Abstract
Objective
Few studies have looked at outcomes of adults with pediatric-onset morphea. The objective of the present study was to compare clinical outcomes and health-related quality of life in adults with pediatric-onset morphea to those of patients with adult-onset morphea.
Methods
Participants in the study were drawn from the Morphea in Adults and Children Cohort and included 68 adults with pediatric-onset morphea and 234 patients with adult-onset morphea. Outcome measures included the Localized Scleroderma Cutaneous Assessment Tool (LoSCAT), physical exam findings, and quality of life questionnaires.
Results
Adults with pediatric-onset morphea were younger, had longer disease duration, and were more likely to have the linear subtype of morphea. Patients with pediatric-onset disease were less likely to have active disease. Among patients with active disease, those with pediatric-onset morphea had less disease activity as measured by the LoSCAT. Patients with pediatric-onset disease had higher disease damage as measured by the Physician Global Assessment of Damage, but similar disease damage as measured by the Localized Scleroderma Skin Damage Index. Patients with pediatric-onset disease had more favorable quality of life scores for all measures that reached statistical significance.
Conclusion
Adults with pediatric-onset morphea differ from patients with adult-onset disease with respect to subtype, disease activity, disease damage, and health-related quality of life.
Introduction
Morphea (localized scleroderma) is an idiopathic disorder characterized by fibrosis in the skin and underlying tissues that often results in significant cosmetic and functional morbidity. Approximately one-half of patients affected by morphea have disease onset in childhood (1, 2). Current studies describe significant morbidity associated with pediatric morphea, which is predominantly of the linear subtype and may occur on the limbs, trunk, and/or head and face (1–4). Reported complications in children with morphea include loss of range of motion, joint deformity, facial disfigurement, and neurologic manifestations (2–4). However, little is known about the outcomes of pediatric-onset morphea in adulthood.
Two studies to date have sought to describe outcomes in adults with pediatric-onset morphea. Piram et al reviewed charts of 52 adults with pediatric-onset morphea and conducted a telephone survey to assess long-term disease status (5). Notably 9 of 29 patients (31%) with a disease duration of at least 10 years reported active disease (5). While the study was limited by its reliance on a telephone survey to assess disease activity, the finding of a prolonged course of disease activity is consistent with other studies showing a significant rate of disease reactivation (i.e. worsening of existing lesions or appearance of new lesions) in morphea (6–11). A previous prospective study from the current patient cohort described long-term outcomes in 27 adults with pediatric-onset morphea and found a high proportion of patients (24/27) developed new or expanding lesions over time (6). Despite these studies, little is currently known about outcomes in adults with pediatric-onset morphea, and, in particular, how they compare to outcomes in those with adult-onset morphea.
The Morphea in Adults and Children (MAC) cohort is designed to assess the clinical, demographic, and autoimmune features as well as quality of life in adults and children with morphea in a prospective manner. The data gathered at each registry visit allow for comparison of outcomes in adults with pediatric-onset morphea to outcomes in those with adult-onset morphea. The primary objective of the present study was to compare clinical outcomes in adults with pediatric-onset morphea and those with adult-onset morphea. We also compared the impact of morphea on health related quality of life (HRQoL) in patients with pediatric- and adult-onset disease.
Patients and Methods
Study Participants
Participants in this study were drawn from the MAC cohort, an Institutional Review Board approved study, which is comprised of 444 patients with morphea. Established in 2007 at the University of Texas Southwestern Medical Center, the MAC cohort is a prospective registry designed to better understand the demographic, clinical, and autoimmune features of morphea. Patients were enrolled from within the University of Texas Southwestern Medical Center system, which includes a county hospital, a faculty-based practice, and 2 dedicated pediatric care facilities. In addition, patients were recruited through referrals from pediatric and adult rheumatologists and dermatologists at the regional and national levels in an effort to enroll patients of varied disease severity, socioeconomic, and demographic backgrounds.
All patients in the MAC cohort completed a comprehensive health questionnaire which included demographic, clinical, medical, and family history data. It also contained the Self-Administered Comorbidity Questionnaire and quality of life surveys. Patient-reported findings were confirmed by interview, physical examination, and/or requisition of previous medical records. Patients were examined by a single physician with expertise in morphea (HJ), given clinical scores, and assigned subtypes according the criteria of Laxer and Zulian (12). Patients returned to clinic annually for follow-up visits when possible, at which time interval clinical data was obtained and repeat physical examinations were performed.
