Separate measurements of disease activity and damage

The differentiation between activity and damage in our scores is unusual for dermatological scores,

Table 2

Contribution of body areas to the total score in different cutaneous outcome instruments

Table 2

Contribution of body areas to the total score in different cutaneous outcome instruments

Area

CLASI

CLASI

PASI/

Rule of

(activity)

(damage)

DSSI (%)

9 (%)

(%)

(%)

Head

29

36

10

9

Breast

13

12

5

9

Abdomen

7

6

5

9

Back

13

12

10

18

Legs

13

12

40

36

Arms/

13

12

30

18

hands

Mucous

7

6

membrane

however, this distinction is established for scores of SLE, where these aspects are commonly separated. This separation leads to two separate scores results for each patient. We have chosen to calculate the score for activity and damage separately. Activity and damage are distinct aspects of the disease and the damage depends largely on the form of CLE present. Separating damage and activity makes both aspects easily quantifiable and assures that the CLASI is more reactive to therapy-induced changes of activity. In contrast, using one summary score may lead to paradoxically stable scores as the activity decreases and the damage becomes apparent. Thus, the score may remain the same, while the clinical picture changes completely.

7.2.4. Associated symptoms Itch, pain and fatigue have been recorded separately on a visual 1-10 analogue scale by the patients. While itch and pain are relatively easy to associate with skin disease, it is hard to distinguish between fatigue caused by systemic disease and skin disease. Thus, there can be justified debate as to whether it is appropriate to measure it in this context. However, fatigue is a prominent symptom of patients who may have no other symptoms of systemic disease. Fatigue has also been specifically mentioned in the FDA background paper, and therefore we have recorded the level of fatigue for CLE evaluations. Also, fatigue has been shown to be a critical factor in determining HRQL among SLE patients (Hanly, 1997; Hochbert et al., 1990). Integration of these results is not easy though. The attempt to combine subjective patient outcomes and physician's assessment, as for the SCORAD, has been plagued with difficulties. Therefore, the SCORAD has abandoned the use of subjective patient outcomes in drug trials (Anon, 1993; Charman and Williams, 2000). Similarly, the Leicester score for atopic dermatitis distinguishes between recording of pruritus and the physician-administered skin score (Berth-Jones et al., 1995). Based on these precedents we have measured the results of the associated symptoms in terms of percentage change, as the most appropriate description (Farrar et al., 2003).

7.2.5. The Cutaneous LE Activity and Severity Index (CLASI)

As described above, the CLASI has two scores. It is designed as a table where the rows denote anatomical areas, while the columns score major clinical symptoms (see Fig. 1). The left side of the instrument describes the activity of the disease, while the right side describes the damage done by the disease. Activity is scored as a summary score of erythema, scale/hypertrophy, mucous-membrane involvement, acute hair loss and non-scarring alopecia. Damage is scored in terms of dyspigmentation and scarring, including scarring alopecia. Patients are asked whether dyspigmen-tation due to CLE lesions usually remains visible for more than 12 months, which is taken to be permanent. If so, the dyspigmentation score is doubled. The scores are calculated by simple addition based on the extent of the symptoms. The extent of involvement for each of the skin symptoms is documented according to specific anatomic areas that are scored according to the worst affected lesion within that area for each symptom. The subjective symptoms documented by the patient like itch, pain and fatigue are recorded separately on visual 1-10 analogue scales. These symptoms can be important for the assessment of therapeutic success because they can be more reactive than the visual skin to therapeutic improvement.

7.2.6. Validation of the CLASI

The validation of the CLASI is described in detail elsewhere (Albrecht et al., 2005). This process has confirmed content validity. Construct validity is assessed by comparing the instrument to the other outcome instruments for cutaneous lupus. These do not exist, but the measures used in the SLE instruments available correlate with the CLASI. We did not assess criterion validity because the reason for the development of the instrument was that there was no measurement available. Reliability studies demonstrated an intraclass correlation coefficient (ICC) for inter-rater reliability of 0.86 for the activity score [95% confidence interval (CI) 0.73-0.99] and of 0.92 for the damage score (95% CI 0.85-1.00). The Spearman's Rho for in-tra-rater reliability for the activity score was 0.96

Cutaneous LE Disease Area and Severity Index (CLASI)

Select the score in each anatomical location that describes the most severely affected cutaneous lupus-associated lesion activity damage

Anatomical Location

Erythema

Scale/ Hypertrophy

Dyspigmentation

Scarring/ Atrophy/ Panniculitis

Anatomical Location

1-pink; faint erythema

3-dark red; purple/violaceous/ crusted/ hemorrhagic

0-absent;

1-scale

2-verrucous/ hypertrophic

0-absent,

1 - scarring

2 - severely atrophic scarring or panniculitis

Scalp

See below

Scalp

Ears

Ears

Nose (incl. malar area)

