Publications by authors named "Joyce Okawa"

28 Publications

  • Page 1 of 1

Safety, Tolerability, and Activity of ALXN1830 Targeting the Neonatal Fc Receptor in Chronic Pemphigus.

J Invest Dermatol 2021 Jun 11. Epub 2021 Jun 11.

Department of Dermatology, Duke University Medical Center, Durham, NC USA.

Pemphigus is a debilitating immunoglobulin G (IgG)-mediated autoimmune disease in need of better tolerated, more targeted and rapid onset therapies. ALXN1830 is a humanized IgG4 antibody that blocks neonatal Fc receptor (FcRn) interactions with IgG. A multicenter, open-label safety and tolerability phase 1b/2 trial (NCT03075904) was conducted in North America from July 2017 to January 2019 and included patients aged ≥ 18 years with a confirmed diagnosis of pemphigus (vulgaris or foliaceus) and active disease. Dosing included five weekly intravenous doses of ALXN1830 (10 mg/kg), and follow-up through day 112 (study termination). Pharmacokinetics, pharmacodynamics, safety and efficacy, as evaluated by determining the change in the median pemphigus disease area index (PDAI), were determined. In this pilot study of eight patients, five weekly infusions of ALXN1830 produced a rapid improvement in the PDAI score within 14 days of the first dose. PDAI improvement increased further together with reductions in IgG, circulating IgG immune complexes (CIC), and anti-desmoglein antibodies, without affecting albumin, IgM, IgA, or C-reactive protein levels. ALXN1830 was well tolerated with headache as the most common adverse event. This study reveals the importance of FcRn in the biology of pemphigus and potential for use of ALXN1830 in pemphigus treatment.
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http://dx.doi.org/10.1016/j.jid.2021.04.031DOI Listing
June 2021

A prospective cohort study comparing the performance of interferon gamma release assays in autoimmune skin diseases.

J Am Acad Dermatol 2021 Apr 2. Epub 2021 Apr 2.

Corporal Michael J. Crescenz Veterans Affairs Medical Center, Philadelphia, Pennsylvania; Department of Dermatology, University of Pennsylvania, Philadelphia, Pennsylvania. Electronic address:

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http://dx.doi.org/10.1016/j.jaad.2021.03.087DOI Listing
April 2021

Managing interventional clinical trials in the setting of COVID-19: Experience in an autoimmune skin disease unit.

JAAD Int 2021 Mar 9;2:94-95. Epub 2020 Dec 9.

Department of Dermatology, Perelman School of Medicine at the University of Pennsylvania and Corporal Michael J. Crescenz Veterans Affairs Medical Center, Philadelphia, Pennsylvania.

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http://dx.doi.org/10.1016/j.jdin.2020.11.002DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7754881PMC
March 2021

Evaluating the effect of prior authorizations in patients with complex dermatologic conditions.

J Am Acad Dermatol 2020 Dec 2;83(6):1674-1680. Epub 2020 Jul 2.

Dermatology, Hospital of the University of Pennsylvania, Philadelphia, Pennsylvania; Dermatology, CMC VA Medical Center, Philadelphia, Pennsylvania. Electronic address:

Background: In dermatology, prior authorizations can delay treatment, decrease patient adherence, and deter providers from advocating for their patients. Patients with complex dermatologic conditions, often requiring off-label treatments, may face particularly significant insurance barriers.

Objective: Evaluate the effect of prior authorizations in patients with complex dermatologic conditions.

Methods: This prospective cohort study assessed patients treated by a dermatologist during 5 months who specialized in complex dermatology. Patients included were older than 18 years, treated at V.P.W.'s rheumatology-dermatology clinic, and prescribed a medication or ordered a diagnostic procedure that elicited an insurance prior authorization. Data on prior authorization outcome, administrative time, and delay to treatment were collected.

Results: Of 51 prior authorizations, 51% were initially denied, with systemic medications more likely denied than topical ones (P < .001). Total administrative time spent on 50 prior authorizations tracked was 62.5 hours (median time per prior authorization 30 minutes [interquartile range 17-105 minutes]). Time to access treatment was tracked for 80% of prior authorizations; median delay was 12 days [interquartile range 5.5-23 days].

