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Table 5 Patient-reported outcome measures utilized in patients with RDEB

From: A systematic literature review of the disease burden in patients with recessive dystrophic epidermolysis bullosa

PROM Brief description Study, country Patients w RDEB (n) Results
Dermatology-specific instruments
QOLEB First disease-specific QOL tool for EB
17 items with scores ranging from 0 (least impact) to 3 (most impact)
Overall QOL scores range from 0 to 51
Lower values indicate better function/higher QOL
Cestari [69], Brazil 13 (child)
6 (adult)
Children with RDEB reported lowest overall QOL (14.3 [SD, 9.7]) followed by EBS (10.6 [7.1]), DDEB (9.7 [7.9]), and JEB (5.0 [NA]); non-significant difference
Adults with RDEB (20.2 [9.2]) reported lowest overall QOL followed by EBS (12.5 [10.0]), DDEB (12.0 [5.8]), and JEB (2.0 [NA]); non-significant difference
Choi [61], US 32 Patients reported frequent or constant pain (69%) and a high or severe level of psychological and social impact on finances (50%), friendships (41%), anxiety (41%), depression (31%), family (22%), and embarrassment (16%)
Patients reported severely impaired function in eating (63%), bathing (53%), moving outside the home (38%), writing (28%), and moving around the home (22%)
Eismann [70], US 32 Children with RDEB reported lowest overall QOL (23 [IQR, 13–27]) followed by JEB (21 [13–26]), EBS (19 [5–30]), and DDEB (13 [6–18]); significance not measured
Items associated with the worst QOL (score ≥ 2) include bathing/showing (2.45 [SD, 2.45]), sports (2.45 [0.68]), physical pain (2.06 [0.95]), and eating (2.06 [0.95])
Eng [54], International 81 QOLEB score in patients with RDEB did not vary significantly by patient-reported disease severity (mild [mean, 19, SD, 3.4], moderate [7, 20], severe [6, 24]); p = 0.36
QOLEB score significantly differed by the size of patients’ predominant wounds; patients with large wounds (> 7.5 cm) had worse QOL (median score, 27) than patients with medium wounds (2.5–7.5 cm; median score, 22.5) or small wounds (< 2.5 cm; median score, 14); p = 0.02
Frew [71], Australia 16 Patients with RDEB reported worst overall QOL (35.5 [SD, 12.7]) followed by JEB (31.5 [17.6]), DDEB (18.1 [10.9]), and EBS (13.7 [8.7]); significance not reported
Jeon [59], South Korea 13 Patients with severe subtype of RDEB (N = 7) reported worse overall QOL (30.1 [SD, 8.8]) than those with intermediate (N = 6; 23.2 [3.8]); non-significant difference
Patients with very severe perceived disease (N = 11) reported lower overall QOL (28 [7.8]) than those with severe perceived disease (N = 2; 21 [NA]); p < 0.05
Patients with RDEB hospitalized for > 7 days (N = 5) in the past year reported lowest overall QOL (29.8 [8.7]) compared to patients hospitalized 1–6 days (N = 1; 25 [NA]) or 0 days (N = 7; 25.14 [7.35]); non-significant difference
iscorEB Comprised of clinical score (5 domains) and patient score (7 domains)
Scores range from 0–120
Designed to capture changes over time
Higher score indicates worse burden
Bruckner [68], US 16 Mean clinical and patient scores significantly higher in patients with RDEB (clinical, 19.9; patient, 41.0) than other subtypes of EB (clinical, 3.2; patient, 24.7) p < 0.0001 (clinical difference) and p = 0.004 (patient difference)
Schwieger-Briel [72],
Canada
NR Patients with severe subtypes of EB significantly lower QOL (64.5 [SD, 22.6]) than those with moderate (41.0 [19.4]) or mild subtypes (17.3 [9.6]); p < 0.001
Patients with DEB report significantly lower QOL (57.2 [24.6]) than patients with EB (30.6 [19.2]); p = 0.007
Birmingham EB Severity score Method of scoring clinical severity
Scores range from 0–100
Higher score indicates worse burden
Moss [74], UK 34 Patients with the severe subtype of RDEB had higher median score (22.9 [range, 2.8–27.8]) than those with non-severe subtype (7.8 [2.8–27.8])
Scores in the severe subtype of RDEB were significantly associated with age (demonstrating disease progression); p = 0.001
FDLQI Measures adverse impact of HRQOL on family members with disease
10 questions on 4-point scale
Scores range from 0–30, higher score indicates worse QOL
Not specific to EB
