defined: limited, generalized, linear, and mixed. To prevent possible sequelae of the disease, the diagnosis should be made as early as possible and therapy should be initiated at specialized centers in multiprofessional pediatric and dermatologic collaboration. In this review, we present the main clinical, laboratory, and therapeutic characteristics of juvenile localized scleroderma and summarize recommendations.

[Radiation-induced morphea-an overview]. / Postradiogene Morphea ­ eine Übersicht.

BACKGROUND: Radiation-induced morphea is a fibro-inflammatory remodelling process of the subcutaneous connective tissue caused by ionising radiation, most commonly in the context of breast cancer treatment. The underlying pathomechanisms and putative risk factors are unknown. Therefore, misdiagnosis and inappropriate treatment pose a significant problem in the care of those patients. OBJECTIVES: The aim of the study was to provide an overview as well as guidance for the diagnosis and treatment of radiation-induced morphea based on current case reports and review articles. RESULTS AND CONCLUSIONS: Radiation-induced morphea is a rare condition that represents an interdisciplinary challenge for (gynaecological) oncology, radiotherapy and dermatology. Frequent misdiagnoses include infection (erysipelas), cancer recurrence or radiation dermatitis. Early histological diagnosis and the initiation of anti-inflammatory therapy using topical glucocorticoids or calcineurin inhibitors in combination with phototherapy and/or methotrexate are the most relevant success factors for an adequate clinical response.

Morphea as an isotopic response to pigmented purpuric dermatosis and lichen striatus.

Morphea is an uncommon inflammatory and fibrosing disorder that has a polymorphous clinical presentation. We report two cases of morphea developing as an isotopic response after a preceding benign skin disease, accompanied by a review of the literature. This case series highlights the importance of return to care recommendations for benign skin conditions such lichen striatus and pigmented purpuric dermatoses due to the rare possibility of subsequent morphea development.

Systematic Review of Health-Related Quality of Life Impact in Juvenile Localized Scleroderma.

OBJECTIVE: The prevalence and types of psychosocial complications of juvenile localized scleroderma (JLS), also known as morphea, an inflammatory and sclerosing disease involving the skin, fascia, muscle, and bone, are poorly understood. METHODS: We performed a systematic review of literature published between 2000 and 2020 in PubMed, EMBASE, the Cochrane Skin Group Specialized Register, the Cochrane Central Register of Controlled Trials, and the Cumulative Index to Nursing and Allied Health Literature using the search terms "scleroderma, localized," "Morphea," "anxiety," "depression," "resilience," "social stigma," "quality of life," "mood," or "stress" and limited the search to pediatric patients and English language. Patient demographics, characteristics of JLS, and comorbidities were extracted. The outcomes included measures of health-related quality of life (HRQoL), psychosocial functioning, evaluation of self-perception, and the treatment burden of the study population. The protocol was registered with PROSPERO (CRD42021257124). Thematic synthesis generated descriptive analysis. RESULTS: Thirteen studies fulfilled the inclusion criteria: three retrospective cohort studies, two prospective cohort studies, and eight cross-sectional studies. A total of 690 pediatric patients with JLS were included (n = 484 with linear scleroderma). Six studies used the Children's Dermatology Life Quality Index, reporting little to no effect on HRQoL. One study used the Health-Related Quality of Life in Children and Adolescents Questionnaire and did not find differences between children with JLS or atopic dermatitis and healthy controls. One study used a self-perception questionnaire that showed normal self-worth of patients with JLS. Two studies used focus groups, both reporting elevated levels of stress, decreased self-worth, "feeling different," and bullying/teasing in patients with JLS. These emotions were associated with skin symptoms (pain, itch, and tightness), physical limitations, and treatment burden. CONCLUSION: Overall, quantitative studies did not report a statistically significant impairment in HRQoL in JLS. However, qualitative studies (focus groups) reported significant psychosocial impacts related to JLS. There is a need to develop a JLS-specific tool for the HRQoL evaluation of this population.

Successful treatment with baricitinib of linear morphea following the lines of Blaschko mimicking lichen striatus.

Linear morphea, also known as linear scleroderma, is a localized form of scleroderma characterized by the presence of lesions that follow a linear distribution pattern. Apart from the typical inflammation and fibrosis of the skin, the linear subtype of morphea often affects underlying structures such as muscles and bones, which can lead to functional limitations. Lichen striatus, a linear inflammatory skin condition, primarily affects children aged 5 to 15 years. Interestingly, both diseases can exhibit lesions that follow the lines of Blaschko. Here we report a case with linear morphea following the lines of Blaschko mimicking lichen striatus in a 4-year-old child. This unique case represents the first documented instance of linear morphea exhibiting a precise Blaschko pattern and being successfully treated with baricitinib. The patient received oral baricitinib at a daily dosage of 2 mg for a duration of 1 year, resulting in remarkable improvement. The majority of the lesions softened, and there was no significant disease progression or occurrence of adverse events throughout the treatment period. Recognizing linear morphea at an early stage is of utmost importance in ensuring effective treatment and preventing disfiguring sequelae. Patients suspected of lichen striatus should also be closely followed and linear morphea should be excluded during the follow-up. The recent breakthrough in the application and the safety of baricitinib in scleroderma is also reviewed.

Ocular and eyelid involvement in collagen vascular diseases. Part II. Dermatomyositis, scleroderma, and sarcoidosis.

Collagen vascular disease is a heterogeneous group of autoimmune diseases that affect multiple organ systems. Sjögren syndrome, dermatomyositis, scleroderma, systemic lupus erythematosus, and sarcoidosis are collagen vascular diseases that often present with characteristic cutaneous manifestations. Although less known, various ocular manifestations that affect both external and internal structures of the eye can also be seen in these conditions. Multidisciplinary management between dermatologists and ophthalmologists is essential in the early diagnosis and management of collagen vascular diseases affecting both the skin and eye. In part II of our series, we discuss the ocular manifestations, diagnosis, and therapeutic options of dermatomyositis, scleroderma, and sarcoidosis.