Limitations: Single-center, single-provider patient panel.

Conclusion: Patients with complex dermatologic conditions face a significant barrier to care because of prior authorizations. The administrative burden for provider practices to address these prior authorizations is substantial and may warrant a streamlined system in collaboration with insurers.
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http://dx.doi.org/10.1016/j.jaad.2020.06.998DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7936393PMC
December 2020

Malignancy in dermatomyositis: A retrospective study of 201 patients seen at the University of Pennsylvania.

J Am Acad Dermatol 2020 Jul 2;83(1):117-122. Epub 2020 Mar 2.

Corporal Michael J. Crescenz Veterans Affairs Medical Center, Philadelphia, Pennsylvania; Warren Alpert Medical School at Brown University, Providence, Rhode Island. Electronic address:

Background: There is an increased incidence of malignancy in patients with dermatomyositis. It is unknown if the risk differs between the subtypes of dermatomyositis.

Objective: To (1) compare the prevalence of malignancy-associated dermatomyositis between patients with classic and clinically amyopathic disease and (2) determine factors associated with an increased risk of malignancy-associated disease.

Methods: Retrospective cohort study of 201 patients with adult-onset dermatomyositis prospectively enrolled in a longitudinal dermatomyositis database between July 2008 and April 2018 at an outpatient dermatology urban tertiary referral center. The main outcome measure was a diagnosis of malignancy, excluding nonmelanoma skin cancer.

Results: There were 201 patients with adult-onset dermatomyositis: 142 (71%) classic and 59 (29%) clinically amyopathic. Within 2 years of diagnosis, the prevalences of malignancy-associated classic and clinically amyopathic dermatomyositis were 9.9% and 1.7%, respectively. In this time period, patients who were older at dermatomyositis diagnosis (P = .01) and had the classic subtype (P = .04) were significantly more likely to have an underlying malignancy on multivariable regression analysis.

Limitations: This was a retrospective study of prospectively collected data at a single tertiary referral center.

Conclusion: Older age and classic dermatomyositis are independent risk factors for malignancy-associated dermatomyositis within 2 years of disease onset.
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http://dx.doi.org/10.1016/j.jaad.2020.02.061DOI Listing
July 2020

Oxygeneo-A Unique Three-in-one Treatment of Exfoliation, Infusion, and Oxygenation via the Bohr Effect and TriPollar™ Radiofrequency for Skin Rejuvenation.

J Clin Aesthet Dermatol 2017 Nov 1;10(11):22-25. Epub 2017 Nov 1.

All authors are with the University of Pennsylvania Perelman School of Medicine in Philadelphia, Pennsylvania.

Oxygenation of the skin has been shown to improve cell growth and cell biosynthesis, which can subsequently improve the skin's appearance.1,2 However, the majority of skin oxygenation techniques are invasive.3,4 A noninvasive skin oxygenation treatment, also known as a carboxytherapy facial, with TriPollar radiofrequency device has emerged called OxyGeneo™, which is provided by the geneO+™ skin care platform (Pollogen Ltd., Tel Aviv, Israel). This study addresses the clinical effectiveness of the aforementioned noninvasive skin oxygenation treatment on skin texture, fine lines/wrinkles, and skin pigmentation over an eight-week time period. Ten patients with fine lines, wrinkles, hyperpigmentation, and rough skin texture received six weekly treatments over a two-month period. Five patients received NeoRevive™ and five received NeoBright™ topical infusions, with the selection made according to each individual's skin conditions and type. These patients were evaluated using the VISIA complexion analysis system (Canfield Scientific, Inc., Parsippany, New Jersey) and patient and evaluator assessments and satisfaction surveys. Each individual measurement varied by patient, but the change in value of each category that was assessed prior to treatment and post-treatment indicated an improvement. All patients in the study stated an improvement in overall skin appearance, skin texture, brightness, and shininess. Nine out of the 10 patients reported that their skin was softer and had a more youthful appearance after the treatments, and seven out of the 10 patients saw a minor improvement in fine lines and wrinkles. Lastly, five out of the 10 patients noticed an improvement in skin pigmentation. The results indicated the combination of the three-in-one OxyGeneo treatment of exfoliation, infusion and oxygenation using TriPolar radiofrequency prompted an improvement in skin texture and tone. This is an optimal procedure that can be implemented in patients looking for noninvasive, safe, and effective rejuvenation treatments with no associated downtime post-procedure.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5774907PMC
November 2017

