Dermatology Life Quality Index (DLQI)

The DLQI is a widely used dermatology-specific quality of life instrument. It is a 10-item questionnaire that assesses six different aspects that may affect quality of life.^33,34 These aspects are: symptoms and feelings, daily activities, leisure, work and school performance, personal relationships, and treatment.^33,34 The maximum score per aspect is either 3 (with a single question) or 6 (with two questions), and the scores for each can be expressed as a percentage of either 3 or 6. Each of the 10 questions is scored from 0 (not at all) to 3 (very much), and the overall DLQI is calculated by summing the score of each question resulting in a numeric score between 0 and 30 (or a percentage of 30).^33,34 The higher the score, the more quality of life is impaired. The meaning of the DLQI scores on a patient’s life is as follows:³²

• 0 to 1 = no effect;
• 2 to 5 = small effect;
• 6 to 10 = moderate effect;
• 11 to 20 = very large effect;
• 21 to 30 = extremely large effect.

The DLQI has shown good test-retest reliability (correlation between overall DLQI scores was 0.99, P < 0.0001, and of individual question scores was 0.95 to 0.98, P < 0.001),³³ internal consistency reliability (with Cronbach’s alpha coefficients ranging from 0.75 to 0.92 when assessed in 12 international studies),³² construct validity (as 37 separate studies have mentioned a significant correlation of the DLQI with either generic or dermatology-specific and disease-specific measures),³² and responsiveness (the DLQI being able to detect changes before and after treatment in patients with psoriasis in 17 different studies).³²

Estimates of the minimally important difference (MID: the smallest difference a patient would regard as beneficial) have ranged from 2.2 to 6.9.^32,34 It should be noted that some of the anchors that were used in order to obtain the DLQI MID were not patient-based (i.e., Basra et al.³² derived estimates from PASI and PGA anchors, as well as a distribution-based approach).

Limitations associated with the DLQI are as follows:

• Concerns have been identified regarding unidimensionality and the behaviour of items of the DLQI in different psoriatic patient populations with respect to their cross-cultural equivalence and age and gender; however, these concerns were only identified in two citations out of the 12 international studies identified.³²
• The patient’s emotional aspects may be underrepresented and this may be one reason for unexpectedly low DLQI scores in patients with more emotionally disabling diseases such as vitiligo. To overcome this, it is suggested that the DLQI be combined with more emotionally-oriented measures such as the mental health component of the SF-36 scales or Hospital Anxiety and Depression Scale (HADS).³²
• The non-availability of benchmarks for the MCID of DLQI scores in general dermatological conditions, although there have been some attempts to determine these differences for specific conditions such as psoriasis.³²
• DLQI may lack sensitivity in detecting change from mild to severe psoriasis.⁴³

Investigator Global Assessment (IGA)

The static IGA scale is based on a point-in-time assessment, as opposed to the dynamic IGA scale, which is based on a recollection of the baseline disease severity.³⁵ The Physician Global Assessment (PGA) denotes scales used by clinicians, whereas the IGA is used by investigators in clinical trials.³⁵

The following outlines the possible scores on the IGA modified (mod) 2011 scale:³⁵

• 0 = clear (e.g., no signs of psoriasis, some post-inflammatory hyperpigmentation may be present);
• 1 = almost clear (e.g., no thickening, normal or pink coloration);
• 2 = mild (e.g., mild thickening, pink to light red coloration);
• 3 = moderate (e.g., moderate thickening, dull to bright red);
• 4 = severe (e.g., severe thickening, bright to deep red).

A recent review of the IGA scale reported the following advantages: it is relatively simple and easy to use; shows good correlation with PASI; it has high clinical construct validity (i.e., correlation with other severity measures); and has high test-retest reliability; there is good usage of the entire range of the scale; and there is moderate agreement among multiple assessors.³⁵ Limitations of the scale include: its inability to measure the extent of psoriasis; it may not be able to discriminate small changes in severity; there is no consideration for nonskin symptoms; and multiple versions of the scale limit study or trial comparisons.³⁵ In addition, no MCID has been established for psoriasis at this time.

