Novel multispectral imaging to predict disease progression in pediatric morphea.

BACKGROUND: Morphea, or localized scleroderma, is an inflammatory, fibrosing skin disorder that can be progressive and debilitating. Infrared thermography frequently has false positive results. The aim of this study was to assess the ability of multispectral imaging to predict disease progression in children with morphea. METHODS: Children with morphea were recruited between 2016 and 2022. Multispectral images of affected and matched contralateral unaffected sites were obtained using the Antera™ 3D camera. Clinical assessment was performed using the Localized Scleroderma Assessment Tool (LoSCAT). Children were followed up every 3 months for imaging and clinical review. The main outcome measurement was correlation of hemoglobin gradient between affected and matched contralateral unaffected tissue and progression. RESULTS: Of 17 children, the average age was 12 years (range 6-18 years); most were female (76.5%) and white (94.1%). Nearly two-thirds (64.7%) had linear morphea, 35.2% had plaque morphea; 58.8% had been treated with systemic agents. The average LoSCAT score was 20.6 (range 5-73). The average hemoglobin gradient between affected and matched contralateral unaffected skin was four times higher in those who had progression (average differential 0.3, range 0.1-0.4) compared to those who did not (average differential 0.08, range 0.02-0.15). Using a cut off of a 0.18 hemoglobin gradient between affected and unaffected skin, the sensitivity of multispectral imaging for detecting progression in pediatric morphea is 90% with specificity of 100%. CONCLUSIONS: Multispectral imaging is a novel assessment tool with promising accuracy in predicting progression as an adjunct to clinical assessment in pediatric morphea. Further research should examine its performance against thermography.

Use of 3-Dimensional Stereophotogrammetry to Detect Disease Progression in Craniofacial Morphea.

Importance: Objectively determining disease progression in craniofacial morphea (CM) is challenging, as clinical findings of disease activity are often lacking. Objective: To evaluate the utility of 3-dimensional (3D) stereophotogrammetry in detecting disease progression in CM over time. Design, Setting, and Participants: This prospective cohort study included 27 pediatric and adult patients with CM from 2 hospitals in Boston (Boston Children's Hospital and Brigham & Women's Hospital) consecutively enrolled from April 1, 2019, to March 1, 2023. Review of 3D stereophotogrammetry images and data analysis occurred from March 1 to April 1, 2023. Main Outcomes and Measures: Clinical and 3D stereophotogrammetry assessments were performed at 2- to 12-month intervals, depending on the clinical context. The 3D stereophotogrammetry images were then qualitatively rated as demonstrating no progression or definitive progression by an expert (board-certified plastic craniofacial surgeon) and nonexpert (board-certified dermatologist) in 3D stereophotogrammetry. In addition, κ coefficients were calculated for interrater reliability. Results: Of 27 patients with CM (19 female; median age, 14 [range, 5-40] years) and 3D stereophotogrammetry images obtained from a minimum of 2 time points (median, 4 [range, 2-10] images) spaced a median of 3 (range, 2-12) months apart, 10 experienced progression of their disease based on clinical assessments performed during the study period. In all cases in which clinical progression was favored, blinded qualitative assessment of 3D stereophotogrammetry images also favored progression with substantial interrater reliability (κ = 0.80 [95% CI, 0.61-0.99]). Furthermore, review of 3D stereophotogrammetry detected occult progression of asymmetry not noted on clinical examination in 3 additional patients. Conclusions and Relevance: In this prospective cohort study, blinded assessment of sequential 3D stereophotogrammetry images in patients with CM not only corroborated clinical assessment of disease progression but also detected occult progression of facial asymmetry not appreciable on clinical examination alone. Therefore, 3D stereophotogrammetry may serve as a useful adjunct to clinical examination of patients with CM over time. Future investigations are warranted to validate 3D stereophotogrammetry as an outcome measure in CM.

Color Doppler Ultrasound Assessment of Subclinical Activity With Scoring of Morphea.

