Introduction
The EQ-5D is a widely used generic preference-accompanied measure of health-related quality of life (HRQoL), recommended for use in economic evaluations across multiple countries [1]. It has been validated and is commonly employed in various dermatological diseases [2]. The EQ-5D is a short instrument with only five dimensions: mobility, self-care, usual activities, pain/discomfort and anxiety/depression. In health conditions where common symptoms fall outside these five areas, the accuracy of measurement and the ability to capture potential improvement through treatment, may be suboptimal. To address this limitation, there has been a growing interest in the literature in developing additional dimensions to the EQ-5D, known as ‘bolt-ons’. Bolt-ons typically have a similar format to the dimensions of the core EQ-5D instrument (e.g., short dimension title, same number of response levels and severity scale) and are intended to assess specific aspects of HRQoL that may not be fully captured by the five EQ-5D dimensions, offering a more comprehensive assessment of HRQoL [3]. Various bolt-on dimensions, such as cognition, relationships, sleep, vision, hearing and breathing, have been identified to improve its validity in specific patient populations [4, 5]. In the field of dermatology, two additional dimensions, skin irritation (itching) and self-confidence have been developed for the five-level EQ-5D (EQ-5D-5L) in psoriasis patients [6]. The two bolt-ons showed good validity and responsiveness in psoriasis patients [6‐8]. Furthermore, recent evidence suggests that the two bolt-ons can be applied in other dermatological conditions, such as atopic dermatitis and chronic urticaria, as well as in systemic diseases (e.g., chronic kidney disease) causing itching [9‐11].
Darier’s disease (DD, follicular hyperkeratosis, ORPHA:218, OMIM 124200) and Hailey-Hailey disease (HHD, benign chronic familial pemphigus, ORPHA:2841, OMIM 169600) are two rare skin fragility disorders with an autosomal dominant inheritance, present unique challenges for clinicians [12‐14]. The global prevalence of DD is estimated at 1:30000–1:100000, and approximately 1:50000 for HHD [15]. DD is characterized by reddish-brown, keratotic papules in seborrheic regions that can merge into widespread lesions. In contrast, HHD predominantly exhibits intertriginous papulovesicles and small blisters, evolving into erythematous plaques accompanied by erosions and painful fissures [15]. Neuropsychiatric comorbidities are common in both conditions [15‐17]. Although there is currently no effective treatment for DD and HDD, off-label use of certain disease-modifying therapies (such as dupilumab and apremilast) may offer promise for patients [15, 18‐23].
The chronic, intense pain, along with resulting mobility limitations and frequent superinfections, can lead to disability or reduced work capacity [15, 24‐27]. The affected body sites may be itchy and emit an unpleasant odor. Beyond the physical symptoms, similar to other chronic skin conditions, interpersonal connections and the perception of one’s self-image may also be significantly impaired [24, 28]. DD and HHD therefore have a profound impact on patients’ HRQoL [24, 28‐31]. So far, only the three-level EQ-5D (EQ-5D-3L) has been used in DD in one study, which reported overall good known-group validity [28]. Recently, a condition-specific HRQoL measure (Darier’s disease quality of life, DD-QOL) has been developed for DD [28]. However, it is not suitable for capturing broader aspects of HRQoL, such as the impact of comorbidities and it does not allow the estimation of health utilities, making it unsuitable for economic evaluations of new treatments. It is also available in only few languages, and there is limited evidence regarding its validity. In contrast, the EQ-5D, along with the skin irritation and self-confidence bolt-ons, is available in nearly 50 languages, and the core instrument has been validated in over 100 studies [9, 32]. To our knowledge, no studies have used the EQ-5D in HHD patients. The EQ-5D-5L and the skin irritation and self-confidence bolt-ons may serve as useful tools to assess the HRQoL impacts of DD and HHD.
The aim of this study is therefore to investigate the content validity (relevance, comprehensiveness and comprehensibility) of EQ-5D-5L and two bolt-ons among patients with DD and HHD.
Methods
Participants, study design
This study followed the Standards for Reporting Qualitative Research (SRQR) recommendations [33]. Qualitative, semi-structured interviews were conducted with patients diagnosed with DD or HHD. The two patient populations are similar in prevalence, gender distribution, patient experience, symptoms, and treatment, with comparable HRQoL impairment; therefore, were considered together for this study.
