Joyce Okawa

Reliability and Convergent Validity of Two Outcome Instruments for Pemphigus

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 Physicians Global Assessment (PGA). Reliability studies demonstrated an intra-class correlation coefficient (ICC) for inter-rater reliability of 0.76 (95% confirdence interval (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.

Response to Antimalarial Agents in Cutaneous Lupus Erythematosus: A Prospective Analysis

OBJECTIVE To demonstrate response to antimalarial agents in patients with cutaneous lupus erythematosus (CLE) using activity scores from the Cutaneous Lupus Erythematosus Disease Area and Severity Index, a validated outcome measure. DESIGN Prospective, longitudinal cohort study. SETTING University cutaneous autoimmune disease clinic. PARTICIPANTS A total of 128 patients with CLE who presented from January 2007 to July 2010 and had at least 2 visits with activity scores. INTERVENTION Administration of antimalarial agents. MAIN OUTCOME MEASURES Response was defined by a 4-point or 20% decrease in activity score. Response to initiation was determined by the difference between the scores before treatment and at the first visit at least 2 months after treatment. Response to continuation was determined by the difference between the scores at the first visit and the most recent visit while undergoing treatment. RESULTS Of 11 patients who initiated treatment with hydroxychloroquine, 55% were responders (n = 6), showing a decrease in median (interquartile range [IQR]) activity score from 8.0 (3.5-13.0) to 3.0 (1.8-7.3) (P = .03). Of 15 patients for whom hydroxychloroquine failed, 67% were responders to initiation of hydroxychloroquine-quinacrine therapy (n = 10), showing a decrease in median (IQR) activity score from 6.0 (4.8-8.3) to 3.0 (0.75-5.0) (P = .004). Nine of 21 patients who continued hydroxychloroquine treatment (43%), and 9 of 21 patients who continued hydroxychloroquine-quinacrine (43%) were responders, showing a decrease in median (IQR) activity score from 6.0 (1.5-9.5) to 1.0 (0.0-4.5) (P = .01) and 8.5 (4.25-17.5) to 5.0 (0.5-11.5) (P = .01), respectively. CONCLUSIONS The use of quinacrine with hydroxychloroquine is associated with response in patients for whom hydroxychloroquine monotherapy fails. Further reduction in disease activity can be associated with continuation of treatment with antimalarial agents.

Quality of life in cutaneous lupus erythematosus

BACKGROUND Little is known about quality of life in patients with cutaneous lupus erythematosus. OBJECTIVE We sought to determine how cutaneous lupus affects quality of life and which independent variables are associated with poor quality of life. METHODS A total of 157 patients with cutaneous lupus completed surveys related to quality of life, including the Skindex-29 and the Short Form-36. RESULTS Quality of life in cutaneous lupus is severely impaired, particularly with respect to emotional well-being. Patients with cutaneous lupus have worse quality of life than those with other common dermatologic conditions, such as acne, nonmelanoma skin cancer, and alopecia. With respect to mental health status, patients with cutaneous lupus have similar or worse scores than patients with hypertension, type 2 diabetes mellitus, recent myocardial infarction, and congestive heart failure. Factors related to poor quality of life include female gender, generalized disease, severe disease, distribution of lesions, and younger age. LIMITATIONS The study was done at a single referral-only center. CONCLUSION Patients with cutaneous lupus have very impaired quality of life, particularly from an emotional perspective.