BACKGROUND: Detection of activity in morphea is paramount for adequately managing the disease. Subclinical ultrasound involvement on inactive lesions or healthy skin areas adjacent to morphea has not been described to date. OBJECTIVES: The study aimed to detect morphea's subclinical activity by Color Doppler ultrasound not identified with the clinical scorings. MATERIALS & METHODS: This cross-sectional retrospective study was done from January 2014 to July 2019 in patients with a clinicopathological diagnosis of morphea. The modified Localized Scleroderma Skin Severity Index (mLoSSI) and The Ultrasound Morphea Activity Score (US-MAS) were used to correlate clinical and subclinical activity. RESULTS: A total of 36 patients met the inclusion criteria. 54% of cases presented subclinical activity in areas adjacent to the clinically active lesion, 23% in nonadjacent regions, and 23% demonstrated activity at a clinically inactive lesion site.100% of patients with morphea "en coup de sabre" involving the frontal region of the face concomitantly presented both subclinical activities of morphea on the frontal facial region and the scalp following the same axis.A positive relationship was observed between the degree of clinical activity measured by mLoSSI and US-MAS scoring.The main limitations of our study were the low number of patients and the inability to detect alterations < 0.1 mm. CONCLUSIONS: Subclinical activity is frequent in morphea, can extend beyond the lesional areas, including apparently noninvolved adjacent and distant corporal regions, and can be detected by color Doppler ultrasound.

Role of imaging in morphea assessment: A review of the literature.

BACKGROUND: Localized scleroderma, known as morphea, is a connective tissue disorder characterized by inflammation and fibrosis of the skin and the soft tissue. There exist no universally accepted validated outcome measures in order to monitor the disease activity. Besides clinical scores to evaluate outcome measures, imaging modalities are increasingly utilized in assessing patients with morphea, such as high-frequency ultrasonography (US), shear-wave elastography (SWE), and magnetic resonance imaging (MRI). However, the accuracy of these imaging modalities in monitoring morphea activity is not yet clear. AIMS: To review the literature regarding the role of imaging modalities in assessing patients with morphea. MATERIALS & METHODS: In this study, we searched the PubMed/Medline database for articles published from inception until February 2023. RESULTS: A total number of 23 original articles in three categories of US, elastography, and MRI were included. DISCUSSION: Regarding US, criteria, including increased dermal thickness, increased echogenicity of the subcutaneous tissue, and decreased dermal echogenicity, were indicators of active morphea lesions when using high frequencies probe (18-20 MHz) color Doppler sonography. Moreover, studies evaluating SWE, a novel method to quantitatively assess tissue stiffness, demonstrated increased dermal stiffness in active lesions. CONCLUSION: Studies showed that MRI can help to determine the depth of disease, particularly as a first-line and follow-up diagnostic tool, especially in generalized and deep morphea. In addition, brain MRI may be useful for patients with localized craniofacial scleroderma experiencing new or worsening neurological symptoms.

Ultrasound Morphea Activity Scoring (US-MAS): Modified US-MAS.

Morphea, an autoimmune connective tissue disease that affects the skin, can be supported by color Doppler ultrasound in its diagnosis and assessment of activity. To date, there are no reliable laboratory parameters to track activity, and ultrasound presents a higher axial spatial resolution than magnetic resonance imaging and computed tomography, which is critical for studying the superficial layers. The quality of the ultrasonographic assessment of activity in morphea depends on the standardization and features of the acquisition of the anatomical data. We propose a detailed ultrasound morphea activity scoring called modified US-MAS (mUS-MAS) that could allow us to systematically register the cutaneous abnormalities in the corporal regions and their subregions. The selection of the scanning sites will depend on the corporal regions of involvement and their adjacent segments. Through systematic and sequential ultrasound data analysis, we propose that this scoring system can better support description and activity tracking accuracy.

Differentiating morphea from lichen Sclerosus by using multiphoton microscopy combined with U-Net model for elastic fiber segmentation.

This paper describes a methodology to differentiate morphea from lichen sclerosus based on examination with multiphoton microscopy (MPM) composed of two-photon excited fluorescence (TPEF) and second harmonic generation (SHG). Subcellular-resolution images were acquired by MPM from unstained lesion tissues then process spectral analysis to quantify the TPEF and SHG signals. Moreover, U-Net was employed to segment elastic fiber in TPEF images to combine with collagen fiber in SHG images for precise fiber quantification. Predictions of segmentation showed excellent performance on several evaluation indicators. The mIoU, mPA, and F1 score reach 0.8516, 0.9281, and 0.941. The quantitative analysis demonstrated the increase of collagen fibers in morphea compared to that in lichen sclerosus cases. Meanwhile, the great diminution of elastic fiber in the dermis of lichen sclerosus was depicted based on MPM imaging. Thus, MPM was comparable to the histopathological examination and our experimental results accurately distinguish between morphea and lichen sclerosus.