Comparative Study of Compounded Anesthetic Benzocaine/Lidocaine/Tetracaine (BLT) Cream with and without Abrasive Particles.

J Clin Aesthet Dermatol 2017 Apr;10(4):30-36

Cosmetic Enhancement Center, Penn Medicine Radnor, University of Pennsylvania, Radnor, Pennsylvania.

The purpose of this study was to compare the use of benzocaine, lidocaine, tetracaine (BLT) cream with and without abrasive particles to see which type of cream is more effective in reducing discomfort during cosmetic dermatologic procedures, specifically procedures using hyaluronic acid (HA) injectables. The study was conducted as a single-site, double-blind, paired study. Thirty-one subjects were enrolled. Men and women over 18, but not more than 75 years of age, were included. Participants were randomized to receive two types of BLT creams in a split-face fashion to two opposite anatomical face locations that require a similar amount of filler. The study found a statistically significant difference (<0.05) in the mean pain level as measured by the VAS and Wong-Baker Faces Pain Rating Scale when compared between baseline and the time when the procedure was started at the first needle stick. Subjects expressed significantly less pain with baseline and more pain when the procedure was done. However, the authors found that the mean pain level at first needle stick is lower with the abrasive type of BLT. The study demonstrated that subjects experienced a higher mean pain level (but not statistically significant) when using the BLT with smooth texture compared to the BLT with abrasive particles when applied before HA dermal filler injection.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5404778PMC
April 2017

Using the American College of Rheumatology (ACR) and Systemic Lupus International Collaborating Clinics (SLICC) criteria to determine the diagnosis of systemic lupus erythematosus (SLE) in patients with subacute cutaneous lupus erythematosus (SCLE).

J Am Acad Dermatol 2016 May 18;74(5):862-9. Epub 2016 Feb 18.

Corporal Michael J. Crescenz Philadelphia Department of Veterans Affairs Medical Center, Philadelphia, Pennsylvania; Department of Dermatology, University of Pennsylvania, Philadelphia, Pennsylvania. Electronic address:

Background: Approximately 50% of patients with subacute cutaneous lupus erythematosus (SCLE) meet criteria for systemic lupus erythematosus (SLE). The Systemic Lupus International Collaborating Clinics (SLICC) developed new SLE criteria to improve the American College of Rheumatology (ACR) criteria but the SLICC criteria have not been evaluated in patients with SCLE.

Objective: We sought to determine how patients with SCLE/SLE meet the ACR and SLICC criteria to compare the 2 sets of criteria.

Methods: This was a retrospective analysis of 107 patients with SCLE enrolled in a database at the University of Pennsylvania.

Results: Patients with SCLE/SLE were more likely than those with only SCLE to have oral ulcers, positive anti-double-stranded DNA antibodies, and positive antinuclear antibody test findings using both sets of criteria. Patients with SCLE/SLE were also more likely to have low complement using the SLICC criteria. There was a statistically insignificant increase in individuals meeting the SLICC criteria.

Limitations: Not all patients received comprehensive laboratory testing.

Conclusions: Most patients with SCLE who formally meet criteria for SLE do so based on the laboratory and mucocutaneous criteria. Neither the ACR nor SLICC criteria distinguish patients with SCLE and major internal disease from patients with SCLE without major internal disease.
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http://dx.doi.org/10.1016/j.jaad.2015.12.029DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4879000PMC
May 2016

A cross-sectional study of untreated depression and anxiety in cutaneous lupus erythematosus and dermatomyositis.