Medical Outcomes Study Short Form (36) Health Survey (SF-36)

The SF-36 is a 36-item, general health status instrument that has been used extensively in clinical trials in many disease areas.¹⁹ The SF-36 consists of eight health domains: physical functioning (PF); role physical (RP); bodily pain (BP); general health (GH); vitality (VT); social functioning (SF); role emotional (RE); and mental health (MH).¹⁹ For each of the eight domains, a subscale score can be calculated. The SF-36 also provides two component summaries: the physical component summary (PCS) and the mental component summary (MCS), derived from aggregating the eight domains according to a scoring algorithm. The PCS, MCS, and eight dimensions are each measured on a scale of 0 to 100, which are t scores (mean of 50 and standard deviation of 10) that have been standardized to the US general population. Thus, a score of 50 on any scale would be at the average or norm of the general US population and a score 10 points lower (i.e., 40) would be one standard deviation below the norm. On any of the scales, an increase in score indicates improvement in health status.¹⁹

Validity and reliability of the SF-36 in patients with psoriasis is lacking; however, in one systematic review by Frendl and Ware⁴¹ that examined SF-36 concordance and its MCID across many different indications in studies that looked at drug therapy effectiveness, the SF-36 was observed to be responsive (when compared with primary clinical measures) in patients with psoriasis. In addition, of the ten psoriasis studies identified, net PCS or MCS improvement of at least 3 points was observed in 70% of these studies.

Based on anchor data, the SF-36 User’s Manual also proposed the following minimal mean group differences, in terms of t score points, for SF-36 version 2 (v2) individual dimension scores: PF = 3; RP = 3; BP = 3; GH = 2; VT = 2; SF = 3; RE = 4; and MH = 3. It should be noted that these minimally important difference (MID) values were determined as appropriate for groups with mean t score ranges of 30 to 40. For higher t score ranges, MID values may be higher.¹⁹ MID values do not represent patient-derived scores. The MIDs for the SF-36v2 are based on clinical and other non-patient-reported anchors.

Nail Psoriasis Severity Index (NAPSI)

The NAPSI was intended to both quantify the severity of psoriatic nail disease and assess the efficacy of drug therapy by looking at the nail involvement.³⁶ It was developed in part because the PASI does not incorporate anything that focuses on the severity of nail disease and the involvement of nail disease can predict higher disease severity and lower quality of life.⁴⁴ The main purpose of the NAPSI is to determine the degree of involvement of the psoriatic nail unit;⁴⁵ however, it was noted in the Augustin and Ogilvie⁴⁴ systematic overview of outcomes (which assessed nail involvement in patients with psoriasis) that these outcomes are not frequently performed. A larger value indicates more nail involvement and hence, potentially worse disease.⁴⁶

In order to obtain NAPSI scores, the nail is divided into four quadrants with each quadrant being assessed for nail matrix disease (described as pitting, lunular red spots, crumbling, and leukonychia) and nail bed disease (described as onycholysis, splinter hemorrhages, subungual hyperkeratosis, and salmon-patch dyschromia).^36,45,46 Each nail is given a score of 0 to 8 for a total score of 0 to 80 for the fingernails and 0 to 160 if the toenails are also included in the analysis.

Inter-observer reliability of the NAPSI was assessed in one study in which three dermatologists assessed all fingernails and toenails of 25 consecutive patients with psoriatic nail involvement in a dermatology outpatient clinic.⁴⁵ The nail quadrants were assessed for nail matrix disease and nail bed disease with a total score between 0 and 160 (as all 20 nails were scored). The authors computed the intraclass correlation coefficient (ICC) total NAPSI as 0.781, indicating that there was moderate to good inter-observer agreement in the total score. The ICC for the nail bed score was 0.869, which was considerably better than the nail matrix ICC at 0.584 (which does not meet the acceptable threshold of 0.70, and thus is inadequate). The authors speculated that the main difference between the two scores may be due to the difficulty in obtaining accurate evaluations of the smaller nail surfaces of the toes.⁴⁵ Limitations associated with the study were the small sample size and the lack of longitudinal observation that would incorporate repeated measures after treatment with various therapies.⁴⁵ NAPSI inter-rater correlation was also assessed in another study whose authors examined 45 patients who visited another outpatient dermatology clinic.⁴⁷Two investigators independently assessed the nails using the NAPSI on the same day and under the same conditions. A strong Pearson’s correlation (r) of 0.768, P < 0.001 was obtained for the inter-rater correlation; however, while a strong correlation between the two dermatologists existed when fingernails were scored (r of 0.690, P < 0.001) there was weak correlation between when examining the toenails (r of 0.183, P > 0.05).⁴⁷

While the NAPSI has been used in several studies on psoriasis as an outcome measure,^48–50 it has not yet been formally validated and it has shown significant inter-observer variability,⁴⁵ especially when examining affected toenails of patients with psoriasis.^45,47 In addition, there is no MCID associated with this instrument when assessing patients with psoriasis.