Study about evaluation of efficacy of methotrexate in localized scleroderma using ultrasonography.

BACKGROUND: The treatment and curative effect evaluation of localized scleroderma (LS) still perplexes many clinical workers. PURPOSE: To investigate the efficiacy of methotrexate in the treatment of LS by the evaluation of ultrasonography. METHODS: A prospective study enrolled 10 patients treated with MTX for at least 6 months was conducted. Treatment outcome was evaluated by a clinical score and 15-MHz ultrasonography. Safety assessment included the monitoring of adverse drug reactions and clinical laboratory examinations. RESULTS: Eight of the 10 patients achieved clinical remission only with MTX. One patient was relieved after MTX combined with corticosteroids, while another one does not improve after the treatment of mycophenolate mofetil and corticosteroids. The effective rate of MTX is 80%. Nine patients were significantly improved with a decrease of the Localized Scleroderma Cutaneous Assessment Tool (the mean score of the LoSCAT cutaneous activity dropped from 5.2 to 1.0, p < 0.001, the mean score of the LS cutaneous damage dropped from 4.3 to 2.3, p = 0.002). The average difference of thickness between skin lesions and normal skin evaluated by ultrasonography decreased from 0.13 cm to 0.04 cm (p = 0.009) in eight patients. No serious adverse reactions occurred. CONCLUSION: Methotrexate is a safe and effective treatment for patients with LS. Ultrasonography can be considered as an efficient assessment tool for evaluation LS.

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.

The value of dermoscopy and high-frequency ultrasound in staging morphea.

Morphea is an autoimmune disease characterized by skin sclerosis. According to the disease progression, morphea can be divided into inflammatory, sclerotic, and atrophic stages. Dermoscopy and high-frequency ultrasound (HF-US) have been applied in the noninvasive evaluation of many inflammatory diseases, but studies on the skin imaging features of the different stages of morphea are limited. To analyze the dermoscopic and HF-US features of the different stages of morphea and explore their auxiliary value in staging the disease, we followed 34 patients with histopathology-confirmed morphea between April 2018 and July 2021 who underwent dermoscopy and 50 and 20 MHz HF-US. Fisher's exact test was used to assess the differences in dermoscopic and HF-US features among patients with different stages of morphea. Seven patients were classified as the inflammatory stage, 20 as the sclerotic stage, and seven as the atrophic stage by histopathology. The most common dermoscopic features of inflammatory lesions were red structureless areas (100%) and linear curved vessels (85.7%). White clouds and shiny white streaks could be seen in 100% and 90% of sclerotic lesions, respectively. Among atrophic lesions, pigmentary structures (100%) and red structureless areas (85.7%) were the main features. In the HF-US examination, inflammatory lesions showed hypoechogenicity around the appendages (85.7%), a hypoechogenic dermis (71.4%), and an unclear boundary between the dermis and the subcutaneous fat (71.4%). Among lesions of the sclerotic stage, the main HF-US characteristics included a hyperechogenic dermis (85.0%), acoustic attenuation of the dermis (70.0%), and an unclear boundary between the dermis and the subcutaneous fat (85.0%). All atrophic lesions showed a hyperechogenic dermis, and 28.6% showed an unclear boundary between the dermis and the subcutaneous fat. Dermoscopy and HF-US can reveal the characteristic features of the different stages of morphea and show good correspondence with the histopathology. Dermoscopy and HF-US can provide important information for the staging of morphea.

The Value of High-Resolution Ultrasound Combined with Shear-Wave Elastography under Artificial Intelligence Algorithm in Quantitative Evaluation of Skin Thickness in Localized Scleroderma.