Development of the CLASI as a Tool to Measure Disease Severity and Responsiveness to Therapy in Cutaneous Lupus Erythematosus

OBJECTIVE To determine how to use the Cutaneous Lupus Erythematosus Disease Area and Severity Index (CLASI) to classify patients according to disease severity (mild, moderate, and severe) and to identify which patients respond to therapy. DESIGN Cohort. SETTING The connective-tissue disease clinic at the Hospital of the University of Pennsylvania, Philadelphia. PATIENTS Seventy-five patients with clinical or histopathologic evidence of cutaneous lupus erythematosus or systemic lupus erythematosus were included in the study. MAIN OUTCOME MEASURES The CLASI, Skindex-29, and the physicians subjective assessment of severity and improvement were completed at every visit. RESULTS Disease severity was assessed with 45 patient visits. Mild, moderate, and severe disease corresponded with CLASI activity score ranges of 0 to 9, 10 to 20, and 21 to 70, respectively. Improvement in disease activity was assessed in 74 patients. A clinical improvement was associated with a mean 3-point or 18% decrease in the CLASI activity score. However, receiver operating characteristic analysis demonstrated an increased percentage of patients correctly classified when a 4-point (sensitivity, 39%; specificity, 93%; correctly classified, 76%) or 20% (sensitivity, 46%; specificity, 78%; correctly classified, 67%) decrease in the CLASI activity score was used instead to identify improvement. CONCLUSION The CLASI can be used to classify patients into groups according to disease severity and to identify clinically significant improvements in disease activity.

Comparison of the reliability and validity of outcome instruments for cutaneous dermatomyositis

Background  Reliable and validated measures of skin disease severity are needed for cutaneous dermatomyositis (DM). Cutaneous Dermatomyositis Disease Area and Severity Index (CDASI), Dermatomyositis Skin Severity Index (DSSI) and Cutaneous Assessment Tool (CAT) skin indices have been developed as outcome instruments.

Cross-sectional Analysis of a Collaborative Web-Based Database for Lupus Erythematosus–Associated Skin Lesions: Prospective Enrollment of 114 Patients

OBJECTIVES To assess disease severity in subsets of patients with cutaneous lupus erythematosus (CLE) by using outcome and quality-of-life measures, and to determine treatment responsiveness by establishing a Web-based database of patients with skin manifestations of lupus. DESIGN Prospective, cross-sectional study. SETTING University hospital cutaneous autoimmunity outpatient clinic. PATIENTS One hundred fourteen patients who presented from January 15, 2007, to November 8, 2007, and met the criteria for having CLE or lupus-nonspecific skin disease. MAIN OUTCOME MEASURES Scores on the CLE Disease Activity and Severity Index and the modified Skindex-29 (a quality-of-life measure) completed at each visit. RESULTS Seven patients (6.1%) presented with acute CLE, 21 (18.4%) with subacute CLE, 77 (67.5%) with chronic CLE, 7 (6.1%) with systemic lupus erythematosus and LE-nonspecific skin lesions, and 1 (0.9%) with LE-nonspecific skin disease only. The mean baseline CLE Disease Activity and Severity Index activity/damage scores in patients with acute, subacute, and chronic CLE were 6.4/5.1, 11.1/1.6, and 7.5/10.2, respectively. The mean baseline modified Skindex-29 scores were 76.3, 79.4, and 82.7, respectively (P = .80). The disease in 11 of the patients (9.6%) was considered refractory to conventional therapies. Significantly more patients in the refractory group than the nonrefractory group were current smokers (P = .006). CONCLUSION This Web-based database should allow collection of data related to disease activity, quality of life, and response to therapy at multiple centers.

