Morphea In Inflammation: Highest And Lowest Dermal Readings
Overview
To date, there are no standardized outcome measures for monitoring morphea, and establishing consensus on specific monitoring criteria has been challenging. Few studies have evaluated the criterion validity of skin ultrasound in morphea. This study aims to investigate ultrasound findings in morphea lesions.
This retrospective-analytical study was conducted from December 2021 to May 2023. Patients were evaluated at a dermatology outpatient clinic and referred for high-frequency ultrasound (HF-US) evaluation. The study included patients with lesions confirmed by histopathology. Sonographic assessments were performed on both the lesion site and the symmetrical uninvolved side, recording dermal thickness and echogenicity. Group differences were analyzed using the 2-tailed Student t-test, with a p-value of less than 0.05 considered statistically significant.
The study included 41 morphea lesions in the inflammatory phase from 27 patients. The mean dermal thickness of the morphea lesions was 1107.97 ± 414.3, while the control side measured 1094.65 ± 331.06. The difference in dermal thickness between the two groups was not statistically significant. The mean dermal density of the lesions was 49.13 ± 18.97, compared to 52.22 ± 25.33 on the control side. This difference in dermal density was also not statistically significant.
This study indicates that HF-US shows an increase in dermal thickness and a decrease in dermal density in morphea lesions during the inflammatory phase, as confirmed by histopathology.
Introduction
Morphea, also known as localized scleroderma, is a chronic autoimmune condition marked by inflammation and fibrosis of the skin and subcutaneous tissues. It is associated with significant morbidity, disability, and disfigurement. Early diagnosis and thorough assessment of disease activity can enhance outcomes for patients. Clinical examinations and imaging techniques are essential in evaluating morphea.
Clinical scoring tools are commonly used to assess skin lesions in morphea. One such tool is the Modified Rodnan Skin Score (mRSS), which evaluates skin thickening across various anatomic areas. However, mRSS has not been validated specifically for morphea. The Localized Scleroderma Cutaneous Assessment Tool (LoSCAT) is a more promising method, measuring both disease activity and skin damage.
LoSCAT scores parameters such as erythema, skin thickness, lesion extension, dermal atrophy, subcutaneous atrophy, and dyspigmentation. While clinical signs are crucial for diagnosing morphea, the clinical exam alone may not fully evaluate the deep dermis due to the inflammatory processes occurring there. Thus, imaging modalities are increasingly used alongside clinical exams for a comprehensive assessment of morphea.
Various imaging tools have been used to evaluate morphea, including shear-wave elastography (SWE) for assessing tissue stiffness, MRI for monitoring deep muscle inflammation, and high-frequency ultrasonography (HF-US) for examining superficial to intermediate tissue layers. HF-US, in particular, is accessible, relatively inexpensive, and noninvasive. The DUB Skin Scanner, a high-frequency and high-resolution ultrasound system, is widely used for non-invasive skin analysis, with the 22 MHz DUB skin scanner being a prevalent method.
Despite the reliability of these imaging modalities in diagnosing and monitoring morphea lesions, there is still no consensus on specific monitoring criteria. Additionally, few studies have assessed the criterion validity of HF-US in morphea. This study aims to determine the validity and reliability of findings obtained from the 22 MHz DUB skin scanner in patients with morphea.
Method
This retrospective-analytical study was carried out at the Center for Research and Training in Skin Disease and Leprosy (Tehran University of Medical Sciences) between December 2021 and May 2023. Patients were first clinically assessed at a dermatology outpatient clinic before being referred for high-frequency ultrasound (HF-US) evaluation. Only those whose lesions were confirmed by histopathology were included in the study. The CRTSDL institutional review board approved the study in accordance with the Declaration of Helsinki.
The study focused on morphea lesions exhibiting characteristics indicative of the inflammatory phase of the disease. Specifically, it included lesions that were recently formed, representing primary cutaneous morphea, characterized by an erythematous and slightly edematous appearance.
Morphea lesions were initially examined to determine if they were solitary or multiple. Sonographic evaluations were conducted on both the morphea lesion and the symmetrical uninvolved skin. The most recent and active plaques were selected for evaluation. Measurements of dermal thickness and dermal echogenicity were taken. The involvement of deeper structures within the lesional area was also assessed, limited by the probe’s depth of view.
A 22 MHz DUB skin scanner (tpm Company, Germany) was used to measure dermal thickness and echogenicity, comparing the lesional skin to its symmetrical uninvolved counterpart. The scanner has a penetration depth of up to 8 mm and a maximum axial resolution of 72 μm, with a scan width of 12.8 mm linear (approximately 33 μm step width). Water was used as a coupling medium between the transducer and the skin surface, and the ultrasound probe was held perpendicular to the skin to avoid compression.
In the HF-US images, the entire dermis was visible, with its lower boundary marked by a dark, hypo-reflective layer. The physician recorded the type and location of the disease, categorizing the lesion locations into head and neck, upper limb, lower limb, and trunk. Types of morphea were classified into linear, plaque, and generalized.