The aim of this study was to explore the value of high-resolution ultrasound combined with shear-wave elastography (SWE) in measuring skin thickness in patients with localized scleroderma (LS). Fifty patients with LS diagnosed by pathology in the hospital were selected as the research object, with a total of 96 lesions. Healthy people (50 cases) in the same period were selected as the control group. The skin thickness of the abdomen, chest, and left finger of the two groups was compared. The traditional nonlocal means (NLM) algorithm was improved by changing the Euclidean distance and introducing a cosine function, which was applied to the ultrasonic imaging intelligent diagnosis of patients with localized scleroderma. SWE imaging was evaluated, and the results demonstrated that LS lesion edema stage accounted for 7.29%, hardening stage occupied 43.75%, and the proportion of atrophy stage reached 48.96%. When the size of shell was 1 mm, maximum elastic modulus (E max) was 0.984, mean of elastic modulus (Emean) was 0.926, and electro-static discharge (Esd) was 0.965. When the size of shell was 2 mm, the elastic moduli around lesions were as follows: Emax was 0.998, Emean was 0.968, and Esd was 0.997. By comparing the skin thickness of the abdomen, chest, and left finger, it was found that there was a significant difference between the LS group and the control group (P < 0.05). When the shell was 2 mm, the effect of sensitivity specificity on SWE imaging was better than that when the shell was 1 mm. In summary, the improved NLM algorithm showed excellent denoising effects on the ultrasonic images of LS patients. Besides, it could assist clinicians in ultrasonic imaging diagnosis for LS patients and effectively improve the diagnostic accuracy of diseases.

Rarities in rare: illuminating the microvascular and dermal status in juvenile localised scleroderma. A case series.

OBJECTIVES: To assess the (structural and functional) characteristics of the microvascular and dermal status in juvenile localised scleroderma (jLoS), using novel non-invasive standardised research tools commonly used in adult systemic sclerosis (SSc). METHODS: Ten consecutive patients with a confirmed jLoS diagnosis were studied cross-sectionally in this two-centre case series. For each patient, the most prominent lesion (i.e., "target lesion") was chosen for further examination of the centre, edge and contralateral unaffected site. High-frequency ultrasonography was used to determine dermal thickness, durometer for skin hardness, and laser speckle contrast analysis (LASCA) for a dynamical evaluation of the microcirculation. The structure of the microcirculation was evaluated at the nailfolds of the 2nd-5th finger bilaterally, using nailfold videocapillaroscopy (NVC). RESULTS: 6 linear and 4 plaque subtype jLoS lesions were included. Dermal thickness was thinner at the centre of the "target lesions" vs. the edges (p<0.001) and control sites (p<0.001). Skin hardness was harder at the centre of the "target lesions" vs. the edges (p=0.012) and control sites (p=0.003). A higher perfusion was found in the centre of the "target lesion" (124.87±66.40 PU) vs. the edges (87.27±46.40 PU; p<0.001) and control sites (67.85±37.49; p<0.001). Of note, all patients had a "non-scleroderma" pattern on NVC. CONCLUSIONS: This case series suggests the supportive value of both microcirculatory and dermal assessments of skin lesions using novel non-invasive research tools, adopted from adult SSc, for (j)LoS.

Morphea After Liposuction Ultrasonography.

Liposuction is a common aesthetic procedure; however, to date, liposuction has not been linked to morphea. The aim was to review cases with a history of liposuction that presented active morphea lesions in the same surgery regions and were confirmed by ultrasound and histology. A retrospective descriptive analysis of the clinical, ultrasonographic, and pathology database took place (2014-2020). Eleven patients met the criteria. Ultrasound supported the diagnosis, and the ultrasonographic signs of activity in these cases matched the features described in the literature in 100% of cases. In summary, morphea may appear after liposuction and ultrasound can support its early detection.

Neuroimaging findings of linear scleroderma of the head and face: a case report.

Linear scleroderma of the head and face is a rare connective tissue disorder characterized by linear depressed scarring in the frontoparietal area of the face. Here, we report a patient with linear scleroderma of the head and face with neurological symptoms such as spontaneous epilepsy and numbness of the right limb as well as the presence of white matter lesions. The patient underwent computed tomography and 3.0-T magnetic resonance examinations including diffusion weighted imaging, diffusion tensor imaging, and perfusion imaging. The imaging findings suggested a disrupted fiber tract and decreased relative cerebral blood flow. Our observation may help to improve the diagnosis and treatment of linear scleroderma of the head and face.