Lenalidomide for the Treatment of Resistant Discoid Lupus Erythematosus

BACKGROUND Discoid lupus erythematosus (DLE) is a chronic, disfiguring disease that is characterized by scaly, erythematous, disk-shaped patches and plaques followed by atrophy, scarring, and dyspigmentation. It is refractory to standard therapies in a small population of patients. We investigated the use of lenalidomide, a thalidomide analogue, as a novel alternative therapy in 2 cases of refractory DLE and report our results. OBSERVATIONS Two patients with chronic, severe DLE were treated with low-dose lenalidomide. Improvement was noted within 1 month at a dosage of 5 mg/d in one case and was maintained for 10 months before the dosage was doubled to 10 mg/d for 12 months because of a slight worsening of symptoms. Clinical improvement was demonstrated by a sustained reduction in the Cutaneous Lupus Erythematosus Disease Area and Severity Index activity score, with no change in the Cutaneous Lupus Erythematosus Disease Area and Severity Index damage score. Within 5 months, oral prednisone therapy (60 mg/d) was tapered and discontinued; it was restarted at a low dosage (5 mg/d), however, to manage the symptoms of systemic LE. Of note, the patient experienced mild neutropenia after taking 10 mg/d of lenalidomide, which carries a black box warning regarding neutropenia; therefore, the complete blood cell count should be monitored weekly for the first 2 months and then monthly thereafter. The second case failed to show clinical improvement, and lenalidomide therapy was discontinued after 6 months. CONCLUSIONS Lenalidomide therapy is a potential alternative or adjunctive treatment for patients with severe, chronic DLE that is refractory to standard therapies. A larger study is needed to clarify its role in the treatment of DLE and other forms of cutaneous LE.

Interstitial Lung Disease in Classic and Skin-Predominant Dermatomyositis: A Retrospective Study With Screening Recommendations

OBJECTIVES (1) To determine the prevalence of interstitial lung disease (ILD) and isolated low diffusing capacity for carbon monoxide (DLCO) in a large cohort of outpatients with dermatomyositis. (2) To compare the pulmonary abnormalities of patients with classic dermatomyositis and those with skin-predominant dermatomyositis. DESIGN Retrospective cohort study. SETTING University hospital outpatient dermatology referral center. Patients Medical records of 91 outpatients with adult-onset dermatomyositis seen between May 26, 2006, and May 25, 2009, were reviewed. MAIN OUTCOME MEASURES Presence of ILD on thin-slice chest computed tomographic (CT) scans and DLCO. RESULTS Of the 71 patients with dermatomyositis who had CT or DLCO data, 16 (23%; 95% confidence interval [CI], 13%-33%) had ILD as defined by CT results [corrected]. All patients with ILD had a reduced DLCO, and the ILD prevalence was not different between patients with skin-predominant dermatomyositis (10 of 35 [29% ]) and those with classic dermatomyositis (6 of 36 [17% ]) (P = .27). Eighteen of 71 patients with dermatomyositis (25%; 95% CI, 15%-36%) (7 of 35 [20%] with skin-predominant dermatomyositis; 11 of 36 [31%] with classic dermatomyositis; P = .41) had a low DLCO in the absence of CT findings showing ILD. The prevalence of malignant disease was higher in patients with classic dermatomyositis than in those with skin-predominant dermatomyositis (P = .02), and no patients with skin-predominant dermatomyositis had internal malignant disease. CONCLUSIONS Radiologic ILD and isolated DLCO reductions, which may signify early ILD or pulmonary hypertension, are common in dermatology outpatients with both classic and skin-predominant dermatomyositis. Because DLCO testing is both inexpensive and sensitive for pulmonary disease, it may be appropriate to screen all patients with dermatomyositis with serial DLCO measurements and base further testing on DLCO results.

The interferon‐regulated gene signature is elevated in subacute cutaneous lupus erythematosus and discoid lupus erythematosus and correlates with the cutaneous lupus area and severity index score

Background  There is increased expression of type I interferon (IFN)‐regulated proteins in the blood and target tissues of patients with cutaneous lupus erythematosus (CLE) and systemic lupus erythematosus (SLE). Patients with SLE have increased IFN‐regulated gene expression pointing towards a possible underlying genetic defect.Background There is increased expression of type I interferon (IFN)-regulated proteins in the blood and target tissues of patients with cutaneous lupus erythematosus (CLE) and systemic lupus erythematosus (SLE). Patients with SLE have increased IFN-regulated gene expression pointing towards a possible underlying genetic defect.

Modification of the Cutaneous Dermatomyositis Disease Area and Severity Index, an outcome instrument

Background  Validated outcome measures in dermatology help standardize and improve patient care. A scoring system of skin disease severity in dermatomyositis known as the Cutaneous Dermatomyositis Disease Area and Severity Index (CDASI) has been developed.