J Am Acad Dermatol 2016 Feb;74(2):377-9

Corporal Michael J. Crescenz VA Med Center, Philadelphia, PA; Department of Dermatology, University of Pennsylvania, Philadelphia, PA. Electronic address:

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http://dx.doi.org/10.1016/j.jaad.2015.09.016DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4878998PMC
February 2016

Reliability of the autoimmune bullous disease quality of life (ABQOL) questionnaire in the USA.

Qual Life Res 2015 Sep 21;24(9):2257-60. Epub 2015 Mar 21.

Department of Dermatology, University of New South Wales, St George Hospital Campus, Sydney, Australia.

Purpose: To evaluate the reliability of the autoimmune bullous diseases quality of life (ABQOL) questionnaire in a North American patient cohort.

Methods: Patients attending the dermatology clinics of the University of Pennsylvania with a histological diagnosis of an autoimmune bullous disease (AIBD) and self-reported proficiency in English were recruited to participate in the study. Patients completed the ABQOL questionnaire at Day 0 and Day 3. Internal consistency was calculated through Cronbach's alpha. Test-retest reliability was determined by the intraclass correlation coefficient.

Results: Of the 45 patients enrolled in the study, 39 patients (87 %) participated to completion. The mean age was 60.7 years with an equal sex distribution observed. Patients had a range of AIBD including pemphigus vulgaris, bullous pemphigoid, pemphigus foliaceus, epidermolysis bullosa acquisita, mucous membrane pemphigoid and linear IgA disease. Cronbach's alpha was calculated to be 0.90. The intraclass correlation coefficient was calculated to be 0.93 (95 % confidence interval 0.88-0.94).

Conclusion: The ABQOL was found to be reliable tested by internal consistency and test-retest reliability in an American patient cohort. It represents a promising disease-specific outcome measure for patients with AIBD.
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http://dx.doi.org/10.1007/s11136-015-0965-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4767525PMC
September 2015

Lenalidomide in treatment-refractory cutaneous lupus erythematosus: Efficacy and safety in a 52-week trial.

J Am Acad Dermatol 2014 Mar;70(3):583-4

Philadelphia Veterans Affairs Medical Center, Philadelphia, PA; Department of Dermatology, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA. Electronic address:

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http://dx.doi.org/10.1016/j.jaad.2013.11.007DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4333148PMC
March 2014

Systemic symptoms in the progression of cutaneous to systemic lupus erythematosus.

JAMA Dermatol 2014 Mar;150(3):291-6

Department of Dermatology, Philadelphia Veterans Affairs Medical Center, Philadelphia, Pennsylvania2Department of Dermatology, University of Pennsylvania, Philadelphia.

Importance: Patients with cutaneous lupus erythematosus (CLE) who develop systemic lupus erythematosus (SLE) may have few and mild systemic symptoms.

Objective: To characterize the types and severity of systemic symptoms in a longitudinal cohort of patients with CLE.

Design, Setting, And Participants: Prospective, longitudinal cohort study of 77 patients with CLE who presented between January 2007 and April 2011 at a university autoimmune skin disease clinic.

Main Outcomes And Measures: Systemic symptoms and severity were determined from data recorded at each study visit and from medical records.

Results: Of 77 patients with CLE, 13 (17%) went on to meet criteria for SLE, with a mean (SD) time from CLE diagnosis to SLE of 8.03 (6.20) years. Of the 13 patients, 1 (8%) solely met the mucocutaneous American College of Rheumatology (ACR) criteria of malar rash, discoid rash, photosensitivity, and oral ulcers, and 3 (23%) met the mucocutaneous ACR criteria plus positive antinuclear and other antibody titers. After a mean (SD) follow-up time of 2.81 (1.34) years, only 5 of the 13 patients with CLE (38%) who progressed to meet SLE criteria developed moderate to severe additional systemic disease.