Patients were recruited at the Department of Dermatology, Venereology and Dermatooncology at Semmelweis University, Budapest in Hungary between February and September 2023. The inclusion criteria for this study were as follows: (1) aged 18 years or above; (2) histopathological or genetic diagnosis of DD or HHD; (3) cognitive ability to participate in the interview as judged by physicians; (4) ability to understand the questions in Hungarian; and (5) written informed consent. Patients were enrolled in the study until data saturation was reached (i.e. when no important new themes emerged in the last three interviews) [34]. We aimed for a heterogeneous sample in terms of age, diagnosis and disease severity, and monitored the composition of the sample during the data collection according to these characteristics. However, no formal quotas were used. Disease severity was assessed considering the number of affected body areas. The study protocol was approved by the Semmelweis University Regional and Institutional Committee of Science and Research Ethics (No. 220/2022, SE RKEB).
Interviews
The interviews were conducted at pre-arranged appointments in a quiet room at the university’s dermatology clinic. All interviews were performed by the first author (D.P.). A topic guide was developed by the research team building on two similar studies with psoriasis and atopic dermatitis patients in Hungary (Online Resource 1) [8, 9]. In the first part, the objectives of the study and the interview procedure were explained. Patients were then asked to summarize their personal observations regarding their illness, with a focus on the most important aspects related to health and HRQoL.
The second part involved the completion of the EQ-5D-5L descriptive system, followed by the EQ VAS (EuroQol visual analogue scale), by using a concurrent think-aloud technique, as the focus was on delving into the fundamental cognitive processes of patients, rather than simply capturing their responses to the questionnaire items [35, 36]. Patients verbalized their thoughts when filling in the questionnaire. Exploratory questions were used to investigate three areas of content validity (relevance, comprehensiveness, comprehensibility) as recommended by the COnsensus-based Standards for the selection of health Measurement INstruments (COSMIN) standards [37]. Patients were asked about the meaning and relevance of the dimensions in this clinical context, potential overlaps between concepts, missing concepts related to HRQoL, appropriateness of the response levels, wording and recall period. In the third part, patients were asked to complete the EQ-5D-5L again, but this time together with the two bolt-ons (i.e. a total of 7 dimensions). Note that no EQ VAS was filled in afterward. Throughout the second and third parts, patients were encouraged to share their thoughts about the questions and response levels. Furthermore, patients were asked to compare the EQ-5D-5L with and without the two bolt-ons. At the end of each interview, patients completed a short questionnaire about their socio-demographic and clinical background (sex, age, age of onset, comorbidities, education, number of affected body areas and current treatments). As part of this questionnaire, we used a self-reported 0–10 VAS to assess patients’ subjective disease severity, with 0 indicating ‘not severe at all’ and 10 indicating ‘extremely severe’.
Measures
The official Hungarian version of each questionnaire was applied. The EQ-5D-5L comprises a descriptive system and a vertical visual analogue scale (EQ VAS) that ranges from 0 (representing ‘the worst health you can imagine’) to 100 (representing ‘the best health you can imagine’) [38, 39]. The descriptive system covers five aspects of HRQoL: mobility, self-care, usual activities, pain/discomfort, and anxiety/depression. Each dimension has five response options: no problems, slight problems, moderate problems, severe problems and extreme problems/unable to. Two previously developed bolt-ons, skin irritation and self-confidence were used [6]. The skin irritation bolt-on mentions itching as an example both in the dimension title and response levels (e.g., ‘I have no itching’). The bolt-on dimensions also have five different response levels ranging from ‘no problems’ to ‘extreme problems’. The recall period for each dimension, including the bolt-ons, is the day of completion (‘today’).
Qualitative data analysis
The interviews were conducted anonymously, and audio recordings were transcribed verbatim. A thematic analysis was carried out through a multi-stage process [40]. Initially, the first author carefully reviewed all transcripts, extracting initial themes and aspects through an inductive process. Categories and subcategories were then formulated to articulate the emerging themes. The coding was performed by three researchers, although there was only one main coder. The codes were checked by one of the senior authors, and any disagreements were resolved through discussion with the other senior author. The main coder (D.P.) is a medical doctor and PhD student in dermatology. The main supervisor of the coding is a health outcomes researcher with a PhD in dermatology (F.R.), and the third researcher involved is a senior dermatologist and clinical geneticist consultant with a PhD in dermatology (M.M.). A data extraction matrix was created using Microsoft Excel 2016 to report categories and subcategories, along with related patient quotations along with their corresponding interview IDs. English translations of the most noteworthy quotes from the interviews were also performed.
Results
Sample characteristics
A total of 25 (13 DD and 12 HHD) patients were invited into the study. Nine chose to withdraw, and one participant did not show up, resulting a final sample of 15 patients (8 DD and 7 HHD, 80% female, age range 35 to 77 years). The mean interview duration was 48 min. No significant new themes emerged after the twelfth interview, indicating that data saturation had been achieved. The sample covered a wide range of age groups and education levels, exhibiting diverse clinical characteristics (Table 1). All but one interview was conducted in person, while one interview via online video-interviewing. In one case, a DD patient using a wheelchair, who was recently diagnosed with multiple sclerosis, preferred to attend the in-person interview with her husband present.
