The scientific focus of this proposal is patient-oriented research (POR) in lupus erythematosus (LE). Our laboratory studies the genetics of photosensitivity in LE (supported by a VA Merit Review), as well as fundamental POR needed for development of new therapies in LE (the current proposal). Our recent studies are developing and validating outcome measures needed for measuring cutaneous LE activity and severity.
Aim I. Expansion of inter-rater and intra-rater validation studies Our current published studies with a small number of patients and evaluating dermatologists suggest excellent inter-rater and intra-rater variability with the cutaneous lupus erythematosus disease activity and severity index (CLASI) measure of cutaneous LE activity and damage. It is important to expand the current studies that have been done to include more patients, including those with acute LE changes in the skin, to validate the CLASI with both more dermatologists, and to extend the studies to include rheumatologists. The proposed studies will allow progression to Aim II, which involves use of the CLASI to evaluate large referral populations of cutaneous LE patients, in addition to quality of life studies and POR translational studies.
Aim II. Prevalence of clinical severity of cutaneous lupus erythematosus requiring novel interventions, quality of life (QOL) measurement of cutaneous LE and the correlation of the CLASI with QOL measurement. There are currently a number of new therapies that should be tested in patients with cutaneous LE. A prospective study we recently completed showed excellent responsiveness of the CLASI after drug intervention. Improvement in the CLASI correlated with improvement in both patient and physician global measures of skin health. With the recent availability of this instrument to quantify skin-specific LE disease activity and damage, as well as a quality of life (QOL) index specific to skin (Skindex 29), and after further validation studies proposed in Aim I, it is now possible to evaluate the severity of disease in patients who are using currently available drugs. Thus, it is proposed in this application to use tools for quantifying skin disease activity and QOL measurements to cross-sectionally evaluate subsets of cutaneous LE. The purpose will be to examine the severity of various subsets of cutaneous LE, their QOL, and the correlation of the QOL measures with the CLASI. In particular, it is necessary to evaluate how many patients with severe cutaneous LE are currently experiencing significant disease despite use of available agents, in order to assess the need for new therapies and to design trials of new agents. This will facilitate future genetic, focused microarray and PCR studies, as well as mechanistic studies related to subsets of cutaneous lupus erythematosus. These studies will allow further careful validation of the CLASI, as well as aid in planning of future trials.

Agency
National Institute of Health (NIH)
Institute
National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
Type
Midcareer Investigator Award in Patient-Oriented Research (K24)
Project #
5K24AR002207-10
Application #
8228173
Study Section
Arthritis and Musculoskeletal and Skin Diseases Special Grants Review Committee (AMS)
Program Officer
Cibotti, Ricardo
Project Start
2001-07-25
Project End
2013-02-28
Budget Start
2012-03-01
Budget End
2013-02-28
Support Year
10
Fiscal Year
2012
Total Cost
$153,485
Indirect Cost
$11,369
Name
University of Pennsylvania
Department
Dermatology
Type
Schools of Medicine
DUNS #
042250712
City
Philadelphia
State
PA
Country
United States
Zip Code
19104
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Verma, S M; Okawa, J; Propert, K J et al. (2014) The impact of skin damage due to cutaneous lupus on quality of life. Br J Dermatol 170:315-21
Okon, Lauren; Rosenbach, Misha; Krathen, Michael et al. (2014) Lenalidomide in treatment-refractory cutaneous lupus erythematosus: Efficacy and safety in a 52-week trial. J Am Acad Dermatol 70:583-4
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Okon, Lauren; Werth, Victoria P (2014) Challenges in measuring outcomes: size assessment of an individual cutaneous lesion. J Am Acad Dermatol 71:402-4
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Xu, Hong-Hui; Werth, Victoria P; Parisi, Ernesta et al. (2013) Mucous membrane pemphigoid. Dent Clin North Am 57:611-30
Foering, Kristen; Chang, Aileen Y; Piette, Evan W et al. (2013) Characterization of clinical photosensitivity in cutaneous lupus erythematosus. J Am Acad Dermatol 69:205-13
Ghazi, Elizabeth; Sontheimer, Richard D; Werth, Victoria P (2013) The importance of including amyopathic dermatomyositis in the idiopathic inflammatory myositis spectrum. Clin Exp Rheumatol 31:128-34

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