Skip to main content

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