Blood samples were collected from patients for immunological studies of sera. Autoantibody testing for antinuclear antibodies (ANA) was performed in a single laboratory by a single investigator (Frank Arnett). The details of the methods for immunofluorescence testing for ANA are available in a prior publication (13). All patients in the MAC cohort who had a clinical registry visit at age 17 or older were included in the study. Patients were excluded if the age of morphea onset was unknown or for incomplete information. Adult-onset morphea was defined as disease onset at 17 years of age or later. Pediatric-onset morphea was defined as disease onset before 17 years of age. Data from each patient’s first registry visit as an adult was used for analysis.
Assessment of Outcomes
All patients were evaluated and assigned a clinical severity score and assessed for the presence of functional impairment, which was defined as presence of limited range of motion, contractures, and/or joint deformity due to morphea involvement. All patients in the MAC cohort are evaluated and scored by a single, experienced examiner (HJ) using predefined criteria and scoring measures. Patients were assessed for deep involvement, which was defined as involvement of the subcutaneous tissue or underlying tissues as demonstrated by biopsy or imaging.
Patients were given clinical scores using validated clinical scoring systems, including the Modified Rodnan Skin Score (mRSS) and Localized Scleroderma Cutaneous Assessment Tool (LoSCAT). At the time of the MAC cohort inception in 2007, the LoSCAT was not yet available and the mRSS was selected for clinical scoring. Since the development of the LoSCAT, patients in the MAC cohort were assessed with both the LoSCAT and the mRSS.
The LoSCAT is comprised of the modified Localized Scleroderma Skin Severity Index (mLoSSI), Physician Global Assessment of Disease Activity (PGA-A), Localized Scleroderma Skin Damage Index (LoSDI), and Physician Global Assessment of Disease Damage (PGA-D). The LoSCAT is a previously-published, reliable and valid tool for the evaluation of disease activity and damage in morphea (14–16). The mLoSSI includes the sum of 3 activity scores (erythema, peripheral induration, and new lesion/lesion extension) for 18 cutaneous anatomic sites and ranges from 0 (no activity) to 162 (high activity). The LoSDI includes the sum of 4 damage scores (dermal atrophy, subcutaneous atrophy, pigmentary alteration, and central thickness) for 18 sites and ranges from 0 (no damage) to 216 (high damage). The PGA-A and PGA-D are 100-mm analog scales, with scores ranging from 0 (no activity/damage) to 100 (high activity/damage). In contrast to the LoSDI the PGA-D takes both cutaneous and extracutaneous damage into account, including physical disability, joint contracture, bone or skeletal muscle atrophy, eye involvement, and central nervous system findings (15).
Questionnaires were used to measure HRQoL, including the Medical Outcome Study Short Form 36 (SF-36), Dermatology Life Quality Index (DLQI), and Skindex-29. The SF-36 is a general health questionnaire, while the other measures are skin-specific. Results from the SF-36 were scored using the methods provided by the publisher (17, 18). The scores for each dimension and component summary measure are normalized for gender and age to a mean of 50 with a standard deviation of 10. Lower scores represent increased disability. The Skindex-29 is comprised of 3 scales (reflecting emotion, symptom, and function) with scores ranging from 0 to 100. DLQI scores range from 0 to 30 and measure the effects of a skin problem over the previous 7 days. For both the Skindex-29 and DLQI, higher scores represent an increased effect on HRQoL. All three validated tools have been used in the study of skin diseases (19–22).
Statistics
For continuous variables, means and standard deviations were calculated and the Student t test was used for analysis. For categorical variables, total counts and percentages were calculated. The 2-tailed Fisher exact test and chi-squared tests were used for analysis. Statistical analysis was performed using GraphPad Prism software version 6.04 (GraphPad Software Inc., La Jolla, CA). P values less than 0.05 were considered significant.
Results
Demographic Characteristics
Of the 444 patients in the cohort, 302 met the inclusion criteria, including 68 with pediatric-onset morphea and 234 with adult-onset morphea. Patients were excluded for the following reasons: age less than 17 (102), unknown age of onset (5), and incomplete information on variables of interest (35). The demographic features of the patients are provided in Table 1. The age of the pediatric-onset patients was lower than the age of adult-onset patients (mean [SEM] visit age, 23.8 [1.3] vs 49.2 [1.0]; p<0.0001), as was the age of disease onset (10.8 [0.5] vs 44.8 [1.1]; p<0.0001). The duration of disease was higher in pediatric-onset patients (13.0 years [1.5] vs 4.4 years [0.4]; p<0.0001). Sex was similar in the two study groups. Race was statistically different in the two groups (p<0.0001), with a higher proportion of white and African-American patients in the adult-onset group, and a higher proportion of Hispanic patients in the pediatric-onset group.