Psoriasis Area and Severity Index (PASI)

The PASI is a widely used instrument in psoriasis trials that assesses and grades the severity of psoriatic lesions and the patient’s response to treatment. It produces a numeric score ranging from 0 to 72. In general, a PASI score of 5 to 10 is considered moderate disease, and a score over 10 is considered severe. A 75% reduction in the PASI score (PASI 75) is the current benchmark for most clinical trials in psoriasis and the criterion for efficacy of new psoriasis treatments approved by the FDA.²⁰

In calculating the PASI, severity is determined by dividing the body into four regions: head (h), upper extremities (u), trunk (t) and lower extremities (l), that account for 10%, 20%, 30%, and 40% of the total body surface area (BSA), respectively.³⁸ Each of these areas is assessed separately for erythema, induration, and scaling, which is rated on a scale of 0 (none) to 4 (very severe). Extent of psoriatic involvement is graded as follows:

• 0 = no involvement;
• 1 = 1% to 9%;
• 2 = 10% to 29%;
• 3 = 30% to 49%;
• 4 = 50% to 69%;
• 5 = 70% to 89%;
• 6 = 90% to 100%.

The following formula is used to calculate the PASI score:

PASI = 0.1 (Eh + lh + Sh) Ah + 0.2 (Eu + lu + Su) Au + 0.3 (Et +lt + St) At + 0.4 (El +ll +Sl) Al³⁸

Where E = erythema, I = induration, S = scaling, A = area, h = head score, u = upper extremities, t = trunk score, and l = lower extremities score. PASI 75 is a dichotomous scale (Yes/No; patient achieved greater than and equal to 75% improvement from baseline PASI score).

A number of limitations of the PASI have been identified and include the following:

• The PASI has been criticized as not correlating the clinical extent of the disease with quality of life and the psychological stress caused by psoriasis. The patient’s measure of quality of life is often worse than the physician-rated clinical severity.⁵¹
• There are significant inter-rater reliability issues regarding the measurement of BSA.^37,38 There has been some work regarding the development of imaging and analysis systems to objectively measure BSA.⁵²
• PASI scores can vary substantially between experienced and inexperienced physicians, raising concerns for inter-rater reliability.⁵³
• Improvements in PASI score are not linearly related to severity or improvements in psoriasis.^20,38 The extent of psoriatic involvement is measured using a scale of 1 to 6 and the areas corresponding to each score are nonlinear.
• Some severe disease (clinically) may be scored low. For example, scores as low as 3 (on palms and soles) may represent psoriasis that disables a patient from work and other life activities.
• Most patients fall into a narrow band of scores, thereby decreasing the usefulness of the full range of scores (i.e., scores above 40 are rare).³⁷ Validity of this scale may be overrated, in part because of the skew toward lower scores.³⁹
• There is little research on the reliability of the assessments for erythema, desquamation, and induration, together with overall PASI scores.³⁷
• Criterion validity is restricted by the lack of a ‘gold standard’ measure of psoriatic severity.⁵⁴
• The PASI lacks sensitivity as erythema, desquamation, and induration are scored with equal weight within each of the four body regions. Thus, a reduction in scaling with a concomitant increase in skin erythema could be recorded with the same PASI score.
• Improvement of the histological phenotype of psoriasis can be underestimated by the per cent improvement in PASI (e.g., reduction of T cells, loss of keratin 16 (K16) expression and reduction in epidermal thickness).²⁰
• Little work has been done to determine the clinical relevance of derived PASI scores.³⁷

Physician Global Assessment (PGA)

The PGA is used to determine a single estimate of the patient’s overall severity of disease at a given point in time. Various PGAs have been used in psoriasis with different descriptions and scores.⁵³ Psoriatic lesions are graded for induration, erythema, and scaling based on scales of 0 to 4 that are then averaged over all lesions.⁵⁵ The following table highlights the scoring for induration, erythema, and scaling:

The sum of the three scales are added and then divided by three (I + E + S/3) to obtain a final PGA score as follows:

• 0 = cleared, except for residual discoloration;
• 1 = minimal – majority of lesions have individual scores for I + E + S/3 that average 1;
• 2 = mild – majority of lesions have individual scores that average 2;
• 3 = moderate – majority of lesions have individual scores that average 3;
• 4 = severe – majority of lesions have individual scores that average 4.

The PGA is more subjective than PASI in that there is no attempt to quantify the individual elements of plaque morphology or BSA involvement.^38,40 There have also been fewer studies using PGA than PASI. This outcome is considered reliable using test-retest data and internal consistency.⁴⁰ However inter-rater reliability is poor, due to variability, especially in untrained observers.⁴⁰ Many studies now employ only the final value of clear or almost clear as treatment success. Although it would seem that the PGA may be less likely to be open to interpretation, different studies have used different definitions of clear or almost clear, making comparisons between treatments difficult.⁴⁰ Construct and content validity are considered strong within a study, but comparison with other studies as well as relationship to other methods are problematic due to the variability in data collection, analysis, and reporting method.⁴⁰ No MCID has been identified in patients with psoriasis.