Inclusion Criteria
Inclusion criteria for the study were: (a) a clinical diagnosis of morphea; (b) ultrasonography of both the lesional and symmetrical uninvolved skin on the opposite side; and (c) histological confirmation of the diagnosis.
Exclusion Criteria
Exclusion criteria were: (a) a recent history of any other significant skin diseases in the evaluated areas; (b) any operations in the assessed regions; (c) use of any systemic or topical treatment for skin disease in the previous two weeks; (d) any systemic disease that could affect skin status; and (e) HF-US evaluation performed more than one month after clinical examination.
Statistical Analysis
Data analysis was conducted using IBM SPSS Statistics 24 (SPSS Inc., Chicago, IL, USA). Group differences were statistically analyzed using the two-tailed Student’s t-test, with a threshold for statistical significance set at p < 0.05.
Result
The study analyzed 41 morphea lesions in 27 patients, consisting of 4 men and 23 women, with a mean age of 25.87 ± 15.13 years, ranging from 5 to 60 years. Detailed information about the types and locations of the morphea lesions is presented in Table 1 of the study.
The research focused on comparing dermal thickness and dermal density between morphea-affected skin and healthy control skin. The average dermal thickness in morphea lesions was found to be 1107.97 ± 414.3, while the control side had an average dermal thickness of 1094.65 ± 331.06. The difference in dermal thickness between the morphea lesions and the control skin was not statistically significant, with a p-value greater than 0.05, indicating that the thickness of the skin was relatively similar in both the affected and unaffected areas.
Similarly, the study measured dermal density in both the morphea lesions and the control skin. The mean dermal density in the morphea lesions was 49.13 ± 18.97, compared to 52.22 ± 25.33 in the control side. Again, the difference between these measurements was not statistically significant (p-value > 0.05), suggesting that the density of the skin in the morphea lesions did not differ significantly from that of the healthy skin.
Overall, the study concluded that there were no significant differences in dermal thickness or density between morphea-affected skin and healthy control skin in the patients examined. This finding suggests that, in this sample, morphea lesions did not significantly alter the structural properties of the skin compared to unaffected areas.
Conclusion
This study observed an increase in dermal thickness and a decrease in dermal density in morphea lesions during the inflammatory phase. This aligns with Ranosz-Janicka et al.’s findings, which used high-frequency ultrasound (HF-US) on 92 morphea lesions and noted similar changes. This indicates HF-US’s effectiveness in precisely assessing inflammation in localized scleroderma. Our study also found that morphea lesions in the inflammatory stage appeared hypoechogenic, a result consistent with Shan Zhang et al.’s research on 34 lesions. This supports the utility of HF-US in staging morphea.
In 2019, Arisi et al. also demonstrated a decrease in dermal density and an increase in dermal thickness in morphea lesions using HF-US. More recent research has shown that increased disease activity correlates with heightened cutaneous blood flow and subcutaneous tissue hyperechogenicity, though our study could not assess these characteristics. Nevertheless, dermal thickening and reduced echogenicity were sensitive indicators of disease activity, consistent with our findings.
Although our study noted an increase in dermal thickness and a decrease in dermal density in morphea lesions compared to control sites, these findings were not statistically significant. This may be due to unaccounted effects of lesion and non-lesion locations on dermal thickness and a limited sample size.
Higher ultrasound frequencies offer better resolution but decreased tissue penetration. Guidelines recommend using probes with frequencies between 15 and 30 MHz for dermatologic ultrasound studies. Our study used a 22 MHz frequency, which provided an optimal balance between resolution and measurement depth for morphea assessment. The 22 MHz DUB skin scanner is recognized for its noninvasive, high-resolution ultrasonography, offering superior spatial resolution compared to other methods like MRI, which remains the gold standard for evaluating subcutaneous tissue in generalized and deep morphea.
The Clarius L20 HD3 Ultra-High Frequency Linear Scanner, with a frequency of 20 MHz and a depth of up to 4 mm, features Doppler mode, advanced specialty software, iCloud storage, telemedicine capabilities, and compatibility with iOS and Android. However, the 22 MHz DUB skin scanner is preferred for initial imaging in morphea due to its comprehensive capabilities.
Assessing dermal thickness and echogenicity lacks absolute standards, and finding reproducible sites for evaluating morphea is challenging. Comparing lesions to clear sites can enhance sensitivity and reproducibility, a methodology incorporated in our study. However, our study’s limitations include a focus on inflammatory-phase lesions, leading to selection bias, exclusion of lesion locations from statistical analysis, and a small sample size, which may affect the results’ power.
Overall, this study demonstrates that high-frequency ultrasound monitoring reveals increased dermal thickness and reduced dermal density in morphea lesions during the inflammatory phase, confirmed by histopathological methods. HF-US provides valuable information for assessing morphea disease.