Health‐related quality of life among patients with ichthyosis

ARTICLE

Auteur(s) : Agneta GÅNEMO¹, Per-Olow SJÖDEN², Eva JOHANSSON², Anders VAHLQUIST³, Magnus LINDBERG⁴

¹ Department of Medical Sciences, Section of Dermatology, Uppsala University, Uppsala, Sweden
² Department of Public Health and Caring Sciences, Section of Caring Sciences, Uppsala University, Uppsala, Sweden
³ Department of Medical Sciences, Section of Dermatology, Uppsala University, Uppsala, Sweden
⁴ Occupational and Environmental Dermatology, Department of Medicine, Karolinska Institutet, and Department of Occupational and Environmental Medicine, Norrbacka, SE-171 76, Stockholm, Sweden

Article accepted on 17/11/2003

Ichthyosis of the non-bullous type encompasses a heterogeneous group of hereditary skin disorders, all characterised by more or less generalised dryness, hyperkeratosis, and scaliness that is present at birth or develops in early childhood. There are at least 20 types of ichthyosis, the main types being ichthyosis vulgaris (IV), x-linked recessive ichthyosis (XRI), and lamellar ichthyosis (LI) [1, 2]. IV and XRI are the two most common forms, in most populations occurring at frequencies of about 1/300 and 1/3,000 respectively, and the skin symptoms are mild to moderate. LI or congenital ichthyosiform erythroderma [1] is congenital, rare (prevalence < 1/100,000) and often accompanied by severe skin symptoms. Persons with LI may be born as collodion babies and often have persistent erythema, ectropion and anhidrosis [3]. There is presently no permanent cure for ichthyosis. The treatment is often time-consuming and includes baths, topical emollients with the addition of various keratolytic agents [4-7] and, for the severe forms, also oral retinoids [8]. Despite treatment, skin symptoms often remain problematic and are likely to affect quality of life although this seems never to have been adequately assessed.
During the past few decades, many studies have evaluated the effects of chronic diseases on health and quality of life. Both generic and disease-specific instruments have been developed for assessing health-related quality of life (HRQoL) [9-11]. Dermatological disorders are often chronic and their consequences may be both physically and psychosocially disabling thereby potentially affecting HRQoL [13-16].
The aim of the present study was to investigate the HRQoL of patients with any of these three types of ichthyosis (LI, XRI and IV). To this end, we employed the dermatology-specific quality-of-life instrument DLQI [10], the generic quality-of-life instrument SF-36 [11, 12], and a subjective measure of disease activity using visual analogue scales (VAS).

Patients and methods

Study group

The study group initially comprised 144 patients diagnosed with LI, XRI or IV. They were recruited as follows (i) 18% from patients attending the Dermatology Outpatient Clinic at the University Hospital in Uppsala between January 1995 and April 2000, (ii) 37% from participants in three other studies of ichthyosis [6, 17, 27]; (iii) 33% from the register of the Swedish Ichthyosis Association, and (iv) 12% close relatives of the above-mentioned persons, affected by similar symptoms. The study was performed between April and August 2000.
The patients were invited to participate by mail. Of the 122 patients who responded, the response rates in the four recruitment groups were (i) 81%, (ii) 85%, (iii) 83% and (iv) 94%, respectively. For the different diagnoses, the response rates were LI 82.2%, XRI 87.8%, and IV 84.5%. The proportion of males was 55% in the total sample, 32% in LI, 100% in XRI and 38% in IV. The diagnosis was based on signs and symptoms reported in the patients' medical records and/or in their questionnaire answers.

Design of the study

A self-administered questionnaire was mailed to the patients together with a letter explaining the purpose and design of the study and asking for consent. The questionnaire included sociodemographic questions and questions about ichthyosis (Table I). A subjective measure of disease activity (VAS), and the quality-of-life instruments DLQI [10] and SF-36 [12] were also enclosed. One reminder was sent if there was no reply within 3 weeks. The Research Ethics Committee of the Faculty of Medicine, Uppsala University, approved the study.

