Ichthyosis vulgaris

Chronic vulvar lichen sclerosus (LS) is most often seen in women over 50. The exact cause of LS is unknown. Reports of family members with a history of LS make one suspect the possibility of a genetic link. There is also the possibility that it has an autoimmune component. The occurrence and prevalence rates are possibly vague or understated because women do not come forward and talk about their disease until and unless the disease activity becomes intolerable. The extent of quality of life (QOL) impact with this condition, however, has not been systematically assessed, and is known largely from anecdotal reports from patients. The dermatology-specific quality of life (DSQL) instrument that has been validated in several skin diseases such as acne, contact dermatitis, and psoriasis, has been adapted to effectively evaluate the impact of LS on the women's quality of life. The severity of the disease as measured by the physician is very well correlated with the quality of life scores as evaluated by the subjects. The scales of the instrument were shown to be highly reliable. It is concluded that the DSQL instrument can effectively evaluate the impact of chronic vulvar lichen sclerosus, its treatment, and outcomes from medical care.

Key Words: Quality of life; Vulvar lichen sclerosus

INTRODUCTION

CHRONIC VULVAR DERMATOSES such as that due to lichen sclerosus (formerly known as lichen sclerosus et atrophicus) impact the quality of life of women to a great extent. Bellman (1) has performed a thorough literature search from 1966 to the present day and found no appreciable research literature on QOL assessment for chronic vulvar dermatoses. Existing QOL instruments for dermatological conditions such as the Dermatology Life Quality Index (2) are not sufficient to measure the sensitive features inherent in chronic vulvar dermatoses. The dermatology-specific quality of life instrument was adapted to produce a quality of life instrument that can effectively measure such impact and monitor progress from treatment.

Lichen sclerosus is more common in women than men. It can occur at any age; in a study among 350 women with lichen sclerosus, the onset of the disease was during childhood in 31 of them, all with anogenital lesions. LS has been noted in patients as young as six months of age (3,4). A recent series described 15 cases in girls (5). Occurrence and prevalence rates are pretty vague or understated because women do not come forward and talk openly until the disease activity becomes intolerable.

Occurrence and Etiology

LS occurs most commonly on genital skin. In women, this results in a white fragile vulva. Anogenital LS often involves the perianal area, labia minora, inner aspect of the labia minora, clitoris, introitus, and to a lesser extent the vestibule. There appears to be a greater occurrence among whites than among other racial groups (6).

The link with autoimmune disease is well substantiated. In a study of 350 women (3), 22% had a family history of autoimmune disease, 21% had an autoimmune disorder, and 44% had one or more autoimmune antibodies. Familial incidence in LS is well recognized. Human leukocyte antigen (HLA) typing has been of uncertain significance (7); these discrepancies were attributed by Purcell et al. (8) to population variability, technical limitations, and, possibly, clinical patterns (sex and site) of the disease.

Diagnostic Characteristics

LS lesions appear as small white patches that are thin and have a crinkled appearance. They look like a cigarette paper at times and may involve the entire vulvar area (from clitoris to the anus). Scarring of the clitorial foreskin often hides the clitoris. Labia minora almost disappear completely at times. Often, splitting of the skin in the midline is seen. Tears may also develop in the natural folds of the vulva. The vaginal opening may become smaller, interfering with intercourse. Occasionally, the tissue breaks down, forming an ulcerative lesion. It is usually a chronic process with no defined cure. Itching is the primary symptom initially, and pain often occurs in more advanced disease, due to erosions, fissures, and excoriation. Surprisingly, the disease does not spread into the vaginal mucosa (9).

METHODS

In two medical centers in the southeastern United States, 45 female subjects were enrolled in the study and 43 subjects were included in the data analysis; two subjects under the age of 16 who did not answer the majority of items were excluded from the analysis.

The severity of lichen sclerosus was evaluated by the treating dermatologist who remained blinded to the subject's QOL evaluations, using the following guidelines:

Mild disease-Some visible skin changes but not acutely inflamed, where the patient has some awareness of symptoms,

Moderate disease-Some acute inflammation, where patient describes occasional but intense discomfort, and

Severe disease-Bright red skin with fissures and erosions, where patient describes constant intense discomfort.