Usefulness of high-frequency ultrasonography in the evaluation and monitoring of sclerosing dermatoses: a cohort study.

BACKGROUND: Monitoring of disease activity in sclerosing dermatoses (SD) can be challenging and tools to support clinical decision-making are lacking. AIM: To analyse the impact of high-frequency ultrasonography (HFUS) on the clinical management of SD and to describe the US characteristics of disease activity. METHODS: This was a cohort study of patients with various SD [morphoea, systemic sclerosis (SS) and chronic graft-versus-host disease (cGvHD)] who underwent HFUS between January 2017 and August 2019. HFUS criteria for diagnosing active SD were increased Doppler vascularity and/or meeting all B-mode greyscale US signs of activity. Discordance in SD activity between HFUS and clinical examination was evaluated at the time of the first US assessment. Changes in patient management were instituted after HFUS were recorded. RESULTS: In total, 72 patients (31 with morphoea, 19 with SS and 22 with cGvHD), who underwent 163 HFUS sessions in total, were included. All HFUS-active morphoea lesions exhibited increased vascularity, and all HFUS-active SS exhibited dermal thickening and dermal hypoechogenicity. HFUS-active cGvHD displayed increased dermal thickness and loss of definition of the dermal-hypodermal junction, and there were signs of panniculitis in 80% of cases and of increased vascularity in 70%. Discordance in disease activity between clinical and HFUS evaluation was found in 17 (23.6%) patients. Changes in clinical management after HFUS were made for 14 (19.4%) patients: treatment discontinuation for 6 patients (42.9%), treatment initiation for 5 (35.7%), medication change for 2 (14.3%) and skin biopsy taken for 1 (7.1%). CONCLUSION: HFUS seems an efficacious support tool in the monitoring of SD activity with a notable impact on clinical management. Further studies are warranted to evaluate the impact of HFUS-supported management changes on SD outcomes.

Dermoscopy, confocal microscopy and optical coherence tomography features of main inflammatory and autoimmune skin diseases: A systematic review.

BACKGROUND/OBJECTIVES: Non-invasive skin imaging features of main skin inflammatory and autoimmune diseases have been reported, although a comprehensive review of their correlation with histopathologic features is currently lacking. Therefore, the aim of this paper was to review the correlation of dermoscopic, reflectance confocal microscopy (RCM) and optical coherence tomography (OCT) criteria of main inflammatory and autoimmune skin diseases with their corresponding histopathologic criteria correlation. METHODS: Studies on human subjects affected by main inflammatory and autoimmune diseases, defining the correlation of dermoscopic, RCM or OCT with histopathologic criteria, were included in the review. Five groups of diseases were identified and described: psoriasiform, spongiotic and interface dermatitis, bullous diseases and scleroderma. RESULTS: Psoriasiform dermatitis was typified by white scales, corresponding to hyperkeratosis, and vessels, observed with RCM and OCT. Spongiosis, corresponding to dark areas within the epidermis with RCM and OCT, was the main feature of spongiotic dermatitis. Interface dermatitis was characterised by dermoepidermal junction obscuration. Blisters, typical of bullous diseases, were visualised as dark areas with RCM and OCT while scleroderma lesions were characterised by dermoscopic fibrotic beams, related to dermal thickness variations, with specific OCT and histopathologic correlations. CONCLUSIONS: Although the role of RCM and OCT has yet to be defined in clinical practice, non-invasive skin imaging shows promising results on inflammatory and autoimmune skin diseases, due to the correlation with histopathologic features.

Linear scleroderma in a child with central nervous system involvement: clinical and radiological features.

Linear scleroderma is the most common type of localized scleroderma in children. Lesions rarely involve areas other than the skin, and nervous system involvement is even rare. We reported a case of a 6-year-old girl who was admitted to the hospital with recurrent seizures for 4 weeks. Before that, she had left frontal plaques for more than 1 year. Radiological imaging of the brain showed multiple abnormal lesions and skin biopsy of the plaques indicated scleroderma. After drug therapy, the girl had no recurrence of epilepsy, and no obvious abnormalities were found in the reexamination of neuroimaging. We performed further radiological examination on this patient and reviewed the literatures for this rare case.