Sampogna [47], Italy 62 QOL was significantly worse in patients with severe disease (14.3) or moderate disease (11.4) than mild disease (3.4); p < 0.001
QOL was significantly worse in patients with > 30% of their body involved (14.4) and 10–30% involved (10.9) than < 10% involved (6.3); p = 0.003
QOL was significantly worse in caregivers who were mothers (10.6) than non-mother caregivers (5.4); p = 0.025
QOL was significantly worse in patients with probable anxiety or depression (measured via GHQ-12; 13.9) than in those without (8.2); p = 0.003
QOL was similar between male (9.4) and female sex (10.1); non-significant difference
QOL was slightly worse in patients with a disease duration of 10 years or more (10.9) compared to a duration of less than 10 years (7.7); non-significant difference
Most frequently reported problems include time spent looking after the patient, emotional distress, affected physical well-being, and increased household expenditure (exact frequencies not reported)
InToDermQOL Parent-reported measure for children with skin diseases aged 0–4 years
Undergoing item testing and validation
Not specific to EB
Chernyshov [19], Ukraine and Romania 12 Over half of parents of infants and toddlers with RDEB mentioned itching (12/12 [100%]), problems with defecation (11/12 [92%]), problems with feeding (9/12 [75%]), pain (8/12 [67%]), sleep problems (7/12 [58%]), and treatment (7/12 [58%]),
Skindex-29 29 items comprising 3 scales (symptom, functioning, emotional burden)
Scores range from 0–100
Higher scores indicate worse QOL
Not specific to EB
Jeon (59),
South Korea
13 Patients with RDEB had the highest symptom scale score (86 [SD, 10]; Fig. 2b) compared to patients with vulvodynia (50 [17]), eczema (48 [23]), dermatomyositis (42 [25]), psoriasis (42 [21]), rosacea (33 [20]), alopecia (31 [24]), and acne vulgaris (30 [19]) as well as people without skin disease (14 [2]); significance not reported
Patients with RDEB had the highest emotion scale score (75 [16]; Fig. 2b) compared to patients with vulvodynia (50 [20]), dermatomyositis (45 [27]), eczema (41 [27]), acne vulgaris (41 [25]), psoriasis (39 [27]), rosacea (33 [20]), and alopecia (27 [33]) as well as people without skin disease (9 [13]); significance not reported
Patients with RDEB had the highest function scale score (77 [12]; Fig. 2b) compared to patients with vulvodynia (44 [22]), dermatomyositis (28 [29]), eczema (26 [26]), psoriasis (23 [27]), acne vulgaris (16 [16]), rosacea (16 [18]), and alopecia (14 [23]) as well as people without skin disease (4 [8]); significance not reported
Generic instruments
Instruments measuring physical functioning
 ABILIHAND Individual item scores range from 0 (impossible) to 2 (easy)
Overall hand function score ranges from 0 to 42
Higher score indicates better hand function
Eismann [70],
US
32 Difficult to impossible items (score ≤ 1) for children with RDEB included opening a jar of jam (0.17 [SD, 0.38]), buttoning up pants (0.43 [0.57]), opening a bag of chips (0.43 [0.63]), buttoning up a shirt or sweater (0.45 [0.57]), unscrewing a bottle cap (0.50 [0.72]), fastening the snap of a jacket (0.77 [0.63]), zipping up pants (0.90 [0.76]), switching on a bedside lamp (0.93 [0.74]), zipping up a jacket (0.97 [0.65]), sharpening a pencil (0.97 [0.78], rolling up a sleeve of a sweater (0.97 [0.82])
Children with RDEB reported lowest hand function (21 [IQR, 17–29]), followed by EBS (28 [21–36]; p = 0.031), JEB (30 [22–37]; p = 0.014), then DDEB (40 [36–42]; p < 0.001)
 ADLs First application in skin diseases
109 items
Rates levels of independence in performing activities of daily living
Fine [58], US 45 Children with RDEB reported being totally dependent at bathing (27%), grooming (20%), dressing (13%), and walking (13%)
Children with RDEB reported being totally independent at feeding (73%), toileting (71%), bathing (47%), dressing (42%), grooming (42%), and walking (24%)
Children with RDEB reported high levels of dependence in bathing (27% totally dependent), grooming (20%), dressing (13%), and walking (13%), similar to children with DEB (bathing, 27%; grooming, 19%; dressing, 15%; walking, 8%); significance not reported