Table 1
Demographic and clinical characteristics of patients
Characteristics of the population | Median (range) or n (%) |
|---|---|
Age (years) | 48 (35–77) |
Gender | |
Female | 12 (80%) |
Male | 3 (20%) |
Education | |
Secondary without certificate | 5 (33%) |
Secondary with certificate | 7 (47%) |
College/university | 3 (20%) |
Employment | |
Employment full time | 5 (33%) |
Retired | 3 (20%) |
Disability pensioner | 3 (20%) |
Employed part time | 1 (7%) |
Unemployed | 1 (7%) |
Homemaker/housewife | 1 (7%) |
Others | 1 (7%) |
Disease duration (years) | 19 (4–47) |
Age at onset (years) | 30 (6–50) |
Comorbiditiesa | |
None | 2 (13%) |
Obesity | 6 (40%) |
Anxiety | 6 (40%) |
Cardiovascular diseases | 4 (40%) |
Depression | 3 (20%) |
Neurological conditions | 3 (20%) |
Diabetes | 2 (20%) |
Cancer | 1 (7%) |
Atopic dermatitis | 1 (7%) |
Asthma | 1 (7%) |
Allergies | 1 (7%) |
Gastroesophageal reflux disease | 1 (7%) |
Diverticulosis | 1 (7%) |
Thyroid disease | 1 (7%) |
Arthritis | 1 (7%) |
Number of body regions affected | |
1–2 | 4 (27%) |
3–4 | 2 (13%) |
> 5 | 9 (60%) |
Current therapya | |
Only topical therapy (antiseptics, corticosteroids) | 4 (27%) |
Oral corticosteroids | 4 (27%) |
Oral retinoids | 6 (40%) |
Laser therapy | 4 (27%) |
Disease modifying therapy | 1 (7%) |
EQ VAS (0–100)b | 81.5 (25–98) |
Self-reported severity VAS (0–10)c | 6 (2–8) |
Symptoms and impacts on patients’ lives
Many patients highlighted how their disease affects multiple areas of their lives. Overall, 46 aspects were identified (Table 2). These aspects were grouped into the following five main categories: [1] triggers, [2] physical symptoms, [3] impact on mental health and social life, [4] everyday difficulties, [5] health care-related issues. The most commonly reported symptom was pain (n = 14, 93%). Further nine (60%) respondents highlighted other specific symptoms, such as leaking, bleeding and superinfection associated with the skin lesions. Patients reported DD and HHD affect numerous areas of their lives. Over half of the patients (n = 8, 53%) emphasized appearance issues, feelings of shame or misconceptions about the disease (e.g., it is considered contagious or caused by poor hygiene). Problems with self-esteem or self-confidence (n = 6, 40%) were also mentioned: “It makes me feel safe that my partner has vision problems (…), that he can’t see me properly, doesn’t pay attention to or care about what’s on my skin.” (Patient 7, HHD). The majority of respondents expressed their difficulties in everyday activities, mobility, sports, work or sleep. Six patients (40%) emphasized difficulties in dressing, while five (33%) patients reported challenges in selecting clothes to cover up their skin lesions, or problems with washing themselves. Some patients have become disabled due to their disease. One patient noted: “I am 42 years old now and I have never had a job before.” (Patient 15, DD).
