A major obstacle in performing multicenter controlled trials for pemphigus is the lack of a validated disease activity scoring system. Here we assess the reliability and convergent validity of the PDAI (pemphigus disease area index). A group of 10 dermatologists scored 15 patients with pemphigus to estimate the inter- and intra-rater reliability of the PDAI and the recently described ABSIS (autoimmune bullous skin disorder intensity score) instrument. To assess convergent validity, these tools were also correlated with the Physician’s Global Assessment (PGA). Reliability studies demonstrated an intra-class correlation coefficient (ICC) for inter-rater reliability of 0.76 [95% CI = 0.61–0.91] for the PDAI and 0.77 [0.63–0.91] for the ABSIS. The tools differed most in reliability of assessing skin activity, with an ICC of 0.39 [0.17–0.60] for the ABSIS and 0.86 [0.76–0.95] for the PDAI. Intra-rater test-retest reliability demonstrated an ICC of 0.98 [0.96–1.0] for the PDAI and 0.80 [0.65–0.96] for the ABSIS. The PDAI also correlated more closely with the PGA. We conclude that the PDAI is more reproducible and correlates better with physician impression of extent. Subset analysis suggests that for this population of mild to moderate disease activity, the PDAI captures more variability in cutaneous disease than the ABSIS.

Human cutaneous photodamage is a major medical problem that includes premature aging and fragility of the skin. Non-xenografted animal models have not been comparatively evaluated for how well they resemble the changes seen in human skin. Here, we sought to identify a suitable mouse model that recapitulates key anatomic, cellular, and molecular responses observed in human skin during acute UV exposure. Adult females from three strains of mice, C57BL/6J, SKH-1, and Balb/c, were exposed to ultraviolet-B, and then evaluated 3h or 20h after the last irradiation. Skin from UVB-exposed C57BL/6J mice showed features resembling human photodamage, including epidermal thickening, infiltration of the dermis with inflammatory cells, induction of TNFα mRNA, accumulation of glycosaminoglycans (GAGs), particularly hyaluronan (HA) in the epidermis, and loss of collagen. Hairless SKH1 mouse skin responded similarly, but without any induction of TNFα mRNA or chondroitin sulfate (CS). Irradiated Balb/c mice were the least similar to humans. Our results in C57BL/6J mice, and to a lesser extent in SKH-1 mice, show cutaneous responses to a course of UVB-irradiation that mirror those seen in human skin. Proper choice of model is critical for investigating cellular and molecular mechanisms of photodamage and photoaging.

Ultraviolet (UV) light alters cutaneous structure and function. Prior work has shown loss of dermal hyaluronan after UV-irradiation of human skin, yet UV exposure increases total glycosaminoglycan (GAG) content in mouse models. To more fully describe UV-induced alterations to cutaneous GAG content, we subjected human volunteers to intermediate-term (5 doses/week for 4 weeks) or single-dose UV exposure. Total dermal uronyl-containing GAGs increased substantially with each of these regimens. We found that UV exposure substantially increased dermal content of chondroitin sulfate (CS), but not hyaluronan, heparan sulfate, or dermatan sulfate. UV induced the accumulation of both the 4-sulfated (C4S) and 6-sulfated (C6S) isoforms of CS, but in distinct distributions. Next, we examined several CS proteoglycan core proteins and found a significant accumulation of dermal and endothelial serglycin, but not of decorin or versican, after UV exposure. To examine regulation in vitro, we found that UVB in combination with IL-1α, a cytokine upregulated by UV radiation, induced serglycin mRNA in cultured dermal fibroblasts, but did not induce the chondroitin sulfate synthases. Overall, our data indicate that intermediate-term and single-dose UVB exposure induces specific GAGs and proteoglycan core proteins in human skin in vivo. These molecules have important biologic functions and contribute to the cutaneous response to UV.

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