The dermatology-specific quality of life instrument (Those interested in seeing the complete contents of the DSQL instrument or DSQL-V instrument may obtain a copy by contacting the author) has been validated and used repeatedly in various diseases such as acne vulgaris and contact dermatitis (10,11), and it is in the last stage of validation for psoriasis (12) and ichthyosis vulgaris. In response to dermatologists who have been treating chronic vulvar lichen sclerosus for a long time, the DSQL has been adapted to use in evaluating the impact of LS on patients' QOL. A patient focus group was also used to further make the DSQL-V instrument relevant to LS. Quality of life evaluation included the following scales: physical symptoms: 12 items; activities of daily living: six items; social functioning: nine items; sexual functioning: four items; work/school functioning: seven items; self-perception: five items, and global items: five items. In addition, five items for mental health and four items for vitality from the Medical Outcomes Trust Instrument Short Form-36) (13) were used.

Symptom Frequency (Unweighted and Weighted by Severity)

Unlike DSQL evaluation in the other diseases, it is found that in LS, quality of life can very well be the primary efficacy parameter because it is the endpoint that is most significantly affected by the disease as well as the treatment. The other variation in this Dermatology-specific Quality of Life in vulvar diseases (DSQL-V) instrument is that the symptoms are evaluated not only by their frequency but also by their severity. Then for purposes of analyses, three methods were tested:

Method A-An unweighted total frequency score was created using the standard formula in the DSQL,

Method B-Each symptom frequency raw score was multiplied by the product of the symptom severity value and the weight (QOL global item score [0.0-1.0]), and

Method C-Each symptom frequency raw score was multiplied by the symptom severity value.

Table 1 compares the efficiencies of the three methodologies.

From the description above, it is clear that using weights (overall quality of life selfevaluated by patient multiplied by symptom severity) is the most appropriate method for the best use of the information on both frequency and severity. In this initial study, many subjects did not respond to both frequency and severity for the items on physical symptoms, perhaps because they did not follow the question formatting. The subjects will have to be educated appropriately in future studies to respond to both the factors.

Construct Validity. Construct validity is concerned with the extent to which a particular measure relates to other measures in a manner consistent with theoretical hypotheses concerning the concepts (or constructs) being measured (14).

The Internal Consistency. The internal consistency reliability score (Cronbach's a) measures the extent to which different items within a particular scale are measuring the same content or characteristic (15). Internal consistency is particularly important in judging whether the items being grouped together measure a united underlying domain. If the coefficient does not meet the 0.80 criterion, the resulting scale score may be too unreliable to accurately detect the presence of the construct or to detect a change following an intervention (16). A reliability coefficient of 0.90 is considered excellent.

RESULTS

A total of 50 patients seen in dermatology clinics at the Wake Forest University School of Medicine (Dr. Sherertz) and at the Carolinas Medical Center in Charlotte (Dr. Edwards) who were diagnosed with vulvar lichen sclerosus were selected to complete the DSQL-V instrument. Patients were included in the study as they came to the clinic seeking either initial treatment or follow-up care. The age range was 11-83 years and the median age was 52.5 years. As per physician evaluations, most women had mild (42%) or moderate (42%) disease.

Physical Symptoms

For two out of three women, symptoms such as soreness, itching, discomfort with sex, cracking, pain, and burning were moderate to severe in intensity (Table 2). These symptoms occurred from once or twice a week to daily for 50-70% of the women. Other symptoms such as dryness, narrowing of the vaginal opening, and wetness/discharge were moderate to severe in 30-40% of the women and were reported in high frequency by about 40% of the women with LS.

Other DSQL-V Scales

At least half the women complained of a negative impact on their quality of life as more than an occasional occurrence, in the areas of activities of daily living (ADL), social functioning, sexual functioning, and self-perception (Table 3).

Construct Validity

Construct validity is concerned with the extent to which a particular measure relates to other measures in a manner consistent with theoretical hypotheses concerning the concepts (or constructs) being measured. Figure 1 shows that at least 25-55% of the respondents reported limitations in activities of daily living, social functioning, sexual functioning, and self-perception "sometimes," "often," or "most of the time/constantly."