Table 1.
Demographics; values expressed as number (%) unless otherwise specified
| Pediatric-onset | Adult-onset | P value | |
|---|---|---|---|
| Number of patients | 68 | 234 | |
| Mean visit age (SEM) | 23.8 (1.3) | 49.2 (1.0) | <0.0001 |
| Mean age of onset (SEM) | 10.8 (0.5) | 44.8 (1.1) | <0.0001 |
| Mean disease duration (SEM) | 13.0 (1.5) | 4.4 (0.4) | <0.0001 |
| Female gender | 54 (79) | 201 (86) | 0.25 |
| Race | <0.0001 | ||
| White | 43 (63) | 167 (71) | |
| Hispanic | 15 (22) | 35 (15) | |
| African-American | 1 (1) | 18 (8) | |
| Morphea subtype | <0.0001 | ||
| Linear | 55 (81) | 56 (24) | |
| Plaque | 4 (6) | 42 (18) | |
| Generalized | 5 (7) | 109 (47) | |
| SCQ, number assessed | 28 | 107 | |
| Comorbid condition | 7 (25) | 72 (67) | <0.0001 |
| Condition limiting activity | 3 (11) | 37 (35) | 0.02 |
| Treatments for Morphea1 | |||
| Systemic steroids and/or MTX | 29 (43) | 65 (28) | 0.03 |
| Phototherapy | 14 (21) | 41 (18) | 0.59 |
| Topical therapy | 49 (72) | 163 (70) | 0.76 |
Past or current use at time of visit
Pediatric- and adult-onset patients differed with regard to morphea subtype (p<0.0001). Patients with pediatric-onset morphea were more likely to have the linear subtype (81% [55/68] vs 24% [56/234]), and less likely to have the generalized subtype, plaque subtype, and other subtypes. Patients with pediatric-onset morphea were less likely to have comorbid medical conditions (25% [7/28] vs 67% [72/107]; p<0.0001), including conditions unrelated to morphea that limited their activity (11% [3/28] vs 35% [37/107]; p=0.02). The proportion of patients with positive ANAs was similar in the two groups (42% [14/33] in pediatric-onset patients vs 27% [28/104] in adult-onset patients; p=0.13), as was personal and family history of autoimmune disease.
Outcome Measures
Patients from both groups had similar mRSS scores. LoSCAT data was available for 55 patients with pediatric-onset morphea and 186 patients with adult-onset morphea. Patients with pediatric-onset morphea were less likely to have active disease, defined as a mLoSSI score greater than 0 (38% [21/55] vs 77% [144/186]; p<0.0001). Patients with pediatric-onset morphea had lower mLoSSI scores (4.2 [1.3] vs 15.6 [1.6]; p=0.0002), lower PGA-A scores (11.1 [2.5] vs 34.6 [2.3]; p<0.0001), and higher PGA-D scores (37.7 [3.3] vs 27.2 [1.5]; p=0.002). LoSDI scores were similar in the two groups (16.1 [2.0] in pediatric-onset vs 17.3 [1.2] in adult-onset; p=0.62). Functional impairment was more likely to be found in patients with pediatric-onset morphea, but the difference did not reach statistical significance (30% [21/68] vs 20% [46/232]; p=0.07). Patients with pediatric-onset disease were more likely to have deep involvement (70% [49/68] vs 45% [106/232]; p=0.0002).
Additional analysis was performed to compare patients with active disease (defined as mLoSSI scores greater than 0) separately from those with inactive disease, and results can be found in Table 3. Of the 165 patients with active disease, 139 (84%) had erythema, 140 (85%) had induration, and 115 (70%) had new lesion/lesion extension. Among patients with active disease, those with pediatric-onset disease had lower PGA-A scores (27.7 [4.7] vs 44.6 [2.4]; p=0.01) and higher PGA-D scores (47.1 [5.6] vs 28.5 [1.7]; p=0.0003). Patients with pediatric-onset morphea with active disease also had a trend toward lower mLoSSI scores, but the difference did not meet statistical significance (11.1 [2.9] vs 20.2 [1.9]; p=0.07). Among patients with inactive disease, pediatric-onset patients had a trend toward higher PGA-D scores (31.8 [3.8] vs 22.6 [3.3]; p=0.07).