Table 2
Important aspects of live affected by Darier’s disease and Hailey-Hailey disease
Main categories | Subcategory | n | % | |
|---|---|---|---|---|
Triggers | Seasonal fluctuations | 8 | 53 | P10 (HHD): It’s much harder during the summer months, I suppose because of the heat and sweating |
Sun exposure | 5 | 33 | P8 (DD): Well, when I was eight years old, I had a rash on my forehead on the beach, and we thought it was a sun allergy | |
Stress | 5 | 33 | P2 (DD): So when I’m a bit more stressed, it completely exacerbates the symptoms | |
Onset in childhood | 5 | 33 | P15 (DD): According to my parents, I was five years old when my disease started | |
Period-related | 3 | 33 | P10 (HHD): A week before menstruation, my skin starts to feel tense | |
Physical symptoms | Pain | 14 | 93 | P02(HHD): It is so painful sometimes that I could cry |
Superinfection, prolonged wound healing | 9 | 60 | P15 (DD): Since 2005, my skin in the groin has been constantly sore, and the problem is not just that, but it also gets infected and warts appear | |
Skin bleeding and leaking | 9 | 60 | P4 (DD): It’s uncomfortable when it [skin lesion] comes out in the groin area, and then it’s leaking | |
Skin irritation (e.g., tightness, burning sensation) | 8 | 53 | P06 (DD): My skin feels tight and burns | |
Appearance | 8 | 53 | P02 (DD): It feels bad that until I was a teenager, I never had a pimple, my skin was so clear and beautiful. And then I have to face the fact that I have an ugly skin like this | |
Itching | 7 | 47 | P07 (HHD): Well, it burns, it itches, it prevents me from moving | |
Odor | 4 | 27 | P11 (DD): This inflammation I have now, which is accompanied by such an unpleasant odor, is particularly uncomfortable for me | |
Facial symptoms | 3 | 20 | P02 (DD): I was in eighth grade when it [the disease] started on my face | |
Impact on mental health and social life | Adaptation | 11 | 73 | P13 (HHD): I have reluctantly dealt my illness |
Shame | 8 | 53 | P03(HHD): I clench my armpits and walk in that way so that no one can see it [the symptoms] P04 (DD): The feeling of shame will always be there in a me | |
Others’ misconceptions about the illness | 8 | 53 | P11 (DD): It happened once on a public transport, when I didn’t even notice that skin lesions were visible, a pregnant woman asked me if it was chickenpox P02 (HHD): Sometimes people think that I have burned myself | |
Mental health problems | 6 | 40 | P01 (HHD): It has definitely affected me emotionally, it is terrible, not knowing what this is and why I am not getting better | |
Self-esteem or self-confidence problems | 6 | 40 | P10 (HHD): I don’t see anything else on myself but ugliness, and this affects things like my anxiety, self-esteem, and emotional balance, so basically everything | |
Romantic relationship problems, break up/divorce | 5 | 33 | P06 (DD): When Darier breaks out, I can become very self-conscious, then I’m afraid of being in a relationship | |
Social network, support from friends, family, and colleagues | 5 | 33 | P01 (HHD): My family gives me a lot of mental strength… they keep me going, I try to be better for them | |
Social relationship problems | 5 | 33 | P07 (HHD): I find it much harder to handle interactions at home during flare-ups; my mood changes are extremely difficult for the people around me | |
Anxiety | 4 | 27 | P14 (HDD): The lesions in my armpit make my anxious | |
Fear of heredity | 3 | 20 | P07 (HHD): I’m afraid because it is a 50% risk for even my two children got it [the disease] | |
Everyday difficulties | Mobility issues | 11 | 73 | P01 (HHD): When my disease flares up, it’s impossible even to walk |
Problems with leisure activities, sports, physical exercise | 11 | 73 | P2 (HHD): I can’t go swimming; I can’t go to the baths | |
Dressing issues (due to pain) | 6 | 40 | P2 (DD): I had such pain or I had to ask for help just to be able to put on a pyjama at all | |
Dressing issues (due to shame related to skin lesions) | 5 | 33 | P1 (HHD): I was constantly getting sores… I kept changing my clothes constantly because the sores touched every single piece of a clothing I put on P02 (DD): There are limited types of clothes I can wear because, you know, they irritate my skin, so I have to look for cotton clothes and find something that covers all my lesions | |
Working issues | 10 | 67 | P01 (HHD): I worked as a nanny for eighteen years, but I can’t do it anymore because of my skin condition | |
Changes in life due to the illness (e.g., slowing down and limited activities due to the symptoms) | 8 | 53 | P02 (HHD): It affects our sexual life, everyday activities, work, and sports | |
Assistance needed to perform daily tasks | 7 | 47 | P15(DD): For example, when my skin feels really tight, I can’t put my shoes on by myself | |
Need for special cosmetics | 7 | 47 | P01 (HHD): The shower cream that I can only use for washing is like a pharmacy product | |
Limitations in certain activities (e.g., going to the beach or vacation) | 6 | 40 | P02 (DD): For the past 20 years, I definitely haven’t been to the beach | |
Sitting difficulties | 6 | 40 | P07 (HHD): I can’t sit for long periods because the wound gets stuck to the clothes | |
Frequent need to change clothes and take a shower | 5 | 33 | P04 (DD): I usually take a shower 10 times a day | |