Patients who were rated as having severe disease as evaluated by their physician also evaluated the impact on their quality of life to be severe. Figure 2 shows the gradient in physician-assessed severity closely matching the patients' evaluation of their quality of life in all the scales except work/school functioning. Recall that the physician and subjects were blinded to each other's evaluation. Similarly, the global item on self-rated severity of the disease by the patients matches closely with the patients' evaluation of their quality of life in all the scales except work/school functioning (Figure 3).

Reliability

Chosen global items were tested for correlation with symptom total scores by all the three methods. All the correlations were significant; however, symptom total scores obtained by Method b where the symptom frequency raw score was multiplied by the product of the symptom severity value and the weight (QOL global item score [0.0-1.0]) had the maximum correlation with the global items. The number of observations in Methods b and c for symptom total scores was only 25 compared to 43 in the unweighted Method a because many patients did not check any box for severity; still the correlations were quite high in Method b.

The weighted symptom total accounts for a higher proportion of the variability (R2) in the global item response than the unweighted symptom total score (Table 4). The analysis will be revisited when the data collection has a reduced proportion of missing data for the frequency score.

The internal consistency reliability score (Cronbach's or) measures the extent to which different items within a particular scale are measuring the same content or characteristic. A reliability coefficient of 0.90 is considered excellent. Cronbach's a for all QOL scales ranged from 0.83-0.93 (Table 5).

Finally, the scale total scores were tested for relative validity with chosen global items such as bothersome symptoms, self-perceived severity of the disease over the last month, and overall QOL score. The correlation coefficients displayed in Table 6 show the high degree of correlation among the scale total scores and the global items except the work/school functioning and vitality scales.

CONCLUSION

The construct validity data show that the severity of chronic vulvar dermatoses is directly proportional to the impact they produce on the patients' quality of life. There is a definite need for QOL measurement with an instrument that is sensitive to changes in disease severity due to time and intervention. Patients seeking care for vulvar dermatoses (eg, lichen sclerosus) have considerable quality of life impairment. In this study, not only did a majority of patients report an impact on sexual functioning, but they also reported frustration, and a significant impact on general happiness. Their self-esteem and confidence were affected too. Data in this study show that all major quality of life domains are affected except work/school functioning. The latter scale will be refined to be more sensitive to issues faced by women at work such as repetitive motion related to tasks and sitting for extensive periods. Although there are various effective treatments for lichen sclerosus, their impact on quality of life have not been measured at this time; that will be the authors' next step. DSQL scales demonstrate excellent internal consistency. The DSQL instrument duly refined based on these results will be ready for use in clinical trials to compare QOL outcomes before and after treatment. Further, the sensitivity of the instrument and its subscales will also be tested for differences in treatment impact on QOL between comparative treatments.

Acknowledgment-The study has been conducted with a grant from Glaxo Welcome Inc., Research Triangle Park, North Carolina.

REFERENCES

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New England Medical Center, Boston MA, 1993. 14. Jaesekhe R, Guyatt GH. How to develop and validate a new quality of life instrument. In Spilker B, ed. Quality of Life Assessments in Clinical Trials. New York, NY; Raven Press: 1990:47-57. 15. Gilford JP. Psychometric Methods. 2nd ed. New

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16. Anderson RT, Hays RD, Revicki D. Psychometric and related considerations in dermatological assessments of health-related quality of life. In Rajagopalan R, Sherertz EF, Anderson RT, eds. Care Management of Skin Diseases-Life Quality and Economic Impact. New York, NY: Marcel Dekker Inc.; 1997: 35-48.

RUKMINI RAJAGOPALAN, DRPH, MBA, RN

Glaxo Wellcome Inc., Research Triangle Park, North Carolina

ROGER T. ANDERSON, PHD, AND ELIZABETH F.SHERERTZ, MD

Wake Forest University School of Medicine, Winston-Salem, North Carolina

LIBBY EDWARDS, MD

Carolina Medical Center, Charlotte, North Carolina

Presented at the DIA Fifth Annual Symposium "Quality of Life Evaluation," April 5-7, 1998, Hilton Head, South Carolina.

Reprint address: Rukmini Rajagopalan, DrPH, MBA, RN, Glaxo Dermatology, A division of Glaxo Wellcome Inc., Five Moore Drive, Research Triangle Park, North Carolina.

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