Table 3.
Clinical features in patients with active morphea; values expressed as mean (SEM) unless otherwise specified
| Pediatric-onset | Adult-onset | P value | |
|---|---|---|---|
| Number of patients | 21 | 144 | |
| Visit age | 20.3 (1.0) | 49.7 (1.3) | <0.0001 |
| Age of onset | 11.9 (0.9) | 45.8 (1.4) | <0.0001 |
| Disease duration | 8.5 (1.7) | 3.9 (0.4) | 0.0005 |
| MRSS, number scored | 21 | 142 | |
| MRSS score | 6.6 (1.3) | 7.0 (0.5) | 0.81 |
| LoSCAT, number scored | 21 | 144 | |
| mLoSSI | 11.1 (2.9) | 20.2 (1.9) | 0.07 |
| LoSDI | 17.5 (3.6) | 18.5 (1.4) | 0.8 |
| PGA-A | 27.7 (4.7) | 44.6 (2.4) | 0.01 |
| PGA-D | 47.1 (5.6) | 28.5 (1.7) | 0.0003 |
| Functional impairment, n (%) | 8 (38) | 34 (24) | 0.18 |
| Deep involvement, n (%) | 15 (71) | 74 (51) | 0.1 |
A subanalysis was performed to compare clinical outcomes in patients previously treated with methotrexate (MTX) to patients who did not have prior history of MTX treatment, and results can be found in Table 4. The percentage of patients with active disease was similar in both groups (61% [22/36] of patients with previous MTX treatment vs 70% [143/205] of patients not previously treated with MTX; p=0.33), a finding that persisted when further divided into pediatric-onset disease and adult-onset disease. Patients previously treated with MTX were more likely to have functional impairment (55% [23/42] vs 17% [44/260]; p<0.0001), deep involvement (71% [30/42] vs 48% [125/260]; p=0.007), and more severe damage as assessed by both LoSDI (26.7 [3.3] vs 15.3 [1.0]; p<0.0001) and PGA-D (42.8 [4.4] vs 27.3 [1.4]; p<0.0001). Records for patients with active disease (as defined by the present study’s inclusion criteria) were reviewed to determine therapies initiated during the visit of interest. Information was available for 145 of 165 patients, and of these, 130 (90%) received treatment. Treatments included phototherapy (61 patients, 42%), MTX with or without steroids (45 patients, 31%), combined phototherapy and MTX (6 patients, 4%), topical treatments (12 patients, 8%), and other systemic therapies (6 patients, 4%). Three patients (2%) underwent further studies to determine treatment choice (magnetic resonance imaging or biopsies to determine whether inflammation was present). Twelve patients (8%) received no treatment, including 2 patients who declined phototherapy. Of patients with mLoSSI scores between 1 and 4, 21 of 32 (66%) received treatment. Treatments for this group included MTX or other systemic therapies (10 patients, 31%), phototherapy alone (6 patients, 19%), and topical treatment (5 patients, 16%). Of patients with mLoSSI scores between 5 and 25, 73 of 74 patients (99%) received treatment or underwent further studies to determine treatment choice. Treatments for this group included phototherapy alone (38 patients, 53%), MTX or other systemic therapies (27 patients, 38%), and topical treatment (6 patients, 8%). Of patients with mLoSSI scores above 25, all 39 (100%) received treatment or underwent further studies to determine treatment choice. Treatments for this group included MTX or other systemic therapies (20 patients, 51%), phototherapy alone (44%), and topical treatment (1 patient, 3%).
Table 4.