Children with DEB and EBS reported low levels of dependence (DDEB, 0% throughout; EBS, 2% totally dependent in bathing, grooming and walking)
Instruments measuring performance and mental health
 Achenbach’s Child Behavior Checklist Parent-reported measure
T-scores for respective sex/age group available (50 being normal)
Feldmann [24], Germany 9a Parents of children with RDEB severe subtype and children with other subtypes of EBS (including RDEB intermediate) reported no significant differences between groups in total competence score (38.3 [SD, 14.3] vs. 43.3 [7.8]), internalizing (62.4 [8.9] vs. 57.1 [15.1]), externalizing (49.9 [7.7] vs. 56.9 [10.3]), and total problem score (59.3 [8.8] vs. 58.8 [12.5]); non-significant difference
All scores were in the normal range
 GHQ-12 12-items
Designed to detect presence of minor non-psychotic psychiatric disorders
Sampogna [47], Italy 62 QOL was significantly worse in patients with probable anxiety or depression (measured via GHQ-12; 13.9) than in those without (8.2); 0.003
 Graphic tests Projective test designed to measure personality Andreoli [67], Italy 11 When measuring intellectual development, all children with RDEB were labeled normal (18%) or above normal (82%) intellectual development. All children with EBS, JEB and DDEB were labeled as above normal; significance not reported
When measuring affective development, a higher proportion of children with RDEB were labeled with immaturity (46%) than maturity (36%) or forced growth (18%). All patients with EBS and DEDB and 80% of patients with JEB were labeled as mature; significance not reported
When measuring scholastic/working efficiency, a higher proportion of children with RDEB were labeled as adequate or high (73%) than inadequate (27%). All patients with EBS, JEB and DDEB were labeled as adequate or high; significance not reported
When measuring drive display, a higher proportion of children with RDEB were labeled as adequate (64%) than coarctate (18%) or excessive (18%). All patients with DDEB, 80% of patients with JEB, and 33% of patients with EBS were labeled as adequate; significance not reported
When measuring psychosocial development, a higher proportion of children with RDED were labeled with accommodating adjustment (46%) or assimilative adjustment (36%) than reported maladjustment (18%). All patients with EBS and DDEB and 80% of patients with JEB were labeled as accommodating or assimilative adjustment; significance not reported
 Strengths and difficulties questionnaire Completed by caregiver
Includes 6 subscales and combined total difficulties scale
Soon [73], UK 18 Parents reported higher proportion of children with RDEB than children with EBS scored in clinical range for emotional symptoms (66% vs. 50%) and peer-relationship problems (50% vs. 40%); significance not reported
Children with RDEB 2–3 × more likely to have clinically significant difficulties in these areas than a non-RDEB population
 Wechsler Intelligence Scale Separate scales for children and adults Feldmann [24], Germany 9a Children with the RDEB severe subtype reported significantly lower performance (75.6 [SD, 18.1] vs. 99.2 [14.7]), verbal (77.6 [16.7] vs. 101.6 [9.4]) and full scale scores (74.3 [18.0] vs. 100.6 [12.5]) than patients with other subtypes of EB (including RDEB intermediate subtype); p < 0.05
Instruments measuring pain and itch
 Pain and pruritus scalesb Measured on a scale of 1 to 10 with higher scores indicating higher/more frequent pain or itch Bruckner [53],
US
19 (patient)
34 (caregiver)
Patients with RDEB reported higher acute pain (5.6 [SD NR]) than patients with DDEB (4.4), JEB (4.4), or EBS subtypes (4.3); significance not reported
Patients with RDEB reported similar chronic pain (5.3) to patients with JEB (5.3) and higher chronic pain than patients with DDEB (4.6) or EBS (3.2); significance not reported
Patients with RDEB reported similar levels of itch (6.7) to patients with JEB (6.5) and higher levels of itch than patients with DDEB (5.5) or EBS (4.4); significance not reported
Caregivers reported their patients with RDEB had similar levels of acute pain (6.4) to patients with JEB (6.3) and higher levels of acute pain than patients with EBS (5.3) or DEB (5.0); significance not reported
