14-MHz Ultrasonography as an Outcome Measure in Morphea (Localized Scleroderma) FREE

The determination of therapeutic efficacy in morphea (aka, localized scleroderma) is difficult owing to a lack of validated outcome measures.^1- 2 Outside of the United States, 20- to 25-MHz ultrasonography has demonstrated its validity, reproducibility, and responsiveness to change.³ Preliminary studies on the lower-frequency ultrasonography available in the United States (10-15 MHz) demonstrate that it may have similar attributes.^4- 6 However, studies correlating ultrasonographic findings with lesion stage (inflammatory, sclerotic, or atrophic), clinical scoring systems, or histologic traits have not been conducted.

We identified 14 patients with 16 morphea lesions (Table) from the University of Texas Southwestern Medical Center Morphea Registry and DNA repository. Each patient and lesion was assessed for morphea subtype and clinical stage and was assigned a Modified Rodnan Skin Score (mRSS) by a single board-certified dermatologist (H.T.J.).

A single site for ultrasonography and biopsy, as well as a control site, was chosen by the dermatologist and marked with a surgical pen. Ultrasonographic examination was performed by 2 radiologists blinded to the results of the clinical assessment of each patient. Each lesion had dermal thickness measured and echogenicity determined as compared with site-matched, unaffected skin (hypoechogenic, isoechogenic, and hyperechogenic) (Figure 1 and Figure 2).

One board-certified dermatopathologist (J.S.S.), blinded to both clinical and sonographic data, graded each specimen for inflammation, edema, and sclerosis using a previously published scoring system⁷ and calculated dermal thickness.

To examine the correlation between ultrasonographic finding and clinical stage, mRSS, dermal thickness, and grade of fibrosis, the Fisher exact test was used. To examine the correlation between thickness on ultrasonography and histologic findings, the Spearman correlation coefficient was used. The intrarater correlation and interrater correlation of ultrasonographic measurements was analyzed using the intraclass correlation coefficient.

Prior studies identified assessment of disease stage as important features in the evaluation and treatment of morphea.⁸ Ultrasonography was able to reliably differentiate between the clinical stages of morphea. A significant number of inflammatory lesions were isoechogenic (5 of 6) (P  =  .04). Most sclerotic lesions were hyperechogenic (5 of 6) (P  =  .01). Atrophy appeared on ultrasonography as hypoechogenicity in 2 of 3 lesions that were deemed to be atrophic on the clinical examination (P  =  .03) (Figure 3A).

No significant relationship was found between mRSS and ultrasonography findings of echogenicity or dermal depth measurement (P  =  .60 and P  =  .40, respectively).

Ultrasonography measurements of dermal thickness were reproducible by a single clinician and between clinicians (intrarater and interrater correlation, 0.99 and 0.97, respectively).

Ultrasonography findings were compared with the putative gold standard for evaluation of morphea, histologic analysis. Hyperechogenicity on ultrasonography was significantly associated (P  =  .04) with grades of moderate or extensive sclerosis on dermatopathologic examination (Figure 3B). There was not a significant relationship between the depth of sclerosis as measured by ultrasonography and histologic analysis (R  =  0.75; P  =  .33).

The high validity and reliability demonstrated by 14-MHz ultrasonography in this study indicates it might be a useful outcome measure. Fourteen-MHz ultrasonography could differentiate between all the clinical stages of disease. It could also differentiate active disease, which appeared hyperechoic (sclerosis) or isoechoic (inflammation), from atrophy or damage, which appeared hypoechoic. We also found that ultrasonography demonstrated a significant correlation between the amount of sclerosis on histologic examination and degree of echogenicity.

There was no significant association between mRSS and echogenicity or dermal depth on ultrasonography. This discrepancy highlights the inadequacy of the mRSS, which relies solely on the investigator's ability to pinch or move skin.

As in prior studies, the measurements obtained by 14-MHz ultrasonography demonstrated extremely high reliability. Both the intrarater and interrater reliability of ultrasonography exceeded the reliability of existing clinical sclerosis scores.^9- 10

The main limitation of this study was the small number of patients included and the smaller number of lesions with suitable, full-thickness biopsies. Depth of disease is important for selection of therapy. Biopsies, which are both invasive and unreliable in their ability to assess the depth of sclerosis, are not always helpful. Fourteen-MHz ultrasonography, which penetrates up to 40 mm, may be a useful, noninvasive tool to investigate the depth of involvement beyond the dermis. Fourteen-MHz ultrasonography is likely better suited than 20-MHz for this function owing to its deeper penetration.

The value of ultrasonography as an outcome measure will depend on its ability to demonstrate that it can detect changes in lesions over time. If ultrasonography assessment is found to distinguish longitudinal changes in plaque sclerosis and depth, it could be a very valuable tool in following up entire cohorts of patients in a clinical trial, or it could give the clinical dermatologist a follow-up tool for individual patients with morphea.