Frequent change of bedding | 5 | 33 | P10 (HHD): I continuously used up five to six sets of bed linens in one day | |
Washing or bathing problems | 5 | 33 | P13 (HHD): Water absolutely irritates my skin, even bathing is very painful for me | |
Being disabled | 4 | 27 | P07 (HHD): The disability assessment process is humiliating. You have to appear before a committee | |
Financial implications | 3 | 20 | P10 (HHD): The medications cost a lot of money | |
Sleeping problems | 3 | 20 | P10 (HHD): I cried in my sleep because every movement hurt | |
Required to take a special diet | 3 | 20 | P07 (HHD): I don’t want to constantly take antibiotics, so I try to make dietary and lifestyle changes | |
Health care related issues | Treatment difficulties | 13 | 87 | P05 (HHD): I was allergic to some ingredient of the cream and that contributed to the worsening of the symptoms |
Loss of therapy effectiveness | 11 | 73 | P02 (DD): I have used a lot of different medications and creams… | |
Late diagnosis or misdiagnosis | 10 | 67 | P13 (HHD): Yes, I didn’t get the diagnosis right away when lesions first appeared… it took approximately three or four years | |
Hospitalization due to the skin condition | 5 | 33 | P2 (DD): But I know that when pain appears, there’s an 80% chance that hospitalization follows, because by then it’s [skin lesion] already become infected | |
Dissatisfaction with doctors | 4 | 27 | P05 (HHD): I visited the dermatologist multiple times because they didn’t know what to do with me | |
Trust in the treatment, faith in doctors | 3 | 20 | P07 (HHD): You’re there to help and you’re trying to research this disease |
Relevance and comprehensibility of the EQ-5D-5L and bolt-ons
Most patients found the EQ-5D-5L easy to complete and comprehensible: “Indeed, it’s succinct and clearly written. It’s not a lengthy, twenty-page-long document; it’s phrased concisely and nicely” (Patient 2, HHD). All participants considered the five dimensions relevant to their disease: “This contains everything that I feel, have experienced, and gone through.” (Patient 13, HHD). Moreover, patients provided positive feedback regarding the importance of the skin irritation and self-confidence bolt-ons: “Really good question! It’s brutal, just imagine (…) when ants crawl on you…” (Patient 1, HHD). Another shared, “I have a serious issue with self-confidence, or rather, the lack thereof, and it is likely related to the illness (…) I was often teased, bullied and excluded, so I turned to eating, which led me to become overweight as a child (…) Unfortunately, I still struggle with this.” (Patient 11, DD). One HHD patient elaborated on the complexity of self-confidence problems related to their illness: “…it’s not just about sexuality; but anything that connects to self-confidence… how we dress, how many layers should we put on to hide it [the skin lesions]. I haven’t worn sleeveless clothes in public for two years, and I rarely wear shorts, if ever.” (Patient 14, HHD). Interestingly, some patients interpreted self-care differently not as the psychical act of dressing or washing, but rather as the choice of clothes or cosmetics: “That’s why I need to pay attention to what shower gel to use or clothes to wear, making sure it’s cotton.” (Patient 4, DD).
Ranking of dimensions
After completing EQ-5D-5L, six patients (40%) ranked every dimension as equally relevant to their disease, stating: “Each point enquires about the most critical aspects. My experience is that all of them affect me.” (Patient 11, DD). Four (27%) patients considered usual activities as the most important, followed by mobility, self-care and pain/discomfort dimensions, each mentioned by three patients (20%). However, when patients completed the EQ-5D-5L with the two bolt-on dimensions, the most relevant dimension in this clinical context shifted to self-confidence (n = 5, 33%), followed by skin-irritation (n = 3, 20%), Additionally, five patients (33%) considered all seven dimensions equally relevant to their disease. Interestingly, only one patient indicated a ‘least relevant’ dimension, which was self-care (Table 3).
Table 3
Ranking of dimensions in the EQ-5D-5L and EQ-5D-5L + bolt-ons
EQ-5D-5L | EQ-5D-5L + bolt-ons | |||||||
|---|---|---|---|---|---|---|---|---|
Most relevant | Least relevant | Most relevant | Least relevant | |||||
Dimension | n | % | n | % | n | % | n | % |
Mobility | 3 | 20 | 0 | 0 | 2 | 13 | 0 | 0 |
Self-care | 3 | 20 | 1 | 7 | 2 | 13 | 1 | 7 |
Usual activities | 4 | 27 | 0 | 0 | 2 | 13 | 0 | 0 |
Pain/discomfort | 3 | 20 | 0 | 0 | 2 | 13 | 0 | 0 |
Anxiety/depression | 1 | 7 | 0 | 0 | 0 | 0 | 0 | 0 |
Skin irritation | n/a | n/a | n/a | n/a | 3 | 20 | 0 | 0 |
Self-confidence | n/a | n/a | n/a | n/a | 5 | 33 | 0 | 0 |
All equally relevant | 6 | 40 | 0 | 0 | 5 | 33 | 0 | 0 |
Overlapping dimensions
Two patients reported an overlap between usual activities and self-care, as they considered washing a usual activity: “For me, usual activities include waking up, showering in the morning or at night.” (Patient 2, DD). Another patient identified a conceptual overlap between discomfort and skin irritation, stating: “It is not like pain. It is itchy, it burns, but I would not call it pain.” (Patient 6, DD).
