We identified 21 localized scleroderma patients: 9 patients (A1–A9) with clinically active skin lesions, 4 patients (M10–M13) with both clinically active and inactive skin lesions, and 8 patients (I14–I21) with clinically inactive skin lesions at the time of their scan. There were a total of 32 (61.5%) ultrasound scans of active skin lesions and 20 (38.5%) scans of inactive skin lesions. All active skin lesion scans were acquired within 1 month of a clinic visit, with 25 scans acquired on the day of their clinic visit. Sixteen inactive scans were acquired within 1 month of a clinic visit, the other 4 between 31 and 44 days from a clinic visit.
Demographics and disease characteristics of patients.
Table 1 shows the study patients' demographics. There were no significant differences between active and inactive groups for sex, age at diagnosis, age at time of scan, localized scleroderma subtype, treatment, or disease duration. The disease activity state was specified by the clinician and based upon her evaluation of the appearance of the patient's lesion(s). In Table 1, inactive patients are those that only had inactive lesions at the time of the scan; the 4 patients that had both active and inactive lesions at the time of the scan (M10–M13) are listed in the active patient group. Most patients (n = 12) had linear scleroderma. At the time of their scan, 11 of the patients with active and 2 of the patients with inactive lesions had extracutaneous manifestations, most commonly musculoskeletal. Eight patients with active skin lesions had joint limitation (n = 6), arthralgia (n = 4), myalgia (n = 3), and/or arthritis (n = 2), and 9 patients had bone size differences, primarily of the extremities. Other extracutaneous manifestations in the active skin lesion group included headache (only neurologic manifestation), decreased diffusing capacity for carbon monoxide in 2 patients (1 of these also had pulmonary hypertension), stomach aches, eye pain (associated with headache), eyelash abnormalities (in patient with Parry-Romberg syndrome), and cold hands. Two of the patients with inactive skin lesions had musculoskeletal manifestations at the time of their scans, arthralgia in one and joint limitation and bony size difference in the other. Three patients with active skin lesions had laboratory abnormalities at the time of their scans (1 patient with elevated C-reactive protein level and 2 with elevated IgE). None of the patients had eosinophilia.
Table 1. Demographics and disease features of 21 juvenile localized scleroderma patients*
|Age at time of scan, mean ± SD (range) years||12.2 ± 3.7 (4.6–18)||12.0 ± 4.0 (4.6–16.80)||12.5 ± 3.5 (8.0–18)|
|Age at disease onset, mean ± SD (range) years||7.6 ± 4.0 (2.1–13.9)||7.8 ± 4.5 (2.5–13.9)||6.9 ± 3.6 (2.1–11.7)|
|Disease duration at time of scan, mean ± SD (range) years||4.6 ± 4.0 (0.42–13.5)||4.1 ± 4.3 (0.42–13.5)||5.6 ± 3.6 (0.67–12)|
|Localized scleroderma subtype|| || || |
| Linear of extremity/trunk||5||4||1|
| Linear of face/scalp||2||0||2|
| Circumscribed deep||3||2||1|
| Circumscribed superficial||3||1||2|
| Generalized morphea||2||1||1|
| Pansclerotic morphea||1||0||1|
| Mixed morphea||5||5†||0|
|Treatment at time of scan|| || || |
| Topical medications||3||1||2|
|Extracutaneous manifestations|| || || |
| Arthralgia/arthritis/joint limitation|| ||8||2|
| Myalgia|| ||3||0|
| Bone size difference|| ||9||1|
| Cardiac/pulmonary|| ||2||0|
| Eye|| ||2||0|
| Gastrointestinal|| ||3||0|
| Neurologic|| ||3||0|
| Vascular|| ||1||0|
|Laboratory abnormalities‡|| ||6||2|
| ANA positive|| ||5 of 12||2 of 6|
| RF positive|| ||1 of 3||0 of 2|
| Elevated ESR or CRP level|| ||1||0|
| Elevated Ig|| ||2||0|
For our initial evaluation of the U-DA, we evaluated only 1 lesion scan per patient, selecting the skin lesion that the clinician considered to be most active for the active group. The 13 active skin lesions, from patients A1–A9 and M10–M13, consisted of 7 linear scleroderma lesions, 5 circumscribed morphea lesions, and 1 generalized morphea lesion. The 8 inactive skin lesions, from patients I14–I21, consisted of 3 linear scleroderma lesions, 3 circumscribed morphea lesions, 1 generalized morphea lesion, and 1 pansclerotic morphea lesion.