Conclusions And Relevance: Patients with CLE who developed SLE during our study did so mostly by meeting the mucocutaneous ACR criteria, and the majority developed none to mild additional systemic disease during the study period. Thus, our study suggests that a small percentage of patients with CLE eventually develop SLE and that even if they do, most patients will have mild systemic disease.
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http://dx.doi.org/10.1001/jamadermatol.2013.9026DOI Listing
March 2014

Characterization of clinical photosensitivity in cutaneous lupus erythematosus.

J Am Acad Dermatol 2013 Aug 3;69(2):205-13. Epub 2013 May 3.

Philadelphia Department of Veterans Affairs Medical Center, Philadelphia, Pennsylvania, USA.

Background: Photosensitivity (PS) in lupus erythematosus (LE) is frequently determined by patient report.

Objective: We sought to characterize self-reported PS in cutaneous LE (CLE).

Methods: The PS survey was used to classify subject responses into 5 phenotypes: direct sun-induced CLE flare (directCLE); general exacerbation of CLE (genCLE); polymorphic light eruption-like reactions (genSkin); general pruritus/paresthesias (genRxn); and sun-induced systemic symptoms (genSys). In all, 91 subjects with CLE alone or with CLE and systemic LE were interviewed.

Results: In all, 81% ascribed to 1 or more PS phenotypes. CLE-specific reactions (direct sun-induced CLE flare or general exacerbation of CLE) were reported by 86% of photosensitive subjects. Higher CLE disease activity (measured by CLE Disease Area and Severity Index activity scores) was suggestive of direct sun-induced CLE flare reactions (P = .09). In all, 60% of photosensitive subjects described CLE-nonspecific reactions: polymorphic light eruption-like rash and general pruritus/paresthesias. These phenotypes often co-occurred with CLE-specific reactions and were predicted by more systemic disease activity as measured by Physicians Global Assessment (PGA) scores in regression analyses (genSkin, P = .02) and (genRxn, P = .05). In all, 36% of subjects reported systemic reactions and higher PGA scores were predictive of the sun-induced systemic symptoms phenotype (P = .02); a diagnosis of systemic LE was not (P = .14).

Limitations: PS was inferred from patient report and not directly observed.

Conclusions: Characterization of self-reported PS in LE reveals that patients experience combinations of CLE-specific, CLE-nonspecific, and systemic reactions to sunlight. Sun-induced CLE flares are associated with more active CLE disease. Polymorphic light eruption-like, generalized pruritus/paresthesias, and systemic reactions are associated with more active systemic disease. Recognition of PS phenotypes will permit improved definitions of clinical PS and allow for more precise investigation into its pathophysiology.
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http://dx.doi.org/10.1016/j.jaad.2013.03.015DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3928014PMC
August 2013

Evaluation of reliability, validity, and responsiveness of the CDASI and the CAT-BM.

J Invest Dermatol 2012 Apr 5;132(4):1117-24. Epub 2012 Jan 5.

Philadelphia VA Medical Center, Philadelphia, Pennsylvania, USA.

To properly evaluate therapies for cutaneous dermatomyositis (DM), it is essential to administer an outcome instrument that is reliable, valid, and responsive to clinical change, particularly when measuring disease activity. The purpose of this study was to compare two skin severity DM outcome measures, the Cutaneous Disease and Activity Severity Index (CDASI) and the Cutaneous Assessment Tool-Binary Method (CAT-BM), with the Physician Global Assessment (PGA) as the "gold standard". Ten dermatologists evaluated 14 patients with DM using the CDASI, CAT-BM, and PGA scales. Inter- and intra-rater reliability, validity, responsiveness, and completion time were compared for each outcome instrument. Responsiveness was assessed from a different study population, where one physician evaluated 35 patients with 110 visits. The CDASI was found to have a higher inter- and intra-rater reliability. Regarding construct validity, both the CDASI and the CAT-BM were significant predictors of the PGA scales. The CDASI had the best responsiveness among the three outcome instruments examined. The CDASI had a statistically longer completion time than the CAT-BM by about 1.5 minutes. The small patient population may limit the external validity of the findings observed. The CDASI is a better clinical tool to assess skin severity in DM.
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http://dx.doi.org/10.1038/jid.2011.440DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3752293PMC
April 2012

Impact of smoking in cutaneous lupus erythematosus.