Clinical features of patients with and without past history of methotrexate (MTX) use; values expressed as mean (SEM) unless otherwise specified
| Past MTX | No past MTX | P value | |
|---|---|---|---|
| Number of patients | 42 | 260 | |
| Visit age | 37.2 (2.8) | 44.5 (1.1) | 0.02 |
| Age of onset | 29.7 (3.2) | 38.4 (1.3) | 0.02 |
| Disease duration | 7.6 (1.1) | 6.2 (0.5) | 0.32 |
| MRSS, number scored | 42 | 258 | |
| MRSS score | 9.9 (1.5) | 5.4 (0.3) | <0.0001 |
| LoSCAT, number scored | 36 | 205 | |
| mLoSSI | 17.1 (3.7) | 12.3 (1.4) | 0.18 |
| LoSDI | 26.7 (3.3) | 15.3 (1.0) | <0.0001 |
| PGA-A | 26.4 (4.6) | 29.8 (2.2) | 0.54 |
| PGA-D | 42.8 (4.4) | 27.3 (1.4) | <0.0001 |
| Active disease, n (%) | 22 (61) | 143 (70) | 0.33 |
| Functional Impairment, n (%) | 23 (55) | 44 (17) | <0.0001 |
| Deep involvement, n (%) | 30 (71) | 125 (48) | 0.007 |
Records were available for 21 of the 22 patients previously treated with MTX who had active disease at the time of the study. Nine of 21 patients (43%) were treated again with MTX. Other therapies prescribed for this group included phototherapy (6 patients, 29%), other systemic treatment (2 patients, 10%), further studies to determine treatment (2 patients, 10%), and no treatment (2 patients, 10%). Four of the 21 patients had failed previous courses of MTX according to MAC cohort protocol, which defines treatment failure as continued activity or increased activity while on therapy or within 1 month of discontinuation. Three of these patients were offered phototherapy (1 declined) and the remaining patient was treated with MTX with plans to add other systemic therapies if needed.
Quality of Life
Quality of life as measured by Skindex-29, DLQI, and SF-36 can be found in Table 5. Patients with pediatric-onset disease had more favorable HRQoL scores for all measures that reached statistical significance, including lower symptom scores as measured by the Skindex-29 (16.3 [3.5] vs 34.6 [2.4]; p=0.0003) and lower DLQI scores (4.5 [0.7] vs 6.3 [0.4]; p=0.049). They also had higher SF-36 scores for physical functioning (53.2 [1.6] vs 45.1 [1.3]; p=0.003), physical role (52.0 [1.7] vs 45.2 [1.2]; p=0.007), vitality (51.4 [2.2] vs 44.5 [1.1]; p=0.005), and physical component summary (51.7 [1.8] vs 46.2 [1.3]; p=0.043). Additional analysis was performed to separate scores in patients with active disease from those with inactive disease, and results are shown in Table 6.
Table 5.
Quality of life in patients with pediatric- and adult-onset morphea; values expressed as mean (SEM)
| Pediatric-onset | Adult-onset | P value | |
|---|---|---|---|
| Skindex-29, number scored | 29 | 110 | |
| Emotion score | 31.7 (5.3) | 37.8 (2.4) | 0.29 |
| Symptom score | 16.3 (3.5) | 34.6 (2.4) | 0.0003 |
| Function score | 12.8 (3.6) | 20.7 (2.2) | 0.09 |
| DLQI, number scored | 60 | 219 | |
| DLQI score | 4.5 (0.7) | 6.3 (0.4) | 0.049 |
| SF-36, number scored | 28 | 107 | |
| Physical | |||
| Physical functioning | 53.2 (1.6) | 45.1 (1.3) | 0.003 |
| Physical role | 52.0 (1.7) | 45.2 (1.2) | 0.007 |
| Bodily pain | 51.1 (3.3) | 48.7 (1.5) | 0.48 |
| General health | 47.9 (2.5) | 45.5 (1.0) | 0.32 |
| Mental | |||
| Vitality | 51.4 (2.2) | 44.5 (1.1) | 0.005 |
| Social functioning | 50.2 (2.0) | 45.0 (1.3) | 0.054 |
| Emotional role | 50.5 (2.0) | 45.2 (1.3) | 0.058 |
| Mental health | 50.2 (2.2) | 46.7 (1.0) | 0.13 |
| Physical component summary | 51.7 (1.8) | 46.2 (1.3) | 0.043 |
| Mental component summary | 49.6 (2.1) | 45.6 (1.1) | 0.09 |
Table 6.