Table 2 shows the U-DA and individual parameter scores for these lesions. Active lesions showed varying patterns of sonographic differences, with most showing both echogenicity and vascularity differences (A1–A3, A5, A6, A9, M11, M13), some showing only echogenicity differences (A7, A8, M10, M12), and 1 showing no sonographic difference (A4). Lesions also varied in the location of these differences. Echogenicity differences were either found in all tissue layers (A6, M10, M13), or one (A9) or both deeper layers (A1, A2, A7, A8, M11, M12). Hyperemia was localized to one (A2, M9, M11, M13) or both deeper tissue layers (A1, A6) (Table 2).
Table 2. U-DA and parameter scores for 21 juvenile localized scleroderma patients*
|Dermis||Hypo-dermis||Deep tissue||Dermis||Hypo-dermis||Deep tissue|
|A1||Linear scleroderma, extremity/trunk||Lower leg||0||2||1||0||1||2||6|
|A2||Circumscribed deep morphea||Thigh||0||1||1||0||0||3||5|
|A3||Circumscribed deep morphea||Face, cheek||1||2||NP||0||2||NP||5|
|A4||Circumscribed super morphea||Breast||0||0||0||0||0||0||0|
|A5||Linear scleroderma, face/scalp||Temple||1||2||NP||0||1||NP||4|
|A6||Generalized morphea||Mid back||1||2||1||0||1||1||6|
|A7||Linear scleroderma, extremity/trunk||Thigh||0||1||1||0||0||0||2|
|A8||Linear scleroderma, extremity/trunk||Forearm||0||3||2||0||0||0||5|
|A9||Linear scleroderma, extremity/trunk||Upper arm||0||1||0||0||0||2||3|
|M10||Circumscribed super morphea||Breast||1||2||2||0||0||0||5|
|M11||Linear scleroderma, extremity/trunk||Scapula||0||3||1||0||0||1||5|
|M12||Linear scleroderma, extremity/trunk||Thigh||0||2||1||0||0||0||3|
|M13||Linear scleroderma, extremity/trunk||Chest||1||1||2||0||0||1||5|
|I14||Linear scleroderma, extremity/trunk||Lower leg||0||0||0||0||0||0||0|
|I15||Circumscribed deep morphea||Forehead||0||2||0||0||0||0||2|
|I16||Linear scleroderma, face/scalp||Forehead||0||0||NP||0||0||NP||0|
|I17||Linear scleroderma, face/scalp||Forehead||1||1||NP||0||0||NP||2|
|I19||Circumscribed super morphea||Back||1||1||NP||0||2||NP||4|
|I21||Circumscribed super morphea||Foot||0||0||NP||0||0||NP||0|
The 1 clinically active A4 skin lesion with a U-DA score of 0 (A4) was classified as circumscribed superficial morphea. One of the other 3 circumscribed superficial morphea lesions also had a U-DA score of 0 (I21, inactive), while the other 2 circumscribed superficial morphea lesions had U-DA scores of 5 (M10, active) and 4 (I19, inactive). Both M10 and I19 showed sonographic differences in the hypodermis; M10 also had deep tissue layer differences.
For these 21 skin lesions, significant differences were found for mean U-DA scores between active and inactive skin lesions (P = 0.0045). The mean ± SD U-DA score was 4.15 ± 1.70 for active lesions and 1.38 ± 1.60 for inactive skin lesions (Table 3). Significant differences between active and inactive skin lesions were found for the U-DA parameters hypodermis echogenicity (P = 0.0081) and deep tissue echogenicity (P = 0.0124). Deep tissue vascularity approached significance (P = 0.0885). No significant differences were found for dermis echogenicity or vascularity (Table 3).