Comprehensiveness of the EQ-5D-5L and bolt-ons
All patients considered the EQ-5D-5L and the two bolt-ons comprehensive; however, some missing concepts were mentioned. Following the EQ-5D-5L, four patients (27%) identified six concepts that were not included in the five core dimensions. After introducing the EQ-5D-5L plus two bolt-ons, six patients (40%) reported a total of 12 missing concepts (Table 4). Among these, the most commonly reported missing concept was the financial impact of the disease (n = 4, 27%). Difficulties with intimacy were articulated by one patient and issues related to sex life were mentioned by two patients. Two patients highlighted aspects of work difficulties. They emphasized the importance of education, which can enable someone to pursue non-physical work, as physical work is often impossible due to their conditions. Another patient emphasized the employers’ tolerance. Other comments, made by only one patient each, discussed the difficulties in social life and relationships, the importance of special care or diet, seasonal fluctuations, and other factors not considered a usual activity but related to the disease. For example one patient noted, ‘What precautions to take… For example, last year I had surgery, and forgot to mention that my skin can’t tolerate adhesive tape (…) where they taped and removed it, that area swelled up completely (Patient 14, HHD). One patient mentioned the absence of a self-esteem dimension in the EQ-5D-5L, which is closely linked to self-confidence and each influences the other in significant ways.
Table 4
Missing concepts in EQ-5D-5L and EQ-5D-5L + bolt-ons
Patients mentioning each concept | ||||
|---|---|---|---|---|
EQ-5D-5L | EQ-5D-5L + bolt-ons | |||
Concepts | n | % | n | % |
Financial impact | 2 | 13 | 4 | 27 |
Impacts of any medical procedures affecting the skin (e.g., the use of adhesive tapes for wounds) | 0 | 0 | 1 | 7 |
Intimacy | 0 | 0 | 1 | 7 |
Seasonal fluctuation | 0 | 0 | 1 | 7 |
Self-esteem | 1 | 7 | 0 | 0 |
Sexual life | 1 | 7 | 2 | 13 |
Shame caused by the disease | 1 | 7 | 1 | 7 |
Social life, relationships | 1 | 7 | 1 | 7 |
Special care (clothing, food, cosmetics, detergents etc.) | 0 | 0 | 1 | 7 |
Special diet | 0 | 0 | 1 | 7 |
Work issues: employer’s toleration | 0 | 0 | 1 | 7 |
Work issues: physical work limitations | 1 | 7 | 1 | 7 |
All patients preferred the EQ-5D-5L with the two bolt-ons over the EQ-5D-5L alone. One participant stated, “I would choose the one with the skin-irritation and self-confidence questions because I can express my condition in a more complex way” (Patient 2, HHD). Another remarked, “I didn’t know it was missing, but now that it’s in the other one, I am missing it” (Patient 8, DD). Adding the bolt-ons did not change any of the responses on the core five dimensions in any of the patients.
Suggested changes in descriptors
Five patients (33%) suggested at least one change to one or more of the seven dimensions (Table 5). Suggestions for changes were made to all but one dimension (i.e. skin irritation). Three participants (20%) recommended splitting the anxiety/depression composite into two separate dimensions. The usual activities dimension was suggested to be divided based on whether the examples involve physical activity or not. Wording changes were suggested in three instances. One patient pointed out the distinction between ‘walking’ and ‘mobility’ and also suggested expanding the self-care dimension to include eating. Another participant expressed concerns about the word ‘dressing’.
Table 5
Suggested changes
Themes | n | % | Example quote |
|---|---|---|---|
Mobility | |||
Use the same terminology in the dimension title and response levels (i.e. mobility or walking) | 1 | 7 | P14 (HHD): Mobility for me doesn’t necessarily only refer to walking but fundamentally to movement itself. I don’t have a problem with walking, but mobility, in general, is already problematic for me. By mobility, I mean physical mobility in a general sense. Either change the word ‘mobility’ or the word ‘walking’, depending on what you’re interested in |
Self-care | |||
Rephrase the word ‘dressing’ | 1 | 7 | P12 (HHD): ‘Dressing’ (Hungarian: öltözködés) means how someone appears, how they dress, in my opinion… it’s more like ‘getting dressed’ (Hungarian: felöltözni) |
Expand it to include eating | 1 | 7 | P14 (HHD): For me, self-care includes eating as well |
Usual activities | |||
Split usual activities based on whether they include physical activity or not | 1 | 7 | P14 (HHD): Here, I might consider separating it. I think, for most people, usual activities are related to mobility, physical movement. I might somehow reorganize it, distinguishing between activities that require physical activity and those that do not or involve less physical activity for example when someone has a physical job versus works when you mostly sit in front of a computer, sleeping, social life like going out, meeting friends, waiting for guests, studying, hobbies… even cooking |
