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

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.

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

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.

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).

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.

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

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.

Characterization of clinical photosensitivity in cutaneous lupus erythematosus.

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.

Prevalence of self-report photosensitivity in cutaneous lupus erythematosus.

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.

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

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.

Safety and Efficacy of Lenabasum, a Cannabinoid Receptor Type 2 Agonist, in Patients with Dermatomyositis with Refractory Skin Disease: A Randomized Clinical Trial.

BACKGROUND: Treatment options are limited for skin disease in dermatomyositis. Lenabasum is a cannabinoid receptor type 2 agonist that triggers the resolution of inflammation. OBJECTIVE: The objective of this study was to evaluate the safety and efficacy of lenabasum in patients with refractory cutaneous dermatomyositis. DESIGN: This study was a single-center, double-blind, randomized, placebo-controlled phase 2 study conducted from July 2015 to August 2017. POPULATION: The population included subjects aged ≥18 years with at least moderately active dermatomyositis skin activity by Cutaneous Dermatomyositis Disease Area and Severity Index activity ≥ 14 and failure or intolerance to hydroxychloroquine. INTERVENTION: Participants received 20 mg lenabasum daily for 28 days and then 20 mg twice per day for 56 days or placebo. MAIN OUTCOMES AND MEASURES: The primary outcome was a change in Cutaneous Dermatomyositis Disease Area and Severity Index activity. Safety and other secondary efficacy assessments were performed till day 113. RESULTS: A total of 22 subjects were randomized to lenabasum (n = 11) or placebo (n = 11). No serious or severe adverse events were related to lenabasum, and no participants discontinued the study. The adjusted least-squares mean for Cutaneous Dermatomyositis Disease Area and Severity Index activity decreased more for lenabasum, and the difference was significant on day 113 (least-squares mean [standard error] difference = ‒6.5 [3.1], P = 0.038). Numerically greater improvements were seen in multiple secondary efficacy outcomes and biomarkers with lenabasum. CONCLUSION: Lenabasum treatment was well tolerated and was associated with greater improvement in Cutaneous Dermatomyositis Disease Area and Severity Index activity and multiple efficacy outcomes. TRIAL REGISTRATION: This study was registered at ClinicalTrials.gov, NCT02466243.

Cannabinoid type 2 receptor (CB2R) distribution in dermatomyositis skin and peripheral blood mononuclear cells (PBMCs) and in vivo effects of LenabasumTM.

BACKGROUND: Lenabasum is a cannabinoid type 2 receptor (CB2R) reverse agonist that demonstrates anti-inflammatory effects in vivo and in vitro in dermatomyositis (DM) and is currently being investigated for therapeutic potential. The purpose of our study is to investigate CB2R distribution as well as the effects of lenabasum in DM. METHODS: Immunohistochemistry staining (IHC) was utilized to examine immune cell and cytokine production changes in lesional DM skin biopsies from lenabasum and placebo-treated patients. CB2R expression in various immune cell populations within DM skin was investigated with image mass cytometry (IMC), whereas flow cytometry elucidated CB2R expression in DM peripheral blood mononuclear cells (PBMCs) as well as cytokine production by CB2R-expressing cell populations. RESULTS: After 12 weeks of lenabasum treatment, IHC staining showed that CD4+ T cells, CB2R, IL-31, IFN-γ, and IFN-ß cytokines were downregulated. IFN-γ and IFN-ß mRNA decreased in lesional DM skin but not in PBMCs. IMC findings revealed that CB2R was upregulated in DM lesional skin compared to HC skin and DM PBMCs (p<0.05). In DM skin, CB2R was upregulated on dendritic cells, B cells, T cells, and macrophages while dendritic cells had the greatest expression in both DM skin and PBMCs (p<0.05). These CB2R+ cells in the skin produce IL-31, IL-4, IFN-γ, and IFN-ß. CONCLUSION: Our findings of differential CB2R expression based on location and cell type suggest modes by which lenabasum may exert anti-inflammatory effects in DM and highlights dendritic cells as potential therapeutic targets.

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.

Quality of life in dermatomyositis.

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.

Cutaneous lupus concerns from the patient perspective: a qualitative study.

OBJECTIVE: There is a need to identify concerns unique to patients with cutaneous lupus erythematosus (CLE), which may not be captured by current common-practice dermatological quality-of-life tools. This study formally characterises what bothers patients with CLE about their disease by conducting semistructured, qualitative interviews. METHODS: Sixteen patients with CLE were interviewed about how their cutaneous findings impact their daily life. Each interview was transcribed, coded and categorised for recurrent themes. Current CLE activity and damage were also assessed by the Cutaneous Lupus Activity and Severity Index tool. RESULTS: Responses were categorised into six themes, including Fear of Disease Progression, Unwanted Attention, Self-Consciousness, Physical Signs/Symptoms, Emotional Symptoms and Functional Decline. The most commonly reported themes were Self-Consciousness, mentioned by 13 of 16 (81.3%) patients, Physical Symptoms, mentioned by 12 of 16 (75%), and then Fear of Disease Progression, by 11 of 16 (68.8%). Frequently mentioned physical signs/symptoms included erythema, itch, dyspigmentation, scar and alopecia. The physical signs/symptoms were categorised as activity signs/symptoms, damage signs and other. For activity signs, erythema was mentioned most frequently (5 of 16), then scale (2 of 16). For activity symptoms, itch was mentioned most frequently (6 of 16), then pain (5 of 16). For damage signs, dyspigmentation was mentioned most frequently (4 of 16), followed by scarring (3 of 16). Patients less than 60 years old were more likely to report emotional symptoms than older patients (p<0.05), but there was no significant variation in frequency of reported themes between race, sex or subtype of CLE. CONCLUSIONS: These patient experiences and resultant themes elucidated by this study are worth noting in future standardised estimations of the quality of life of patients with CLE. Additionally, the concerns shown by these interviews are important topics for providers to discuss when evaluating patient disease progression.

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

Pemphigus is a debilitating IgG-mediated autoimmune disease requiring better tolerated, more targeted, and rapid onset therapies. ALXN1830 is a humanized IgG4 antibody that blocks neonatal Fc receptor 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, were determined. In this pilot study of eight patients, five weekly infusions of ALXN1830 produced a rapid improvement in the pemphigus disease area index score within 14 days of the first dose. Pemphigus disease area index improvement increased further together with reductions in IgG, circulating immune complexes of IgG, 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 neonatal Fc receptor in the biology of pemphigus and the potential for use of ALXN1830 in pemphigus treatment.

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

Objective: 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. Methods: The study was conducted as a single-site, double-blind, paired study. Participants: 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. Results: The study found a statistically significant difference (P<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. Conclusion: 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.

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

Background: 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). Objective: 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. Methods and materials: 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. Results: 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. Conclusion: 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.