Table 3. U-DA scores and TTS for 2 sets of analyzed skin lesion scans*
| ||Set 1†||Set 2‡|
|Scans, no.||13||8|| ||32||20|| |
|U-DA score||4.15 ± 1.70||1.38 ± 1.60||0.0045||3.78 ± 1.83||1.85 ± 2.08||0.0010|
|Echogenicity|| || || || || || |
| Total||2.85 ± 1.46||0.75 ± 1.04||0.0042||2.66 ± 1.26||1.10 ± 1.41||0.0014|
| Dermis||0.38 ± 0.51||0.25 ± 0.46||NS||0.47 ± 0.51||0.30 ± 0.47||NS|
| Hypodermis||1.69 ± 0.85||0.50 ± 0.76||0.0081||1.44 ± 0.88||0.60 ± 0.75||0.0023|
| Deep tissue layer||1.09 ± 0.71||0 ± 0||0.0124||0.85 ± 0.66||0.40 ± 0.52||0.095|
|Vascularity|| || || || || || |
| Dermis||0 ± 0||0 ± 0||NS||0 ± 0||0 ± 0||NS|
| Hypodermis||0.38 ± 0.65||0.50 ± 0.93||NS||0.47 ± 0.72||0.70 ± 1.03||NS|
| Deep tissue layer||0.91 ± 1.04||0 ± 0||0.0885||0.78 ± 0.93||0.10 ± 0.32||0.0374|
|TTS|| || || || || || |
| Dermal||0.54 ± 0.88||−0.13 ± 0.83||NS||0.38 ± 0.83||−0.056 ± 0.94||0.0697|
| Hypodermis||1.62 ± 1.04||0.88 ± 1.64||NS||1.67 ± 0.96||1.12 ± 1.41||NS|
| Deep tissue layer||0.50 ± 2.12||1.33 ± 1.15||NS||1.14 ± 1.07||0.57 ± 1.13||NS|
We next analyzed U-DA scores for all scans acquired from these 21 patients on their acquisition date to evaluate a larger number of lesions and the variation in U-DA scores between different skin lesions from a given patient. Nine patients had scans acquired of multiple distinct lesions; 3 of circumscribed (I18, I19, I21), 4 of both linear scleroderma and circumscribed (A5, M10, M11, M13), 1 of 2 different linear scleroderma (M12), and 1 of different generalized morphea lesions (A6). Eight patients had scans acquired at 2 or more portions of a large lesion. Seven patients (A7–A9, M10–M13) had linear scleroderma involving the entire extremity. The other patient had pansclerotic morphea of the arm (I20).
Thirty-two scans of active skin lesions were acquired from 13 patients (range 1–5 per patient, median 2), with 20 scans from 9 patients considered to have only active lesions and 12 from 4 patients considered to have both active and inactive skin lesions. Twenty scans were acquired of inactive skin lesions (range 1–4 per patient, median 1), with 14 scans from 8 patients considered to have only inactive lesions and 6 from 4 patients considered to have both active and inactive skin lesions. No correlation was found between specific clinical features of activity and U-DA score, or with its parameters. The average U-DA score was 3.8 for the 16 skin lesions (50%) with erythema, 4.1 for the 16 skin lesions (50%) with warmth, 4.3 for the 7 skin lesions (21.9%) with a violaceous color, 3.3 for the 6 new skin lesions (18.8%), 4.8 for the 5 skin lesions (15.6%) with increased tissue loss, and 3.6 for the 5 skin lesions (15.6%) with induration. Three skin lesions had increased pigmentation, visible veins, or thinning; their U-DA scores were 5, 5, and 3, respectively. Fifteen skin lesions (46.9%) had 2 features, most commonly warmth and erythema (n = 10, mean ± SD U-DA score 3.5 ± 2.0), and 6 skin lesions (18.8%) had 3 features (mean ± SD U-DA score 4.8 ± 2.5).