Pain/discomfort | |||
Split into 2 questions | 1 | 7 | P4 (DD): Pain is different from discomfort. These could be two separate questions |
Anxiety/depression | |||
Split into 2 questions | 3 | 20 | P14 (HHD): I think it might be worth separating them because, I believe, they have different symptoms. I had a period of depression, and for me, depression and anxiety have different symptoms |
Change the word ‘anxiety’ and ‘depression’ to shame | 1 | 7 | P04 (DD): For me, it’s not so much anxiety. It’s more like fear or a bad feeling… Instead of depression, it’s more about mood… There’s a sense of shame in me (…) but that doesn’t necessarily mean I should feel anxious or be depressed |
Self-confidence | |||
Specify whether the lack of self-confidence is related to the disease | 1 | 7 | P14 (HHD): Here, I think it’s important to indicate whether this is related to it. Because I can easily imagine that someone might generally lack it, but not because of this |
The whole questionnaire | |||
Specify if the questionnaire is meant to be generic | 2 | 13 | P14 (HHD): I might specify this a bit. For example, if I kicked the door frame or got my period yesterday, I might be in pain, but it doesn’t mean I have any issues with Hailey-Hailey now |
Response levels
The majority of the respondents were satisfied with the five-level scale (Table 6). In total, two participants suggested reducing the response levels from five to four or three in one or two EQ-5D-5L dimensions (mobility or self-care) or for the skin irrigation bolt-on. Some participants found the expressions ‘no problem’ and ‘unable to’ unsuitable to describe their conditions. One participant mentioned that the difference between levels was unclear: “I think there should be a consensus about what we call as ‘no problem’ or mild or moderate” (Patient 2, HHD). A patient suggested illustrating with examples what constitutes mild or severe pain. Finally, it was suggested that the description of itching should refer not only to its intensity but also to its duration.
Table 6
Comments on the response levels
Themes | n | % | Example quote |
|---|---|---|---|
Mobility | |||
‘Unable’ is an inaccurate term | 1 | 7 | P10 (HHD): Well, saying ‘I’m unable’ isn’t entirely true in this disease… it’s a fact that it came with brutal pain when the skin around my knee was inflamed, but if you are forced to, you have to move as best as you can |
Self-care | |||
‘Unable’ is an inaccurate term | 2 | 13 | P07 (HHD): I don’t know how others feel about it, but in my opinion, ‘I am unable’ isn’t quite accurate (….) ‘Severe’ is okay, that’s fine, but the ‘I am unable’ part, I think, is not the thing in our cases. ‘I am unable’ is for someone who has no hands or feet… |
No need for a ‘no problem’ level | 1 | 7 | P07(HHD): I believe that every patient like this has a problem |
Pain/discomfort | |||
Illustrate the severity of the pain with examples | 1 | 7 | P14 (HHD): I think it would be useful to illustrate the severity of the pain with examples |
Skin irritation | |||
Four levels would be sufficient | 1 | 7 | P07 (HHD): I don’t think the word ‘extremely’ is necessary (…) ‘Severe’ is good, but to make it ‘extreme’, there’s nothing like that in Hailey-Hailey… there’s no such thing as wanting to scrape my skin down to the bone, for example, that would be extreme for me |
Consider the duration of itching | 1 | 7 | P14 (HHD): One aspect is the intensity of the itching, and another thing is the duration. For instance, sometimes it itches intensely for a short period, or it itches all day but with low intensity |
All | |||
Difficult to differentiate between levels 2 and 3 | 2 | 14 | P05 (DD): I sometimes don’t know what the difference is between mild and moderate |
EQ VAS
Eight patients (53%) referencing the top endpoint of the EQ VAS (100: the best health you can imagine) and nine of them (60%) referencing the lowest endpoint (0: the worth health you can imagine) considered only their skin status: “I am 100 when my skin doesn’t odor, I can walk properly, cycle or go to a swimming pool.” (Patient 15, DD). A smaller group of the participants (n = 5, 33%) interpreted the two endpoints in general: “Zero is when someone is hospitalized and cannot get up at all, and is unable to take care of oneself, so if someone needs diapering” (Patient 1, HHD). Three patients mentioned that they have already reached the zero endpoint in their lives: “Zero is my actual condition due to multiple sclerosis” (Patient 8, DD) or “That was my condition three years ago when even moving hurt (…) The pain, and also the constant leaking (…) I haven’t even talked about the smells yet (…)” (Patient 10, HHD). One patient was uncertain whether ‘health status’ in the instruction line of EQ VAS refers to the skin lesions as well. Another participant had problems with interpreting the two endpoints, such as questioning the plausibility of achieving a health status of ‘100’.