Table I. Some characteristics of survey respondents

Quality-of-life instruments

The DLQI [10] consists of 10 questions, with a time frame of the previous seven days covering relevant aspects of quality-of-life related to skin disease. The Swedish version of the DLQI has been validated (Prof. A Finlay personal communication). The ten items are summarised in six dimensions and one overall summary score (0-30). The six dimensions are (i) symptoms and feelings; (ii) daily activities; (iii) leisure; (iv) work and school; (v) personal relationships; and (vi) problems with treatment. Higher scores indicate a poorer quality of life. The DLQI is a dermatology-specific instrument and there are no norm data for a healthy population. However, healthy controls reportedly have a very low mean total DLQI score of approximately 0.5 [10].
The SF-36 [11, 12] is a multi-dimensional, self-administered and validated instrument. The SF-36 has been translated and adapted to Swedish conditions [12]. The questions concern quality of life today compared to one year ago', the patient's typical day, and during the previous four weeks. The SF-36 measures HRQoL using 36 items arranged in eight dimensions: (i) general health (GH), (ii) physical functioning (PF), (iii) role-physical (RP), (iv) role-emotional (RE), (v) social functioning (SF), (vi) bodily pain (BP), (vii) vitality (VT) and (viii) mental health (MH). Scores range from 0 to 100, higher scores indicating a better quality of life. Normative data have been presented for the Swedish general population [12]. Age- and gender- adjusted norm scores were calculated according to Hjermstad et al. [20].

Subjective measure of disease activity

Six questions were used to assess the patient's perception of symptoms on a visual analogue scale. The end-points were no symptom (0)-worst symptom (100). The first three questions concerned symptoms at the time of the survey and the other three elicited how the respondent perceived these symptoms when at their worst. Symptoms asked for were dryness, scaling and erythema. Scores were obtained by measuring the distance, in mm, from “no symptom” to the patient's mark on the VAS.

Statistical methods

Chi-square analysis was used to compare the three diagnosis groups regarding marital status, education, employment, and geographical area. Kruskal-Wallis ANOVA by ranks was used to compare the groups regarding the HRQoL instruments and for a separate comparison of males from the diagnostic groups. Post-hoc analyses were performed according to Siegel and Castellan [18]. The Mann-Whitney U test was used to compare genders in the total group, for a separate comparison of genders in LI and IV, and a comparison of females in groups LI and IV. Spearman rank order correlations were used to study associations between SF-36 and DLQI scores and between those of the SF-36, the DLQI, and the VAS. The level of significance was set at 5% for the between-groups analyses, and at 1% or 0.1% for the correlational analyses.

The z test (19) was used to compare patient mean SF-36 scores with Swedish norm data from a study by Sullivan et al. 1994 [12]. For the analysis of SF-36, age- and gender-adjusted scores were calculated using a direct standardisation method [20]. The one-sample t test [19] was used to compare patient mean SF-36 scores and the age- and gender adjusted norm data. For the latter comparisons we used parametric methods as the the norm data was given as mean and not median values.

Results

Participants

A total of 122 patients (age range 17-78 years) completed the questionnaires, giving an overall response rate of 84.7% (for details see Material, Methods). One patient was excluded because of incomplete answers and three more were excluded because of missing data on the subjective measure of disease activity. For participants' characteristics see Table I. The age distribution in the total sample was < 35 years 33%, 35-54 years 33%, and > 55 years 34%. There were no significant differences between the three groups in age, marital status, education, employment or geographical area.

DLQI

The DLQI scores are given in Table II. There was a significant overall difference between the groups (p < 0.05) and post hoc analyses revealed that group LI had a higher score than XRI, and IV had higher score than XRI. Females had significantly higher scores than males in the total study group (p < 0.05).

Table II. Dermatology Life Quality Index (DLQI) scores for male and female patients with different types of ichthyosis. Median and (25-75th quartile) are given

SF-36

There were no significant differences for the eight SF-36 dimensions between groups or genders or between genders within groups (Table III). However, when the total study group was compared with the Swedish norm data the study group had significantly worse scores on six of the eight dimensions (GH, RP, RE, SF, VT and MH). When the total study group was compared with the age-and gender-adjusted norm scores, the study group had significantly worse scores on the four dimensions RE, VT, SF and MH. The adjusted age and gender norm scores for the study population were very similar to the Swedish norm data mean scores (see Table III).