Arch Dermatol 2012 Mar 21;148(3):317-22. Epub 2011 Nov 21.

Philadelphia VA Medical Center, Philadelphia, PA, USA.

Objective: To investigate cigarette smoking in cutaneous lupus erythematosus (CLE).

Design: Prospective longitudinal cohort study.

Setting: Urban cutaneous autoimmune disease clinic.

Participants: A total of 218 individuals with CLE or systemic lupus erythematosus and lupus nonspecific skin disease seen between January 5, 2007, and July 30, 2010.

Main Outcome Measures: Cutaneous Lupus Erythematosus Disease Area and Severity Index (CLASI) scores to assess disease severity and response to treatment and Skindex 29+3 scores to assess patient quality of life.

Results: Current smokers with lupus erythematosus had higher median CLASI scores (9.5) than did never (7.0) and past (6.0) smokers with CLE (P = .02). Current smokers had higher median scores on all the Skindex 29+3 subsets. Current smokers taking hydroxychloroquine sulfate had higher quinacrine hydrochloride use than did nonsmokers (P = .04). Two to 7 months after enrollment, current smokers (median CLASI change, -3) treated with only antimalarial agents improved more than never (1) and past (0) smokers (P = .02). Eight months or more after enrollment, current smokers (CLASI change, 3.5) treated with antimalarial drugs plus at least 1 additional immunomodulator improved less than never (-1.5) and past (0) smokers (P = .04).

Conclusions: Current smokers with lupus erythematosus had worse disease, had worse quality of life, and were more often treated with a combination of hydroxychloroquine and quinacrine than were nonsmokers. Never and past smokers showed greater improvement when treated with antimalarial agents plus at least 1 additional immunomodulator. Current smokers had greater improvement when treated with antimalarial drugs only.
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http://dx.doi.org/10.1001/archdermatol.2011.342DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3309110PMC
March 2012

Lenalidomide therapy in treatment-refractory cutaneous lupus erythematosus: histologic and circulating leukocyte profile and potential risk of a systemic lupus flare.

J Am Acad Dermatol 2012 Apr 6;66(4):571-82. Epub 2011 Aug 6.

Dermatology Section, Philadelphia Veterans Affairs Medical Center, Philadelphia, Pennsylvania, USA.

Background: Lenalidomide is a thalidomide analogue that may serve as an adjunctive therapy for treatment-refractory cutaneous lupus erythematosus (CLE).

Objectives: We evaluate the use of lenalidomide in CLE and describe the skin and circulating leukocyte profile of treatment-refractory patients before and after treatment.

Methods: Five subjects were treated with lenalidomide in an unblinded open-label study. Immunohistochemistry of skin was performed for T-cell markers, glycosaminoglycans, and CXCL10, an interferon-inducible chemokine, before and after treatment. Immunophenotyping and measurement of interferon-inducible genes from peripheral blood mononuclear cells was also performed before and after treatment.

Results: Four subjects demonstrated clinical improvement of their skin, however one of these responders subsequently developed symptoms of systemic lupus erythematosus. Small changes in rare circulating leukocyte subsets, plasmacytoid dendritic cells, and regulatory T cells were observed with treatment and may correlate with clinical response. Treatment was associated with increased circulating HLA-DR expression and decreased markers of interferon-mediated pathways, regardless of clinical response.

Limitations: Our results are limited by small sample size and the measurement of rare populations of circulating cell subsets.

Conclusions: Lenalidomide may have usefulness as therapy for severe, treatment-refractory CLE. However, our preliminary data suggest that lenalidomide may activate T cells and trigger systemic disease in some patients with CLE. We also saw a different histologic and circulating leukocyte phenotype in the nonresponding subject. Further characterization of the skin and circulating leukocyte profile of treatment-refractory patients will improve our understanding of CLE.
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http://dx.doi.org/10.1016/j.jaad.2011.01.015DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3306524PMC
April 2012

Response to antimalarial agents in cutaneous lupus erythematosus: a prospective analysis.