Recall period
Two patients used an incorrect recall period in both EQ-5D-5L and EQ-5D-5L plus bolt-ons. None of the patients spontaneously indicated any problems with the recall period of ‘today’. When the interviewer asked about the appropriateness of ‘today’, one patient considered it appropriate, seven patients mentioned that a recall period of 1 week to 3 months would be more suitable, and seven patients expressed that the questions should focus on symptomatic periods.
Discussion
This is the first study investigating the content validity of the EQ-5D-5L and two bolt-on dimensions in two rare inherited skin diseases, DD and HHD. Notably, most patients considered all five EQ-5D-5L dimensions relevant to their skin diseases. During the discussions before completing the questionnaires, multiple HRQoL areas related to the EQ-5D-5L and two bolt-ons were mentioned by the majority of patients, such as pain, mobility, work-related problems, various forms of skin irritation (such as itching, tightness and burning sensation), as well as issues related to self-confidence or self-esteem. Although the EQ-5D-5L, was generally viewed positively by the patients, adding the two bolt-ons seems to further improve its content validity in this population. One-third of the patients considered self-confidence as the most relevant area for them out of the seven domains within this clinical context, followed by skin irritation, mentioned by one-fifth of the patients. After adding the two bolt-ons, only two missing HRQoL areas were reported by two or more patients: financial impact and sex life.
It is worthwhile to compare our results to those of previous studies in psoriasis and atopic dermatitis from Hungary, and atopic dermatitis and chronic urticaria from the UK [8‐10]. In general, while the comprehensiveness of the EQ-5D-5L was suboptimal in the other three chronic skin conditions, the instrument seems to show acceptable content validity in DD and HHD patients. This was clearly further improved by the two bolt-ons. Another important finding from our study is that self-confidence was even more preferred than in previous studies, possibly due to the high mental burden associated with unpleasant symptoms, such as skin oozing and odor, which are absent in psoriasis, atopic dermatitis and chronic urticaria. All three earlier studies confirmed the relevance and comprehensibility of the two bolt-ons and noted some conceptual overlaps between the bolt-ons and the five core dimensions, particularly between skin irritation and pain/discomfort and anxiety/depression and self-confidence. Our analysis revealed similar overlaps, but only in one instance, compared to the multiple overlaps observed in other skin conditions. This potential conceptual overlap appears to be a limitation of these bolt-ons, as it could lead to double-reporting of certain problems. However, existing evidence suggests that this affects only a fraction of patients and varies across different skin conditions [8‐10]. Further psychometric work across various populations is needed to better understand the extent and determinants of this overlap, as well as differences in this regard across skin conditions.
Some patients provided suggestions for improving the items, but these did not reveal any clear patterns and were mentioned by a limited number of patients. For example, some patients suggested adjustments to the response levels of skin irritation dimension, such as having four response levels instead of five, and the consideration of both intensity and duration of itching in the response levels. Others recommended a longer recall period or suggested splitting the composite dimensions. However, any modifications to the EQ-5D-5L could compromise the comparability of the widely used descriptive system across different diagnoses. Based solely on the findings from this specific study, no immediate actionable evidence emerged that would necessitate changes to the bolt-ons. Regarding the future development of the two bolt-ons, patients’ suggestions will feed into a pool of recommendations collected across different study populations and countries.
One limitation of our study was that all patients were recruited from a single center. Despite DD and HHD affecting males and females equally, our sample contained mostly female patients, reflecting the male–female ratio of regularly monitored DD and HHD patients at our clinic. At the beginning of each interview, participants were asked about the challenges they faced regarding their HRQoL specifically related to their skin condition. This approach might have led to an intensified focus on their skin symptoms when completing the EQ-5D-5L, as we observed it in some aspects (e.g., EQ VAS), patients appeared to use the instrument more as if it were condition-specific. Lastly, during the interviews, participants often interpreted the concepts of self-confidence and self-esteem as synonyms or substantially overlapping. Consequently, we decided to combine these two concepts when presenting the impacts of DD and HHD on patients’ lives. This may represent a language- or culture-specific issue that requires attention in future qualitative research involving the self-confidence bolt-on.
In conclusion, our findings suggest that there is no actionable evidence indicating gaps in the content validity of the EQ-5D-5L with two bolt-ons in DD and HHD. This is promising for future quantitative testing, which aims to confirm the instrument’s measurement performance, including its ability to differentiate across different severity groups and its responsiveness to changes in HRQoL.
Declarations
Conflict of interest
Fanni Rencz is a member of the EuroQol Group. Views expressed in the article are those of the authors and are not necessarily those of the EuroQol Research Foundation. The other authors have no conflicts of interest to declare.
Ethical approval
All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards. The study protocol was approved by the Semmelweis University Regional and Institutional Committee of Science And Research Ethics (No. 220/2022, SE RKEB).
Informed consent
Informed consent was obtained from all patients included in the study.
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