Table III. Scores (median and means) for the eight dimensions of the SF-36 (range 0-100) in patients with ichthyosis

Spearman correlations, DLQI and SF-36

The DLQI “total” correlated significantly with all eight SF-36 dimensions (p < 0.001). The strongest correlation was seen between the DLQI “total” and the “social functioning” of the SF-36 (-0.53).

Subjective disease activity, VAS score

Table IV presents the VAS scores for disease activity “today” and “when at its worst”. For “today”, there was a significant overall difference between the three groups for “dryness”, and post-hoc analyses showed that IV had higher scores than XRI (p = 0.041). In the case of activity “at its worst” there was a significant difference for “erythema” and LI scored higher than XRI (p = 0.021). For males in the three groups, there was a significant difference in “erythema” “at its worst” and LI had a higher score than both XRI and IV (p = 0.049).

Table IV. Subjective disease activity (VAS) for male and female patients with different types of ichthyosis.
Median and (25-75th quartile) are given

Spearman correlations, DLQI, SF-36 and VAS

Spearman correlations between subjective measures of disease activity and the quality-of-life dimensions of the SF-36 and the DLQI total are given in Table V. The DLQI total correlated significantly with the skin symptoms (p < 0.001). The SF-36 domains, except bodily pains, correlated significantly (p < 0.001 or p < 0.01) with the skin symptoms “scaling” and “dryness” but to a minor extent with erythema.

Table V. Spearman correlation coefficients between the subjective ratings of disease activity “today” and the Quality of Life dimensions of the SF-36 and the DLQI

Discussion

Interest in HRQoL in dermatology is relatively new [26] but several studies have already shown that skin diseases may have an adverse impact on quality of life [13-15, 21, 24, 26, 28]. However, there is very little research on ichthyosis [27]. The results of the present study demonstrate that health related quality-of-life is reduced in ichthyosis.
An important consideration is the representativity of our patients. Previous studies show that the LI group included in this study (n = 37) represents over 65% of the estimated total number of adults with LI in Sweden (population 9 million). On the other hand, the IV and XRI groups included probably represent only about 0.15% and 1%, respectively, of the estimated number in Sweden afflicted by these types of ichthyosis [1, 2]. The possibility that our results are biased due to selective inclusion of patients with more severe forms of IV and XRI must therefore be considered, particularly as a significant proportion were recruited from either hospital files or a patient organisation where mild forms of XRI and IV may be underrepresented. Another question is the accuracy of the diagnosis of clinical sub-groups. We believe that the diagnostic sub-grouping was good, despite some possible overlap between the three groups. Of our participants, 88% were diagnosed at a hospital visit, or by a nurse at the Swedish Ichthyosis Association; only 12% were self-diagnosed. This should not affect the overall result.
In HRQoL studies of diseases such as ichthyosis, which may affect the patient's life broadly, it is important to use instruments that capture the multidimensional aspects of the disease. As suggested by Illiew [22], we used the SF-36 as a complement to the dermatology-specific tool DLQI in patients with chronic skin disease. Our results demonstrate that ichthyosis influences HRQoL, confirming that chronic skin diseases affect quality-of-life [13-15, 21].
In addition, we used a VAS method to assess patients' perception of their own skin symptoms. This method has previously been used for other skin diseases [13, 23]. In the VAS, patients rate their personal view of their symptoms. It may be that people with clinically more severe forms have adjusted to their symptoms and their lifelong skin disease differently from those with minor symptoms [27]. This hypothesis requires further study.
IV and XRI are usually considered clinically milder forms of ichthyosis than LI [1, 2]. Our LI patients had a significantly higher “total DLQI” score than did the XRI patients. The alleged differences in clinical severity of these diseases might explain some of the differences observed. This partly contradicts the VAS findings. However, the DLQI covers many dimensions of everyday life, which we think better represent the actual effect of a skin disease on quality of life. The mean total DLQI score was 6.1, approximately the same as in a previous study of psoriasis and atopic dermatitis [13 but lower than in several other studies of these diseases [10, 21, 24].
There were no significant differences between the three diagnostic groups in the SF-36. Previous studies of patients with psoriasis and atopic dermatitis have demonstrated both better [21] and worse [13, 15] SF-36 scores than ours. Our study group had significantly lower (worse) scores than the Swedish norm data in six of the eight SF-36 domains. In comparison with age and gender-adjusted norm scores, the group had significantly lower scores in four of the eight SF-36 domains. Although different groups of skin diseases have different clinical appearances and severity, this is not necessarily reflected in variations in their effect on quality of life. The results of the present and previous investigations do, however, indicate that the DLQI and, to a lesser extent, the SF-36 are sensitive to variations in the clinical expression of skin diseases, e.g. psoriasis, atopic dermatitis and ichthyosis. The outcome of HRQoL measurements will probably also depend on the age of onset of the skin disease and the time elapsed since then. Another factor of importance when comparing the SF-36 and the DLQI is the fact that the DLQI has only one question (embarrassed and self conscious) related to the mental health (MH) domain in SF-36.
An influence of gender was seen on the DLQI domains “daily activities” and “treatment” in the total group, where women scored significantly higher (worse) than did men. Other studies have reported that female psoriatic patients have higher DLQI scores [13, 21] than male patients. On the VAS, women scored higher (worse) than did men for scaling. Thus, women appear to experience their skin symptoms and the effect of these on everyday life more negatively than do men.
The correlations between the DLQI and the SF-36 can be seen as a test of how adequately the latter instrument captures the quality of life of patients with ichthyosis (assuming that the DLQI gives a “true” picture). The strongest correlation was found between the DLQI total and the social functioning of the SF-36. This is relevant since psychosocial domains are very important for patients with skin disease (13,21). The lowest correlations were found for “bodily pain” and “role-physical”, which suggests that pain and physical problems are not the predominant symptoms in ichthyosis (1,2). Thus, the DLQI is a suitable method for measuring the quality of life in patients with ichthyosis and is simpler to apply than the SF-36.
We also assessed the correlations between the measure of subjective disease activity and the two quality-of-life instruments. The DLQI domains correlated well with the skin symptoms “scaling” and “dryness” but less well with erythema.