Arch Dermatol 2011 Nov 18;147(11):1261-7. Epub 2011 Jul 18.

Philadelphia Veterans Affairs Medical Center, Philadelphia, Pennsylvania, USA.

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.
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http://dx.doi.org/10.1001/archdermatol.2011.191DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3282057PMC
November 2011

Prevalence of self-report photosensitivity in cutaneous lupus erythematosus.

J Am Acad Dermatol 2012 Feb 13;66(2):220-8. Epub 2011 Jul 13.

Philadelphia Department of Veterans Affairs Medical Center, Philadelphia, Pennsylvania, USA.

Background: Little is known about the prevalence of self-reported photosensitivity (PS) and its effects on quality of life in a US cutaneous lupus population.

Objective: We sought to determine the prevalence of self-reported PS among a cutaneous lupus population and to examine its impact on quality of life.

Methods: A total of 169 patients with lupus were interviewed about PS symptoms and completed the modified Skindex-29+3, a quality-of-life survey. A complete skin examination was conducted and the Cutaneous Lupus Erythematosus Disease Area and Severity Index was completed.

Results: In all, 68% of patients reported some symptoms of PS. The PS group (those who reported a history of and current PS) scored worse on PS-related items of the modified Skindex-29+3 and had higher cutaneous disease activity as determined by the Cutaneous Lupus Erythematosus Disease Area and Severity Index. Patients with PS had worse symptoms and emotions and experienced significant functional impairments compared with patients who had cutaneous lupus without PS.

Limitations: This study was done at a single referral center.

Conclusions: Self-reported PS is very common among patients with cutaneous lupus and is associated with significant impairments related to symptoms, emotions, and daily functioning.
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http://dx.doi.org/10.1016/j.jaad.2010.12.006DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3193852PMC
February 2012

Quality of life in dermatomyositis.

J Am Acad Dermatol 2011 Dec 1;65(6):1107-16. Epub 2011 Jul 1.

Philadelphia Department of Veterans Affairs Medical Center, Philadelphia, Pennsylvania, USA.

Background: Quality of life (QoL) for patients with inflammatory skin disease can be significant, but has been evaluated in just one study in dermatomyositis (DM).

Objective: We sought to examine the relationship between the Cutaneous Dermatomyositis Area (CDASI) and Severity Index, a DM-specific cutaneous severity instrument, and various QoL study instruments and to determine the impact of DM on QoL.

Methods: Skin-specific QoL instruments, the Skindex and the Dermatology Life Quality Index, and global medical QoL instruments, the Short Form 36 and the Health Assessment Questionnaire-Disability Index, were used. Pruritus was evaluated by a visual analog scale and a 0-to-10 scale in DM and cutaneous lupus erythematosus (CLE) populations, respectively.

Results: There was a significant correlation between the CDASI and all skin-specific QoL scores (lowest P = .0377). Using the Short Form 36, DM population was found to have significantly worse QoL scores than the general population with the exception of bodily pain (all subscore P values < .01). Furthermore, DM had a significantly lower vitality score, representing energy level, compared with CLE, hypertension, diabetes, and recent myocardial infarction scores (lowest P = .003). There was a significantly lower mental health score, representing overall mood, to all compared diseases except CLE and clinical depression (P values < .01 when significant). We found that DM produces more pruritus than CLE (P < .0001).

Limitations: A larger patient population needs to be studied to further assess QoL in patients with DM.

Conclusion: We conclude that DM has a large impact on QoL, even when compared with other diseases, and that DM skin disease activity correlates with a poorer QoL.
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http://dx.doi.org/10.1016/j.jaad.2010.10.016DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3189436PMC
December 2011

Quality of life in cutaneous lupus erythematosus.

J Am Acad Dermatol 2011 May 12;64(5):849-58. Epub 2011 Mar 12.

Philadelphia Department of Veterans Affairs Medical Center, Philadelphia, Pennsylvania, USA.