Caregivers reported their patients with RDEB had similar levels of chronic pain (4.2) to patients with JEB (4.0) and higher levels of chronic pain than patients with EBS (3.6) or DDEB (3.4); significance not reported
Caregivers reported their patients with RDEB had higher levels of itch (7.2) than patients with EBS (4.4), DDEB, (4.3), and JEB (4.0); significance not reported
Measured on a 5-point Likert scale with higher scores indicating more frequent itch Danial [57] 77 When asked frequency of itch per day, patients with RDEB reported the highest scores (3.9 [SD, 0.8]) compared to patients with JEB (3.6 [0.8]), DDEB (3.5 [1.2]), and significantly higher than EBS (3.1 [1.0]); p = 0.01
Patients with RDEB reported highest itch at bedtime (4.0 [NR])
Itch was the most bothersome symptom of EB (3.3 [1.1]), compared to acute pain (2.9 [1.3]), chronic pain (2.7 [1.5]), and problems eating (2.7 [1.4])
Itch was more bothersome in RDEB patients (3.5) than DDEB (3.1) and EBS (2.7)
Itch was most severe in patients with self-reported severe disease (4.0 [0.8]), compared with moderate EB (3.8 [0.9]), and mild EB (3.2 [1.0])
 PQAS Scores range from 0 (no pain/sensation) to 10 (most pain/sensation) Schräder [60], Netherlands 5 Patients with RDEB (compared to EBS) reported significantly higher levels of unpleasant (6.4 [3.5] vs. 3.5 [2.6]), intense (5.4 [2.8] vs. 2.4 [2.4]), surface (5.2 [2.6] vs. 2.4 [2.3]), itchy (4.8 [3.3] vs. 2.1 [2.5]), sharp (5.8 [2.9] vs. 1.7 [2.1]) and shooting pain (5.2 [2.5] vs. 1.3 [2.2]); p < 0.05
Patients with RDEB reported higher unpleasant (6.4 [3.5] vs. 4.5 [3.0]), sharp (5.8 [2.9] vs. 3.4 [3.3]), intense (5.4 [2.8] vs. 3.8 [3.1]), tender (5.4 [3.6] vs. 3.7 [2.9]), surface (5.2 [2.6] vs. 3.7 [2.9]), deep (5.2 [4.0] vs. 3.4 [3.1]), shooting (5.2 [2.5] vs. 2.7 [3.2]), itchy (4.8 [3.3] vs. 3.5 [3.5]), heavy (4.8 [3.4] vs. 3.3 [3.7]), hot (4.6 [3.9] vs. 2.8 [3.0]), aching (4.4 [3.2] vs. 3.4 [3.2]), sensitive (4.0 [2.6] vs. 3.4 [2.6]), dull (4.0 [3.9] vs. 2.5 [2.9]), tingling (4.0 [3.4] vs. 2.5 [2.8]), throbbing (3.8 [3.6] vs. 3.0 [2.9]), radiating (3.8 [3.8] vs. 2.1 [2.87]), cramping (3.6 [3.5] vs. 1.7 [2.3]), and cold pain (2.0 [2.3] vs. 1.0 [1.9]) than all EB types; significance not reported
 VAS Linear, visual analog scale from 0 (no pain/itch) to 10 (most severe pain/itch)
Differences of 6–10 mm considered clinically meaningful
Fine [58],
US
45 (child)
35 (adult)
A higher proportion of adults with RDEB reported an average pain severity of greater than 5 points (26%) than adults with EBS (18%), DDEB (8%), but a lower proportion than adults with JEB (33%); significance not reported
A higher proportion of children with RDEB reported an average pain severity of greater than 5 points (32%) than children with EBS (19%), DDEB (14%), or JEB (15%); significance not reported
Jeon [59],
South Korea
13 Patients with RDEB reported a higher mean score on the VAS-pain (6.54 [SD, 1.56]) than patients with herpes zoster (5.20 [1.61]) or oral lichen planus (4.12 [0.36]); significance not reported
Patients with RDEB reported a similar but slightly lower mean score on the VAS-pruritus (7.54 [2.07]) than patients with prurigo nodularis (8.0 [1.7]), chronic urticaria (7.9 [1.44]), and atopic dermatitis (7.9 [2.2])
  1. ADL, activities of daily living; DDEB, dominant dystrophic epidermolysis bullosa; EB, epidermolysis bullosa; EBS, epidermolysis bullosa simplex; FDLQI, Family Dermatology Life Quality Index; InToDermQOL, Infants and Toddlers Dermatology Quality of Life; GHQ-12, General Health Questionnaire-12; HRQOL, health-related quality of life; iscorEB, instrument for scoring clinical outcomes of research for epidermolysis bullosa; JEB, junctional epidermolysis bullosa; PQAS, Pain Quality Assessment Scores; QOL, quality of life; QOLEB, Quality of Life in Epidermolysis Bullosa; RDEB, recessive dystrophic epidermolysis bullosa; UK, United Kingdom; US, United States; VAS, visual analog scale; SD, standard deviation
  2. aChildren with severe subtype of RDEB
  3. bSpecific measurement names not reported
  4. Some studies [24, 47, 58, 59, 70] report on multiple PROMs and are listed multiple times within the table