Conclusion

In conclusion, the present study shows that patients with ichthyosis report a reduced quality of life as reflected by the DLQI and by some domains of the SF-36. In some of the DLQI dimensions and on the subjective measures of disease activity (VAS), we also detected some differences between women and men. Most of the dimensions of the DLQI and the SF-36 correlated significantly with each other and with the subjective measure of disease activity “today”. The results suggest that the DLQI is suitable for use in patients with ichthyosis. This finding does not exclude that SF-36 can be a more sensitive instrument in other types of skin diseases.

Acknowledgements. We are grateful to all the patients who participated in this study. The study was supported by grants from the Welander-Finsen Foundations. Part of the material was presented as an oral presentation at the 29^th Nordic Congress of Dermatology and Venereology in Gothenburg. n

References

1. Traupe H. The Ichthyoses: A guide to clinical Diagnosis, Genetic Counselling, and Therapy. Berlin: Springer-Verlag, 1989.

2. DiGiovanna J J. Ichthyosiform Dermatoses. In: Fitzpatrick Th B, et al. eds. Dermatology in General Medicine. 5^th edition. New York and London: The McGraw-Hill, 1999: 581-603.

3. Vahlquist A. Ichthyosis – An Inborn Dryness of the Skin. In: Lodén M., Mainbach H, eds. Dry Skin and Moisturisers. Chemistry and Function. Baton Rouge: CRC-Press, 2000:121-33.

4. Swanbeck G. A new treatment of ichthyosis and other hyperkeratotic conditions. Acta Derm Venereol 1968; 48: 123-7.

5. Van Scott EJ, Yu RJ. Control of keratinization with alpha-hydroxy acids and related compounds. I. Topical treatment of ichthyotic disorders. Arch Dermatol 1974; 110: 586-90.

6. Gnemo A, Virtanen M, Vahlquist A. Improved topical treatment of lamellar ichthyosis: a double-blind study of four different cream formulations. Br J Dermatol 1999; 141: 1027-32.