Generally different skin lesions from a given patient had similar U-DA scores (data not shown). As was seen with the first set of scans, significant differences between active and inactive scans were found for mean U-DA scores, hypodermis echogenicity, and total echogenicity in the second set (P = 0.0010, 0.0023, and 0.0014, respectively) (Table 3). Results from these 2 sets of scans differed for mean deep tissue echogenicity and vascularity, with mean deep tissue vascularity now found significantly different, whereas mean deep tissue echogenicity was not significantly different (P = 0.0374 and P = 0.095, respectively) (Table 3).
The increased power from the larger sample size likely enabled us to find deep tissue vascularity to be significantly different in the 52-scan analysis. The failure to find a significant difference between active and inactive skin lesions for deep tissue echogenicity in the larger scan set may represent inaccurate clinical assessment of activity. None of the scans from patients that were classified as only having inactive skin lesions had increased deep tissue echogenicity, while 4 of the 5 inactive skin lesion scans from patients considered to have both active and inactive skin lesions had increased deep tissue echogenicity (data not shown). These patients are discussed further in the next section.
Patients with both active and inactive skin lesions.
Four patients (M10–M13) had scans acquired of both clinically active and inactive skin lesions on the same day (Table 4). Two patients (M10 and M12) showed the expected pattern of lower U-DA scores for skin lesions rated clinically inactive compared with those rated active. The other 2 patients (M11 and M13), however, showed similar or even higher scores in the skin lesions rated as inactive. Over ∼4 years the linear scleroderma of one patient (M11) progressed from her hand to scapula, and she developed new circumscribed morphea lesions on her face and chest. The active scapula, cheek, chin, and chest lesions had erythema, violaceous color, warmth, and/or were new or larger, and had U-DA scores ranging from 2–5 (Table 4). Her affected hand showed only chronic atrophy, but was imaged because of intermittent hand pain. Ultrasound imaging showed robust hyperemia of hypodermis and muscle layers, and increased echogenicity of all hand tissue layers (U-DA score of 9) (Table 4). Another patient (M13) had a 10-year history of linear scleroderma extending up her arm with recent extension to her anterior chest. The chest and upper arm portions of her lesion were erythematous, while the older lower portion and an older abdominal lesion showed only chronic changes. All had similar U-DA scores (5, 4, 3, and 4, respectively) (Table 4).
Table 4. Clinical features and U-DA scores from scans of 4 patients with both active and inactive skin lesions*
|Patient||Lesion location||Disease activity†||Clinical feature(s)||Total echogenicity‡||Total vascularity§||U-DA score|
|M10||Arm||I||Chronic atrophy, dyspigmentation||2||0||2|
| ||Forearm||I||Chronic atrophy, dyspigmentation||0||0||0|
| ||Scapula||A||Lesion extension, warmth||3||3||6|
| ||Back||A||Erythema, warmth||3||3||6|
| ||Breast||A||Erythema, warmth||5||0||5|
|M12||Foot||I||Dyspigmentation, moderate atrophy||0||0||0|
| ||Calf||A||Erythema, violaceous, warmth||5||4||9|
| ||Left thigh||A||Erythema, warmth||3||0||3|
| ||Right thigh||A||New lesion||3||0||3|
|M11||Hand||I||Chronic atrophy, shorter finger/hand||4||5||9|
| ||Scapula||A||Erythema, violaceous, lesion extension, warmth||4||1||5|
| ||Infraclavicular||A||New lesion, warmth||3||0||3|
| ||Cheek||A||New lesion, erythema, shinier||3||0||3|
| ||Chin||A||New lesion, violaceous||2||0||2|
|M13||Wrist||I||Chronic atrophy, dyspigmentation||3||0||3|
| ||Abdomen||I||Chronic atrophy, dyspigmentation||4||0||4|
| ||Chest||A||New lesion, erythema, warmth||4||1||5|
| ||Upper arm||A||Erythema||2||2||4|