Quality of life in patients with active morphea; values expressed as mean (SEM)
| Pediatric-onset | Adult-onset | P value | |
|---|---|---|---|
| Skindex-29, number scored | 10 | 77 | |
| Emotion score | 38.3 (7.2) | 40.5 (2.8) | 0.78 |
| Symptom score | 21.8 (5.5) | 39.5 (3.0) | 0.04 |
| Function score | 11.7 (5.9) | 23.5 (2.8) | 0.15 |
| DLQI, number scored | 18 | 134 | |
| DLQI score | 4.8 (1.5) | 7.3 (0.6) | 0.15 |
| SF-36, number scored | 10 | 73 | |
| Physical | |||
| Physical functioning | 53.4 (2.3) | 44.1 (1.6) | 0.04 |
| Physical role | 51.3 (2.6) | 45.2 (1.4) | 0.13 |
| Bodily pain | 55.3 (3.6) | 48.0 (1.9) | 0.17 |
| General health | 47.8 (4.7) | 44.9 (1.2) | 0.44 |
| Mental | |||
| Vitality | 52.6 (3.4) | 43.9 (1.4) | 0.03 |
| Social functioning | 49.5 (3.4) | 44.3 (1.6) | 0.25 |
| Emotional role | 49.0 (3.6) | 43.8 (1.6) | 0.26 |
| Mental health | 47.5 (3.1) | 45.1 (1.2) | 0.49 |
| Physical component summary | 53.8 (2.4) | 46.1 (1.5) | 0.07 |
| Mental component summary | 47.4 (3.4) | 44.2 (1.3) | 0.39 |
Discussion
This cross-sectional study is the largest to date examining outcomes in adults with pediatric-onset morphea and the first to include validated clinical scoring measures. Differences were found between the two patient groups with regard to subtype, disease activity and damage, and quality of life.
In agreement with previous studies, adults with pediatric-onset morphea were found to predominantly have the linear subtype (1, 3, 4). Functional impairment was found in 30% of pediatric-onset patients, in accordance with the idea that morphea often leads to permanent functional sequelae. Over a third (38%) of pediatric-onset morphea patients had active disease despite a mean disease duration of 13.0 years, consistent with findings of Piram et al (5) and our group’s prior study (6). Previous studies have shown a significant rate of disease reactivation after treatment with MTX, and in this study 61% (22/36) of patients previously treated with MTX had active disease, including 43% (6/14) of adults with pediatric-onset disease (7–11). Notably, the majority of these patients had adequate therapeutic response to their initial course of methotrexate, and thus were not considered treatment failures.
Results show patients with pediatric-onset morphea were less likely to have active disease than those with adult-onset morphea, a finding that may be explained in part by disease duration. Patients with adult-onset morphea had a mean duration of disease of 4.4 years, within the traditionally-accepted 3 to 5 year range of active disease (23). Among patients with active disease, those with pediatric-onset had less severe activity as measured by the mLoSSI and PGA-A. Given the longer duration of disease in these patients, the lower activity scores may reflect differences between initial onset and morphea relapse. It is currently unknown how relapses of morphea compare in severity to primary disease, although relapses have been subjectively reported to be mild in one study (9). It is possible that relapsing patients are able to detect new or expanding lesions earlier in the disease course and seek care appropriately. Previous treatments may also have an effect on the severity of disease recurrences.
In comparison to patients with adult-onset morphea, patients with pediatric-onset morphea had higher disease damage as measured by PGA-D scores, while LoSDI scores were similar. This discrepancy in scores may be explained by the difference in the two scoring measures. In addition to cutaneous damage, the PGA-D reflects extracutaneous manifestations of morphea, such as physical disability, joint contracture, limb-length discrepancy, deep involvement (atrophy of skeletal muscle or bone), and central nervous system symptoms (15). In our study, two measures correspond to extracutaneous damage—functional impairment (defined as limited range of motion, joint contracture, and/or joint deformity) and deep involvement. In patients with pediatric-onset disease, we observed a trend toward more functional impairment as well as a significantly higher proportion of deep involvement, which is consistent with the increased PGA-D score in this group. The findings of this study suggest patients with pediatric-onset morphea have similar cutaneous damage to adult-onset patients, but increased extracutaneous damage when compared to those with adult-onset morphea. This is consistent with previous studies that have reported extracutaneous manifestations of morphea in children–particularly in those with the linear subtype (2, 4). Despite the presence of increased disease damage, patients with pediatric-onset morphea had more favorable quality of life scores than patients with adult-onset disease. As measured by the SF-36, adults with pediatric-onset disease had similar HRQoL to the age- and gender-matched general population in the United States (24). This finding contrasts with studies of adults with pediatric-onset disease in several other rheumatologic conditions, in which overall HRQoL is negatively impacted in at least some dimensions (25–27). Previous studies have shown that children with morphea have a normal self-worth and at most a moderate impairment in quality of life and physical function, and it appears that the relatively preserved overall HRQoL persists into adulthood (28–30).
