The Pemphigus Disease Area Index (PDAI) was developed by international consensus by the International Pemphigus Definitions Committee, led by Victoria Werth and Dédée Murrell, as an extent measure to objectively assess bullous disease activity. The skin and scalp are assessed for disease extent and damage, and the oral mucosa is assessed for activity alone (Fig. 68.2). In the skin assessment, 12 anatomical sites (ears, nose, face, neck, chest, abdomen, back/buttocks, arms, hands, legs, feet, genitals) are reviewed and assigned a score according to disease activity—0 (no lesions), 1 (1–3 lesions, all ≤6 cm, up to 1 >2 cm), 2 (2–3 lesions, all ≤6 cm, at least 2 lesions >2 cm), 3 (>3 lesions, all ≤6 cm), 5 (>3 lesions and/or 1 lesion >6 cm), or 10 (>3 lesions and/or at least 1 lesion >16 cm). When a score of 1 is given, a lesion count is also incorporated, with a score of 1 given if 1 lesion is present, 1.3 for 2 lesions, and 1.6 for 3 lesions. The 12 sites are also reviewed for the presence of post-inflammatory hyperpigmentation or erythema from resolving lesions and assigned a score of 0 (absent) or 1 (present) to assess damage. Damage scores are not included in the overall activity score—they are there to remind graders that not all visible lesions represent activity. The scalp is assigned a score based on the presence of bullae, erosions, or new erythema of 0 (no activity), 1 (one quadrant affected), 2 (two quadrants affected), 3 (three quadrants affected), 4 (whole scalp affected), or 10 (at least 1 lesion >6 cm). A damage score of 0 or 1 is given to the entire scalp based on the presence of features previously described for the skin damage score. Mucosal activity is assessed by reviewing 12 mucosal sites (eyes, nose, buccal, hard palate, soft palate, upper gingiva, lower gingiva, tongue, floor of the mouth, labial mucosa, posterior pharynx, anogenitalia) and assigning a score based on the presence of erosions and blisters—0 (absent), 1 (1 lesion), 2 (2–3 lesions), 5 (>3 lesions or 2 lesions >2 cm), or 10 (entire area). The total possible score for the PDAI ranges from 0 to 130 for the skin score (120 points for body, 10 points for scalp) and up to 120 points for mucosal activity, with 13 points for damage. These are not combined. Validation studies, both in person and by photovalidation, have been conducted for the PDAI [8, 9].

One study compared the ABSIS and PDAI to evaluate the inter- and intra-rater reliability of the two instruments [8]. Ten dermatologists traveled to the University of Pennsylvania and evaluated 15 pemphigus patients using the ABSIS, PDAI, and the Physician’s Global Assessment (PGA)—a 10-point visual analogue scale used as a marker for convergent validity. Physicians were divided into two groups with half the physicians scoring patients with the ABSIS first, then the PDAI with the order reversed in the second group. Each physician returned to the original group 2 h later and re-rated two randomly assigned patients to evaluate intra-rater reliability. Both instruments demonstrated validity when correlated against the PGA with a correlation of 0.60 (0.49–0.71) for the PDAI and 0.43 (0.30–0.55) for the ABSIS. Inter-rater reliability had an overall intraclass correlation coefficient (ICC) of 0.76 (0.61–0.91) for the PDAI and 0.77 (0.63–0.91) for the ABSIS. The ABSIS was accordingly slightly better in terms of inter-rater reliability; however, for skin activity, the PDAI activity score had an ICC of 0.86 and the ABSIS 0.39, suggesting that the PDAI might be better at detecting differences in cutaneous disease. Intra-rater reliability was 0.98 (0.96–1.0) for the PDAI and 0.80 (0.65–0.96) for the ABSIS indicating that PDAI scores were more reproducible. The results of the study demonstrated that both instruments are validated extent measures for AIBD though it is possible that the PDAI may be more reliable.

An extent measure has also been developed for bullous pemphigoid, devised by The International Pemphigoid Committee led by Victoria Werth and Dédée Murrell. The BPDAI has an objective physician reported component and a subjective patient reported component.

Similar to the PDAI, the BPDAI has separate scores for activity and damage. The scoring of skin activity is the same as for the PDAI; however, activity is comprised of a section for erosions and blisters out of 120 and a section for erythema and urticaria out of 120 (Fig. 68.3). The erosions and blisters section also reports mucosal involvement out of 120, because although mucosal involvement in BP is uncommon, it was included in the BPDAI so that mucous membrane disease could be compared across different autoimmune bullous dermatoses. Damage scores are not included in the overall severity score—they are there to remind graders that not all visible lesions represent activity. The total objective physician reported score is out of 360.

As pruritus is a significant symptom for BP and may herald recurrence, a distinct subjective evaluation of this has been incorporated into the BPDAI. Patients are required to complete a visual analogue scale (VAS) on a 0–10 scale answering the questions “how severe has your itching been over the last 24 h?”, “how severe has your itching been the past week?”, and “how severe has your itching been in the past month?” each scored from 0 to 10 according to the distance on the scale. A total score is then calculated from this out of 30. If a patient is unable to complete this reliably (in the setting of cognitive impairment for instance), the degree of pruritus is inferred based on the extent of excoriation graded as either 0 (no excoriations), 10 (isolated excoriations at up to two body sites), 20 (excoriations on ≥ three body sites or impairment of activities of daily living), or 30 (generalized excoriation or sleep impairment) (Fig. 68.4).

Both the BPDAI and ABSIS have been shown to significantly correlated with anti-BP180 titers but not with anti-BP230 titres [13]. Anti-BP180, but not anti-BP230, titers have been established to correlate well with disease activity [14–16]. BPDAI correlated well with other clinical parameters of disease activity and proposed a cut-off value of 56 for severe BP [17]. Responsiveness of the BPDAI has been demonstrated to therapy and correlations to quality of life measures [18].

A range of severity measures have been published for the objective evaluation of disease activity in AIBD, though the majority have not been evaluated and have been constructed arbitrarily for use in clinical trials.

One instrument which has been validated is the Index of Skin and Mucous in Pemphigus Vulgaris (ISMIPV) [19]. Patients are scored according to the number of blisters (0–25 points), the size of blisters or erosions (0–25 points), presence of Nikolsky sign (0−20 points) and the involvement of mucous membranes or sepsis (0–30 points). It has been validated in a small cohort of 7 patients with active disease over 76 visits and was found to have a high inter-rater reliability with a Pearson’s correlation of 0.93 (0.89–0.95) and weighted kappa coefficient of 0.92 (0.89–0.96) between paired scorings of patients. The ISMPIV was also able to categorize patients as having mild, moderate, or severe disease to stratify disease severity. To the authors’ knowledge, it is the only extent measure other than the ABSIS and PDAI to have been validated for use in AIBD.

One of the earliest disease activity scores employed was the Pemphigus Area and Activity Score (PAAS) [20]. The PAAS divides the body into head, trunk, upper limbs, and lower limbs. Each division is assigned a score based on the number of new blisters, extension of existing blisters, and the presence of the Nikolsky sign and then multiplied by the area involved and an index, with the four scores totalled. Patients with mucosal involvement are also assigned a mucous membrane score by adding the number of mucosal sites involved to a severity score to ascertain a mucous membrane score.