7. Lodén M. Keratolytics. In: Gabard B, Elsner P, Surber C, Treffel P, eds. Dermatopharmacology of Topical Preparations – A Product Development-Oriented Approach. Berlin: Springer-Verlag, 2000: 255-80.

8. Vahlquist A. Role of retinoids in normal and diseased skin. In: Blomhoff Red. Vitamin A in Health and Disease. New York: Marcel Dekker Inc., 1994:365

9. Wiklund I. The Nottingham Health Profile – A Measure of Health-related Quality of Life. Scand J Prim Health Care. Suppl 1990; 1: 15-18.

10. Finlay AY, Khan GK. Dermatology Life Quality Index (DLQI)- a simple practical measure for routine clinical use. Clin Exp Dermatol 1994; 19: 210-16.

11. Ware JE, Snow KK, Kosinski M, Gandek B. SF-36 Health Survey Manual and Interpretation Guide. Boston, MA: New England Medical Center, Health Institute, 1993.

12. Sullivan M, Karlsson J, Ware JE. SF-36 Hälsoenkät: Svensk manual och tolkningsguide (SF-36 Health survey: Swedish manual and interpretation guide). Gothenburg: Sahlgrenska University Hospital, 1994 (in Swedish).

13. Lundberg L, Johannesson M, Silverdahl M, et al. Health-related Quality of Life in Patients with Psoriasis an Atopic Dermatitis Measured with SF-36, DLQI and a Subjective Measure of Disease Activity. Acta Derm Venereol 2000; 80: 430-4.

14. Lundberg L, Johannesson M, Silverdahl M, et al. Quality of life, health-state utilities and willingness to pay in patients with psoriasis and atopic eczema. Br J Dermatol 1999; 141: 1067-75.

15. Wahl A, Loge JH, Wiklund I, Hanestad BR. The burden of psoriasis: A study concerning health – related quality of life among Norwegian adult patients with psoriasis compared with general population norms. J Am Acad Dermatol 2000; 43: 803-8.

16. Finlay AY. Dermatology patients: what do they really need? Clin. Exp. Dermatol. 2000; 25: 444-50.

17. Öhman H, Vahlquist A. The pH Gradient over the Stratum Corneum Differs in X-Linked Recessive and Autosomal Dominant Ichthyosis: A Clue to the Molecular Origin of the “Acid Skin Mantle” J Invest Dermatol 1998; 111: 674-7.

18. Siegel S, Castellan NJ. Nonparametric statistics for the behavioural sciences. Second edition. New York: McGraw-Hill Book Company, 1988.

19. Howell DC. Statistical methods for psychology. Third edition. Belmont, California: Duxbury Press, 1992.

20. Hjermstad M J, Fayers P M, Bjordal K, Kaasa S. Using Reference Data on Quality of life – the Importance of Adjusting for Age and gender, Exemplified by the EORTC QLQ-C30 (+ 3). Eur J Cancer 1998; 34: 1381-9.

21. Nichol M B, Margolies JE, Lippa E, et al. The Application of Multiple Quality-of-Life Instruments in Individuals with Mild-to-Moderate Psoriasis. Pharmaco Economics 1996; 10: 644-53.

22. Iliev D, Furrer L, Elsner P. Zur Einschätzung der Lebensqualität von Patienten in der Dermatologie. Der Hautarzt 1998; 49: 453-6.

23. Parslew R, Pryce D, Ashworth J, Friedmann PS. Warfarin treatment of chronic idiopathic urticaria and angio-oedema. Clin and Exp Allergy 2000; 30: 1161-5.

24. Kurwa HA, Finlay AY. Dermatology in-patient management greatly improves life quality. Br J Dermatol 1995; 133: 575-8.

25. Finlay AY. Quality of life measurement in dermatology: a practical guide. Br J Dermatol 1997; 136: 305-14.

26. Harlow D, Poyner T, Finlay AY, Dykes PJ. Impaired quality of life of adults with skin disease in primary care. Br J Dermatol 2000; 143: 979-82.

27. Gnemo A, Lindholm C, Lindberg M, et al. Quality of life in adults with congenital ichthyosis: a life-time perspective on an inherited skin disease. J of Advanced Nursing 2003; 44: 412-19.