In contrast to those with pediatric-onset disease, adult-onset patients had poorer HRQoL as measured by the SF-36 when compared the general population (24). Patients with adult-onset disease had SF-36 component summary scores similar to those seen in other dermatologic conditions, including psoriasis, atopic dermatitis, and hand eczema (22, 31). Compared to pediatric-onset patients, adult-onset patients were more affected by disease-related symptoms (such as itch and pain) as measured by the Skindex-29, and had less favorable skin-specific HRQoL as measured by the DLQI. These findings are consistent with a previous study from the current cohort, which demonstrated that increased symptoms and mLoSSI scores had a negative impact on DLQI in adults (32). Adult-onset patients had a significantly higher comorbid disease burden (non morphea-related) than pediatric-onset patients, a finding likely due to the difference in ages between the groups, which might also contribute to the greater impact on life quality observed in adults.
To our knowledge, no studies to date have sought to determine the clinical significance of the magnitude of the mLoSSI and/or PGA-A scores. In our retrospective chart review of patients with active disease, we found that 11 of 32 patients (34%) with mLoSSI scores between 1 and 4 received no treatment, while nearly all patients with mLoSSI scores greater than 4 received treatment or underwent further studies (132 of 133, 99%). The type of treatment also varied by score, as patients with scores between 5 and 24 most commonly received phototherapy alone and patients with scores over 25 most commonly received MTX with or without systemic steroids. This suggests that patients with low mLoSSI scores (<4) may not have clinically significant disease despite placement in the active disease category for purposes of this study, while patients with scores greater than 25 may indicate greater clinical severity as determined by use of systemic immunosuppressants. It may be useful for future studies to determine what mLoSSI and PGA-A scores correspond to mild, moderate, and severe disease. Patients previously treated with MTX were found to have higher damage scores as measured by the LoSDI and PGA-D than patients without a past history of MTX use, and were also found to have a higher proportion of deep involvement. These results are likely due to confounding by indication—patients with more severe disease were more likely to be treated with MTX.
Limitations of the study include its cross-sectional design, which did not allow for longitudinal follow-up in patients to evaluate progression of disease. Although this is the largest study to date of adults with pediatric-onset disease, patient numbers were small, particularly when divided into subgroups. This limited analysis in some cases. Results of the study have several implications for practice. Many patients with pediatric-onset morphea will experience active disease into adulthood. Patients should have regular follow-up into adulthood and be counseled appropriately to self-monitor for disease reactivation. Patients with morphea onset in adulthood may have increased severity of disease, including impairment due to symptoms of their skin lesions. These aspects should be considered when deciding on optimal treatment.
Table 2.
Clinical features of patients with pediatric- and adult-onset morphea; values expressed as mean (SEM) unless otherwise specified
| Pediatric-onset | Adult-onset | P value | |
|---|---|---|---|
| MRSS, number scored | 68 | 232 | |
| MRSS score | 5.2 (0.6) | 6.3 (0.4) | 0.2 |
| LoSCAT, number scored | 55 | 186 | |
| mLoSSI | 4.2 (1.3) | 15.6 (1.6) | 0.0002 |
| LoSDI | 16.1 (2.0) | 17.3 (1.2) | 0.62 |
| PGA-A | 11.1 (2.5) | 34.6 (2.3) | <0.0001 |
| PGA-D | 37.7 (3.3) | 27.2 (1.5) | 0.002 |
| Active disease, n (%) | 21 (38) | 144 (77) | <0.0001 |
| Functional impairment, n (%) | 21 (30) | 46 (20) | 0.07 |
| Deep involvement, n (%) | 49 (70) | 106 (45) | 0.0002 |
Acknowledgments
Grants/Financial Support:
Research for this manuscript was supported in part by NIH Grant No. K23AR056303-5.
This work was conducted with support from UT-STAR, NIH/NCRR/NCATS Grant Number UL1TR000451. The content is solely the responsibility of the authors and does not necessarily represent the official views of UT-STAR, The University of Texas Southwestern Medical Center at Dallas and its affiliated academic and health care centers, the National Center for Research Resources, or the National Institutes of Health.
Footnotes
Conflicts of Interest: None
Contributor Information
Daniel Condie, Email: daniel.condie@utsouthwestern.edu.
Daniel Grabell, Email: daniel.grabell@utsouthwestern.edu.
Heidi Jacobe, Email: heidi.jacobe@utsouthwestern.edu.
References
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