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.
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http://dx.doi.org/10.1016/j.jaad.2010.02.008DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3079065PMC
May 2011

Development of the CLASI as a tool to measure disease severity and responsiveness to therapy in cutaneous lupus erythematosus.

Arch Dermatol 2011 Feb;147(2):203-8

Department of Dermatology, Hospital of the University of Pennsylvania, Philadelphia, PA 19104, USA.

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 physician's 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.
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http://dx.doi.org/10.1001/archdermatol.2010.435DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3282059PMC
February 2011

Interstitial lung disease in classic and skin-predominant dermatomyositis: a retrospective study with screening recommendations.

Arch Dermatol 2010 Jul;146(7):729-38

Department of Dermatology, Hospital of the University of Pennsylvania, 3400 Civic Center Blvd, Philadelphia, PA 19104, USA.

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.
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http://dx.doi.org/10.1001/archdermatol.2010.134DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3010864PMC
July 2010

Reliability and convergent validity of two outcome instruments for pemphigus.

J Invest Dermatol 2009 Oct 9;129(10):2404-10. Epub 2009 Apr 9.

Department of Dermatology, University of Pennsylvania, Philadelphia, PA 19119, USA.

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% 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.
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http://dx.doi.org/10.1038/jid.2009.72DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3010359PMC
October 2009

Lenalidomide for the treatment of resistant discoid lupus erythematosus.

Arch Dermatol 2009 Mar;145(3):303-6

Department of Dermatology, University of Pennsylvania, 3600 Spruce St, Philadelphia, PA 19104, USA.

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.
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http://dx.doi.org/10.1001/archdermatol.2009.30DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2739109PMC
March 2009

Cross-sectional analysis of a collaborative Web-based database for lupus erythematosus-associated skin lesions: prospective enrollment of 114 patients.

Arch Dermatol 2009 Mar;145(3):255-60

Department of Dermatology, University of Pennsylvania, Philadelphia, PA 19104-4283, USA.

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.
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http://dx.doi.org/10.1001/archdermatol.2008.594DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2830744PMC
March 2009

The cutaneous lupus erythematosus disease area and severity index: a responsive instrument to measure activity and damage in patients with cutaneous lupus erythematosus.

Arch Dermatol 2008 Feb;144(2):173-80

Department of Dermatology, University of Pennsylvania, 2 Rhodes Pavilion, 3600 Spruce St, Philadelphia, PA 19119, USA.

Objective: To assess the clinical responsiveness of the CLASI (Cutaneous Lupus Erythematosus [CLE] Disease Area and Severity Index).

Design: Validation cohort.

Setting: Tertiary referral center. Patients Eight patients with CLE. Intervention Assessment of patients with CLE from baseline until day 56 after starting a new standard of care therapy.

Main Outcome Measures: Correlation of the baseline to day-56 change in 2 CLASI scales (disease activity and damage), with baseline to day-56 change in the physicians' and patients' assessments of patient's global skin health scores, and the patients' assessments of pain and itch.

Results: The change in CLASI activity score highly correlated with the changes in 3 clinical validation measures: physicians' assessment of skin health (r = 0.97; P = .003; n = 7), patients' global skin health score (r = 0.85; P = .007; n = 8), and pain (r = 0.98; P = .004; n = 5). Using the Wilcoxon signed-rank test, paired baseline to day-56 changes in CLASI activity and damage scores were analyzed for the 2 subgroups (meaningful change vs nonmeaningful change) composing each validation variable. Change in CLASI activity was significantly different for patients who had a meaningful change in their global skin self-ratings (Z = 1.07; P = .03) and approached statistical significance for patients who had a meaningful change in their level of itching (Z = 1.83; P = .06) and their physicians' global skin rating (Z = 1.84; P = .06). The CLASI activity score decreases after successful therapeutic intervention, whereas the damage score may increase in scarring forms of CLE. Conclusion The activity score of the CLASI correlates with the improvement of global skin health, pain, and itch and is thus a useful tool to measure clinical response.
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http://dx.doi.org/10.1001/archderm.144.2.173DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2829653PMC
February 2008