Nose (incl. malar area)

Rest of the face

Rest of the face

V-area neck (frontal)

V-area neck (frontal)

Post. Neck &/or shoulders

Post. Neck &/or shoulders

Chest

Chest

Abdomen

Abdomen

Back, buttocks

Back, buttocks

Arms

Arms

Hands

Hands

Legs

Legs

Feet

Dyspigmentation

Mucous membrane lesions (examine if patient confirms involvement)

Report duration of dyspigmentation after active lesions have resolved (verbal report by patient - tick appropriate box)

0-absent;

1-lesion or ulceration

Dyspigmentation usually lasts less than 12 months (dyspigmentation score above remains)

Dyspigmentation usually lasts at least 12 months (dyspigmentation score is doubled)

Alopecia

Recent Hair loss

(within the last 30 days / as reported by patient)

NB: if scarring and non-scarring aspects seem to coexist in one lesion, please score both

1-Yes 0-No

Divide the scalp into four quadrants as shown. The dividing line between right and left is the midline. The dividing line between frontal and occipital is the line connecting the highest points of the ear lobe. A quadrant is considered affected if there is a lesion within the quadrant.

Alopecia (clinically not obviously scarred)

Scarring of the scalp (judged clinically)

0-absent

1-diffuse; non-inflammatory

2-focal or patchy in one quadrant;

3-focal or patchy in more than one quadrant

3- in one quadrant

4- two quadrants

5- three quadrants

6- affects the whole skull

(For the activity score please add up the scores of the left side i.e. for Erythema, Scale/Hypertrophy, Mucous membrane involvement and Alopecia)

Total Damage Score

(For the damage score, please add up the scores of the right side, i.e. for Dyspigmentation, Scarring/Atrophy/Panniculitis and Scarring of the Scalp)

Total Activity Score

(For the activity score please add up the scores of the left side i.e. for Erythema, Scale/Hypertrophy, Mucous membrane involvement and Alopecia)

Total Damage Score

(For the damage score, please add up the scores of the right side, i.e. for Dyspigmentation, Scarring/Atrophy/Panniculitis and Scarring of the Scalp)

Figure 1. Cutaneous LE Disease Area and Severity Index (CLASI).

(95% CI 0.89-1.00) and for the damage score Spearman's Rho was 0.99 (95% CI 0.97-1.00). Currently, we are conducting a clinical study to demonstrate clinical responsiveness of the CLASI on 10 patients who are started on a new treatment. During this observational study we correlate treatment response as measured with the CLASI with a 0-10 visual analogue scale measurements of pain, itch and fatigue by the patients, and assessment of skin health by the patients and the physician. In addition, the patients are photographed and the skin is assessed by an independent observer. Preliminary analysis of the first half of the patients shows that the CLASI reflects treatment success and demonstrates clinical responsiveness, but remains unchanged if the treatment fails.

Conclusion

This chapter is part of a book on autoimmune diseases and the skin. The development of two skin-specific outcome instruments for autoimmune diseases within 1 year is an important step forward. However, this small step only makes painfully clear that these instruments are lacking for all the other diseases discussed in this book. We hope that this discussion and the workshop will motivate others to extend the range of instruments available to more of cutaneous autoimmune diseases and that these instruments will be used frequently. It is important to note that from the beginning the development of a new outcome instrument for a disease must be an interactive process in as broad a disease community as possible. The experience with SLE illustrates that a large community can develop a variety of instruments. This abundance makes the comparison of clinical trials more difficult and limits the experience with each instrument. To avoid this, an open and interactive development process is needed.

Key points

• Without adequate outcome instruments, clinical research and therapeutic advances cannot be achieved.

• Cutaneous autoimmune diseases need outcome instruments that are skin specific.

• There is a body of experience on which the design and validation of cutaneous outcome instruments can be based.

• New outcome instruments need to be thoroughly evaluated in multiple stages to define their usefulness and biometric properties.

• Ideally, one outcome instrument is used as the basis for clinical research in any disease to allow standardization and comparability of clinical research.

• There are few outcome instruments for cutaneous autoimmune diseases, except the CLASI for CLE and the DSSI for DM and even these two instruments have not been fully evaluated.

• More instruments should be developed for cutaneous autoimmune diseases.

• Their development should be an open and interactive process within the disease community in order to avoid the development of scores that do not reach broad acceptance and the parallel development of more than one instrument.

Acknowledgement

This research was supported by NIH K24-AR 02207 (VPW) and a research training grant in dermatology NIH 2T32-AR-007465 (JA).

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Handbook of Systemic Autoimmune Diseases, Volume 5 The Skin in Systemic Autoimmune Diseases

Piercarlo Sarzi-Puttini, Andrea Doria, Giampiero Girolomoni and Annegret Kuhn, editors

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